This page has only limited features, please log in for full access.
Endothelial and epithelial barrier function is crucial for the maintenance of physiological processes. The barrier paracellular permeability depends on the composition and spatial distribution of the cell-to-cell tight junctions (TJ). Here, we provide an experimental workflow that yields several layers of physiological data in the setting of a single endothelial cell monolayer. Human umbilical vein endothelial cells were grown on Transwell filters. Transendothelial electrical resistance (TER) and 10 kDa FITC dextran flux were measured using Alanyl-Glutamine (AlaGln) as a paracellular barrier modulator. Single monolayers were immunolabelled for Zonula Occludens-1 (ZO-1) and Claudin-5 (CLDN5) and used for automated immunofluorescence imaging. Finally, the same monolayers were used for single molecule localization microscopy (SMLM) of ZO-1 and CLDN5 at the nanoscale for spatial clustering analysis. The TER increased and the paracellular dextran flux decreased after the application of AlaGln and these functional changes of the monolayer were mediated by an increase in the ZO-1 and CLDN5 abundance in the cell–cell interface. At the nanoscale level, the functional and protein abundance data were accompanied by non-random increased clustering of CLDN5. Our experimental workflow provides multiple data from a single monolayer and has wide applicability in the setting of paracellular studies in endothelia and epithelia.
Maria Bartosova; David Ridinger; Iva Marinovic; Jana Heigwer; Conghui Zhang; Eszter Levai; Jens Westhoff; Franz Schaefer; Stefan Terjung; Georg Hildenbrand; Damir Krunic; Felix Bestvater; Michael Hausmann; Claus Schmitt; Sotirios Zarogiannis. An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept. International Journal of Molecular Sciences 2021, 22, 8178 .
AMA StyleMaria Bartosova, David Ridinger, Iva Marinovic, Jana Heigwer, Conghui Zhang, Eszter Levai, Jens Westhoff, Franz Schaefer, Stefan Terjung, Georg Hildenbrand, Damir Krunic, Felix Bestvater, Michael Hausmann, Claus Schmitt, Sotirios Zarogiannis. An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept. International Journal of Molecular Sciences. 2021; 22 (15):8178.
Chicago/Turabian StyleMaria Bartosova; David Ridinger; Iva Marinovic; Jana Heigwer; Conghui Zhang; Eszter Levai; Jens Westhoff; Franz Schaefer; Stefan Terjung; Georg Hildenbrand; Damir Krunic; Felix Bestvater; Michael Hausmann; Claus Schmitt; Sotirios Zarogiannis. 2021. "An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept." International Journal of Molecular Sciences 22, no. 15: 8178.
Background The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient’s outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. Results Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4.1%). Genetically confirmed diagnoses were reported in 24% of all pediatric and 12% adult patients, whereas glomerulopathies had been confirmed by kidney biopsy in 80.4% adult versus 38.5% pediatric glomerulopathy cases. Conclusions ERKReg is a rapidly growing source of epidemiological information and patient cohorts for clinical research, and an innovative tool to monitor management quality and patient outcomes.
Giulia Bassanese; Tanja Wlodkowski; Aude Servais; Laurence Heidet; Dario Roccatello; Francesco Emma; Elena Levtchenko; Gema Ariceta; Justine Bacchetta; Giovambattista Capasso; Augustina Jankauskiene; Marius Miglinas; Pietro Manuel Ferraro; Giovanni Montini; Jun Oh; Stephane Decramer; Tanja Kersnik Levart; Jack Wetzels; Elisabeth Cornelissen; Olivier Devuyst; Aleksandra Zurowska; Lars Pape; Anja Buescher; Dieter Haffner; Natasa Marcun Varda; Gian Marco Ghiggeri; Giuseppe Remuzzi; Martin Konrad; Germana Longo; Detlef Bockenhauer; Atif Awan; Ilze Andersone; Jaap W. Groothoff; Franz Schaefer. The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results. Orphanet Journal of Rare Diseases 2021, 16, 1 -15.
AMA StyleGiulia Bassanese, Tanja Wlodkowski, Aude Servais, Laurence Heidet, Dario Roccatello, Francesco Emma, Elena Levtchenko, Gema Ariceta, Justine Bacchetta, Giovambattista Capasso, Augustina Jankauskiene, Marius Miglinas, Pietro Manuel Ferraro, Giovanni Montini, Jun Oh, Stephane Decramer, Tanja Kersnik Levart, Jack Wetzels, Elisabeth Cornelissen, Olivier Devuyst, Aleksandra Zurowska, Lars Pape, Anja Buescher, Dieter Haffner, Natasa Marcun Varda, Gian Marco Ghiggeri, Giuseppe Remuzzi, Martin Konrad, Germana Longo, Detlef Bockenhauer, Atif Awan, Ilze Andersone, Jaap W. Groothoff, Franz Schaefer. The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results. Orphanet Journal of Rare Diseases. 2021; 16 (1):1-15.
Chicago/Turabian StyleGiulia Bassanese; Tanja Wlodkowski; Aude Servais; Laurence Heidet; Dario Roccatello; Francesco Emma; Elena Levtchenko; Gema Ariceta; Justine Bacchetta; Giovambattista Capasso; Augustina Jankauskiene; Marius Miglinas; Pietro Manuel Ferraro; Giovanni Montini; Jun Oh; Stephane Decramer; Tanja Kersnik Levart; Jack Wetzels; Elisabeth Cornelissen; Olivier Devuyst; Aleksandra Zurowska; Lars Pape; Anja Buescher; Dieter Haffner; Natasa Marcun Varda; Gian Marco Ghiggeri; Giuseppe Remuzzi; Martin Konrad; Germana Longo; Detlef Bockenhauer; Atif Awan; Ilze Andersone; Jaap W. Groothoff; Franz Schaefer. 2021. "The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results." Orphanet Journal of Rare Diseases 16, no. 1: 1-15.
Background The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW. Methods Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients (1–25 years, 52 girls). Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis. Results The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (p < 0.001, n = 22) correlated with the change in body weight (R 2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW. Conclusion BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future.
Sandra M. Frey; Bruno Vogt; Giacomo D. Simonetti; Rainer Büscher; Sandra Habbig; Franz Schaefer. Differential assessment of fluid compartments by bioimpedance in pediatric patients with kidney diseases. Pediatric Nephrology 2021, 36, 1843 -1850.
AMA StyleSandra M. Frey, Bruno Vogt, Giacomo D. Simonetti, Rainer Büscher, Sandra Habbig, Franz Schaefer. Differential assessment of fluid compartments by bioimpedance in pediatric patients with kidney diseases. Pediatric Nephrology. 2021; 36 (7):1843-1850.
Chicago/Turabian StyleSandra M. Frey; Bruno Vogt; Giacomo D. Simonetti; Rainer Büscher; Sandra Habbig; Franz Schaefer. 2021. "Differential assessment of fluid compartments by bioimpedance in pediatric patients with kidney diseases." Pediatric Nephrology 36, no. 7: 1843-1850.
Background Approximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant. Methods This is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed. Discussion The study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols. Trial registration This trial was prospectively registered to the Clinicaltrial.gov (NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/) and Clinical Trials Registry of India (CTRI/2019/04/018517 dated 09/04/2019).
Biswanath Basu; Stella Preussler; Anja Sander; T. K. S. Mahapatra; Franz Schaefer. Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome. BMC Nephrology 2020, 21, 1 -11.
AMA StyleBiswanath Basu, Stella Preussler, Anja Sander, T. K. S. Mahapatra, Franz Schaefer. Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome. BMC Nephrology. 2020; 21 (1):1-11.
Chicago/Turabian StyleBiswanath Basu; Stella Preussler; Anja Sander; T. K. S. Mahapatra; Franz Schaefer. 2020. "Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome." BMC Nephrology 21, no. 1: 1-11.
Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders presenting with massive proteinuria within the first 3 months of life almost inevitably leading to end-stage kidney disease. The Work Group for the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Pediatric Nephrology (ESPN) has developed consensus statement on genetic aspects of CNS diagnosis and management. The presented expert opinion recommends genetic diagnostics as the key diagnostic test to be ordered already during the initial evaluation of the patient, discusses which phenotyping workup should be performed and presents known genotype–phenotype correlations.
Beata Stefania Lipska-Ziętkiewicz; Fatih Ozaltin; Tuula Hölttä; Detlef Bockenhauer; Sandra Bérody; Elena Levtchenko; Marina Vivarelli; Hazel Webb; Dieter Haffner; Franz Schaefer; Olivia Boyer. Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet–ESPN inherited glomerulopathy working group. European Journal of Human Genetics 2020, 28, 1368 -1378.
AMA StyleBeata Stefania Lipska-Ziętkiewicz, Fatih Ozaltin, Tuula Hölttä, Detlef Bockenhauer, Sandra Bérody, Elena Levtchenko, Marina Vivarelli, Hazel Webb, Dieter Haffner, Franz Schaefer, Olivia Boyer. Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet–ESPN inherited glomerulopathy working group. European Journal of Human Genetics. 2020; 28 (10):1368-1378.
Chicago/Turabian StyleBeata Stefania Lipska-Ziętkiewicz; Fatih Ozaltin; Tuula Hölttä; Detlef Bockenhauer; Sandra Bérody; Elena Levtchenko; Marina Vivarelli; Hazel Webb; Dieter Haffner; Franz Schaefer; Olivia Boyer. 2020. "Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet–ESPN inherited glomerulopathy working group." European Journal of Human Genetics 28, no. 10: 1368-1378.
Patients with chronic kidney disease (CKD) have altered physiologic processes, which result in different treatment outcomes compared with the general population. We aimed to systematically evaluate the efficacy of clinical interventions in reducing mortality of patients with CKD. We searched PubMed, MEDLINE, Embase, and Cochrane Database of Systematic Reviews for meta-analyses of randomized controlled trials (RCT) or observational studies (OS) studying the effect of treatment on all-cause mortality of patients with CKD. The credibility assessment was based on the random-effects summary estimate, heterogeneity, 95% prediction intervals, small study effects, excess significance, and credibility ceilings. Ninety-two articles yielded 130 unique meta-analyses. Convincing evidence from OSs supported mortality reduction with three treatments: angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers for patients not undergoing dialysis, warfarin for patients with atrial fibrillation not undergoing dialysis, and (at short-term) percutaneous coronary intervention compared to coronary artery bypass grafting for dialysis patients. Two treatment comparisons were supported by highly credible evidence from RCTs in terms of all-cause mortality. These were high-flux hemodialysis (HD) versus low-flux HD as a maintenance HD method and statin versus less statin or placebo for patients not undergoing dialysis. Most significant associations identified in OSs failed to be replicated in RCTs. Associations of high credibility from RCTs were in line with current guidelines. Given the heterogeneity of CKD, it seems hard to assume mortality reductions based on findings from OSs.
Jong Yeob Kim; Johanna Steingroever; Keum Hwa Lee; Jun Oh; Min Jae Choi; Jiwon Lee; Nicholas G. Larkins; Franz Schaefer; Sung Hwi Hong; Gwang Hun Jeong; Jae Il Shin; Andreas Kronbichler. Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses. Journal of Clinical Medicine 2020, 9, 394 .
AMA StyleJong Yeob Kim, Johanna Steingroever, Keum Hwa Lee, Jun Oh, Min Jae Choi, Jiwon Lee, Nicholas G. Larkins, Franz Schaefer, Sung Hwi Hong, Gwang Hun Jeong, Jae Il Shin, Andreas Kronbichler. Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses. Journal of Clinical Medicine. 2020; 9 (2):394.
Chicago/Turabian StyleJong Yeob Kim; Johanna Steingroever; Keum Hwa Lee; Jun Oh; Min Jae Choi; Jiwon Lee; Nicholas G. Larkins; Franz Schaefer; Sung Hwi Hong; Gwang Hun Jeong; Jae Il Shin; Andreas Kronbichler. 2020. "Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses." Journal of Clinical Medicine 9, no. 2: 394.
Franz Schaefer. “It’s In Your Genes”. Clinical Journal of the American Society of Nephrology 2019, 15, 10 -12.
AMA StyleFranz Schaefer. “It’s In Your Genes”. Clinical Journal of the American Society of Nephrology. 2019; 15 (1):10-12.
Chicago/Turabian StyleFranz Schaefer. 2019. "“It’s In Your Genes”." Clinical Journal of the American Society of Nephrology 15, no. 1: 10-12.
Erratum zu: Der Nephrologe 2019 https://doi.org/10.1007/s11560-019-0357-4 Im ursprünglich veröffentlichten Beitrag (online) fehlten der Interessenkonflikt und einige Abbildungen. In der Online- und...
C. S. Haas; M. Nitschke; J. Menne; M. Guthoff; A. Gäckler; H. Bruck; L. Pape; U. Vester; E. Wühl; H. Billing; R. Herbst; F. Thaiss; B. Hoppe; L. T. Weber; S. Zschiedrich; T. Feldkamp; J. Oh; M. Bald; B. Schröppel; J. B. Holle; W. Jabs; J. Beckermann; K. Budde; R. Faulhaber-Walter; F. Schaefer. Erratum zu: Charakterisierung von Patienten mit atypischem hämolytisch-urämischen Syndrom (aHUS) in Deutschland. Der Nephrologe 2019, 14, 505 -505.
AMA StyleC. S. Haas, M. Nitschke, J. Menne, M. Guthoff, A. Gäckler, H. Bruck, L. Pape, U. Vester, E. Wühl, H. Billing, R. Herbst, F. Thaiss, B. Hoppe, L. T. Weber, S. Zschiedrich, T. Feldkamp, J. Oh, M. Bald, B. Schröppel, J. B. Holle, W. Jabs, J. Beckermann, K. Budde, R. Faulhaber-Walter, F. Schaefer. Erratum zu: Charakterisierung von Patienten mit atypischem hämolytisch-urämischen Syndrom (aHUS) in Deutschland. Der Nephrologe. 2019; 14 (6):505-505.
Chicago/Turabian StyleC. S. Haas; M. Nitschke; J. Menne; M. Guthoff; A. Gäckler; H. Bruck; L. Pape; U. Vester; E. Wühl; H. Billing; R. Herbst; F. Thaiss; B. Hoppe; L. T. Weber; S. Zschiedrich; T. Feldkamp; J. Oh; M. Bald; B. Schröppel; J. B. Holle; W. Jabs; J. Beckermann; K. Budde; R. Faulhaber-Walter; F. Schaefer. 2019. "Erratum zu: Charakterisierung von Patienten mit atypischem hämolytisch-urämischen Syndrom (aHUS) in Deutschland." Der Nephrologe 14, no. 6: 505-505.
Failure of statural growth is one of the major long-term sequelae of chronic kidney disease (CKD) in children. In recent years effective therapeutic strategies have become available that lead to evidence based practice recommendations. To assess the current growth performance of European children and adolescents with CKD, we analyzed a cohort of 594 patients from 12 European countries who were followed prospectively for up to 6 years in the 4C Study. While all patients were on conservative treatment with a mean estimated glomerular filtration rate of 28 ml/min/1.73 m2 at study entry, 130 children commenced dialysis during the observation period. At time of enrolment the mean height standard deviation score (SDS) was −1.57; 36% of patients had a height below the third percentile. The prevalence of growth failure varied between countries from 7 to 44% Whereas patients on conservative treatment showed stable growth, height SDS gradually declined on those on dialysis. Parental height, pubertal status and treatment with recombinant growth hormone (GH) were positively, and the diagnosis of syndromic disease and CKD stage were negatively associated with height SDS during the observation period. Unexpectedly, higher body mass index (BMI) SDS was associated with lower height SDS both at enrolment and during follow up. Renal anemia, metabolic acidosis, and hyperparathyroidism were mostly mild and not predictive of growth rates by multivariable analysis. GH therapy was applied in only 15% of growth retarded patients with large variation between countries. When adjusting for all significant covariates listed above, the country of residence remained a highly significant predictor of overall growth performance. In conclusion, growth failure remains common in European children with CKD, despite improved general management of CKD complications. The widespread underutilization of GH, an approved efficacious therapy for CKD-associated growth failure, deserves further exploration.
Rouven Behnisch; Marietta Kirchner; Ali Anarat; Justine Bacchetta; Rukshana Shroff; Yelda Bilginer; Sevgi Mir; Salim Çalışkan; Dusan Paripovic; Jerome Harambat; Francesca Mencarelli; Rainer Büscher; Klaus Arbeiter; Oguz Soylemezoglu; Ariane Zaloszyc; Aleksandra Zurowska; Anette Melk; Uwe Querfeld; Franz Schaefer; and the 4C Study Consortium. Determinants of Statural Growth in European Children With Chronic Kidney Disease: Findings From the Cardiovascular Comorbidity in Children With Chronic Kidney Disease (4C) Study. Frontiers in Pediatrics 2019, 7, 278 .
AMA StyleRouven Behnisch, Marietta Kirchner, Ali Anarat, Justine Bacchetta, Rukshana Shroff, Yelda Bilginer, Sevgi Mir, Salim Çalışkan, Dusan Paripovic, Jerome Harambat, Francesca Mencarelli, Rainer Büscher, Klaus Arbeiter, Oguz Soylemezoglu, Ariane Zaloszyc, Aleksandra Zurowska, Anette Melk, Uwe Querfeld, Franz Schaefer, and the 4C Study Consortium. Determinants of Statural Growth in European Children With Chronic Kidney Disease: Findings From the Cardiovascular Comorbidity in Children With Chronic Kidney Disease (4C) Study. Frontiers in Pediatrics. 2019; 7 ():278.
Chicago/Turabian StyleRouven Behnisch; Marietta Kirchner; Ali Anarat; Justine Bacchetta; Rukshana Shroff; Yelda Bilginer; Sevgi Mir; Salim Çalışkan; Dusan Paripovic; Jerome Harambat; Francesca Mencarelli; Rainer Büscher; Klaus Arbeiter; Oguz Soylemezoglu; Ariane Zaloszyc; Aleksandra Zurowska; Anette Melk; Uwe Querfeld; Franz Schaefer; and the 4C Study Consortium. 2019. "Determinants of Statural Growth in European Children With Chronic Kidney Disease: Findings From the Cardiovascular Comorbidity in Children With Chronic Kidney Disease (4C) Study." Frontiers in Pediatrics 7, no. : 278.
C. S. Haas; M. Nitschke; J. Menne; M. Guthoff; A. Gäckler; H. Bruck; L. Pape; U. Vester; E. Wühl; H. Billing; R. Herbst; F. Thaiss; B. Hoppe; L. T. Weber; S. Zschiedrich; T. Feldkamp; J. Oh; M. Bald; B. Schröppel; Johannes Holle; W. Jabs; J. Beckermann; Klemens Budde; R. Faulhaber-Walter; F. Schaefer. Charakterisierung von Patienten mit atypischem hämolytisch-urämischen Syndrom (aHUS) in Deutschland. Der Nephrologe 2019, 14, 496 -504.
AMA StyleC. S. Haas, M. Nitschke, J. Menne, M. Guthoff, A. Gäckler, H. Bruck, L. Pape, U. Vester, E. Wühl, H. Billing, R. Herbst, F. Thaiss, B. Hoppe, L. T. Weber, S. Zschiedrich, T. Feldkamp, J. Oh, M. Bald, B. Schröppel, Johannes Holle, W. Jabs, J. Beckermann, Klemens Budde, R. Faulhaber-Walter, F. Schaefer. Charakterisierung von Patienten mit atypischem hämolytisch-urämischen Syndrom (aHUS) in Deutschland. Der Nephrologe. 2019; 14 (6):496-504.
Chicago/Turabian StyleC. S. Haas; M. Nitschke; J. Menne; M. Guthoff; A. Gäckler; H. Bruck; L. Pape; U. Vester; E. Wühl; H. Billing; R. Herbst; F. Thaiss; B. Hoppe; L. T. Weber; S. Zschiedrich; T. Feldkamp; J. Oh; M. Bald; B. Schröppel; Johannes Holle; W. Jabs; J. Beckermann; Klemens Budde; R. Faulhaber-Walter; F. Schaefer. 2019. "Charakterisierung von Patienten mit atypischem hämolytisch-urämischen Syndrom (aHUS) in Deutschland." Der Nephrologe 14, no. 6: 496-504.
Beata S. Lipska-Ziętkiewicz; Franz Schaefer. NUP Nephropathy: When Defective Pores Cause Leaky Glomeruli. American Journal of Kidney Diseases 2019, 73, 890 -892.
AMA StyleBeata S. Lipska-Ziętkiewicz, Franz Schaefer. NUP Nephropathy: When Defective Pores Cause Leaky Glomeruli. American Journal of Kidney Diseases. 2019; 73 (6):890-892.
Chicago/Turabian StyleBeata S. Lipska-Ziętkiewicz; Franz Schaefer. 2019. "NUP Nephropathy: When Defective Pores Cause Leaky Glomeruli." American Journal of Kidney Diseases 73, no. 6: 890-892.
This report describes the rationale and design of a study assessing tolvaptan in children with autosomal dominant polycystic kidney disease (ADPKD). Phase A is a 1-year, randomized, double-blind, placebo-controlled, multicenter trial. Phase B is a 2-year, open-label extension. The target population is at least 60 children aged 12-17 years, diagnosed by family history and/or genetic criteria and the presence of ≥ 10 renal cysts, each ≥ 0.5 cm on magnetic resonance imaging. Subjects will be allocated into 4 groups: females 15-17 years; females 12-14 years; males 15-17 years; and males 12-14 years. Up to 40 subjects aged 4-11 years may also enroll, provided they meet the entry criteria. Weight-adjusted tolvaptan doses, titrated once to achieve a tolerated maintenance dose, and matching placebo will be administered twice-daily. Assessments include spot urine osmolality and specific gravity (co-primary endpoints), height-adjusted total kidney volume, estimated glomerular filtration rate, pharmacodynamic parameters (urine volume, fluid intake and fluid balance, serum sodium, serum creatinine, free water clearance), pharmacokinetic parameters, safety (aquaretic adverse events, changes from baseline in creatinine, vital signs, laboratory values including liver function tests), and generic pediatric quality of life assessments.Conclusion: This will be the first clinical study to evaluate tolvaptan in pediatric ADPKD. What is Known: • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder causing the development of cysts that impede kidney function over time and eventually induce renal failure • There are few data on the effects of tolvaptan, the only treatment approved for adults to slow disease progression, in pediatric ADPKD patients with early-stage disease What is New: • A phase 3, placebo-controlled study is evaluating tolvaptan over 3 years in children and adolescents with ADPKD • This study is designed to account for challenges of tolvaptan dosing and outcome assessment specific to the pediatric population.
Franz Schaefer; Djalila Mekahli; Francesco Emma; Rodney D. Gilbert; Detlef Bockenhauer; Melissa A. Cadnapaphornchai; Lily Shi; Ann Dandurand; Kimberly Sikes; Susan E. Shoaf. Tolvaptan use in children and adolescents with autosomal dominant polycystic kidney disease: rationale and design of a two-part, randomized, double-blind, placebo-controlled trial. European Journal of Nuclear Medicine and Molecular Imaging 2019, 178, 1013 -1021.
AMA StyleFranz Schaefer, Djalila Mekahli, Francesco Emma, Rodney D. Gilbert, Detlef Bockenhauer, Melissa A. Cadnapaphornchai, Lily Shi, Ann Dandurand, Kimberly Sikes, Susan E. Shoaf. Tolvaptan use in children and adolescents with autosomal dominant polycystic kidney disease: rationale and design of a two-part, randomized, double-blind, placebo-controlled trial. European Journal of Nuclear Medicine and Molecular Imaging. 2019; 178 (7):1013-1021.
Chicago/Turabian StyleFranz Schaefer; Djalila Mekahli; Francesco Emma; Rodney D. Gilbert; Detlef Bockenhauer; Melissa A. Cadnapaphornchai; Lily Shi; Ann Dandurand; Kimberly Sikes; Susan E. Shoaf. 2019. "Tolvaptan use in children and adolescents with autosomal dominant polycystic kidney disease: rationale and design of a two-part, randomized, double-blind, placebo-controlled trial." European Journal of Nuclear Medicine and Molecular Imaging 178, no. 7: 1013-1021.
Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (rs). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (rs −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.
Evelien Snauwaert; Els Holvoet; Wim Van Biesen; Ann Raes; Griet Glorieux; Johan Vande Walle; Sanne Roels; Raymond Vanholder; Varvara Askiti; Karolis Azukaitis; Aysun Bayazit; Nur Canpolat; Michel Fischbach; Nathalie Godefroid; Saoussen Krid; Mieczyslaw Litwin; Lukasz Obrycki; Fabio Paglialonga; Bruno Ranchin; Charlotte Samaille; Franz Schaefer; Claus Peter Schmitt; Brankica Spasojevic; Constantinos J. Stefanidis; Maria Van Dyck; Koen Van Hoeck; Laure Collard; Sunny Eloot; Rukshana Shroff. Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins 2019, 11, 235 .
AMA StyleEvelien Snauwaert, Els Holvoet, Wim Van Biesen, Ann Raes, Griet Glorieux, Johan Vande Walle, Sanne Roels, Raymond Vanholder, Varvara Askiti, Karolis Azukaitis, Aysun Bayazit, Nur Canpolat, Michel Fischbach, Nathalie Godefroid, Saoussen Krid, Mieczyslaw Litwin, Lukasz Obrycki, Fabio Paglialonga, Bruno Ranchin, Charlotte Samaille, Franz Schaefer, Claus Peter Schmitt, Brankica Spasojevic, Constantinos J. Stefanidis, Maria Van Dyck, Koen Van Hoeck, Laure Collard, Sunny Eloot, Rukshana Shroff. Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins. 2019; 11 (4):235.
Chicago/Turabian StyleEvelien Snauwaert; Els Holvoet; Wim Van Biesen; Ann Raes; Griet Glorieux; Johan Vande Walle; Sanne Roels; Raymond Vanholder; Varvara Askiti; Karolis Azukaitis; Aysun Bayazit; Nur Canpolat; Michel Fischbach; Nathalie Godefroid; Saoussen Krid; Mieczyslaw Litwin; Lukasz Obrycki; Fabio Paglialonga; Bruno Ranchin; Charlotte Samaille; Franz Schaefer; Claus Peter Schmitt; Brankica Spasojevic; Constantinos J. Stefanidis; Maria Van Dyck; Koen Van Hoeck; Laure Collard; Sunny Eloot; Rukshana Shroff. 2019. "Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population." Toxins 11, no. 4: 235.
Das hämolytisch-urämische Syndrom (HUS) ist als Trias von hämolytischer Anämie, Thrombozytopenie und akuter Niereninsuffizienz definiert. Das HUS ist die häufigste Ursache des kindlichen akuten Nierenversagens jenseits der Neugeborenenperiode. Die jährliche Inzidenz beträgt ca. 3 Fälle pro 100.000 Kinder unter 5 Jahren. Man unterscheidet eine typische und eine atypische Form der Erkrankung. Das klassische HUS macht 90 % der HUS-Fälle aus. Es tritt überwiegend bei Kindern unter 5 Jahren im Anschluss an eine Darminfektion (Diarrhö) auf (D+-Form). Die atypische HUS-Variante kann in jedem Lebensalter auftreten und beginnt meist schleichend ohne gastrointestinale Prodromalerkrankung (D−-Form). Dem atypischen HUS liegen zumeist genetische oder erworbene Anomalien des alternativen Komplementwegs zugrunde.
Franz Schaefer. Hämolytisch-urämisches Syndrom. Psychiatrie und Psychotherapie des Kindes- und Jugendalters 2019, 1 -5.
AMA StyleFranz Schaefer. Hämolytisch-urämisches Syndrom. Psychiatrie und Psychotherapie des Kindes- und Jugendalters. 2019; ():1-5.
Chicago/Turabian StyleFranz Schaefer. 2019. "Hämolytisch-urämisches Syndrom." Psychiatrie und Psychotherapie des Kindes- und Jugendalters , no. : 1-5.
Die chronische Niereninsuffizienz (CNI) wird in 5 Schweregrade unterteilt (Klassifikation der KDOQI, Kidney Disease Outcomes Quality Initiative). Im CNI-Stadium 1 besteht eine chronische Nierenschädigung bei noch erhaltener oder sogar gesteigerter glomerulärer Filtrationsrate (GFR >90 ml/min/1,73 m2 KOF). Im Stadium 2 liegt eine leichte (GFR 60–90), im Stadium 3 eine mäßige (GFR 30–60), im Stadium 4 eine fortgeschrittene (GFR 15–30) und im Stadium 5 eine subtotale Einschränkung oder vollständiger Verlust der Nierenfunktion vor (GFR 0–15 ml/min/1,73 m2 KOF). Durch Normierung auf die Körperoberfläche ist diese für erwachsene Patienten konzipierte Klassifikation auch auf Kinder anwendbar. Bei Säuglingen ist allerdings zu berücksichtigen, dass die untere Grenze des GFR-Normbereichs erst gegen Ende des 1. Lebensjahres erreicht wird. Reife Neugeborene weisen eine GFR von etwa 30 ml/min/1,73 m2 KOF auf.
Franz Schaefer. Chronische Niereninsuffizienz bei Kindern und Jugendlichen. Klinische Angiologie 2019, 1 -5.
AMA StyleFranz Schaefer. Chronische Niereninsuffizienz bei Kindern und Jugendlichen. Klinische Angiologie. 2019; ():1-5.
Chicago/Turabian StyleFranz Schaefer. 2019. "Chronische Niereninsuffizienz bei Kindern und Jugendlichen." Klinische Angiologie , no. : 1-5.
While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry. The overall prevalence of underweight, and overweight/obesity at start of CPD was 8.9% and 19.7%, respectively. Underweight was most prevalent in South and Southeast Asia (20%), Central Europe (16.7%) and Turkey (15.2%), whereas overweight and obesity were most common in the Middle East (40%) and the US (33%). BMI SDS at PD initiation was associated positively with current eGFR and gastrostomy feeding prior to PD start. Over the course of PD BMI SDS tended to increase on CPD in underweight and normal weight children, whereas it decreased in initially overweight patients. In infancy, mortality risk was amplified by obesity, whereas in older children mortality was markedly increased in association with underweight. Both underweight and overweight are prevalent in pediatric ESKD, with the prevalence varying across the globe. Late dialysis start is associated with underweight, while enteral feeding can lead to obesity. Nutritional abnormalities tend to attenuate with time on dialysis. Mortality risk appears increased with obesity in infants and with underweight in older children.
Franz Schaefer; International Pediatric Peritoneal Dialysis Network (IPPN) Registry; Laura Benner; Dagmara Borzych-Dużałka; Joshua Zaritsky; Hong Xu; Lesley Rees; Zenaida L. Antonio; Erkin Serdaroglu; Nakysa Hooman; Hiren Patel; Lale Sever; Karel Vondrak; Joseph Flynn; Anabella Rébori; William Wong; Tuula Hölttä; Zeynep Yuruk Yildirim; Bruno Ranchin; Ryszard Grenda; Sara Testa; Dorota Drożdz; Attila J. Szabo; Loai Eid; Biswanath Basu; Renata Vitkevic; Cynthia Wong; Stephen J. Pottoore; Dominik Müller; Ruhan Dusunsel; Claudia Gonzalez Celedon; Marc Fila; Lisa Sartz; Anja Sander; Bradley A. Warady. Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis: A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network. Scientific Reports 2019, 9, 1 -10.
AMA StyleFranz Schaefer, International Pediatric Peritoneal Dialysis Network (IPPN) Registry, Laura Benner, Dagmara Borzych-Dużałka, Joshua Zaritsky, Hong Xu, Lesley Rees, Zenaida L. Antonio, Erkin Serdaroglu, Nakysa Hooman, Hiren Patel, Lale Sever, Karel Vondrak, Joseph Flynn, Anabella Rébori, William Wong, Tuula Hölttä, Zeynep Yuruk Yildirim, Bruno Ranchin, Ryszard Grenda, Sara Testa, Dorota Drożdz, Attila J. Szabo, Loai Eid, Biswanath Basu, Renata Vitkevic, Cynthia Wong, Stephen J. Pottoore, Dominik Müller, Ruhan Dusunsel, Claudia Gonzalez Celedon, Marc Fila, Lisa Sartz, Anja Sander, Bradley A. Warady. Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis: A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network. Scientific Reports. 2019; 9 (1):1-10.
Chicago/Turabian StyleFranz Schaefer; International Pediatric Peritoneal Dialysis Network (IPPN) Registry; Laura Benner; Dagmara Borzych-Dużałka; Joshua Zaritsky; Hong Xu; Lesley Rees; Zenaida L. Antonio; Erkin Serdaroglu; Nakysa Hooman; Hiren Patel; Lale Sever; Karel Vondrak; Joseph Flynn; Anabella Rébori; William Wong; Tuula Hölttä; Zeynep Yuruk Yildirim; Bruno Ranchin; Ryszard Grenda; Sara Testa; Dorota Drożdz; Attila J. Szabo; Loai Eid; Biswanath Basu; Renata Vitkevic; Cynthia Wong; Stephen J. Pottoore; Dominik Müller; Ruhan Dusunsel; Claudia Gonzalez Celedon; Marc Fila; Lisa Sartz; Anja Sander; Bradley A. Warady. 2019. "Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis: A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network." Scientific Reports 9, no. 1: 1-10.
The zebrafish is being increasingly used in biomedical research and drug discovery to conduct large-scale compound screening. However, there is a lack of accessible methodologies to enable automated imaging and scoring of tissue-specific phenotypes at enhanced resolution. Here, we present the development of an automated imaging pipeline to identify chemical modifiers of glomerular cyst formation in a zebrafish model for human cystic kidney disease. Morpholino-mediated knockdown of intraflagellar transport protein Ift172 in Tg(wt1b:EGFP) embryos was used to induce large glomerular cysts representing a robustly scorable phenotypic readout. Compound-treated embryos were consistently aligned within the cavities of agarose-filled microplates. By interfacing feature detection algorithms with automated microscopy, a smart imaging workflow for detection, centring and zooming in on regions of interests was established, which enabled the automated capturing of standardised higher resolution datasets of pronephric areas. High-content screening datasets were processed and analysed using custom-developed heuristic algorithms implemented in common open-source image analysis software. The workflow enables highly efficient profiling of entire compound libraries and scoring of kidney-specific morphological phenotypes in thousands of zebrafish embryos. The demonstrated toolset covers all the aspects of a complex whole organism screening assay and can be adapted to other organs, specimens or applications.
Gunjan Pandey; Jens H. Westhoff; Franz Schaefer; Jochen Gehrig. A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model. International Journal of Molecular Sciences 2019, 20, 1290 .
AMA StyleGunjan Pandey, Jens H. Westhoff, Franz Schaefer, Jochen Gehrig. A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model. International Journal of Molecular Sciences. 2019; 20 (6):1290.
Chicago/Turabian StyleGunjan Pandey; Jens H. Westhoff; Franz Schaefer; Jochen Gehrig. 2019. "A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model." International Journal of Molecular Sciences 20, no. 6: 1290.
Cardiovascular disease (CVD) is a life-limiting comorbidity in patients with chronic kidney disease (CKD). In childhood, imaging studies have demonstrated early phenotypic characteristics including increases in left ventricular mass, carotid artery intima-media thickness, and pulse wave velocity, which occur even in young children with early stages of CKD. Vascular calcifications are the signature of an advanced phenotype and are mainly found in adolescents and young adults treated with dialysis. Association studies have provided valuable information regarding the significance of a multitude of risk factors in promoting CVD in children with CKD by using intermediate endpoints of measurements of surrogate parameters of CVD. Dialysis aggravates pre-existing risk factors and accelerates the progression of CVD with additional dialysis-related risk factors. Coronary artery calcifications in children and young adults with CKD accumulate in a time-dependent manner on dialysis. Identification of risk factors has led to improved understanding of principal mechanisms of CKD-induced damage to the cardiovascular system. Treatment strategies include assessment and monitoring of individual risk factor load, optimization of treatment of modifiable risk factors, and intensified hemodialysis if early transplantation is not possible.
Uwe Querfeld; Franz Schaefer. Cardiovascular risk factors in children on dialysis: an update. Pediatric Nephrology 2018, 35, 41 -57.
AMA StyleUwe Querfeld, Franz Schaefer. Cardiovascular risk factors in children on dialysis: an update. Pediatric Nephrology. 2018; 35 (1):41-57.
Chicago/Turabian StyleUwe Querfeld; Franz Schaefer. 2018. "Cardiovascular risk factors in children on dialysis: an update." Pediatric Nephrology 35, no. 1: 41-57.
Question Is B-cell–depleting therapy more efficacious than calcineurin inhibition in maintaining relapse-free survival in children with corticosteroid-dependent nephrotic syndrome? Findings In this randomized clinical trial that included 120 children with corticosteroid-dependent nephrotic syndrome, a single course of rituximab therapy was associated with a significantly higher 12-month relapse-free survival rate than daily tacrolimus therapy (90.0% vs 63.3%) during 12 months of follow-up. The mean cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (25.8 vs 86.3 mg/kg). Meaning In children with corticosteroid-dependent nephrotic syndrome, rituximab is more effective than tacrolimus in maintaining disease remission and may be considered as first-line corticosteroid-sparing therapy. Importance Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte–depleting therapy is mostly used as a rescue for calcineurin inhibitor–resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. Objective To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS. Design, Setting, and Participants A parallel-arm, open-label, randomized clinical trial was performed from May 8, 2015, to September 20, 2016, with 1-year follow-up in a single-center, tertiary care unit. A total of 176 consecutive children aged 3 to 16 years with CDNS not previously treated with corticosteroid-sparing agents were screened for eligibility. Interventions The children received either tacrolimus (along with tapering alternate-day prednisolone) for 12 months or a single course of rituximab (2 infusions of 375 mg/m2). Main Outcomes and Measures Twelve-month relapse-free survival in the intention-to-treat population. Results Of the 176 children screened for eligibility, 120 were randomized and all but 3 patients completed 1 year of follow-up. The groups were comparable, with mean (SD) age of 7.2 (2.8) years, 32 boys (53.3%) in each group, mean (SD) disease duration of 2.5 (1.5) years and 2.3 (1.7) in the tacrolimus and rituximab groups, respectively, disease duration less than 1 year among 15 children (25.0%) in each group, median (interquartile range) of 4 (3-5) relapses in each group, and mean (SD) cumulative prednisolone dose of 246 (48) mg/kg and 239 (52) mg/kg in the prestudy year in the tacrolimus and rituximab groups, respectively. Rituximab therapy was associated with a higher 12-month relapse-free survival rate than tacrolimus (54 [90.0%] vs 38 [63.3%] children; P < .001; odds ratio, 5.21; 95% CI, 1.93-14.07). Among the patients who experienced relapse, median time to first relapse was 40 weeks in the rituximab group and 29 weeks in the tacrolimus group. Only 2 patients in the rituximab group had more than 1 relapse during the study period compared with 10 patients in the tacrolimus group. The cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (mean [SD], 25.8 [27.8] vs 86.3 [58.0] mg/kg). Although both treatments were well tolerated, mild to moderate infections were twice as common in the tacrolimus group (26 [43.3%] vs 13 [21.7%] events). Conclusions and Relevance In children with CDNS, rituximab appears to be more effective than tacrolimus in maintaining disease remission and minimizing corticosteroid exposure and, given its good tolerability and lack of nephrotoxic effects, may be considered as first-line corticosteroid-sparing therapy. Trial Registration ClinicalTrials.gov Identifier: NCT02438982; Clinical Trial Registry of India: CTRI/2014/01/004355
Biswanath Basu; Anja Sander; Birendranath Roy; Stella Preussler; Shilpita Barua; T. K. S. Mahapatra; Franz Schaefer. Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome. JAMA Pediatrics 2018, 172, 757 .
AMA StyleBiswanath Basu, Anja Sander, Birendranath Roy, Stella Preussler, Shilpita Barua, T. K. S. Mahapatra, Franz Schaefer. Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome. JAMA Pediatrics. 2018; 172 (8):757.
Chicago/Turabian StyleBiswanath Basu; Anja Sander; Birendranath Roy; Stella Preussler; Shilpita Barua; T. K. S. Mahapatra; Franz Schaefer. 2018. "Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome." JAMA Pediatrics 172, no. 8: 757.
Background: Steroid resistant nephrotic syndrome (SRNS) is a rare condition, accounting for 10–15% of all children with idiopathic nephrotic syndrome. SRNS can be caused by genetic abnormalities or immune system dysfunction. The prognosis of SRNS varies from permanent remission to progression to end-stage kidney disease, and post-transplant recurrence is common. Objectives: The PodoNet registry project aims to explore the demographics and phenotypes of immune-mediated and genetic forms of childhood SRNS, to assess genotype-phenotype correlations, to evaluate clinical management and long-term outcomes, and to search for novel genetic entities and diagnostic and prognostic biomarkers in SRNS. Methods: In 2009, an international registry for SRNS was established to collect retro- and prospective information on renal and extrarenal disease manifestations, histopathological and genetic findings and information on family history, pharmacotherapy responsiveness and long-term outcomes. To date, more than 2,000 patients have been enrolled at 72 pediatric nephrology centers, constituting the largest pediatric SRNS cohort assembled to date. Results: In the course of the project, traditional Sanger sequencing was replaced by NGS-based gene panel screening covering over 30 podocyte-related genes complemented by whole exome sequencing. These approaches allowed to establish genetic diagnoses in 24% of the patients screened, widened the spectrum of genetic disease entities presenting with SRNS phenotype (COL4A3-5, CLCN5), and contributed to the discovery of new disease causing genes (MYOE1, PTPRO). Forty two percent of patients responded to intensified immunosuppression with complete or partial remission of proteinuria, whereas 58% turned out multi-drug resistant. Medication responsiveness was highly predictive of a favorable long-term outcome, whereas the diagnosis of genetic disease was associated with a high risk to develop end-stage renal disease during childhood. Genetic SRNS forms were generally resistant to immunosuppressive treatment, justifying to avoid such pharmacotherapies altogether once a genetic diagnosis is established. Even symptomatic anti-proteinuric treatment with RAS antagonists seems to be challenging and of limited efficacy in genetic forms of SRNS. The risk of post-transplant disease recurrence was around 30% in non-genetic SRNS whereas it is negligible in genetic cases. Conclusion: In summary, the PodoNet Registry has collected detailed clinical and genetic information in a large SRNS cohort and continues to generate fundamental insights regarding demographic and etiological disease aspects, genotype-phenotype associations, the efficacy of therapeutic strategies, and long-term patient and renal outcomes including post-transplant disease recurrence.
Agnes Trautmann; Beata S. Lipska-Ziętkiewicz; Franz Schaefer. Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry. Frontiers in Pediatrics 2018, 6, 1 .
AMA StyleAgnes Trautmann, Beata S. Lipska-Ziętkiewicz, Franz Schaefer. Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry. Frontiers in Pediatrics. 2018; 6 ():1.
Chicago/Turabian StyleAgnes Trautmann; Beata S. Lipska-Ziętkiewicz; Franz Schaefer. 2018. "Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry." Frontiers in Pediatrics 6, no. : 1.