Stephanie Dufek1, Tuula Holtta2, Agnes Trautmann3, Elisa Ylinen2, Harika Alpay4, Gema Ariceta5, Christoph Aufricht6, Justine Bacchetta7, Sevcan A Bakkaloglu8, Aysun Bayazit9, Rumeysa Yasemin Cicek10, Ismail Dursun11, Ali Duzova12, Mesiha Ekim13, Daniela Iancu14, Augustina Jankauskiene15, Günter Klaus16, Fabio Paglialonga17, Andrea Pasini18, Nikoleta Printza19, Valerie Said Conti20, Maria do Sameiro Faria21, Claus Peter Schmitt3, Constantinos J Stefanidis22, Enrico Verrina23, Enrico Vidal24, Karel Vondrak25, Hazel Webb1, Argyroula Zampetoglou22, Detlef Bockenhauer1, Alberto Edefonti17, Rukshana Shroff1. 1. Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. 2. Department of Pediatric Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 3. Center for Pediatric & Adolescent Medicine, Heidelberg, Germany. 4. School of Medicine, Marmara University, Istanbul, Turkey. 5. Hospital MaternoInfantil de la Vall d'Hebron, Barcelona, Spain. 6. Medical University of Vienna, Vienna, Austria. 7. Hôpital Femme Mère Enfant, Lyon, France. 8. Department of Pediatric Nephrology, Gazi University Hospital, Ankara, Turkey. 9. Department of Pediatric Nephrology, Cukurova University, Adana, Turkey. 10. Department of Pediatric Nephrology, Cerrahpasa Medical Faculty, Istanbul, Turkey. 11. Department of Pediatric Nephrology, Erciyes University, Kayseri, Turkey. 12. Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey. 13. Ankara University Hospital, Ankara, Turkey. 14. Center for Nephrology, University College London, London, UK. 15. Center of Pediatrics, Vilnius University, Vilnius, Lithuania. 16. KfH Pediatric Kidney Center, Marburg, Germany. 17. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 18. Azienda Ospedaliero-Universitaria Sant'Orsola-Malpighi, Bologna, Italy. 19. Hippokratio General Hospital, Aristotle University, Thessaloniki, Greece. 20. Department of Pediatrics, Mater Dei Hospital Malta, Msida, Malta. 21. Centro Materno Infantil do Norte, Porto, Portugal. 22. "A & P Kyriakou", Children's Hospital, Athens, Greece. 23. IRCCS Giannina Gaslini, Genova, Italy. 24. Department of Pediatrics, University Hospital of Padova, Padova, Italy. 25. Pediatric Nephrology, University Hospital Motol, Prague, Czech Republic.
Abstract
BACKGROUND: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. METHODS: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. RESULTS: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. CONCLUSION: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
BACKGROUND: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. METHODS: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. RESULTS: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. CONCLUSION: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
Authors: Alexandru R Constantinescu; Tej K Mattoo; William E Smoyer; Larry A Greenbaum; Jianli Niu; Noel Howard; Melissa Muff-Luett; Elizabeth B Benoit; Avram Traum; Ali A Annaim; Scott E Wenderfer; Emilee Plautz; Michelle N Rheault; Robert L Myette; Katherine E Twombley; Yu Kamigaki; Belkis Wandique-Rapalo; Mohammad Kallash; Tetyana L Vasylyeva Journal: Front Pediatr Date: 2022-09-14 Impact factor: 3.569
Authors: Erica Sanford; Terence Wong; Katarzyna A Ellsworth; Elizabeth Ingulli; Stephen F Kingsmore Journal: Cold Spring Harb Mol Case Stud Date: 2020-08-25