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Том 23 №1 2021 год - Нефрология и диализ

Исследование генетических причин врожденного и инфантильного нефротического синдрома у российских детей


Милованова А.М. Пушков А.А. Савостьянов К.В. Зробок О.И. Вашурина Т.В. Ананьин П.В. Столяревич Е.С. Фисенко А.П. Цыгин А.Н.

DOI: 10.28996/2618-9801-2021-1-57-72

Аннотация: Актуальность: врожденный и инфантильный нефротический синдром (ВНС и ИНС соответственно) - особые группы стероид-резистентного нефротического синдрома, подбор терапии в которых вызывает наибольшие трудности, а прогрессирование до 5-й стадии хронической болезни почек (ХБП 5 ст.) имеет неизбежный характер. Ранее опубликованные исследования генетических причин развития ВНС и ИНС в РФ выполнены на крайне малых выборках. Цель: изучение генетических причин ВНС и ИНС у российских детей. Методы: на базе нефрологического отделения ФГАУ «НМИЦ здоровья детей» Минздрава РФ проведено двунаправленное исследование, включившее 43 ребенка с ВНС и ИНС, которые наблюдались в отделении с 2010 по 2020 годы. Всем детям методом секвенирования нового поколения выполнено исследование таргентных областей 57 генов, патогенные варианты в которых описаны у пациентов с симптомокомплексом НС. Результаты. Среди морфологических типов превалировал фокально-сегментарный гломерулосклероз (50%) вне зависимости от выявленного патогенного варианта. У 38 (88,4%) детей выявлены мутации в генах NPHS2 (37,2%), NPHS1 (13,9%), WT1 (9,3%), CUBN (7,0%), PLCE1 и LMX1B (по 4,7%), SMARCAL1, CRB2, KANK2, COQ6 и CFH (по 2,3%, соответственно). На фоне терапии циклоспорином А у 18,5% из 27 детей отмечена частичная либо полная ремиссия, имеющая нестойкий характер. Хроническая болезнь почек 5-й стадии за период наблюдения достигнута у 15 (34,9%) детей в возрасте 4 года 11 месяцев ± 3 г. 3 мес. Трансплантация почки проведена 11 пациентам, годичная выживаемость трансплантата составила 82%. Выводы: проведение молекулярно-генетического исследования у детей с дебютом нефротического синдрома на первом году жизни более информативно в отношении выбора терапевтической тактики и оценки прогноза, чем инвазивный метод - пункционная нефробиопсия. Проведение трансплантации почки в описанной группе детей перспективно в связи с низкими рисками возврата заболевания в трансплантат.

Для цитирования: Милованова А.М., Пушков А.А., Савостьянов К.В., Зробок О.И., Вашурина Т.В., Ананьин П.В., Столяревич Е.С., Фисенко А.П., Цыгин А.Н. Исследование генетических причин врожденного и инфантильного нефротического синдрома у российских детей. Нефрология и диализ. 2021. 23(1):9-126. doi: 10.28996/2618-9801-2021-1-57-72


Весь текст

Ключевые слова: нефротический синдром, врожденный нефротический синдром, инфантильный нефротический синдром, стероид-резистентный нефротический синдром, генетические факторы, патогенные варианты, дети, nephrotic syndrome, congenital nephrotic syndrome, infantile nephrotic syndrome, steroid-resistant nephrotic syndrome, genetic factors, pathogenic variants, children

Список литературы:
  1. KDIGO Clinical Practice Guideline for Glomerulonephritis Kidney International supplements Volume 2/ issue 2/ June 2012 http://www.kidney-international.org
  2. Лойманн Э., Цыгин А.Н., Саркисян А.А. Детская нефрология. Практическое руководство. - М. Издательство «Литтерра» 2010.
  3. Hildebrandt F. Genetic kidney diseases. Lancet 2010 375: 1287-1295
  4. Lipska B., Balasz-Chmielewska I., Morzuch L. et al. Mutational analysis in podocin-associated hereditary nephrotic syndrome in Polish patients: founder effect in the Kashubian population. J Appl Genetics 2013 54:327-333
  5. Smith J.M., Stablein D.M., Munoz R. et al. Contributions of the transplant registry: the 2006 annual report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Pediatr Transplant 2007 11:366-373
  6. Trautmann A., Lipska-Zie˛tkiewicz B.S. and Schaefer F. Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry. Front. Pediatr. 2018 6:200. doi: 10.3389/fped.2018.00200
  7. Mekahli D., Liutkus A., Ranchin B. et al. Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study. Pediatr Nephrol 2009 24:1525-1532
  8. Buscher A.K., Kranz B., Buscher R. et al. Immunosuppression and renal outcome in congenital and pediatric steroidresistant nephrotic syndrome. Clin J Am Soc Nephrol, 2010, 5: 2075-2084
  9. Buscher A.K., Beck B.B., Melk A. et al. Rapid response to cyclosporin A and favorable renal outcome in nongenetic versus genetic steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2016 11: 245-253
  10. Zhao J., Liu Z. Treatment of nephrotic syndrome: going beyond immunosuppressive therapy. Pediatr Nephrol 2019 doi: 10.1007/s00467-019-04225-7
  11. Holmberg C., Jalanko H. Congenital nephrotic syndrome and recurrence of proteinuria after renal transplantation. Pediatr Nephrol 2014 29:2309-2317 DOI 10.1007/s00467-014-2781-z
  12. Kari J.A., Montini G., Bockenhauer D. et al. Clinico-pathological correlations of congenital and infantile nephrotic syndrome over twenty years. Pediatr Nephrol. 2014; 29(11):2173-2180. doi:10.1007/s00467-014-2856-x
  13. [No authors listed] The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. 1981, J Pediatr 98:561-564
  14. Petrosyan E.K., Tsygin A.N., Shestakov A.E. et al. Genetic markers of nephrotic syndrome in children. ISSN 15616274. Nephrology. 2006. 10. №3
  15. Wen Y., Shah S., Campbell K.N. Molecular Mechanisms of Proteinuria in Focal Segmental Glomerulosclerosis. Frontiers in medicine 2018 5, 98. https://doi.org/10.3389/fmed.2018.00098.
  16. Bensimhon A., Williams A., Gbadegesin R. Treatment of steroid-resistant nephrotic syndrome in the genomic era. Pediatric Nephrology 2019 34:2279-2293 https://doi.org/10.1007/s00467-018-4093-1
  17. Bitzan M., Babayeva S., Vasudevan A. et al. TNFα pathway blockade ameliorate toxic effects of FSGS plasma on podocyte cytoskeleton and 3 integrin activation. Pediatr Nephrol 2012 27: 2217-2226
  18. Wei C., El Hindi S., Li J. et al. Circulating urokinase receptor as a cause of focal segmental glomerusclerosis. Nat Med 2011 17:952-960
  19. Preston R., Stuart H. M., Lennon R. Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?. Pediatric nephrology (Berlin, Germany), 2019, 34(2), 195-210. https://doi.org/10.1007/s00467-017-3838-6
  20. Schoeb D.S., Cherni G, Heeringa S.F. et al. Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS), Nephrology Dialysis Transplantation, Volume 25, Issue 9, September 2010, Pages 2970-2976, https://doi.org/10.1093/ndt/gfq088
  21. Patrakka J., Kestilä M., Wartiovaara J. et al. Congenital nephrotic syndrome (NPHS1): features resulting from different mutations in Finnish patients. Kidney Int. 2000; 58(3):972-980. doi:10.1046/j.1523-1755.2000.00254.
  22. Fogo A.B., Lusco M.A., Najafian B. et al. AJKD atlas of renal pathology: congenital nephrotic syndrome of Finnish type. Am J Kidney Dis. 2015; 66(3):e11-e12. doi:10.1053/j.ajkd.2015.07.008
  23. Reynolds В.С., Oswald R.J. A Diagnostic and Management Challenges in Congenital Nephrotic Syndrome. Pediatric Health, Medicine and Therapeutics 2019:10 157-167
  24. Chernin G., Vega-Warner V., Schoeb D.S. et al. Genotype/phenotype correlation in nephrotic syndrome caused byWT1 mutations. Clin J Am Soc Nephrol. 2010; 5(9):1655-1662. doi:10.2215/CJN.09351209
  25. Machuca E., Benoit G., Nevo F. et al. Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome. J Am Soc Nephrol. 2010 21(7):1209. doi:10.1681/ASN.2009121309
  26. Schwartz G.J., Work D.F. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol. 2009 Nov;4(11):1832-43. doi: 10.2215/CJN.01640309. Epub 2009 Oct 9. PMID: 19820136
  27. Sladkov D., Savostyanov K., Nikitin A. et al. High Prevalence of WT1 Gene Mutations in Patients with Steroid-Resistant Nephrotic Syndrome. Archives of Disease in Childhood. 2019. Vol. 104, no. S3 (A1-A428). - P. A4. - doi: 10.1136/archdischild-2019-epa.8.
  28. Savostyanov K., Sladkov D., Tsygin A. et al. Novel Mutations in Children with Steroid-Resistant Nephrotic Syndrome in Russian Population. Archives of Disease in Childhood. 2017. Vol. 102, no. S2. - Pp. A24-A25. - doi: 10.1136/archdischild-2017-313273.63.
  29. Сладков Д.Г., Савостьянов К.В., Цыгин А.Н. и др. Новый метод молекулярно-генетической диагностики стероидрезистентного нефротического синдрома / Медицинская генетика. - 2016. - Т. 15, № 5(167). - С. 38-41. - doi: 10.1234/XXXX-XXXX-2016-5-38-41.
  30. Рыжкова О.П., Кардымон О.Л., Прохорчук Е.Б. и др. Руководство по интерпретации данных последовательности ДНК человека, полученных методами массового параллельного секвенирования (MPS) (редакция 2018, версия 2) // Медицинская генетика. - 2019. Т. 18, № 2. - С. 3-23. - doi: 10.25557/2073-7998.2019.02.3-23.
  31. Genebank https://www.ncbi.nlm.nih.gov/genbank/
  32. Wang F., Zhang Y., Mao J. et al. Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2017;32(7):1181-1192. doi:10.1007/s00467-017-3590-y
  33. Lovric S,. Fang H., Vega-Warner V. et al. Rapid detection of monogenic causes of childhood-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2014;9(6):1109-1116. doi:10.2215/CJN.09010813
  34. Spahiu L., Merovci B., Jashari H. et al. Congenital Nephrotic Syndrome - Finish Type. Med Arch. 2016;70(3):232-234. doi:10.5455/medarh.2016.70.232-234
  35. Tikhomirov E., Averyanova N., Voznesenskaya T. et al. Gene symbol: NPHS1. Disease: Congenital nephrotic syndrome, Finnish type. Hum Genet. 2008 Oct;124(3):304. PMID: 18846635.
  36. Aya K., Tanaka H., Seino Y. Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type. Kidney Int 2000 57: 401-404.
  37. Sadowski C.E., Lovric S., Ashraf S. et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J. Am. Soc. Nephrol. 2015. Vol. 26, no. 6. - Pp. 1279-1289. DOI: 10.1681/ASN.2014050489.
  38. Caridi G., Gigante M., Ravani P. et al. Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations. Clin J Am Soc Nephrol. 2009 Jun;4(6):1065-72. doi: 10.2215/CJN.03910808
  39. Huber T.B., Simons M., Hartleben B. et al. Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. Hum Mol Genet. 2003;12(24):3397-3405. doi:10.1093/hmg/ddg360
  40. Karle S.M., Uetz B., Ronner V. et al. Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2002 13:388-393
  41. Boute N., Gribouval O., Roselli S. et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant NS. Nat Genet, 2000, 24:349-354
  42. Lehnhardt A., Karnatz C., Ahlenstiel-Grunow T. et al. Clinical and molecular characterization of patients with heterozygous mutations in wilms tumor suppressor gene 1. Clin J Am Soc Nephrol. 2015;10(5):825-831. doi:10.2215/CJN.10141014
  43. Köhler B., Biebermann H., Friedsam V, et al. Analysis of the Wilms' tumor suppressor gene (WT1) in patients 46,XY disorders of sex development. J Clin Endocrinol Metab. 2011;96(7):E1131-E1136. doi:10.1210/jc.2010-2804
  44. Boyer O., Woerner S., Yang F. et al. LMX1B mutations cause hereditary FSGS without extrarenal involvement. J. Am. Soc. Nephrol., 2013. Vol. 24, no. 8. - Pp. 1216-1222. DOI: 10.1681/ASN.2013020171
  45. Isojima T., Harita Y., Furuyama M. et al. LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy. Nephrol Dial Transplant. 2014;29(1):81-88. doi:10.1093/ndt/gft359
  46. Hinkes B., Wiggins R.C., Gbadegesin R. et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006; 38(12):1397-1405. doi:10.1038/ng1918
  47. Boerkoel C.F., Takashima H., John J. et al. Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet. 2002;30(2):215-220. doi:10.1038/ng821
  48. Doimo M., Trevisson E., Airik R. et al. Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10 deficiency. Biochim Biophys Acta. 2014;1842(1):1-6. doi:10.1016/j.bbadis.2013.10.007
  49. Tory K., Menyhard D.K., Woerner S. et al. Mutation-dependent recessive inheritance of NPHS2-associated steroid-resistant nephrotic syndrome. Nat Genet 2014 46:299-304
  50. Weber S., Gribouval O., Esquivel E.L. et al. NPHS2 mutation analysis shows genetic heterogeneity of steroidresistant nephrotic syndrome and low post-transplant recurrence. Kidney Int 66: 571-579, 2004
  51. Ruf R.G., Lichtenberger A., Karle S.M. et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 2004 15: 722-732
  52. Santín S., Bullich G., Tazo´n-Vega B. et al. Clinical Utility of Genetic Testing in Children and Adults with Steroid-Resistant Nephrotic Syndrome. Clin J Am Soc Nephrol 2011 6: 1139-1148. doi: 10.2215/CJN.05260610
  53. Kerti A., Csohány R., Szabó A. et al. NPHS2 p.V290M mutation in late-onset steroid-resistant nephrotic syndrome. Pediatr Nephrol 2013 28:751-757
  54. Li G., Cao Q., Shen Q. et al. Gene mutation analysis in 12 Chinese children with congenital nephrotic syndrome. BMC Nephrology 2018 19:382 doi: 10.1186/s12882-018-1184-y
  55. Chen Y., Zhang Y., Wang F. et al. Analysis of 14 Patients With Congenital Nephrotic Syndrome. Front. Pediatr. 2019 7:341. doi: 10.3389/fped.2019.00341
  56. Sako M., Nakanishi K., Obana M. et al. Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome. Kidney Int. 2005; 67:1248-1255
  57. Приходина Л.С., Папиж С.В., Столяревич Е.С. и др. Инфантильный нефротический синдром: клинико-морфологическая характеристика, генетическая гетерогенность, исходы. Опыт одного центра. Нефрология и диализ. 2019. 21(2): 234-242. DOI: 10.28996/2618-9801-2019-2-234-242
  58. Bierzynska A., McCarthy H.J., Soderquest K. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int. 2017; 91(4):937-947. doi:10.1016/
  59. j.kint.2016.10.013
  60. Hinkes B., Mucha B., Vlangos C. et al. Nephrotic Syndrome in the First Year of Life: Two Thirds of Cases Are Caused by Mutations in 4 Genes (NPHS1, NPHS2, WT1, and LAMB2). PEDIATRICS Volume 119, Number 4, April 2007. doi:10.1542/peds.2006-2164
  61. Sharief S., Hefni N., Alzahrani W. et al. Genetics of congenital and infantile nephrotic syndrome. World Journal of Pediatrics 2019 https://doi.org/10.1007/s12519-018-00224-0
  62. HGMD Humal Gene Mutation Database http://www.hgmd.cf.ac.uk/ac/index.php
  63. Trautmann A., Bodria M., Ozaltin F. et al. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin J Am Soc Nephrol 2015 10:592-600
  64. McCarthy H.J., Bierzynska A., Wherlock M. et al. Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2013 8:637-648
  65. Tikhomirov E., Averyanova N., Bayazutdinova G. et al. Novel human pathological mutations. Gene symbol: NPHS2. Disease: steroid-resistant nephrotic syndrome. Hum Genet. 2007; 122(5):549.
  66. Cil O., Besbas N., Duzova A. et al. Genetic abnormalities and prognosis in patients with congenital and infantile nephrotic syndrome. Pediatr Nephrol 2015 DOI 10.1007/s00467-015-3058-x
  67. Bouchireb K., Boyer O., Gribouval O. et al. NPHS2 Mutations in Steroid-Resistant Nephrotic Syndrome: A Mutation Update and the Associated Phenotypic Spectrum. Human mutation 2014. 35. 10.1002/humu.22485.
  68. Frishberg Y., Feinstein S., Rinat C. et al. The heart of children with steroid-resistant nephrotic syndrome: is it all podocin? J Am Soc Nephrol, 2006 17:227-231
  69. Ozaltin F., Heeringa S., Poyraz C. et al. Eye involvement in children with primary focal segmental glomerulosclerosis. Pediatric nephrology (Berlin, Germany). 2008 23. 421-7. 10.1007/s00467-007-0695-8.
  70. Lipska B., Ranchin B., Iatropoulos P. et al. Genotype-phenotype associations in WT1 glomerulopathy. Kidney Int. 2014;85:1169-78
  71. Lennon P.A., Scott D.A., Lonsdorf D. et al. WAGR(O?) syndrome and congenital ptosis caused by an unbalanced t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH. Am J Med Genet A. 2006; 140(11):1214-1218. doi:10.1002/ajmg.a.31229
  72. Lawley L.P., Caruneke F., Weiss S. et al. Expression of Wilms tumor 1 gene distinguishes vascular malformations from proliferative endothelial lesions. Arch Dermatol 2005;141:1291-300
  73. Nakatsuka S., Oji Y., Horiuchi T. et al. Immunohistochemical detection of WT1 protein in a variety of cancer cells. Mod Pathol 2006; 19:804-14.
  74. Al Dhaybi, Rola et al. Differentiation of vascular tumors from vascular malformations by expression of Wilms tumor 1 gene: Evaluation of 126 cases. Journal of the American Academy of Dermatology, Volume 63, Issue 6, 1052 - 1057
  75. Ovunc B., Otto E.A., Vega-Warner V. et al. Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria. J Am Soc Nephrol 2011 22:1815-1820
  76. Lamont R., Tan W., Innes A. et al. Expansion of phenotype and genotypic data in CRB2-related syndrome. Eur J Hum Genet 24, 1436-1444, 2016. https://doi.org/10.1038/ejhg.2016.24
  77. Park E., Ahn Y.H., Kang H.G. et al. COQ6 Mutations in Children With Steroid-Resistant Focal Segmental Glomerulosclerosis and Sensorineural Hearing Loss. Am J Kidney Dis. 2017; 70(1):139-144. doi:10.1053/j.ajkd.2016.10.040
  78. Harita Y., Kitanaka S., Isojima T. et al. Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy. Pediatr Nephrol 2017 32, 1845-1850. https://doi.org/10.1007/s00467-016-3462-x
  79. Taira M., Ishiura H., Mitsui J. et al. Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type. Neurogenetics. 2012; 13(3):237-243. doi:10.1007/s10048-012-0330-0
  80. Harendza S., Stahl R.A., Schneider A. The transcriptional regulation of podocin (NPHS2) by LMX1B and a promoter single nucleotide polymorphism. Cell Mol Biol Lett. 2009;14(4):679-691. doi:10.2478/s11658-009-0026-0
  81. He B., Ebarasi L., Zhao Z. et al. LMX1B and FoxC combinatorially regulate podocin expression in podocytes. J Am Soc Nephrol. 2014; 25(12):2764-2777. doi:10.1681/ASN.2012080823
  82. Santin S., Tazon-Vega B., Silva I. et al. Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011; 6:344-354.
  83. Gellermann J., Stefanidis C.J., Mitsioni A. et al. Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr Nephrol. 2010; 25(7):1285-1289. doi:10.1007/s00467-010-1468-3
  84. Faul C., Donnelly M., Merscher-Gomez S. et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008 14:931-938
  85. Gipson D.S., Trachtman H., Kaskel F.J. et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 2011 80:868-878
  86. Berody S., Heidet L., Gribouval O. et al. Treatment and outcome of congenital nephrotic syndrome. Nephrol Dial Transplant. 2019;34 (3):458-467. doi:10.1093/ndt/gfy015
  87. Klaassen I., Ozgoren B., Sadowski C.E. et al. Response to cyclosporine in steroid-resistant nephrotic syndrome: discontinuation is possible. Pediatr Nephrol 2015 30:1477-1483
  88. Hinkes B., Vlangos C., Heeringa S. et al. Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2008;19:365-371
  89. Dufek S., Holtta T., Trautmann A. et al. Management of children with congenital nephrotic syndrome: challenging treatment paradigms. Nephrol Dial Transplant, 2018. 1-9 doi: 10.1093/ndt/gfy165
  90. Po-Cheng Huang, Ching-Yao Yang, Chih-Yuan Lee, et al. Pediatric renal transplantation: Results and prognostic factors, Asian Journal of Surgery, Volume 36, Issue 2, 2013, Pages 53-57, ISSN 1015-9584, https://doi.org/10.1016/j.asjsur.2012.09.001.
  91. Saeed B. Pediatric renal transplantation. International journal of organ transplantation medicine, 3(2), 62-73, 2012.
  92. Baum M.A. Outcomes after renal transplantation for FSGS in children. Pediatric Transplantation, 2004, 8: 329-333. doi:10.1111/j.1399-3046.2004.00181.x

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