Pediatric Nephrology

No Issue Number

• Unexplained hypothermia and bradycardia in two pediatric patients with Wegener’s granulomatosis
  

  Unexplained hypothermia and bradycardia in two pediatric patients with Wegener’s granulomatosis

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1635-6
  • Authors
    • Lianne M. Geerdink, Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    • Linda Koster-Kamphuis, Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    • Elisabeth A. M. Cornelissen, Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    • Michèl A. Willemsen, Department of Paediatric Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • Nicole C. A. J. van de Kar, Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Cystinosis: practical tools for diagnosis and treatment
  
  Abstract  

  Cystinosis is the major cause of inherited Fanconi syndrome, and should be suspected in young children with failure to thrive and signs of renal proximal tubular damage. The diagnosis can be missed in infants, because not all signs of renal Fanconi syndrome are present during the first months of life. In older patients cystinosis can mimic idiopathic nephrotic syndrome due to focal and segmental glomerulosclerosis. Measuring elevated white blood cell cystine content is the corner stone for the diagnosis. The diagnosis is confirmed by molecular analysis of the cystinosin gene. Corneal cystine crystals are invariably present in all patients with cystinosis after the age of 1 year. Treatment with the cystine depleting drug cysteamine should be initiated as soon as possible and continued lifelong to prolong renal function survival and protect extra-renal organs. This educational feature provides practical tools for the diagnosis and treatment of cystinosis.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1627-6
  • Authors
    • Martijn J. Wilmer, Laboratory of Pediatrics, Katholieke Universiteit Leuven, Leuven, Belgium
    • Joost P. Schoeber, Laboratory of Pediatrics, Katholieke Universiteit Leuven, Leuven, Belgium
    • Lambertus P. van den Heuvel, Laboratory of Pediatrics, Katholieke Universiteit Leuven, Leuven, Belgium
    • Elena N. Levtchenko, Laboratory of Pediatrics, Katholieke Universiteit Leuven, Leuven, Belgium
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Unilateral localized cystic kidney: Answer
  <p class="abstract">Unilateral localized cystic kidney: Answer</p><ul> <li><span class="labelName">Content Type </span><span class="labelValue">Journal Article</span></li><li>DOI 10.1007/s00467-010-1622-y</li><li><span class="labelName">Authors</span><ul> <li>Priya Verghese, Division of Nephrology, Department of Pediatrics, University of Minnesota, Moos 13-148, 420 Delaware Street SE, MMC 491, Minneapolis, MN 55455, USA</li><li>Youngki Kim, Division of Nephrology, Department of Pediatrics, University of Minnesota, Moos 13-148, 420 Delaware Street SE, MMC 491, Minneapolis, MN 55455, USA</li> </ul></li> </ul><ul class="parents"> <ul class="details"> <li><span class="header labelName">Journal </span><span class="labelValue"><a href="http://www.springerlink.com/content/100382/">Pediatric Nephrology</a></span></li><li><span class="labelName">Online ISSN </span><span class="labelValue">1432-198X</span></li><li><span class="labelName">Print ISSN </span><span class="labelValue">0931-041X</span></li> </ul> </ul>
  
• Genetics of congenital anomalies of the kidney and urinary tract
  
  Abstract  

  Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 1 in 500 births and are a major cause of morbidity in children. Notably, CAKUT account for the most cases of pediatric end-stage renal disease and predispose the individual to hypertension and cardiovascular disease throughout life. Although some forms of CAKUT are a part of a syndrome or are associated with a positive family history, most cases of renal system anomalies are sporadic and isolated to the urinary tract. Broad phenotypic spectrum of CAKUT and variability in genotype–phenotype correlation indicate that pathogenesis of CAKUT is a complex process that depends on interplay of many factors. This review focuses on the genetic mechanisms (single-gene mutations, modifier genes) leading to renal system anomalies in humans and discusses emerging insights into the role of epigenetics, in utero environmental factors, and micro-RNAs (miRNAs) in the pathogenesis of CAKUT. Common gene networks that function in defined temporospatial fashion to orchestrate renal system morphogenesis are highlighted. Derangements in cellular, molecular, and morphogenetic mechanisms that direct normal renal system development are emphasized as a major cause of CAKUT. Integrated understanding of how morphogenetic process disruptions are linked to CAKUT will enable improved diagnosis, treatment, and prevention of congenital renal system anomalies and their consequences.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1629-4
  • Authors
    • Renfang Song, Section of Pediatric Nephrology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
    • Ihor V. Yosypiv, Section of Pediatric Nephrology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• The primary cilium in different tissues—lessons from patients and animal models
  
  Abstract  

  Primary cilia are specialized organelles consisting of an axoneme anchored to the plasma membrane through the basal body consisting of two centrioles. They protrude from the cell surface of almost all mammalian cells. Mutations in genes encoding for ciliary proteins cause ciliopathies, which are characterized by a wide spectrum of phenotypes, including polycystic kidney, hepatic disease, malformations in the central nervous system, skeletal defects, retinal degeneration, and obesity. Both clinical studies and animal models have revealed that during embryogenesis, primary cilium play an essential role in defining the correct patterning of the body. In this study, we focused our attention on the tissues mainly affected in ciliopathies, such as the kidney, liver, and central nervous system. Emerging studies reveal that the primary cilium may play similar roles, leading to distinct functions according to the different cell type and developmental stages. The state of the art in primary cilia studies reveals a very complex role. The aim of this review is to evaluate the recent advances in the function of primary cilia in different tissues, underlining similarities and differences.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1650-7
  • Authors
    • Anna D’Angelo, Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy
    • Brunella Franco, Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Intestinal damage in enterohemorrhagic Escherichia coli infection
  
  Abstract  

  Enterohemorrhagic Escherichia coli (EHEC) infection leads to marked intestinal injury. Sigmoid colon obtained from two children during EHEC infection exhibited abundant TUNEL-positive cells. To define which bacterial virulence factors contribute to intestinal injury the presence of Shiga toxin-2 (Stx2), intimin and the type III secretion system were correlated with symptoms and intestinal damage. C3H/HeN mice were inoculated with Stx2-producing (86-24) and non-producing (87-23) E. coli O157:H7 strains and 86-24 mutants lacking eae , encoding intimin (strain UMD619) or escN regulating the expression of type III secretion effectors (strain CVD451). Severe symptoms developed in mice inoculated with 86-24 and 87-23. Few mice inoculated with the mutant strains developed severe symptoms. Strain 86-24 exhibited higher fecal bacterial counts, followed by 87-23, whereas strains UMD619 and CVD451 showed minimal fecal counts. More TUNEL-positive cells were found in proximal and distal colons of mice inoculated with strain 86-24 compared with strains 87-23 and CVD451 ( p  ≤ 0.01) or UMD619 ( p  < 0.05, proximal colon, p  < 0.01, distal colon). The results show that strains 86-24 and 87-23 exhibited better colonic persistence and more symptoms, presumably due to the presence of intimin and type III secretion effectors. Extensive intestinal mucosal cell death was related to the presence of Stx2.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1616-9
  • Authors
    • Zivile D. Békássy, Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden
    • Carla Calderon Toledo, Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden
    • Gustav Leoj, Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden
    • AnnCharlotte Kristoffersson, Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden
    • Shana R. Leopold, Department of Pediatrics, Washington University School of Medicine, St Louis, MO USA
    • Maria-Thereza Perez, Department of Ophthalmology, Clinical Sciences Lund, Lund University, Lund, Sweden
    • Diana Karpman, Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Renal failure induced by Cortinarius poisoning
  

  Renal failure induced by Cortinarius poisoning

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1665-0
  • Authors
    • Alain Wynckel, Nephrology Department, CHU de Reims, 47–51 rue Cognacq Jay, 51092 Reims, France
    • Deborah Talmud, Pediatric Department, American Memorial Hospital, CHU de Reims, Reims, France
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Fatal renal failure caused by Cortinarius mushrooms
  

  Fatal renal failure caused by Cortinarius mushrooms

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1664-1
  • Authors
    • Martin Kirchmair, Institute of Microbiology, University of Innsbruck, Technikerstr. 25, 6020 Innsbruck, Austria
    • Reinhold Pöder, Institute of Microbiology, University of Innsbruck, Technikerstr. 25, 6020 Innsbruck, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Intradialytic hypotension
  
  Abstract  

  Intradialytic hypotension (IDH) is common in children during conventional, 4 hour haemodialysis (HD) sessions. The declining blood pressure (BP) was originally believed to be caused by ultrafiltration (UF) and priming of the HD circuit, however emerging data now supports a multifactorial aetiology. Therefore strategies to improve haemodynamic stability need to be diverse and address specific patient requirements or risks. In the treatment of IDH immediate action is required to stop or reduce the severity of symptoms that may precede or follow. Typically UF is slowed or stopped, a fluid bolus is given and in resistant cases the HD session is prematurely discontinued. Patients complete their treatment under-dialysed and volume expanded. Chronically, repeated episodes of IDH cause devastating, multi-system morbidity with an increased risk of mortality. This had provided the impetus for more haemodynamically friendly dialysis prescriptions that attenuate the risk of IDH. During pediatric HD several preventative strategies have been tested but with variable success. Of these, dialysate sodium profiling, UF guided by relative blood volume (RBV) algorithms, cooling and intradialytic mannitol appear to be the most effective. However in refractory cases one may be left with no option but to switch dialysis modality to haemodiafiltration (HDF) or more frequent or prolonged HD regimens.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1661-4
  • Authors
    • Wesley Hayes, Nephrology Department, Nottingham Children’s Hospital, Nottingham, UK
    • Daljit K. Hothi, Nephrology Department, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH UK
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Advances in our understanding of the pathogenesis of glomerular thrombotic microangiopathy
  
  Abstract  

  Glomerular thrombotic microangiopathy is a hallmark feature of haemolytic uraemic syndrome, the leading cause of acute renal failure in childhood. This paper is a review of the different mechanistic pathways that lead to this histological picture in the kidney. It will focus on atypical HUS and complement dysregulation, but will also highlight some other recent advances in our understanding of this condition, including the potential role of the molecule vascular endothelial growth factor- A (VEGF-A).
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1637-4
  • Authors
    • Lindsay Keir, Department of Medical Pediatrics, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK
    • Richard J. M. Coward, Academic and Children’s Renal Unit, University of Bristol and Bristol Royal Hospital for Children, Bristol, UK
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Pharmacokinetics of cysteamine in a cystinosis patient treated with hemodialysis
  <p class="abstract">Pharmacokinetics of cysteamine in a cystinosis patient treated with hemodialysis</p><ul> <li><span class="labelName">Content Type </span><span class="labelValue">Journal Article</span></li><li>DOI 10.1007/s00467-010-1680-1</li><li><span class="labelName">Authors</span><ul> <li>Martine Besouw, Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium</li><li>Elena Levtchenko, Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium</li> </ul></li> </ul><ul class="parents"> <ul class="details"> <li><span class="header labelName">Journal </span><span class="labelValue"><a href="http://www.springerlink.com/content/100382/">Pediatric Nephrology</a></span></li><li><span class="labelName">Online ISSN </span><span class="labelValue">1432-198X</span></li><li><span class="labelName">Print ISSN </span><span class="labelValue">0931-041X</span></li> </ul> </ul>
  
• Urinary biomarkers to detect acute kidney injury in the pediatric emergency center
  
  Abstract  

  We conducted a prospective study in pediatric patients presenting to an emergency center (EC) to (1) test the ability of urinary acute kidney injury (AKI) biomarkers to predict AKI presence and severity and (2) determine if these biomarkers offer similar precision in patients with versus without a known baseline SCr. The accuracy of five putative urinary biomarkers to detect AKI presence and severity was evaluated in 252 children presenting to our EC. AKI was defined by the modified pediatric RIFLE (pRIFLE) system. Eighteen children had AKI by pRIFLE, yet 33–50% of these AKI cases may have been missed since the EC SCr was <1 mg/dl. Urinary NGAL, Kidney Injury Molecule-1 (KIM-1) and beta-2 microglobulin (β2M) all demonstrated good to very good accuracy (AUC > 0.70 to 0.80) to predict patients with pRIFLE-Injury (>50% decrease in eCCl) versus patients with pRIFLE-Risk (25–50% decrease in eCCl) or without AKI. Our data suggest urinary biomarkers may serve well to detect AKI accurately in the pediatric EC setting, even in cases where SCr levels are normal. Further study is required to determine if these biomarkers obtained in the EC can predict AKI development or progression in hospitalized patients.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1673-0
  • Authors
    • Yue Du, Pediatrics-Renal, Baylor College of Medicine, Houston, TX USA
    • Michael Zappitelli, Pediatrics-Renal, McGill University, Montreal, Quebec Canada
    • Asad Mian, Pediatrics-Emergency Medicine, Baylor College of Medicine, Houston, TX USA
    • Michael Bennett, Nephrology and Hypertension, Cincinnati Children’s Hospital and Medical Center, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH 45229, USA
    • Qing Ma, Nephrology and Hypertension, Cincinnati Children’s Hospital and Medical Center, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH 45229, USA
    • Prasad Devarajan, Nephrology and Hypertension, Cincinnati Children’s Hospital and Medical Center, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH 45229, USA
    • Ravindra Mehta, Internal Medicine-Nephrology, University of California, San Diego, CA USA
    • Stuart L. Goldstein, Nephrology and Hypertension, Cincinnati Children’s Hospital and Medical Center, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH 45229, USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Hypochloremic metabolic alkalosis and failure to thrive: answer
  

  Hypochloremic metabolic alkalosis and failure to thrive: answer

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1667-y
  • Authors
    • Uwe Querfeld, Department of Pediatric Nephrology, Charité Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
    • Silvia Lechner, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria
    • Andreas R. Janecke, Department of Pediatrics II, Innsbruck Medical University, Innsbruck, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Management of toxic ingestions with the use of renal replacement therapy
  
  Abstract  

  Although rare, renal replacement therapy (RRT) for the treatment of the metabolic, respiratory and hemodynamic complications of intoxications may be required. Understanding the natural clearance of the medications along with their volume of distribution, protein binding and molecular weight will help in understanding the benefit of commencing RRT. This information will aid in choosing the optimal forms of RRT in an urgent setting. Overdose of common pediatric medications are discussed with suggestions on the type of RRT within this educational review.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1654-3
  • Authors
    • Timothy E. Bunchman, Pediatric Nephrology and Transplantation, Michigan State University, Grand Rapids, MI 49503, USA
    • Maria E. Ferris, Pediatric Nephrology, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, NC USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues
  
  Abstract  

  Epidemiological and experimental studies show that the risk of cardiovascular and metabolic diseases at adulthood is inversely related to the weight at birth. Although with less evidence, low birth weight has been suggested to increase the risk of chronic kidney disease (CKD). It is well established that the developmental programming of arterial hypertension and of renal disease involves in particular renal factors, especially nephron endowment, which is reduced in low birth weight and maternal diabetes situations. Experimental studies, especially in rodents, have demonstrated the long-term influence of postnatal nutrition and/or postnatal growth on cardiovascular, metabolic and renal functions, while human data are scarce on this issue. Vascular and renal diseases appear to have a “multihits” origin, with reduced nephron number the initial hit and rapid postnatal growth the second hit. This review addresses the current understanding of the role of the kidney, both as a mechanism and as a target, in the developmental origins of adult disease theory, with a particular focus on the long-term effects of postnatal growth and nutrition.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1648-1
  • Authors
    • Umberto Simeoni, Division of Neonatology, Hôpital la Conception, Assistance Publique-Hôpitaux de Marseille, 147 Boulevard Baille, 13385 Marseille, France
    • Isabelle Ligi, Division of Neonatology, Hôpital la Conception, Assistance Publique-Hôpitaux de Marseille, 147 Boulevard Baille, 13385 Marseille, France
    • Christophe Buffat, INSERM UMR608, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
    • Farid Boubred, Division of Neonatology, Hôpital la Conception, Assistance Publique-Hôpitaux de Marseille, 147 Boulevard Baille, 13385 Marseille, France
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Dent’s disease: clinical features and molecular basis
  
  Abstract  

  Dent’s disease is an X-linked recessive renal tubulopathy characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. LMWP is the most constant feature, while the other clinical manifestations show wide variability. Patients also present variable manifestations of proximal tubule dysfunctions, such as aminoaciduria, glucosuria, hyperphosphaturia, kaliuresis, and uricosuria, consistent with renal Fanconi syndrome. Dent’s disease affects mainly male children, and female carriers are generally asymptomatic. In two-thirds of patients, the disease is caused by mutations in the CLCN5 gene, which encodes the electrogenic chloride/proton exchanger ClC-5. A few patients have mutations in OCRL1 , the gene associated with the oculocerebrorenal syndrome of Lowe, which encodes a phosphatidylinositol-4,5-biphosphate-5-phosphatase (OCRL1). Both ClC-5 and OCRL1 are involved in the endocytic pathway for reabsorption of LMW proteins in the proximal tubule. This review will provide an overview of the important phenotypic characteristics of Dent’s disease and summarize the molecular data that have significantly increased our comprehension of the mechanisms causing this disease.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1657-0
  • Authors
    • Félix Claverie-Martín, Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
    • Elena Ramos-Trujillo, Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
    • Víctor García-Nieto, Unidad de Nefrología Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Acute kidney injury in childhood: should we be worried about progression to CKD'
  
  Abstract  

  While emerging evidence indicates that the incidence of both acute kidney injury (AKI) and chronic kidney disease (CKD) in children is rising and that the etiologies are dramatically changing, relatively little is currently known regarding the potential for transition from AKI to CKD. Major barriers to assessing for a potential AKI to CKD link have included lack of a standard pediatric AKI definition, narrow focus only on children with AKI who receive renal replacement therapy, and reliance on serum creatinine as the main biomarker to detect and diagnose AKI and CKD. Recent data have validated a multi-dimensional AKI classification system for children and have suggested chronic kidney sequelae in pediatric populations with AKI or at risk for AKI. In addition, a number of novel AKI biomarkers are being rigorously validated as early indicators of incipient CKD. Our goals for this article are to (1) review the recent changes in pediatric AKI and CKD epidemiology, (2) explore the evidence for a potential AKI to CKD link, and (3) propose new clinical and research paradigms to better elucidate the progression from AKI to CKD.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1653-4
  • Authors
    • Stuart L. Goldstein, Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH 54229-3039, USA
    • Prasad Devarajan, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Diagnosis and management of childhood polycystic kidney disease
  
  Abstract  

  A number of syndromic disorders have renal cysts as a component of their phenotypes. These disorders can generally be distinguished from autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) by imaging studies of their characteristic, predominantly non-renal associated abnormalities. Therefore, a major distinction in the differential diagnosis of enlarge echogenic kidneys is delineating ARPKD from ADPKD. ADPKD and ARPKD can be diagnosed by imaging the kidney with ultrasound, computed tomography, or magnetic resonance imaging (MRI), although ultrasound is still the method of choice for diagnosis in utero and in young children due to ease of use, cost, and safety. Differences in ultrasound characteristics, the presence or absence of associated extrarenal abnormalities, and the screening of the parents >40 years of age usually allow the clinician to make an accurate diagnosis. Early diagnosis of ADPKD and ARPKD affords the opportunity for maximal anticipatory care (i.e. blood pressure control) and in the not-too-distant future, the opportunity to benefit from new therapies currently being developed. If results are equivocal, genetic testing is available for both ARPKD and ADPKD. Specialized centers are now offering preimplantation genetic diagnosis and in vitro fertilization for parents who have previously had a child with ARPKD. For ADPKD patients, a number of therapeutic interventions are currently in clinical trial and may soon be available.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1656-1
  • Authors
    • William E. Sweeney, Department of Pediatrics, Research Center of Excellence in Pediatric Nephrology, Children’s Research Institute, Children’s Hospital Health System of Wisconsin and Medical College of Wisconsin, Milwaukee, WI USA
    • Ellis D. Avner, Department of Pediatrics, Research Center of Excellence in Pediatric Nephrology, Children’s Research Institute, Children’s Hospital Health System of Wisconsin and Medical College of Wisconsin, Milwaukee, WI USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Relevance of a database for monitoring a cooperative paediatric nephrology project in Nicaragua
  

  Relevance of a database for monitoring a cooperative paediatric nephrology project in Nicaragua

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1681-0
  • Authors
    • Giuseppina Marra, Pediatric Nephrology and Dialysis Unit, Clinica Pediatrica G. e D. De Marchi, Fondazione O.M. Policlinico Mangiagalli e Regina Elena, Via Commenda 9, 20122 Milan, Italy
    • Alberto Edefonti, Pediatric Nephrology and Dialysis Unit, Clinica Pediatrica G. e D. De Marchi, Fondazione O.M. Policlinico Mangiagalli e Regina Elena, Via Commenda 9, 20122 Milan, Italy
    • Yajaira Silva Galan, Departamento de Nefrologia y Urologia, Hospital Infantil de Nicaragua “Manuel de Jesus Rivera”, Managua, Nicaragua
    • Mabel Sandoval, Departamento de Nefrologia y Urologia, Hospital Infantil de Nicaragua “Manuel de Jesus Rivera”, Managua, Nicaragua
    • Fabio Sereni, University of Milan Medical School—Associazione per il Bambino Nefropatico Onlus, Milan, Italy
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Hypochloremic metabolic alkalosis and failure to thrive: question
  

  Hypochloremic metabolic alkalosis and failure to thrive: question

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1662-3
  • Authors
    • Uwe Querfeld, Department of Pediatric Nephrology, Charité Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
    • Silvia Lechner, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria
    • Andreas R. Janecke, Department of Pediatrics II, Innsbruck Medical University, Innsbruck, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Recurrence of membranoproliferative glomerulonephritis after renal transplantation in Denys–Drash
  
  Abstract  

  Denys–Drash syndrome (DDS) consists of the triad of nephropathy, male pseudohermaphroditism, and Wilms tumor caused by mutations within exons 8 or 9 of the Wilms tumor suppressor gene 1. Early onset nephrotic syndrome progresses to end-stage renal failure. The characteristic histological lesion is diffuse mesangial sclerosis. Here, we report on a boy with DDS who presented early with diffuse mesangial sclerosis, but subsequently also developed immune complex glomerulonephritis with a membranoproliferative pattern (MPGN-pattern GN) in his native kidneys. Four years after renal transplantation, immune complex glomerulonephritis with an MPGN pattern recurred in the renal graft resulting in proteinuria and progressive renal insufficiency.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1669-9
  • Authors
    • Thomas J. Neuhaus, Department of Pediatrics, Children’s Hospital Lucerne, Spitalstrasse, 6000 Lucerne 16, Switzerland
    • Walter Arnold, Department of Pathology, Cantonal Hospital Lucerne, Lucerne, Switzerland
    • Ariana Gaspert, Department of Pathology, University Hospital Zurich, Zurich, Switzerland
    • Helmut Hopfer, Department of Pathology, University of Basle, Basle, Switzerland
    • Andreas Fischer, Nephrology Unit, Cantonal Hospital Lucerne, Lucerne, Switzerland
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Urinary transforming growth factor beta-1 as a marker of renal dysfunction in sickle cell disease
  
  Abstract  

  Renal dysfunction affects 5–18% of patients with sickle cell disease (SCD). To date, no studies have described urinary levels of transforming growth factor β-1 (TGF-β1), a marker of fibrosis, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute/chronic kidney disease, as biomarkers in identifying patients at risk of developing renal disease in SCD. We hypothesized that SCD subjects will have increased urinary excretion of TGF-β1 and NGAL compared with healthy controls (CTR). We examined 51 SCD subjects: 42 HbSS, 8 HbSC, and 1 HbSD. Sixteen out of 42 patients with HbSS were on hydroxyurea (HU). Urinary excretion of TGF-β1 was 26.4 ± 1.5 pg/mgCr in SCD subjects vs 15.0 ± 2.4 pg/mgCr in CTR ( p  < 0.00001). SCD patients with hemoglobin < 9 g/dl had higher urinary TGF-β1 than patients with milder anemia ( p  = 0.002). Urinary TGF-β1 trended lower in HbSS patients treated with HU (23.61 ± 2.6 pg/mgCr), vs patients not on HU (27.69 ± 1.8 pg/mgCr; p  = 0.055). There was no correlation between urinary TGF-β1 and microalbuminuria or estimated glomerular function. There was no difference in urinary NGAL in SCD patients vs CTR. We suggest that urinary TGF-β1 may serve as a marker of early renal injury in SCD.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1677-9
  • Authors
    • Davoud Mohtat, Department of Pediatric Nephrology, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, 111 East 210th Street, Bronx, NY 10467, USA
    • Rosemary Thomas, Department of Pediatric Nephrology, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, 111 East 210th Street, Bronx, NY 10467, USA
    • Zangfang Du, Department of Pediatric Nephrology, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, 111 East 210th Street, Bronx, NY 10467, USA
    • Yaa Boakye, Department of Pediatric Nephrology, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, 111 East 210th Street, Bronx, NY 10467, USA
    • Thomas Moulton, Department of Pediatric Hematology/Oncology, Bronx Lebanon Hospital, Bronx, NY USA
    • Catherine Driscoll, Department of Pediatric Hematology/Oncology, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY USA
    • Robert Woroniecki, Department of Pediatric Nephrology, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, 111 East 210th Street, Bronx, NY 10467, USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Does immigration background influence outcomes after renal transplantation'
  
  Abstract  

  Migration implies differences in lifestyle, dietary and health behavior practice, and adherence, all of which are relevant factors in terms of disease outcome. However, renal transplantation in immigrant groups has been rarely studied in Europe. We have investigated the effect of immigration on outcomes in all children who underwent renal transplantation (RTx) at the Medical University of Vienna. From 1978 to 2007, 196 children underwent 236 RTx. In comparison to native recipients, immigrant recipients (31 boys, 17 girls) tended to be younger and male, with a higher rate of congenital renal diseases. The percentage of adolescent immigrant recipients tended to be lower, and living donation tended to be higher. In both the immigrant and native groups, RTx outcomes at 1, 5, and 10 years, including acute rejection rate (34 vs. 44, 55 vs. 62, 74 vs. 78%, respectively) and patient (98 vs. 92, 88 vs. 91, 80 vs. 82%, respectively) and graft survival (83 vs. 82, 79 vs. 65, 66 vs. 51%, respectively) were similar. All outcomes improved over time. In conclusion, this study demonstrates that outcomes in RTx are equivalent in immigrants and native recipients. Potential barriers to success among the Austrian immigrant recipient population may have been overcome by protective factors. These results should serve as a catalyst to retrieve data from larger databases to verify these single-center results.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1685-9
  • Authors
    • Fatma Zehra Oztek, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
    • Pinar Tekin, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
    • Marion Herle, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
    • Thomas Mueller, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
    • Klaus Arbeiter, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
    • Christoph Aufricht, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis
  
  Abstract  

  Acute idiopathic tubulointerstitial nephritis (TIN) is considered a condition with a good long-term prognosis. However, there is evidence that some patients develop permanent renal impairment. The aim of this study was to evaluate the clinical characteristics of TIN at the time of diagnosis in children and determine whether the findings upon presentation predict renal outcome. The clinical data and biopsy findings from 26 children with idiopathic TIN admitted to four Finnish university hospitals were analyzed retrospectively. Twenty-five patients (96%) manifested renal insufficiency. After the mean follow-up time of 2.75 years (SD 2.5; 0.9–13.5), 4 patients (15%) had permanent renal insufficiency and 8 patients (31%) had persistent low-molecular weight proteinuria. Uveitis was found in 12 patients (46%). Four of these patients (33%) developed chronic uveitis. Our analysis showed that none of the laboratory or biopsy findings upon presentation prognosticated renal outcome. No correlation between renal disease and uveitis could be found either. The occurrence of uveitis among TIN patients was higher than previously reported. Uveitis may develop late and without recurrence of renal dysfunction. Therefore, follow-up by a pediatrician and by an ophthalmologist is warranted in children with acute TIN for at least 12 months from diagnosis.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1698-4
  • Authors
    • Timo Jahnukainen, Department of Pediatric Nephrology and Transplantation, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, Box 281, 00029 Helsinki, Finland
    • Marja Ala-Houhala, Department of Pediatrics, Tampere University Hospital, Tampere, Finland
    • Riitta Karikoski, Department of Pathology, Helsinki University Hospital, Helsinki, Finland
    • Janne Kataja, Department of Pediatrics, Turku University Hospital, Turku, Finland
    • Ville Saarela, Department of Ophthalmology, Oulu University Hospital, Oulu, Finland
    • Matti Nuutinen, Department of Pediatrics and Adolescence, Oulu University Hospital, Oulu, Finland
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets
  
  Abstract  

  Children with X-linked hypophosphatemic rickets (XLH) are prone to severe stunting. A multicenter mixed-longitudinal study was conducted to assess age-related stature, sitting height, arm and leg length in XLH patients on continuous treatment with phosphate and calcitriol. Mean standard deviation scores (SDS) for all body dimensions were markedly reduced and differed significantly among each other at the initial and subsequent evaluations (baseline: stature −2.48 SDS; sitting height −0.99 SDS; arm length −1.81 SDS; leg length −2.90 SDS; each p  < 0.001). A strong association between stature and leg length ( r ² = 0.87, p  < 0.001) was noted. Leg length SDS decreased progressively during childhood (2–9 years) and adolescence (12–15 years; each p  < 0.001). Sitting height SDS increased significantly during late childhood, indicating uncoupled growth of the legs and trunk and resulting in an ever increasing sitting height index (i.e. ratio of sitting height to stature; age 2 years 2.0 SDS; age 10 years 3.3 SDS; p  < 0.001) that was associated with the degree of stunting ( r ²  = 0.314, p < 0.001). Mean serum phosphate levels were positively associated with stature and leg length, but negatively with sitting height index. Based on these results, we can conclude that growth of the legs and trunk is uncoupled in XLH and related to serum phosphate levels.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1705-9
  • Authors
    • Miroslav Živičnjak, Department of Pediatric Nephrology, Children’s Hospital of Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
    • Dirk Schnabel, Department of Pediatrics, University Children’s Hospital, Charité, 13353 Berlin, Germany
    • Heiko Billing, Department of Pediatrics, University Children’s Hospital, Charité, 13353 Berlin, Germany
    • Hagen Staude, Department of Pediatrics, University of Rostock, 18057 Rostock, Germany
    • Guido Filler, Department of Pediatrics, Children’s Hospital, London Health Science Centre, University of Western Ontario, N6A 5W9 London, ON Canada
    • Uwe Querfeld, Department of Pediatrics, University Children’s Hospital, Charité, 13353 Berlin, Germany
    • Marius Schumacher, Department of Pediatrics, University of Lübeck, 23538 Lübeck, Germany
    • Anke Pyper, Department of Pediatrics, University of Dresden, 01307 Dresden, Germany
    • Carmen Schröder, Department of Pediatrics, University of Greifswald, 17475 Greifswald, Germany
    • Jürgen Brämswig, Department of Pediatrics, University of Münster, 48149 Münster, Germany
    • Dieter Haffner, Department of Pediatrics, University of Rostock, 18057 Rostock, Germany
    • Hypophosphatemic Rickets Study Group of the “Arbeitsgemeinschaft für Pädiatrische Endokrinologie” and “Gesellschaft für Pädiatrische Nephrologie”
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Antioxidant status of children with idiopathic nephrotic syndrome
  
  Abstract  

  The production of free radicals can cause renal injury and play an important role in the pathogenesis of idiopathic nephrotic syndrome. Markers of reactive oxygen species (ROS) were evaluated in 48 patients with active nephrotic syndrome (ANS) and 30 age- and gender-matched healthy children. Plasma malondialdehyde (MDA), protein carbonyl, nitrite, copper, zinc, selenium, ascorbic acid, and superoxide dismutase (SOD) levels were estimated in patients with ANS and controls. Measurements were repeated in 39 cases after achievement of remission, and in 10 other children who were in remission of >6 months’ duration. Plasma MDA and nitrite levels were significantly higher and selenium was lower in ANS patients compared with controls. Plasma protein carbonyl, copper ascorbic acid, zinc, and superoxide dismutase levels were comparable in ANS patients and controls. Plasma copper level was significantly higher in active cases than in the remission and long-term remission groups. Selenium value showed a rise and then normalized in long-term remission. Among different sub-groups of ANS, no significant differences were found in the levels of various parameters, except plasma selenium, which was significantly lower in first-attack nephrotic syndrome (FANS) in comparison to infrequently relapsing nephrotic syndrome (IRNS) and frequently relapsing nephrotic syndrome (FRNS) patients. Thus, we observed evidence of oxidative stress and impaired antioxidant defense during acute nephrotic syndrome. Antioxidant status recovered completely only during long-term remission.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1696-6
  • Authors
    • Om P. Mishra, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Aditya K. Gupta, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Rajniti Prasad, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Ziledar Ali, Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Ram S. Upadhyay, Department of Botany, Faculty of Science, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Surendra P. Mishra, Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Narendra K. Tiwary, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India
    • Franz S. Schaefer, Division of Pediatric Nephrology, Centre for Pediatrics and Adolescent Medicine, University Medical Centre, Heidelberg, Germany
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Taking the pulse of a sick kidney: Arterial stiffness in glomerulonephritis
  
  Abstract  

  Arterial stiffness is an increasingly recognized independent predictor of cardiovascular morbidity. Vessel volume and wall texture are the main determinants of pulse wave velocity (PWV), the most commonly used indicator of arterial elasticity. Hence, measurements of PWV will be affected by the site of measurement and the overall dimensions of the vascular tree as well as by alterations of vascular morphology. In children, methodological heterogeneity and the lack of pediatric reference values complicate the interpretation of PWV. Arterial elasticity is altered in numerous clinical conditions such as vasculitis, end-stage renal disease, and diabetes. Novel evidence suggests that acute postinfectious glomerulonephritis, but not pyelonephritis, is also associated with increased arterial stiffness, the persistence of which may predict the emergence of chronic kidney disease. We review the potential mechanisms underlying the link between acute and chronic kidney disease and impaired arterial elasticity. These might include activation of the renin–angiotensin system, sympathetic hyperactivation, and a subclinical state of inflammation. In view of the excessive cardiovascular comorbidity associated with kidney disease, the increasing evidence of the prognostic relevance of arterial stiffness should encourage further research investigating the usefulness of PWV as a biomarker in acute and chronic kidney disorders.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1730-8
  • Authors
    • Anke Doyon, Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
    • Franz Schaefer, Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Additive effect of PPAR-γ agonist and ARB in treatment of experimental IgA nephropathy
  
  Abstract  

  Our recent in vitro study demonstrated peroxisome proliferator-activated receptor-γ (PPAR−γ) agonist potentiated the anti-inflammatory effect of angiotensin receptor blocker (ARB) in tubular epithelial cell under milieu mimicking IgA nephropathy (IgAN). Here we studied the therapeutic effect of combining a PPAR-γ agonist, rosiglitazone (Ros), with an ARB, losartan (Los), in experimental IgAN induced in Lewis rats by oral and intravenous immunization with bovine gamma-globulin (BGG). The rats were randomly divided into six groups: control, IgAN, IgAN with unilateral nephrectomy (IgAN/1K), and IgAN/1K receiving Ros, Los, or Ros + Los. Medication was given 1 week after nephrectomy until killing. Rats developing IgAN had hematuria, mesangial hypercellularity with IgA deposition, glomerular damage, and tubulointerstitial infiltration of CD25+ leukocytes accompanied by increased renal expression of TGF-β, AngII receptor subtype-1 (ATR1) and ICAM-1. The renal histopathology, albuminuria, and renal expression of TGF-β, ATR1 and ICAM-1 worsened with unilateral nephrectomy. Ros or Los reduced the renal expression of PCNA, TGF-β, ATR1, and ICAM-1 in IgAN rats with nephrectomy. Despite no difference between rats treated with monotherapy, combined therapy offered additive effect with decreased renal expression of TGF-β, ATR1 and ICAM-1 and attenuation of renal injury. Our animal study suggests combined PPAR-γ agonist and ARB holds promise for future therapy for IgAN.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1703-y
  • Authors
    • Kar Neng Lai, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, 102 Pokfulam Road, Hong Kong
    • Loretta Y. Y. Chan, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, 102 Pokfulam Road, Hong Kong
    • Hong Guo, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, 102 Pokfulam Road, Hong Kong
    • Sydney C. W. Tang, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, 102 Pokfulam Road, Hong Kong
    • Joseph C. K. Leung, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, 102 Pokfulam Road, Hong Kong
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Cystatin C, cardiometabolic risk, and body composition in severely obese children
  
  Abstract  

  The aim of this study was to assess the relationship between cystatin C (CysC), cardiometabolic risk factors (CMRFs), and body composition in severely obese children. We evaluated 117 children aged 7–14 years old. Seventy-nine of these were severely obese (body mass index z-score ranging from 2.1 to 8.4), and 38 were children with normal nutrition state. CysC was determined by immunonephelometry. CMRFs (glucose, insulin, high-density lipoprotein cholesterol, triglycerides, homocysteine, uric acid, alanine aminotransferase, and high-sensitivity C-reactive protein) were measured by standard biochemical methods. Blood pressure was evaluated at the clinical examination. Renal function was estimated using the glomerular filtration rate (eGFR) based upon creatinine levels, and body weight (Léger formula). Body composition was assessed by segmental bioelectrical impedance. Obese children at the highest tertile of CysC values were characterized by their aggregation of CMRFs. CysC concentration was associated with insulin resistance, alanine aminotransferase, uric acid, and homocysteine after adjusting for age, gender, and eGFR. CysC values were also correlated with the fat-free mass and specifically with skeletal muscle mass. CysC levels were correlated with CMRFs factors independently of renal function, and affected by skeletal muscle mass in severely obese children, although they are less influenced by this than is creatinine.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1679-7
  • Authors
    • Pilar Codoñer-Franch, Department of Pediatrics, Dr. Peset University Hospital, Avenida Gaspar Aguilar n° 90, 46017 Valencia, Spain
    • Esther Ballester-Asensio, Department of Pediatrics, Dr. Peset University Hospital, Avenida Gaspar Aguilar n° 90, 46017 Valencia, Spain
    • Lorena Martínez-Pons, Laboratory of Clinical Biochemistry, Dr. Peset University Hospital, Valencia, Spain
    • Jorge Vallecillo-Hernández, Laboratory of Clinical Biochemistry, Dr. Peset University Hospital, Valencia, Spain
    • Almudena Navarro-Ruíz, Department of Pediatrics, Dr. Peset University Hospital, Avenida Gaspar Aguilar n° 90, 46017 Valencia, Spain
    • Ramón del Valle-Pérez, Laboratory of Clinical Biochemistry, Dr. Peset University Hospital, Valencia, Spain
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Behavioral disorders and low quality of life in children and adolescents with chronic kidney disease
  
  Abstract  

  Recent years has seen an increasing interest in the quality of life (QOL) of children with chronic kidney disease (CKD). The objective of this cross-sectional study was to investigate the prevalence of behavioral disorders and to assess the health-related QOL (HRQOL) in 136 patients with CKD. To estimate the prevalence of behavior disorders and analyze HRQOL, we used the Strengths and Difficulties Questionnaire (SDQ) and Pediatric Inventory of Quality of Life (PedsQL) Core Scales as assessment tools for both the patients and caregivers. When compared to healthy controls, the CKD group had significantly lower scores in almost all PedsQL domains. After adjustment, only absence of religion/other religions remained significantly associated with a lower global HRQOL score [odds ratio (OR) 6.2, P  = 0.009]. Among the parents, two factors remained significantly associated with a lower global HRQOL score: patients’ age >10 years (OR 5.4, P = 0.033) and absence of religion/other religions (OR  3.2, P  = 0.038). The CKD group demonstrated a higher proportion of behavioral and emotional disorders in all SDQ domains. There was a negative correlation between the presence of behavior and emotional disorders and HRQOL score ( r  = −0.552, P  < 0.001). Our findings suggest the importance of evaluating behavioral and social repercussions of CKD in order to improve the life quality of this pediatric population.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1683-y
  • Authors
    • Renata C. Marciano, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Cristina M. Bouissou Soares, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • José Silvério S. Diniz, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Eleonora M. Lima, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Jose Maria P. Silva, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Monica R. Canhestro, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Andrea Gazzinelli, Nursing School, Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, MG Brazil
    • Carla Cristina D. Melo, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Cristiane S. Dias, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Ana Cristina Simões e Silva, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
    • Humberto Correa, Laboratory of Neuroscience, Department of Pediatrics, Hospital Das Clínicas, Federal University of Minas Gerais, Belo Horizonte, MG Brazil
    • Eduardo A. Oliveira, Pediatric Nephrology Unit, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG Brazil
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Novel mutations in steroid-resistant nephrotic syndrome diagnosed in Tunisian children
  
  Abstract  

  Steroid-resistant nephrotic syndrome (NS) remains one of the most intractable causes of end-stage renal disease in the first two decades of life. Several genes have been involved including NPHS1 , NPHS2 , WT1 , PLCE1 , and LAMB2 . Our aim was to identify causative mutations in these genes, in 24 children belonging to 13 families with NS manifesting with various ages of onset. We performed haplotype analysis and direct exon sequencing of NPHS1 , NPHS2 , PLCE1 , LAMB2, and the relevant exons 8 and 9 of WT1. Ten different pathogenic mutations were detected in seven families concerning four genes ( NPHS1 (3/7), LAMB2 (2/7), NPHS2 (1/7), and WT1 (1/7)). Five of the detected mutations were novel; IVS9 + 2 T > C and p.D616G in NPHS1 ; p.E371fsX16 in NPHS2 , and p.E705X and p.D1151fsX23 in LAMB2. Nine of 24 patients failed to be categorized by mutational analysis. Our study extends the spectrum of abnormalities underlying NS, by reporting novel mutations in the NPHS1 and NPHS2 genes and the first cases of LAMB2 mutations in Tunisia. Congenital and infantile NS can be explained by mutations in NPHS1 , NPHS2 , WT1 , or LAMB2 genes. The identification of additional genes mutated in NS can be anticipated.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1694-8
  • Authors
    • Ibtihel Benhaj Mbarek, Biochemistry Department, Sahloul University Hospital, 4054 Sousse, Tunisia
    • Saoussen Abroug, Pediatric Department, Sahloul University Hospital, Sousse, Tunisia
    • Asma Omezzine, Biochemistry Department, Sahloul University Hospital, 4054 Sousse, Tunisia
    • Audrey Pawtowski, Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France
    • Marie Claire Gubler, Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France
    • Ali Bouslama, Biochemistry Department, Sahloul University Hospital, 4054 Sousse, Tunisia
    • Abdelaziz Harbi, Pediatric Department, Sahloul University Hospital, Sousse, Tunisia
    • Corinne Antignac, Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• In memoriam: Professor Lothar Bernd Zimmerhackl 1952–2010
  

  In memoriam: Professor Lothar Bernd Zimmerhackl 1952–2010

  • Content Type Journal Article
  • Pages 1-2
  • DOI 10.1007/s00467-010-1711-y
  • Authors
    • Burkhard Tönshoff, Department of Pediatrics I (General Pediatrics, Metabolism, Gastroenterology, Nephrology), University Children’s Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Advances in our understanding of the pathogenesis of glomerular thrombotic microangiopathy
  
  Abstract  

  Glomerular thrombotic microangiopathy is a hallmark feature of haemolytic uraemic syndrome, the leading cause of acute renal failure in childhood. This paper is a review of the different mechanistic pathways that lead to this histological picture in the kidney. It will focus on atypical HUS and complement dysregulation, but will also highlight some other recent advances in our understanding of this condition, including the potential role of the molecule vascular endothelial growth factor- A (VEGF-A).
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1637-4
  • Authors
    • Lindsay Keir, Department of Medical Pediatrics, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK
    • Richard J. M. Coward, Academic and Children’s Renal Unit, University of Bristol and Bristol Royal Hospital for Children, Bristol, UK
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Intradialytic hypotension
  
  Abstract  

  Intradialytic hypotension (IDH) is common in children during conventional, 4 hour haemodialysis (HD) sessions. The declining blood pressure (BP) was originally believed to be caused by ultrafiltration (UF) and priming of the HD circuit, however emerging data now supports a multifactorial aetiology. Therefore strategies to improve haemodynamic stability need to be diverse and address specific patient requirements or risks. In the treatment of IDH immediate action is required to stop or reduce the severity of symptoms that may precede or follow. Typically UF is slowed or stopped, a fluid bolus is given and in resistant cases the HD session is prematurely discontinued. Patients complete their treatment under-dialysed and volume expanded. Chronically, repeated episodes of IDH cause devastating, multi-system morbidity with an increased risk of mortality. This had provided the impetus for more haemodynamically friendly dialysis prescriptions that attenuate the risk of IDH. During pediatric HD several preventative strategies have been tested but with variable success. Of these, dialysate sodium profiling, UF guided by relative blood volume (RBV) algorithms, cooling and intradialytic mannitol appear to be the most effective. However in refractory cases one may be left with no option but to switch dialysis modality to haemodiafiltration (HDF) or more frequent or prolonged HD regimens.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1661-4
  • Authors
    • Wesley Hayes, Nephrology Department, Nottingham Children’s Hospital, Nottingham, UK
    • Daljit K. Hothi, Nephrology Department, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH UK
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Hypochloremic metabolic alkalosis and failure to thrive: question
  

  Hypochloremic metabolic alkalosis and failure to thrive: question

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1662-3
  • Authors
    • Uwe Querfeld, Department of Pediatric Nephrology, Charité Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
    • Silvia Lechner, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria
    • Andreas R. Janecke, Department of Pediatrics II, Innsbruck Medical University, Innsbruck, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Hypochloremic metabolic alkalosis and failure to thrive: answer
  

  Hypochloremic metabolic alkalosis and failure to thrive: answer

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1667-y
  • Authors
    • Uwe Querfeld, Department of Pediatric Nephrology, Charité Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
    • Silvia Lechner, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria
    • Andreas R. Janecke, Department of Pediatrics II, Innsbruck Medical University, Innsbruck, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Pharmacokinetics of cysteamine in a cystinosis patient treated with hemodialysis
  <p class="abstract">Pharmacokinetics of cysteamine in a cystinosis patient treated with hemodialysis</p><ul> <li><span class="labelName">Content Type </span><span class="labelValue">Journal Article</span></li><li>DOI 10.1007/s00467-010-1680-1</li><li><span class="labelName">Authors</span><ul> <li>Martine Besouw, Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium</li><li>Elena Levtchenko, Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium</li> </ul></li> </ul><ul class="parents"> <ul class="details"> <li><span class="header labelName">Journal </span><span class="labelValue"><a href="http://www.springerlink.com/content/100382/">Pediatric Nephrology</a></span></li><li><span class="labelName">Online ISSN </span><span class="labelValue">1432-198X</span></li><li><span class="labelName">Print ISSN </span><span class="labelValue">0931-041X</span></li> </ul> </ul>
  
• Successful treatment and clearing of circulating CD19-positive cells by rituximab in a child with idiopathic membranous nephropathy
  

  Successful treatment and clearing of circulating CD19-positive cells by rituximab in a child with idiopathic membranous nephropathy

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1671-2
  • Authors
    • Bizhen Zhu, Department of Pediatrics, Peking University First Hospital, No.1, Xi An Men Da Jie, Beijing, 100034 People’s Republic of China
    • Jianping Huang, Department of Pediatrics, Peking University First Hospital, No.1, Xi An Men Da Jie, Beijing, 100034 People’s Republic of China
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Relevance of a database for monitoring a cooperative paediatric nephrology project in Nicaragua
  

  Relevance of a database for monitoring a cooperative paediatric nephrology project in Nicaragua

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1681-0
  • Authors
    • Giuseppina Marra, Pediatric Nephrology and Dialysis Unit, Clinica Pediatrica G. e D. De Marchi, Fondazione O.M. Policlinico Mangiagalli e Regina Elena, Via Commenda 9, 20122 Milan, Italy
    • Alberto Edefonti, Pediatric Nephrology and Dialysis Unit, Clinica Pediatrica G. e D. De Marchi, Fondazione O.M. Policlinico Mangiagalli e Regina Elena, Via Commenda 9, 20122 Milan, Italy
    • Yajaira Silva Galan, Departamento de Nefrologia y Urologia, Hospital Infantil de Nicaragua “Manuel de Jesus Rivera”, Managua, Nicaragua
    • Mabel Sandoval, Departamento de Nefrologia y Urologia, Hospital Infantil de Nicaragua “Manuel de Jesus Rivera”, Managua, Nicaragua
    • Fabio Sereni, University of Milan Medical School—Associazione per il Bambino Nefropatico Onlus, Milan, Italy
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Minimal change disease: a “two-hit” podocyte immune disorder'
  
  Abstract  

  Minimal change disease (MCD) is the most common nephrotic syndrome in children and is commonly thought to be a T-cell disorder mediated by a circulating factor that alters podocyte function resulting in massive proteinuria. We suggest that MCD is a “two-hit” disorder. As originally hypothesized by Reiser et al. in 2004, we propose that the initial hit is the induction of CD80 (also known as B7.1) on the podocyte, and that this results in an alteration in shape with actin rearrangement that alters glomerular permeability and causes proteinuria. We propose that CD80 expression may result from either direct binding of the podocyte by cytokines from activated T cells or by activation of podocyte toll-like receptors (TLR) by viral products or allergens. We further hypothesize that under normal circumstances, CD80 expression is only transiently expressed and proteinuria is minimal due to rapid autoregulatory response by circulating T regulatory cells or by the podocyte itself, probably due to the expression of factors [cytotoxic T-lymphocyte-associated (CTLA)-4, interleukin (IL)-10, and possibly transforming growth factor (TGF)-β] that downregulate the podocyte CD80 response. In MCD, however, there is a defect in CD80 podocyte autoregulation. This results in persistent CD80 expression and persistent proteinuria. If correct, this hypothesis may lead to both new diagnostic tests and potential therapeutics for this important renal disease.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1676-x
  • Authors
    • Michiko Shimada, Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, CO USA
    • Carlos Araya, Division of Pediatric Nephrology, University of Florida, Gainesville, FL USA
    • Chris Rivard, Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, CO USA
    • Takuji Ishimoto, Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, CO USA
    • Richard J. Johnson, Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, CO USA
    • Eduardo H. Garin, Division of Pediatric Nephrology, University of Florida, Gainesville, FL USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Diagnosis and management of childhood polycystic kidney disease
  
  Abstract  

  A number of syndromic disorders have renal cysts as a component of their phenotypes. These disorders can generally be distinguished from autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) by imaging studies of their characteristic, predominantly non-renal associated abnormalities. Therefore, a major distinction in the differential diagnosis of enlarge echogenic kidneys is delineating ARPKD from ADPKD. ADPKD and ARPKD can be diagnosed by imaging the kidney with ultrasound, computed tomography, or magnetic resonance imaging (MRI), although ultrasound is still the method of choice for diagnosis in utero and in young children due to ease of use, cost, and safety. Differences in ultrasound characteristics, the presence or absence of associated extrarenal abnormalities, and the screening of the parents >40 years of age usually allow the clinician to make an accurate diagnosis. Early diagnosis of ADPKD and ARPKD affords the opportunity for maximal anticipatory care (i.e. blood pressure control) and in the not-too-distant future, the opportunity to benefit from new therapies currently being developed. If results are equivocal, genetic testing is available for both ARPKD and ADPKD. Specialized centers are now offering preimplantation genetic diagnosis and in vitro fertilization for parents who have previously had a child with ARPKD. For ADPKD patients, a number of therapeutic interventions are currently in clinical trial and may soon be available.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1656-1
  • Authors
    • William E. Sweeney, Department of Pediatrics, Research Center of Excellence in Pediatric Nephrology, Children’s Research Institute, Children’s Hospital Health System of Wisconsin and Medical College of Wisconsin, Milwaukee, WI USA
    • Ellis D. Avner, Department of Pediatrics, Research Center of Excellence in Pediatric Nephrology, Children’s Research Institute, Children’s Hospital Health System of Wisconsin and Medical College of Wisconsin, Milwaukee, WI USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• An unusual case of hyperkalaemia in infancy: answer
  

  An unusual case of hyperkalaemia in infancy: answer

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1684-x
  • Authors
    • Mireille Formosa, Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL United Kingdom
    • Nicholas J. Webb, Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL United Kingdom
    • Mohan Shenoy, Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL United Kingdom
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Aciclovir and Varicella-zoster-immunoglobulin in solid-organ transplant recipients
  
  Abstract  

  Clear recommendations for the management of acute varicella-zoster virus (VZV) infections for cases of significant exposure and the use of prophylactic drugs after solid-organ transplantation are missing due to the lack of evidence by prospective studies. Heterogeneity in patient groups, patient numbers, age groups, immunosuppressive regimens, timing, and dosage of aciclovir and/or varicella-zoster immunoglobulin (VZIG), pre-transplant vaccination or VZV wild-type infection and inconsistency of data make comparability of different studies impossible. Although the benefit of aciclovir and/or VZIG is uncertain in immunosuppressed children, prospective controlled double-blind studies are not feasible for ethical considerations as fatal cases with disseminating varicella disease are well known in these patient groups despite the use of aciclovir and/or VZIG, whereas severe side-effects of these drugs are rare. However, a reporting bias is likely as mainly severe or fatal cases might have been predominantly published or cases of successfully used aciclovir and/or VZIG in mild cases or in cases of breakthrough infections after vaccination. As neither VZIG prophylaxis nor treatment with intravenous aciclovir offers complete protection against severe VZV infection to immunosuppressed pediatric solid-organ transplant recipients, high priority should be given to vaccination against VZV prior to transplantation, and, most importantly, in their close contact persons. Clinical observations suggest that only assessment of humoral immunity together with cellular immunity may allow predication about protection in exposed patients.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1666-z
  • Authors
    • Martina Prelog, Department of Pediatrics, Pediatrics I, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria
    • Jörn Schönlaub, Department of Pediatrics, Pediatrics I, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria
    • Lothar Bernd Zimmerhackl, Department of Pediatrics, Pediatrics I, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• An unusual case of hyperkalaemia in infancy: question
  

  An unusual case of hyperkalaemia in infancy: question

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1686-8
  • Authors
    • Mireille Formosa, Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL United Kingdom
    • Nicholas J. Webb, Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL United Kingdom
    • Mohan Shenoy, Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL United Kingdom
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Residual renal function assessment with cystatin C
  
  Abstract  

  Su Jin Kim and coworkers from Korea published an important study on the relationship of residual renal function (RRF) and cystatin in pediatric peritoneal dialysis (PD) patients in this issue of Pediatric Nephrology , both in anuric patients and patients with RRF. Based on a lack of correlation between cystatin C and standard small solute-based dialysis adequacy parameters such as Kt/V _urea but a significant correlation with RRF, the authors concluded that cystatin C may be a good tool to monitor RRF. The editorial reviews the available literature in adults, the different handing between urea and cystatin C, and the determinants of cystatin C clearance in dialysis patients. In adults, cystatin C levels are determined predominantly by RRF, but not exclusively. In anephric hemodialysis and PD patients, there is a correlation with standard weekly Kt/V _urea . Cystatin C levels will also depend on ultrafiltration. Despite these factors that affect cystatin C levels beyond RRF, cystatin C is a useful parameter for monitoring PD patients that may be more closely related to long-term outcomes than small solute adequacy parameters.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1672-1
  • Authors
    • Guido Filler, Division of Nephrology, Department of Pediatrics, The University of Western Ontario, London, Ontario Canada
    • Shih-Han S. Huang, Nephrology Division, Department of Medicine, The University of Western Ontario, London, Ontario Canada
    • Robert M. Lindsay, Nephrology Division, Department of Medicine, The University of Western Ontario, London, Ontario Canada
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Uraemic vasculopathy in children with chronic kidney disease: prevention or damage limitation'
  
  Abstract  

  Since the inception of pediatric dialysis programmes nearly 50 years ago, there have been vast improvements in both the technology and expertise in the care of children with chronic kidney disease (CKD). Nevertheless, children on dialysis continue to have a significantly higher mortality than their healthy peers and cardiovascular disease (CVD) is the most common cause of death in this group. Chronic kidney disease is described as the “perfect storm” of risk factors for CVD development, and vascular calcification is a highly regulated cell-mediated process with several promoters and inhibitors of calcification. CVD begins early in the course of CKD and there is an independent and graded association between cardiovascular morbidity and renal decline. Also, it is shown that once vascular damage and calcification begin, they progress inexorably in the uraemic milieu and may only be partially reversed after successful transplantation. Thus, preventing the development of CVD is key, and early identification and management of specific CVD-related risk factors should begin from the early stages of CKD. While the vasculopathy of childhood CKD is clearly multifactorial, clinical, epidemiological and cell biology studies provide converging evidence pointing to the role of dysregulated mineral metabolism as an important modifiable risk factor in the development of vascular calcification. In this review we focus on the role of calcium, phosphate, parathyroid hormone and vitamin D in ectopic vascular calcification, and discuss the role of screening, early intervention and management of established vascular calcification.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1691-y
  • Authors
    • Rukshana Shroff, Department of Nephrourology, Great Ormond Street Hospital for Children, NHS Trust, Great Ormond Street, London, WC1N 3JH United Kingdom
    • Catherine Quinlan, Department of Nephrourology, Great Ormond Street Hospital for Children, NHS Trust, Great Ormond Street, London, WC1N 3JH United Kingdom
    • Mark Mitsnefes, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Serum cystatin C for estimation of residual renal function in children on peritoneal dialysis
  
  Abstract  

  Residual renal function (RRF) is an important parameter in the management of patients on chronic dialysis. The aim of this cross-sectional study was to determine the efficacy of serum cystatin C (CysC) for RRF estimation in 20 children (16 boys, 4 girls; median age 13.4 years) undergoing peritoneal dialysis (PD). For studies of correlation with serum CysC, the average of creatinine clearance rate (C _cr ) and urea clearance rate (C _urea ), Kt/V _urea , and weekly C _cr were evaluated as parameters reflecting RRF. The serum CysC level was found to be negatively correlated with urine volume ( r  = −0.717, P  < 0.001), average of C _cr and C _urea ( r  = −0.851, P  < 0.001), total and renal weekly C _cr ( r  = −0.795, P  < 0.001; r  = −0.845, P  < 0.001, respectively), and renal Kt/V _urea ( r  = −0.793, P  < 0.001) and positively correlated with peritoneal weekly C _cr ( r  = 0.738, P  < 0.001) and peritoneal Kt/V _urea ( r  = 0.785, P  < 0.001). There was no significant association with total Kt/V _urea ( r  = −0.335, P  = 0.148). In non-anuric group of patients, serum CysC had no link to peritoneal Kt/V _urea ( r  = 0.573, P  = 0.066), but was negatively correlated with renal Kt/V _urea ( r  = −0.609, P  = 0.047). In the multiple regression analysis, renal Kt/V _urea significantly contributed to log CysC concentration rather than peritoneal Kt/V _urea . The results of this study suggest that serum CysC could be an appropriate marker for RRF, independent of total and peritoneal Kt/V _urea .
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1678-8
  • Authors
    • Su Jin Kim, Center for Pediatric Oncology, National Cancer Center, Goyang, Korea
    • Young Bae Sohn, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, 135-710 Gangnam-Gu, Seoul, Korea
    • Sung Won Park, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, 135-710 Gangnam-Gu, Seoul, Korea
    • Dong-Kyu Jin, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, 135-710 Gangnam-Gu, Seoul, Korea
    • Kyung Hoon Paik, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, 135-710 Gangnam-Gu, Seoul, Korea
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Pathogenesis and therapy of focal segmental glomerulosclerosis: an update
  
  Abstract  

  Focal and segmental glomerulosclerosis (FSGS) is an important cause of steroid-resistant nephrotic syndrome in adults and children. It is responsible for 5–20% of all cases of end-stage kidney disease (ESKD) in the United States. The pathogenesis of FSGS has not been fully elucidated; however, data from molecular studies of familial cases in the last two decades suggest that FSGS is a defect of the podocyte. The therapeutic agents available for treatment of FSGS are not very effective and only a small percentage of affected individuals will achieve complete remission. Recent data from molecular biology and molecular genetics has provided insight into the mechanisms of action of old agents and also identification of other novel therapeutic targets. This review focuses on recent advances in the molecular pathogenesis of FSGS and currently available therapeutic agents as well as potential novel therapies.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1692-x
  • Authors
    • Rasheed Gbadegesin, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    • Peter Lavin, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    • John Foreman, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    • Michelle Winn, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Are we ready to use aliskiren in children'
  
  Abstract  

  The objective of this case series was to review the safety and efficacy of aliskiren in combination with losartan in pediatric chronic kidney disease (CKD) patients. This was a retrospective study in which the medical files of all patients who had received aliskiren were reviewed. Four patients were identified between 5 and 18 years of age who had received aliskiren and losartan for the reduction of refractory proteinuria. While proteinuria was reduced in all four of these patients by 45, 96, 53, and 64%, respectively, three patients experienced side effects requiring changes in the aliskiren dose. A significant side effect occurred in the patient with CKD stage 3 who suffered accelerated loss of kidney function leading to dialysis after only a short course of therapy. The data from this preliminary trial strongly suggest that clinicians should exercise caution when prescribing aliskiren in combination with losartan until appropriate pediatric trials establish dosing, efficacy, and safety.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1702-z
  • Authors
    • Erin Elizabeth Kelland, Department of Pediatrics, Children’s Hospital, London Health Sciences Centre, University of Western Ontario, 800 Commissioners Road East, London, N6A 5W9 ON Canada
    • Leanne Michelle McAuley, Department of Pediatrics, Children’s Hospital, London Health Sciences Centre, University of Western Ontario, 800 Commissioners Road East, London, N6A 5W9 ON Canada
    • Guido Filler, Department of Pediatrics, Children’s Hospital, London Health Sciences Centre, University of Western Ontario, 800 Commissioners Road East, London, N6A 5W9 ON Canada
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Autosomal dominant polycystic kidney disease (ADPKD) associated with steroid-sensitive nephrotic syndrome in childhood
  

  Autosomal dominant polycystic kidney disease (ADPKD) associated with steroid-sensitive nephrotic syndrome in childhood

  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1710-z
  • Authors
    • Ekaterini Siomou, Nephrology Department, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH UK
    • Joanna Jarvis, Clinical Genetics Unit, Birmingham Women’s Hospital, Birmingham, B15 2TG UK
    • Sally-Anne Hulton, Nephrology Department, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH UK
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms
  
  Abstract  

  Identifying patients who may develop renal scarring after urinary tract infections (UTI) remains challenging, as clinical determinants explain only a portion of individual risk. An additional factor that likely affects risk is individual genetic variability. We searched for peer-reviewed articles from 1980 to December 2009 in electronic databases that reported results showing an association between gene polymorphims and renal scaring after UTI. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality using an aggregate scoring system. The 18 studies ultimately included in the review had investigated 16 polymorphisms in nine genes in association with renal scarring formation after UTI. Based on the predetermined criteria for assessing the quality of the studies, 12 studies (67%) were identified as being of poor quality design. A meta-analysis of cumulative studies showed on association between renal scarring formation after UTI and the angiotensin converting enzyme insertion/deletion polymorphism [ACE I/D; recessive model for D allele; odds ratio (OR) 1.73, 95% confidence interval (CI) 1.09–2.74, P  = 0.02] or transforming growth factor (TGF)-β1 c.-509 T > C polymorphism (dominant model for T allele; OR 2.24, 95% CI 1.34–3.76, P  = 0.002). However, heterogeneity among studies was large, indicating a strong difference that cannot only be explained by differences in study design. The studies reviewed in this article support a modest involvement of the vasomotor and inflammatory genes in the development of renal scarring after UTIs. This review also shows that only few possible candidate genes have been investigated for an association with renal scarring, raising the hypothesis that some gene polymorphisms may exert their effects through an interaction with as yet uninvestigated factors that may be related to geographic and/or socio-economic differences.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1695-7
  • Authors
    • Marco Zaffanello, Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy
    • Stefano Tardivo, Department of Medicine and Public Health, Section of Hygiene and Preventive, Environmental and Occupational Medicine, University of Verona, Verona, Italy
    • Luigi Cataldi, Division of Neonatology, Catholic University of Sacred Heart, Rome, Italy
    • Vassilios Fanos, Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy
    • Paolo Biban, Neonatal and Paediatric Intensive Care Unit, Division of Paediatrics, Major City Hospital, Verona, Italy
    • Giovanni Malerba, Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Clinical and Molecular Insights into Tuberous Sclerosis Complex Renal Disease
  
  Abstract  

  Patients with tuberous sclerosis complex are at great risk of developing renal lesions as part of their disease. These lesions include renal cysts and tumors. Significant advances in understanding the cell biology of these renal lesions has already led to clinical trials demonstrating that pharmacological interventions are likely possible. This review focuses on the pathology of these renal lesions, their underlying cell biology, and the possible therapeutic strategies that may prove to significantly improve care for these patients.
  • Content Type Journal Article
  • Pages 1-14
  • DOI 10.1007/s00467-010-1689-5
  • Authors
    • Brian J. Siroky, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, MLC 7022, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
    • Hong Yin, Division of Pathology, Cincinnati Children’s Hospital Medical Center, MLC 7022, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
    • John J. Bissler, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, MLC 7022, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Henoch-Schönlein purpura following influenza vaccinations during the pandemic of influenza A (H1N1)
  
  Abstract  

  Although the etiology of Henoch-Schönlein purpura (HSP) remains unclear, influenza vaccinations have been implicated as possible triggers for HSP. We describe four patients with HSP following influenza vaccinations which developed during the pandemic of influenza A (H1N1) 2009 and review the literature concerning HSP associated with this vaccine. HSP in patients developed in October and November, 2009. Four patients exhibited purpura, three patients complained of arthralgias, and one patient had both abdominal pains and renal involvement. Reviewing the literature, 11 patients with HSP following influenza vaccinations have been reported. Eight patients were children and five patients had past histories of immunologically mediated diseases including HSP, drug eruptions, and food allergy. While a favorable outcome was noted in most patients, one patient developed end-stage renal failure and another patient exhibited chronic glomerulonephritis. Although the precise reason for clustering of our patients with HSP following influenza vaccination was unclear, increasing use of the recent influenza vaccine associated with the pandemic of influenza A (H1N1) 2009 might explain this phenomenon. Because the incidence of HSP caused by influenza vaccination was very low, influenza vaccination should not be limited for this reason. However, caution may be required with its use in children with immunologically mediated diseases such as HSP.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1722-8
  • Authors
    • Toru Watanabe, Department of Pediatrics, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata City, 950-1197 Japan
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Problems with 'focal segmental glomerulosclerosis'
  
  Abstract  

  The term 'focal segmental glomerulosclerosis (FSGS)' has been applied to many different conditions. All classifications of 'FSGS', including those describing 'variants', perpetuate the misconceptions that the entities included have something in common and that the term 'FSGS' has some value. With a rigorous approach to renal biopsies showing segmental lesions, especially with knowledge of clinical circumstances and with detailed analysis of features such as the appearance of lesions and their position within glomeruli, a pathologist can provide information that is clinically more useful than merely the bald diagnosis 'FSGS'. More precise terms should be used. 'Overload changes' can be used to describe the changes seen in reduced renal mass. 'Tip changes' can be seen in many conditions and are not a disease in themselves. 'The glomerular tip lesion as originally defined' means the occurrence of tip changes in otherwise normal glomeruli, in the nephrotic syndrome. 'Early classical segmental sclerosing glomerulopathy' is the combination of tip changes and otherwise abnormal glomeruli, in the nephrotic syndrome. 'Late classical segmental sclerosing glomerulopathy' means segmental lesions at various sites within glomeruli, in the nephrotic syndrome. 'Collapsing glomerulopathy' is distinctive, and its inclusion in classifications emphasises the lack of specificity of 'FSGS'.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1701-0
  • Authors
    • Alexander J. Howie, Department of Pathology, University College London, London, WC1E 6JJ UK
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
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• Eculizumab induces long-term remission in recurrent post-transplant HUS associated with C3 gene mutation
  
  Abstract  

  A 15-year-old male patient developed atypical hemolytic uremic syndrome (aHUS) at 16 months of age leading to end-stage renal disease. The family history was suggestive of autosomal dominant aHUS, and he was more recently found to have a C3 heterozygous gene mutation ( 1835C>T mutation in exon 14, which determines the amino-acidic substitution R570W ) with no other complement abnormalities. He had two renal transplants, the first at 2.5 years, and the second at 8 years of age, but allograft dysfunction developed in both transplants leading to graft failure due to recurrent HUS at 5 years and 18 months post-transplantation respectively. At 15 years of age he received a third transplant from a deceased donor with pre-emptive plasmapheresis. He had immediate graft function and nadir serum creatinine was 1.3–1.4 mg/dl. Severe allograft dysfunction and hypertension developed 2 months after transplantation following influenza infection. Renal allograft biopsy showed thrombotic microangiopathy. He received plasmapheresis followed by eculizumab therapy. Allograft function returned to baseline 3 weeks after starting therapy, and post-treatment allograft biopsies showed improvement in thrombotic microangiopathy. He continues to receive eculizumab every 2 weeks with stable graft function 13 months after transplantation.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1708-6
  • Authors
    • Samhar I. Al-Akash, Division of Pediatric Nephrology, Driscoll Children’s Hospital, Corpus Christi, TX 78411, USA
    • P. Stephen Almond, Department of Surgery and Transplantation, Driscoll Children’s Hospital, Corpus Christi, TX USA
    • Van H. Savell, Department of Pathology and Laboratory Medicine, Driscoll Children’s Hospital, Corpus Christi, TX USA
    • Salam I. Gharaybeh, Division of Pediatric Nephrology, Driscoll Children’s Hospital, Corpus Christi, TX 78411, USA
    • Cris Hogue, Pharmacy Department, Driscoll Children’s Hospital, Corpus Christi, TX USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Neonatal nephrotic syndrome associated with placental transmission of proinflammatory cytokines
  
  Abstract  

  Although there are clinical data suggesting a direct relationship between neonatal nephrotic syndrome and placental transfer of proinflammatory cytokines from mothers with HELLP syndrome, there is no direct evidence that these inflammatory cytokines are pathogenic. Here, the first human model of placental transfer of proinflammatory cytokines from a mother with HELLP syndrome to a newborn, resulting in neonatal nephrotic syndrome is described. Forty-eight hours after delivery, the neonate developed nephrotic syndrome and abnormalities in renal function which resolved completely during the 5 days following the initiation of therapy with hydrocortisone, albumin, and furosemide. The newborn’s cord blood showed increased concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha that were identical to those found in the mother’s serum. Hydrocortisone therapy was discontinued after a 2-week course. Clinical and laboratory improvements were associated with a marked decline in serum cytokine levels, indicating that the proinflammatory cytokines were pathogenic. The neonate remained in remission with no recurrence of nephrotic syndrome during 12 months of follow-up. These findings demonstrate that the placental transmission of circulating cytokines causing HELLP syndrome occurred during pregnancy and may have resulted in nephrotic syndrome in the neonate.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1700-1
  • Authors
    • Farahnak Assadi, Section of Nephrology, Department of Pediatrics, Rush University Medical Center, 1725 West Harrison Street, Suite 718 Professional Bldg, Chicago, IL USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Cystic diseases of the kidney: ciliary dysfunction and cystogenic mechanisms
  
  Abstract  

  Ciliary dysfunction has emerged as a common factor underlying the pathogenesis of both syndromic and isolated kidney cystic disease, an observation that has contributed to the unification of human genetic disorders of the cilium, the ciliopathies. Such grouping is underscored by two major observations: the fact that genes encoding ciliary proteins can contribute causal and modifying mutations across several clinically discrete ciliopathies, and the emerging realization that an understanding of the clinical pathology of one ciliopathy can provide valuable insight into the pathomechanism of renal cyst formation elsewhere in the ciliopathy spectrum. In this review, we discuss and attempt to stratify the different lines of proposed cilia-driven mechanisms for cystogenesis, ranging from mechano- and chemo-sensation, to cell shape and polarization, to the transduction of a variety of signaling cascades. We evaluate both common trends and differences across the models and discuss how each proposed mechanism can contribute to the development of novel therapeutic paradigms.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1697-5
  • Authors
    • Cecilia Gascue, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, CP 11400, Uruguay
    • Nicholas Katsanis, Center for Human Disease Modeling, Duke University Medical Center, Box 3709, Durham, NC 27710, USA
    • Jose L. Badano, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, CP 11400, Uruguay
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• The BK virus in renal transplant recipients—review of pathogenesis, diagnosis, and treatment
  
  Abstract  

  The BK virus, a DNA virus from the Polyomavirus group, represents an opportunistic infection of immunosuppressed transplant recipients. Though the virus was discovered approximately 40 years ago, the emergence of BK virus nephropathy since 1995 onwards, with associated high graft loss rates, has revolutionized renal transplantation medicine. Kidney transplant professionals realized that the consequences of over-immunosuppression were as severe as the consequences of under-immunosuppression and we entered the era of immunosuppressive minimization. Despite this recognition, the optimal testing type for BK virus infections and frequency of testing are hotly debated. Similarly, optimal treatment strategies remain sources of intense controversy. The authors review the current strategies of screening, diagnosis, and possible treatment, and also review the amount and quality of evidence in favor or against. Similarities and differences between cytomegalovirus, Epstein-Barr virus, and BV virus, the three major viral infections in kidney transplantation, are highlighted.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1716-6
  • Authors
    • Vikas R. Dharnidharka, Division of Pediatric Nephrology, University of Florida College of Medicine & Shands Children’s Hospital, 1600 SW Archer Road, PO Box 100296/HD 214, Gainesville, FL 32610-0296, USA
    • Husam A. Abdulnour, Division of Pediatric Nephrology, University of Florida College of Medicine & Shands Children’s Hospital, 1600 SW Archer Road, PO Box 100296/HD 214, Gainesville, FL 32610-0296, USA
    • Carlos E. Araya, Division of Pediatric Nephrology, University of Florida College of Medicine & Shands Children’s Hospital, 1600 SW Archer Road, PO Box 100296/HD 214, Gainesville, FL 32610-0296, USA
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  
• Efficacy of eculizumab in a patient with factor-H-associated atypical hemolytic uremic syndrome
  
  Abstract  

  Atypical hemolytic uremic syndrome (aHUS) is a rare, chronic, life-threatening disease due to complement dysregulation. The use of early-onset plasma therapy is recommended, but optimal long-term treatment regimen is not well defined. Eculizumab, a monoclonal humanized anti-C5 antibody, has shown success in patients with aHUS. We report a 7-year-old girl with aHUS associated with factor H mutations successfully treated with eculizumab. Weekly plasma infusion (PI) of 25–30 ml/kg with short-term intensified PI during aHUS exacerbations was effective for 4.3 years. Progressive mild renal failure (stage 2) was attributed to chronic glomerular lesions. Subsequently, she exhibited aHUS exacerbation unresponsive to intensified PI. Eculizumab was initiated at 600 mg, resulting in immediate and complete inhibition of terminal complement activation. During the week following treatment, we observed a complete reversal of aHUS activity. She has been receiving 600 mg eculizumab every 2 weeks for the last 12 months. She had no aHUS exacerbation, and serum creatinine level returned to normal. In this patient, eculizumab led to control of PI-resistant aHUS exacerbation and chronic microangiopathic hemolytic activity. Clinical trials are ongoing to assess the safety and efficacy of this drug in the management of aHUS.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1719-3
  • Authors
    • Anne-Laure Lapeyraque, Division of Nephrology, CHU Sainte-Justine, Montréal, Québec Canada
    • Véronique Frémeaux-Bacchi, Service d’Immunologie Biologique, Hopital Européen Georges Pompidou, Paris, France
    • Pierre Robitaille, Division of Nephrology, CHU Sainte-Justine, Montréal, Québec Canada
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  

  No Issue Number

• Treatment strategies for Henoch-Schönlein purpura nephritis by histological and clinical severity
  
  Abstract  

  The management of Henoch-Schönlein purpura nephritis (HSPN) is controversial. It has been revealed that some patients develop end-stage renal disease and aggressive treatment with drugs such as steroids is increasing, and some of them may be overzealous. At our institutes, our treatment decisions are based on the clinical and pathological severity of the case in an attempt to limit the indications for aggressive therapies such as steroids and immunosuppressive agents. Here, we retrospectively examined the efficacy of treatment for HSPN. Renal biopsy was performed in patients with nephrotic syndrome or persistent proteinuria for more than 3 months and patients were classified by treatment. Patients ( n  = 31) with moderately severe HSPN (histological grade I–III and serum albumin [Alb] >2.5 g/dl) were treated with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. Patients ( n  = 19) with HSPN exceeding grade III or Alb ≤ 2.5 g/dl received combination therapy comprising prednisolone, immunosuppressants, warfarin, and dipyridamole. All patients showed resolution of proteinuria without renal dysfunction during the observation period (3.76 ± 0.37 years). Our findings support those of some earlier reports that treatment strategies for HSPN should depend on the histological and clinical severity. Furthermore, aggressive therapies, particularly combination therapies, are unnecessary for moderate–severe HSPN.
  • Content Type Journal Article
  • DOI 10.1007/s00467-010-1741-5
  • Authors
    • Takeshi Ninchoji, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017 Japan
    • Hiroshi Kaito, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017 Japan
    • Kandai Nozu, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017 Japan
    • Yuya Hashimura, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017 Japan
    • Kyoko Kanda, Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan
    • Ichiro Kamioka, Department of Pediatrics, Kakogawa Municipal Hospital, Hyogo, Japan
    • Yuko Shima, Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
    • Kiyoshi Hamahira, Department of Pediatrics, Himeji Red-Cross Hospital, Hyogo, Japan
    • Koichi Nakanishi, Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
    • Ryojiro Tanaka, Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan
    • Norishige Yoshikawa, Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
    • Kazumoto Iijima, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017 Japan
    • Masafumi Matsuo, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017 Japan
  • Journal Pediatric Nephrology
  • Online ISSN 1432-198X
  • Print ISSN 0931-041X
  
  

  No Issue Number

• Practical aspects of arteriovenous fistula formation in the pediatric population
  

  The principle of “Fistula First” for hemodialysis has been widely adopted among adults with end-stage renal failure (ESRF). UK national targets aim to have 85 % of prevalent patients using permanent access (arteriovenous fistula or graft). Currently, hemodialysis in children relies heavily on central venous catheters (CVC). However, there is significant evidence that arteriovenous fistulae (AVF) are preferable for long-term dialysis in the pediatric population. We describe the principles of fistula formation including pre-operative work-up, surgical techniques for AVF creation, and post-operative monitoring.

  
  
• Therapeutic plasma exchange in the treatment of exertional heat stroke and multiorgan failure
  

  Background

  Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality.

  Case Diagnosis and Treatments

  We present the case of an 11-year-old obese male who suffered EHS with rhabdomyolysis and concurrent renal, pulmonary, and hepatic failure. Conventional therapies including continuous veno-venous hemodiafiltration (CVVHDF) were ineffective in preventing ongoing deterioration in clinical status. Liver biopsy was reported as “extensive hepatocyte ballooning” and liver-kidney transplantation was tentatively planned.

  Conclusions

  The addition of therapeutic plasma exchange using the Prismaflex® system (Gambro, Lakewood, CO, USA) resulted in a reversal of the inflammatory process and recovery from multiorgan failure. Liver biopsy was not a reliable indicator of irreversible hepatic injury.

  
  
• High-dose continuous renal replacement therapy for neonatal hyperammonemia
  

  Background

  Infants with hyperammonemia can present with nonspecific findings so ordering an ammonia level requires a high index of suspicion. Renal replacement therapy (RRT) should be considered for ammonia concentrations of >400 μmol/L since medical therapy will not rapidly clear ammonia. However, the optimal RRT prescription for neonatal hyperammonemia remains unknown. Hemodialysis and continuous renal replacement therapy (CRRT) are both effective, with differing risks and benefits.

  Case-diagnosis/treatment

  We present the cases of two neonates with hyperammonemia who were later diagnosed with ornithine transcarbamylase deficiency and received high-dose CRRT. Using dialysis/replacement flow rates of 8,000 mL/h/1.73 m ² (1,000 mL/h or fourfold higher than the typical rate used for acute kidney injury) the ammonia decreased to <400 μmol/L within 3 h of initiating CRRT and to <100 μmol/L within 10 h.

  Conclusions

  We propose a CRRT treatment algorithm to rapidly decrease the ammonia level using collaboration between the emergency department and departments of genetics, critical care, surgery/interventional radiology, and nephrology.

  
  
• Renal impairment in children with posterior urethral valves
  

  Background

  Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

  Methods

  We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

  Results

  The cohort comprised 68 boys. There was a significant difference in the duration of follow-up ( p  = 0.024), nadir serum creatinine ( p  < 0.001), and last known serum creatinine level ( p  = 0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling ( p  = 0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

  Conclusions

  Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.

  
  
• Rhabdomyolysis and acute kidney injury in two children: Answers
  
• Endoplasmic reticulum stress with low-dose cyclosporine in frequently relapsing nephrotic syndrome
  

  Background

  A possible mechanism of cyclosporine (CsA) nephrotoxicity is tubular apoptosis. Endoplasmic reticulum (ER) stress has been shown to be an apoptosis activator. Glucose-regulated proteins 78 and 94 (GRP78, GRP94, respectively) are ER stress-induced chaperones. Eukaryotic translation initiation factor 2α (EIF2α) attenuates protein synthesis. If stress is prolonged, cells undergo apoptosis, inducing the production of GADD153, a transcription factor, which in turn downregulates anti-apoptotic protein B-cell lymphoma 2 (Bcl-2).

  Methods

  Endoplasmic reticulum stress-related molecules were evaluated by real-time polymerase chain reaction (PCR) using renal biopsy tissues from 17 children with frequently relapsing nephrotic syndrome before and after 2 years of CsA therapy.

  Results

  GRP78, GRP94, eIF2α, and Bcl-2 were significantly upregulated in renal biopsy tissues from children 2 years post-CsA treatment. However, there was almost no change in GADD153. Mean ratios of post- to pre-CsA expression of GRP78, GRP94, eIF2α and Bcl-2 were 2.53, 1.80, 2.38 and 1.92, respectively. Post-CsA administration, GRP78 and eIF2α were upregulated by up to sixfold, and GRP94 and Bcl-2 were upregulated by up to fourfold compared with the respective pre-CsA levels. There were significant correlations between GRP78, GRP94, eIF2α, and Bcl-2 levels. These findings suggest that CsA induced an unfolded protein response due to ER stress, but did not cause apoptosis.

  Conclusions

  An unfolded protein response due to ER stress induced by CsA may function in a defensive manner, with less apoptosis occurring under low-dose conditions. This finding is important for the rationale for CsA administration.

  
  
• Difficulties in diagnosing severe<em class="a-plus-plus"> Pneumocystis jiroveci</em> pneumonia after rituximab therapy for steroid-dependent nephrotic syndrome
  
• L-FABP can be an early marker of acute kidney injury in children
  

  Background

  Acute kidney injury (AKI) is a common postoperative complication following cardiopulmonary bypass (CPB) surgery. New biomarkers to identify patients with early AKI (before increases in serum creatinine) are needed to facilitate appropriate treatment. This study aimed to test the role of urinary liver fatty-acid-binding protein (L-FABP) as an early biomarker for AKI in children undergoing CPB surgery.

  Methods

  This is a case–control study of children undergoing CPB. AKI was defined as 50 % increase in serum creatinine at 48 h after surgery. For each patient, five serum and urine samples were obtained corresponding to time 0 h (presurgery) and 2, 6, 24, and 48 h after surgery.

  Results

  Twenty-seven patients, median age 360 days, were enrolled. AKI developed in 11 patients (41 %); three needed renal replacement therapy (peritoneal dialysis); there were two deaths. There were significant differences between patients with and without AKI in L-FABP levels at 2, 6, and 48 h after surgery, length of hospital stay, and CPB time; there were no differences in gender, patient age, and body weight. L-FABP was normalized to urinary creatinine concentration at all time points, with area under the receiver operator curve (AUC ROC) 0.867 at 2 and 6 h postoperatively. Correlation coefficient between L-FABP and length of hospital stay after surgery was statistically significant ( r  = 0.722, p value = 0.000).

  Conclusions

  Our results suggest that urinary L-FABP can be used to diagnose AKI earlier than rise in serum creatinine in children undergoing CPB.

  
  
• Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome
  

  Background

  Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS).

  Methods

  This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19 >1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %).

  Results

  Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred.

  Conclusion

  The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.

  
  
• Cure of relapsing nephrosis by an allogeneic marrow graft for chronic myelogenous leukemia
  

  Background

  Minimal-change nephrotic syndrome has recently been attributed to an immature, dysfunctional T-cell population.

  Case-diagnosis/treatment

  A woman, now 23 years old, developed nephrotic syndrome when she was 6 years old. Despite treatment with steroids and immunosuppressants such as cyclosporine, mizoribine, mycophenolate mofetil, and tacrolimus, the patient relapsed 14 times. At the age of 19 years, she developed chronic myelogenous leukemia, against which imatinib achieved cytogenetic remission. The patient received an allogeneic bone marrow graft transplantation from an unrelated marrow bank donor, with an uncomplicated recovery and molecular genetic remission. Immunosuppressants were withdrawn within 6 months. The patient is now without drug treatment. Complete remission of nephrotic syndrome has also been maintained for over 4 years without any drug administration.

  Conclusions

  The patient’s course supports suggestions that immunological dysfunction in nephrosis is associated with abnormality of immature, relatively unclassified T cells (CD34 ⁺ ) representing hematopoietic stem cells, as opposed to mature T cells (CD34 ⁻ ).

  
  
• Erratum to: Cardiorenal syndrome: an emerging problem in pediatric critical care
  
• Rhabdomyolysis and acute kidney injury in two children: Questions
  
• Hydronephrosis associated with ureteral wall thickness: Question
  
• Native kidney BK virus nephropathy associated with acute lymphocytic leukemia
  <h3 class="a-plus-plus"> </h3> <span class="a-plus-plus abstract-section id-a-sec1"> <h3 class="a-plus-plus">Background</h3> <p class="a-plus-plus">Polyoma BK virus nephropathy is a common complication after renal transplantation and is rarely seen in non-renal transplant recipients. There are only a couple of case reports of BK virus nephropathy in native kidneys in non-transplant patients, including a recent report of a 73-year-old patient with chronic lymphatic leukemia. A variety of treatment options, including leflunomide and cidofovir, were reported in these patients.</p> </span> <span class="a-plus-plus abstract-section id-a-sec2"> <h3 class="a-plus-plus">Case diagnosis/treatment</h3> <p class="a-plus-plus">Here we report the case of a 10-year-old boy with acute lymphatic leukemia who presented with non-oliguric hypertensive acute kidney injury at the 12th maintenance cycle of his chemotherapy. The workup supported the clear diagnosis of BK virus nephropathy with tubulointerstitial changes, and the patient responded favorably to intravenous immunoglobulin therapy.</p> </span> <span class="a-plus-plus abstract-section id-a-sec3"> <h3 class="a-plus-plus">Conclusions</h3> <p class="a-plus-plus">Pediatric nephrologists need to consider BK virus nephropathy as a differential diagnosis of acute kidney injury in immunocompromised non-transplant patients.</p> </span>
  
• Cardorenal syndrome: an emerging problem in pediatric critical care
  <h3 class="a-plus-plus"> </h3> <p class="a-plus-plus">The cardiorenal syndrome (CRS) refers to a complex pathophysiologic state in which heart and kidney dysfunction coexist. Although a robust amount of adult literature exists, limited reports have been made regarding CRS in pediatric patients. However, CRS is increasingly being recognized as an impactful clinical problem that can have important implications regarding the need for treatment and prognosis. Although wide acceptance of a unified definition of CRS is lacking, a general consensus exists that CRS can be either primarily caused by cardiac disease with secondary effects on the kidney, or vice versa, as well as systemic conditions in which cardiac and renal disease are both considered to be secondary. Convincing data in the pediatric perioperative population have been reported, but there is a paucity of information in acute and chronic heart failure (HF), as well as acute kidney injury (AKI) and chronic kidney disease (CKD). Herein, we briefly report on the adult literature and summarize the current pediatric experience.</p>
  
• Is high-dose cholecalciferol justified in children with chronic kidney disease who failed low-dose maintenance therapy'
  

  Background

  We aimed to investigate the effect of single, high-dose intramuscular cholecalciferol on vitamin D3 and intact parathyroid hormone (iPTH) levels in children with chronic kidney disease (CKD).

  Methods

  Between January 2012 and June 2012, we conducted a prospective, uncontrolled study at the Pediatric Nephrology Unit of King Abdulaziz University Hospital, Jeddah, to investigate the effect of single, high-dose intramuscular vitamin D3 on 25(OH)D3 and iPTH levels in vitamin D insufficient/deficient children with CKD. Serum vitamin D3, iPTH, calcium, phosphate, alkaline phosphatase (ALP), and creatinine levels were measured before intramuscular vitamin D3 (300,000 IU) administration, and these were subsequently repeated at 1 and 3 months after treatment. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA).

  Results

  Nineteen children fulfilled the criteria. At 3 months after treatment, vitamin D3 levels were significantly higher than at baseline ( p  < 0.001) but lower than the levels at 1 month. iPTH levels decreased significantly at 3 months ( p  = 0.01); however, the drop in iPTH levels was not significant at 1 month ( p  = 0.447). There were no changes in calcium, phosphate, ALP, or creatinine levels after treatment.

  Conclusions

  Single-dose intramuscular vitamin D3 (300,000 IU) resulted in significant improvement of vitamin D3 and iPTH levels in children with CKD.

  
  
• Urinary biomarkers and acute kidney injury in children: the long road to clinical application
  <h3 class="a-plus-plus"> </h3> <p class="a-plus-plus">Pediatric acute kidney injury is rising with the advances in technology available for children with chronic conditions or those who are critically ill. Serum creatinine and urine output, traditional markers of renal function, often allow only delayed and unreliable diagnosis of acute kidney injury. Biomarker development in pediatric patients with low disease prevalence is challenging (small cohorts, few analyzable events). In this issue of <em class="a-plus-plus">Pediatric Nephrology</em>, Ivanisevic and colleagues report that urinary liver-type fatty-acid-binding protein (L-FABP) can be used for early identification of pediatric acute kidney injury in a small cohort undergoing cardiac surgery. Addition of the biomarker resulted in an improvement in early diagnosis compared with a clinical model (age, gender, body weight, cardiopulmonary bypass duration, and aortic clamp time). It is noteworthy that the preoperative clinical model performed excellently in predicting postsurgery pediatric acute kidney injury. Further work is needed before this or other novel biomarkers (alone or in combination) can be implemented in clinical practice. Large-scale observational studies are needed to test these biomarkers against hard clinical endpoints, independent of serial measurements of serum creatinine concentrations. Prospective randomized interventional trials using exclusively high biomarker levels to define acute kidney injury should demonstrate improved clinical outcomes.</p>
  
• Hydronephrosis associated with ureteral wall thickness: Answer
  
• Impact of platelet transfusions in children with post-diarrheal hemolytic uremic syndrome
  

  Background

  Platelet transfusions should be avoided in children with post-diarrheal hemolytic uremic syndrome (D + HUS) because they might increase microthrombi formation, thereby aggravating the disease. As this possibility has not yet been explored, we investigated whether platelet transfusion in patients with D + HUS would lead to a worse disease course compared to that in patients who did not receive platelet transfusion.

  Methods

  This was a case–control study in which data from D + HUS children who received platelet transfusions (cases, n   =  23) and those who did not (controls, n   =  54) were retrospectively reviewed and compared.

  Results

  Both patient groups were similar in age ( p  = 0.3), gender ( p   =  0.53), weight ( p   =  0.86), height ( p   =  0.45), prior use of non-steroidal anti-inflammatory drugs ( p   =  0.59) or antibiotics ( p  =  0.45) and presence of dehydration at admission ( p   =  0.79). The two groups also did not differ in initial leukocyte count ( p   =  0.98), hematocrit ( p   =  0.44) and sodium ( p   =  0.11) and alanine aminotransferase levels ( p   =  0.11). During hospitalization, dialysis duration ( p   =  0.08), number of erythrocyte transfusions ( p   =  0.2), serum creatinine peak ( p   =  0.22), presence of severe bowel ( p   =  0.43) or neurologic ( p   =  0.97) injury, arterial hypertension ( p   =  0.71), need for intensive care ( p   =  0.33) and death ( p   =  1.00) were also comparable.

  Conclusion

  Our findings suggest that platelet transfusion does not aggravate the course of the disease. Conversely, no hemorrhagic complications were observed in the group of patients who did not receive a platelet transfusion. Until these observations are confirmed by further studies, the benefits and risk of platelet transfusion should be thoughtfully balanced on an individual case basis.

  
  
• Policy variation in donor and recipient status in 11 pediatric renal transplantation centers
  

  Background

  Evidence-based guidelines for pediatric renal transplantation (Tx) are lacking. This may lead to unwanted treatment variations. We aimed to quantify the variation in treatment policies and its consequences in daily practice in 11 centers that provide renal Tx for children in three European countries.

  Methods

  We surveyed Tx policies in all ten centers in the Netherlands and Belgium and one center in Germany. We compared Tx policies with the therapies actually provided and with recommendations from available published guidelines and existing literature. Information on treatment policies was obtained by a questionnaire; information on care actually provided was registered prospectively from 2007 to 2011. The clinical guidelines were identified by searches of MEDLINE and websites of pediatric nephrology organizations.

  Results

  Between centers, we found discrepancies in policies on: the minimum accepted recipient weight (8–12 kg), the maximum living and deceased donor age (50–75 and 45–60 years, respectively). HLA-match policies varied between acceptation of all mismatches to at least 1A1B1DR match donor transplantations amounting to 49 % in the Netherlands versus 26 % in Belgium ( p  = 0.006).

  Conclusions

  Management policies for renal Tx in children vary considerably between centers and nations. This has a direct impact on the delivered care, and by extrapolation, on health outcome.

  
  
• Restless legs syndrome in children with chronic kidney disease
  

  Abstract

  Background

  Restless legs syndrome (RLS) is considerably more common among adults with chronic kidney disease (CKD) than in the general population and is associated with increased morbidity and mortality. There is limited information on RLS in children with CKD. Failure to account for conditions that might mimic RLS can lead to overdiagnosis of this syndrome.

  Methods

  In a prospective, cross-sectional study, RLS prevalence was compared between pediatric CKD patients and healthy children. RLS was assessed via a questionnaire that included exclusion of mimics. Sleep characteristics and health-related quality of life (HRQoL) were also assessed.

  Results

  Restless legs syndrome was more prevalent in CKD patients ( n  = 124) than in 85 normal children (15.3 vs. 5.9 %; p = 0.04). There was no significant association between RLS and CKD stage, CKD etiology, CKD duration, and dialysis or transplant status. Children with RLS were more likely to rate their sleep quality as fairly bad or very bad (41.2 vs. 8.8 %; p  = 0.003) and report using sleep medications (42.1 vs. 14.7 %; p  = 0.01). RLS was associated with lower HRQoL by parent report ( p  = 0.03). Only five of the 19 patients (26.3 %) with CKD and RLS had discussed RLS symptoms with a healthcare provider, and only one of these patients had been diagnosed with RLS prior to this study.

  Conclusions

  The prevalence of RLS is increased in children with CKD and appears to be underdiagnosed. Systematic screening for RLS and sleep problems would therefore appear to be warranted in children with CKD.

  
  
• Chronic hemodialysis in children weighing less than 10 kg
  

  Abstract

  Background

  Hemodialysis (HD) in infants is usually used when peritoneal dialysis (PD) has failed. We describe our experience with HD, outlining the morbidity, complications, and outcomes for infants weighing less than 10 kg managed with HD for more than 6 months over a 10-year period.

  Methods

  A retrospective review of the clinical notes was conducted to collect demographic information, anthropometric data, dietary history, site and form of vascular access, details of HD prescription, complications, and outcomes.

  Results

  Nine patients weighing less than 10 kg were hemodialyzed for more than 6 months. Median age at commencement was 9 months. Median weight and height standard deviation score (SDS) at commencement of HD were −2.14 and −0.61, respectively, and at the end they were −1.56 and −1.61. Median energy intake was 96.6 kcal/kg/day and protein intake was 1.66 g/kg/day. Median number of line revisions was 0.32 line changes/patient year. Median central venous catheter (CVC) longevity was 13 months. Mean rate of line infection was 0.14/patient year. Median time on HD was 27 months. Median age at transplantation was 3.4 years.

  Conclusions

  This case series shows that chronic HD is a viable management option in children <10 kg. Access issues can be minimized with good line care to maximize line longevity and minimize line infection rates.

  
  
• Neurologic involvement in atypical hemolytic uremic syndrome and successful treatment with eculizumab
  

  Abstract

  Background

  Atypical hemolytic uremic syndrome (aHUS) is associated with defective regulation of the complement pathway. Neurological involvement is the most common extrarenal complication and represents a major cause of mortality and morbidity.

  Case-diagnosis/treatment

  Two girls aged 11 and 6 years, respectively, developed aHUS and were treated immediately with plasma exchange (PE) and fresh frozen plasma infusion (PI). Although initial improvement in renal function was seen in both cases, the first patient showed progressing thrombotic microangiopathy (TMA) despite daily PE, and neurological manifestations (seizures, vision loss, loss of balance, and confusion) developed after 1 month. The second patient developed cerebral TMA (seizures, vision loss, and nystagmus) 6 days after initial presentation and remained unresponsive to PE/PI. Neurological symptoms were similar in both patients, even though they had different complement protein mutations. Treatment with eculizumab achieved complete control of neurological symptoms within 24 h and gradually normalized hematological and renal parameters in both children.

  Conclusions

  Based on our two cases, we conclude that eculizumab is a rapid-acting, effective, and life-saving treatment for pediatric patients with aHUS and severe neurological involvement, which works by inhibiting complement-mediated TMA in the kidney and other organs, such as the brain.

  
  
• New developments in steroid-resistant nephrotic syndrome
  

  Abstract

  Nephrotic syndrome is a disorder of the glomerular filtration barrier, a highly specialised tri-layer structure with unique functional properties. Recent advances emanating from the field of molecular genetics have revealed the podocyte as probably the central player in the control of glomerular filtration. More specifically, the cell–cell junction between adjacent podocyte foot processes, namely, the slit diaphragm, has been revealed to be made up of a sophisticated multi-protein complex which dynamically controls foot process architecture via signalling to the actin cytoskeleton. Key genes that have been identified from the study of inherited nephrotic syndromes include those encoding nephrin, podocin, TRPC6 (transient receptor potential canonical channel-6) and α-actinin-4, and more remain to be found. It is now possible to identify genetic causes underlying a proportion of nephrotic syndromes presenting at any age. The next big challenge for clinicians and researchers is to translate the molecular information learnt into the understanding of acquired, non-inherited forms of the disease and to guide therapeutic options. In this regard several exciting advances have been made, both in understanding the molecular mechanisms of current therapies and in revealing circulating plasma factors and the molecular pathways they trigger in the podocyte, that could be targeted by novel therapies.

  
  
• Renal complications of Fabry disease in children
  

  Abstract

  Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis, and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges, and needs to better approach renal complications of Fabry disease in children.

  
  
• Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome
  

  Abstract

  Background

  About 10–20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS.

  Methods

  Expression of cytoplasmic GRs in lymphocytes (CD3 ⁺ /GR) and monocytes (CD14 ⁺ /GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls.

  Results

  Expression of CD3 ⁺ /GR was significantly lower in SRNS in comparison to SSNS patients and controls ( p  < 0.0001). Similarly, expression of CD14 ⁺ /GR was significantly lower in SRNS in comparison to SSNS patients ( p  < 0.0001) and controls ( p  = 0.002). CD3 ⁺ /GR and CD14 ⁺ /GR expression were not significantly different in SSNS patients compared with controls ( p  = 0.06 and 0.07 respectively).

  Conclusions

  Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.

  
  
• The need for ongoing monitoring of adherence to access targets
  
• Successful management of factor IX inhibitor-associated nephrotic syndrome in a hemophilia B patient
  

  Abstract

  Background

  Nephrotic syndrome (NS) is a recognized complication of immune tolerance induction (ITI) therapy, a treatment strategy used to treat inhibitors in patients with hemophilia B receiving factor IX concentrate.

  Case diagnosis/treatment

  We present a 4-year-old boy with hemophilia B and an inhibitor who underwent ITI, and developed NS 19 months into this therapy. A percutaneous renal biopsy was safely performed with factor IX (FIX) concentrate administration both preceding and following the procedure. The patient’s inhibitor level had increased to 1.4–1.6 Bethesda Units just prior to the onset of proteinuria. Histology confirmed segmental membranous nephropathy (MGN). The patient was continued on FIX concentrate as ITI and also received 4 weekly doses of rituximab and ongoing immunosuppression with mycophenolate mofetil. This resulted in the complete resolution of his inhibitor and his NS. He continues with a modified ITI regimen and remains inhibitor-free without proteinuria >12 months post-biopsy.

  Conclusions

  Hemophilia B patients undergoing ITI should be regularly screened for NS. At first detection of proteinuria, with proper precautions, a percutaneous kidney biopsy can be performed safely in patients with low levels of inhibitor. Our patient had segmental MGN with complete remission of NS.

  
  
• Use of HF20 membrane in critically ill unstable low-body-weight infants on inotropic support
  

  Abstract

  Background

  Initiating continuous renal replacement therapy (CRRT) in infants exposes them to the dual hemodynamic challenges of high circuit extracorporeal volumes and potential membrane reactions, in the case of acrylonitrile AN69 membranes. The use of the new Prismaflex HF20 membrane in hemodynamically unstable low-body-weight infants on inotropic support has not been reported.

  Treatment

  We describe the use of the HF20 (Gambro Lundia AB, Lund, Sweden) membrane in four low-body-weight infants (2.3 to 5.4 kg) with multi-organ dysfunction syndrome who were critically ill in the Pediatric Intensive Care Unit (PICU), hemodynamically unstable, and on inotropes. We were able to achieve target volume loss in all infants without compromising their hemodynamic status. Mean arterial pressures were maintained between 39 and 57 mmHg. The relatively low circuit volume of the HF20 set (60 ml) obviated the need for blood prime in the majority; however, when blood prime was required, there was no adverse reaction with the polyarylethersulfone (PAES) membrane. Solute clearance in these small infants was efficient with correction of metabolic acidosis and electrolyte abnormalities. Excellent circuit lifespan (56.3 ± 32.3 h) was observed.

  Conclusions

  CRRT using the HF20 membrane is safe and hemodynamically well tolerated in high-risk, unstable low-body-weight infants with cardiac dysfunction on multiple inotropes.

  
  
• Hypokalemic paralysis in a girl with dental and renal calculi: Answers
  
• Atypical HUS: time to take stock of current guidelines and outcome measures'
  <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">European guidelines for the assessment and management of atypical HUS were written in 2009. Since then our understanding of this group of diseases has advanced. Evidence is emerging that eculizumab, a monoclonal antibody inhibiting C5 activation, is effective, and potentially superior to current treatment with plasmapheresis. The evidence base for the benefits of plasmapheresis consists of case series and small reports. Before we embark on a change of management policy it is vital that we set up a system for genetic diagnosis, standardised protocols and a means to collect predetermined outcome measures, so that we do not make the same mistakes with assessment of the effectiveness of eculizumab as we did for plasmapheresis.</p>
  
• Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome
  

  Abstract

  Background

  A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1–17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.

  Methods

  Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.

  Results

  Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n  = 15) or enalapril (0.07-0.72 mg/kg/day; n  = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was −6.4 ml/min/1.73 m ² in the losartan group versus −9.1 ml/min/1.73 m ² in the enalapril group. The adverse event incidence was low and comparable in both treatment groups.

  Conclusions

  In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.

  
  
• Two-point normalized protein catabolic rate overestimates nPCR in pediatric hemodialysis patients
  

  Abstract

  Background

  Normalized protein catabolic rate (nPCR) calculation depends on estimating the urea generation between consecutive hemodialysis (HD) treatments. Two-point nPCR using blood urea nitrogen (BUN) before and after the same HD treatment has not been validated in pediatric patients, who typically receive a more intense HD dose than adults. This study aimed to compare nPCR calculated with a two-point vs. a three-point nPCR model in pediatric HD patients.

  Methods

  Pediatric patients receiving HD at 2 units were enrolled. Three BUN measurements were obtained around a midweek HD treatment: one prior to HD (preBUN1), one 30 s after HD (30sBUN), and one prior to the subsequent HD (preBUN2). The two-point nPCR model was calculated using preBUN1 and 30sBUN and the three-point nPCR model was calculated using preBUN2 and 30sBUN.

  Results

  Seventy-six BUN sets from 35 patients were analyzed. Mean age was 16.4 ± 3.5 years. Mean dry weight was 51.4 ± 17.1 kg. Mean spKt/V was 1.54 ± 0.23. Mean preBUN2 was significantly lower than mean preBUN1 (60.2 ± 18.6 vs. 64.0 ± 18.9 mg/dl, p  = 0.0001). nPCR obtained from the three-point model was significantly lower than nPCR obtained from the two-point model (1.07 ± 0.31 vs. 1.17 ± 0.31 g/kg/day, p  = 0.00001). Seven of 76 (9.2 %) paired comparisons yielded three-point nPCR <1 vs. two-point nPCR >1.

  Conclusions

  Our data show that in pediatric patients receiving HD, the ((1) two-point and three-point models lead to significantly different nPCRs, and (2) inaccurate protein intake assessment may result from reliance on a two-point model for nPCR estimates.

  
  
• Prospective 5-year follow-up of cyclosporine treatment in children with steroid-resistant nephrosis
  

  Abstract

  Background

  Cyclosporine has improved remission rates in children with steroid-resistant nephrotic syndrome (SRNS). However, little prospective long-term follow-up data is available.

  Methods

  We prospectively followed and analyzed 5-year outcomes of all 35 patients enrolled in our previous prospective multicenter trial with cyclosporine and steroids in children with SRNS. At enrollment, 23 cases were classified as minimal change (MC), five as diffuse mesangial proliferation (DMP), and seven as focal segmental glomerulosclerosis (FSGS).

  Results

  Renal survival at 5 years (median 7.7 years) was 94.3 %. Patient status was complete remission (CR) in 31 (88.6 %) (MC/DMP, 25; FSGS, 6); partial remission in one (FSGS); and non-remission in three (MC/DMP), including chronic kidney disease and end-stage kidney disease in one each. Among 31 patients with CR, 22 (71.0 %) were receiving treatment with immunosuppressants at 5 years, including cyclosporine in 19, and seven of these 22 continued to show frequent relapse. Response to cyclosporine at 4 months predicted 5-year outcome in 31 of 35 patients.

  Conclusions

  Although SRNS treatment with cyclosporine provides high renal survival and remission rates, many children require ongoing immunosuppression. Management has advanced from the prevention of end-stage kidney disease to the long-term maintenance of remission and management of relapse after induction therapy.

  
  
• Can sonographic peritoneal thickness be used to follow pediatric patients on peritoneal dialysis'
  

  Abstract

  Background

  Peritoneal dialysis (PD) is an effective and successful therapy for end-stage renal disease (ESRD). However, PD does not have a life-long effectiveness, and peritoneal membrane failure is commonly observed in long-term PD patients. We hypothesized that ultrasonography could be used to follow these patients.

  Methods

  We recruited two patient groups (age range 3–18 years), of whom 20 had ESRD with ongoing PD for ≥24 months (study group) and 20 were pre-dialysis non-ESRD patients (control group). None of the patients had peritonitis during the preceding 3 months, and none had a history of abdominal surgery or malignancy. We measured the sonographic thickness of the parietal peritoneum and obtained Doppler indices of the superior mesenteric artery (SMA) by trans-abdominal ultrasonography.

  Results

  Peritoneal thickness as determined by sonography was significantly greater in the PD group than in the controls. The correlation between duration of PD and thickness of the peritoneal membrane was linear and statistically significant. We categorized all 20 patients as either rapid transporters or slow transporters for both creatinine and glucose. The peritoneal membranes of patients who were rapid transporters for both creatinine and glucose were significantly thicker than those of the slow transporters. No statistical difference was found between the Doppler indices of the SMA between the groups.

  Conclusion

  Thickness of the parietal peritoneum as determined by sonography is associated with PD duration and transport characteristics. We conclude that ultrasonography is a non-invasive and practical method which can be useful for following PD patients.

  
  
• Erratum to: Soy protein prevents renal damage in a fructose-induced model of metabolic syndrome via inhibition of NF-kB in male rats
  
• Hypokalemic paralysis in a girl with dental and renal calculi: Questions
  
• In Memoriam: Professor Cornelis Schroder—8 April 1951–19 September 2012
  
• <em class="a-plus-plus">NPHS2</em> p.V290M mutation in late-onset steroid-resistant nephrotic syndrome
  

  Abstract

  Background

  The most frequently mutated gene of steroid-resistant nephrotic syndrome (SRNS) is NPHS2 . Current guidelines propose the sequencing of all NPHS2 exons only in childhood-onset SRNS.

  Methods

  A cohort of 38 Hungarian patients with childhood-onset nephrotic-range proteinuria was screened for NPHS2 mutations. The frequency of the p.V290M mutation in late-onset SRNS was examined in the French and PodoNet cohorts.

  Results

  Of the 38 Hungarian patients screened, seven carried NPHS2 mutations on both alleles, of whom two—diagnosed with proteinuria through school screening programs at the age of 9.7 and 14 years, respectively—did not develop nephrotic syndrome in childhood. The first, an 18-year-old boy, homozygous for p.V290M, has never developed edema. The second, a 31-year-old woman—compound heterozygous for p.V290M and p.R138Q—was first detected with hypoalbuminemia (<30 g/l) and edema at the age of 24.3 and 27.5 years, respectively. Both patients currently have a normal glomerular filtration rate. The mutation p.V290M was carried by three of the 38 patients in the Hungarian cohort, by two of the 95 patients with late-onset SRNS in the PodoNet cohort and by none of the 83 patients in the French cohort.

  Conclusions

  We propose that not only the p.R229Q variant, but also the p.V290M mutation should be screened in Central and Eastern European patients with late-onset SRNS.

  
  
• Additive antiproteinuric effect of enalapril and losartan in children with hemolytic uremic syndrome
  

  Abstract

  Background

  Angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers decrease postdiarrheal hemolytic uremic syndrome (D + HUS) sequelar proteinuria. However, proteinuria may persist in some patients. In nephropathies other than D + HUS, an additive antiproteinuric effect with coadministration of both drugs has been observed.

  Methods

  To assess such an effect in D + HUS, 17 proteinuric children were retrospectively studied. After a median period of 1 year post-acute stage (range 0.5–1.9) patients received enalapril alone for a median of 2.6 years (range 0.33–12.0) at a median dose of 0.4 mg/kg/day (range 0.2–0.56). As proteinuria persisted, losartan was added at a median dose of 1.0 mg/kg/day (range 0.5–1.5) during 2.1 years (range 0.5–5.0).

  Results

  The decrease in proteinuria with enalapril was 58.0 %, which was further reduced to 83.8 % from the initial value after losartan introduction. The percentage of reduction was significantly greater with the association of both drugs ( p  = 0.0006) compared with the effect of enalapril exclusively ( p  = 0.023). Serum potassium, glomerular filtration rate, and blood pressure remained unchanged.

  Conclusions

  Our results suggest that adding losartan to persisting proteinuric D + HUS children already on enalapril is safe and reduces proteinuria more effectively. Whereas this effect is associated with long-term kidney protection, it should be determined by prospective controlled studies.