Childhood Kidney Diseases

Korean Society of Pediatric Nephrology (대한소아신장학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical Evaluation of Nephrotic Syndrome Manifesting in the First Year of Life

1세 이하의 소아에서 발병한 신증후군의 임상적 고찰

  • Cho, Sung-Hee (Department of Pediatrics, Asan Medical Center University of Ulsan College of Medicine) ;
  • Lee, Joo-Hoon (Department of Pediatrics, Asan Medical Center University of Ulsan College of Medicine) ;
  • Cho, Young-Mi (Department of Pathology, Asan Medical Center University of Ulsan College of Medicine) ;
  • Park, Young-Seo (Department of Pediatrics, Asan Medical Center University of Ulsan College of Medicine) ;
  • Cheong, Hae-Il (Department of Pediatrics, Seoul National University Children's Hospital Kidney Research Institute)
  • 조성희 (울산대학교 의과대학 서울아산병원 소아과학교실) ;
  • 이주훈 (울산대학교 의과대학 서울아산병원 소아과학교실) ;
  • 조영미 (울산대학교 의과대학 서울아산병원 병리학교실) ;
  • 박영서 (울산대학교 의과대학 서울아산병원 소아과학교실) ;
  • 정해일 (서울대학교 어린이병원 소아청소년과)
  • Published : 2009.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : This study was performed to report the diagnosis and treatment of nephrotic syndrome manifesting in the first year of life. Methods : We retrospectively reviewed the clinical data with chart review in 7 patients who were diagnosed as nephrotic syndrome manifesting in the first year of life from 1996 to 2007. Results : Three patients had congenital nephrotic syndrome, the other 4 patients had infantile nephrotic syndrome. Their ages ranged from birth to 11 months and male to female ratio was 1 to 6. Renal biopsies were done in 6 patients. One patient had Finnish type congenital nephrotic syndrome, 2 patients had diffuse mesangial sclerosis, 2 patients had focal segmental glomerulosclerosis and 1 patient had minimal change disease. Genetic analyses of NPHS2, PLCE1, and WT1 were done in 4 patients and 2 of them had WT1 mutation. Among 3 patients with congenital nephrotic syndrome, 1 patient was diagnosed as congenital nephrotic syndrome of Finnish type and the other 2 patients were diagnosed as Denys-Drash syndrome. All of the patients with congenital nephrotic syndrome died due to sepsis. Among 4 patients with infantile nephrotic syndrome, 2 patients died and 1 had remission, another patient progressed to end stage renal disease. Conclusion : Most of nephrotic syndrome manifesting in the first year was hereditary renal disease. Patients with nephrotic syndrome manifesting in the 3 month of life had poorer prognosis and needed more aggressive management including early dialysis and renal transplantation might be considered compared with infantile nephrotic syndrome. Further genotype-phenotype correlation studies are needed.

저자들은 1세 이하에 발병한 신증후군 환아 7명의 진단 및 치료를 경험하였기에 보고하는 바이다. 1996년부터 2007년까지 본원에서 1세 이전에 신증후군으로 진단 받은 환아 7명을 대상으로 병록 고찰을 통해 후향적으로 조사하였다. 선천성 신증후군은 3명, 영아형 신증후군은 4명 이었고, 남아가 1명, 여아가 6명으로 여아가 많았다. 6명에서 신생검을 시행하였고, 2명에서 미만성 메산지움 경화증, 2명에서 국소분절사구체경화증, 1명에서 Finnish형 신증후군 그리고 나머지 1명에서는 미세 변화형으로 확인되었다. 4명의 환아에서 NPHS2, PLCE1, 그리고 WT1의 유전자 분석을 시행하였고 2예에서 WT1 변이가 확인되었다. 선천성 신증후군으로 진단받은 3명 중 1명은 Finnish형 신증후군, 2명은 DDS로 진단받았고, 3명 모두 패혈증으로 사망하였다. 영아형 신증후군으로 진단받은 4명 중 2명은 사망하였고, 다른 1명은 관해가 되어 치료되었고, 나머지 1명은 치료 4개월 경 말기 신부전으로 진행하여 복막투석을 하고 있다. 1세 이전에 발병하는 선천성 신증후군은 소아 신증후군에 비하여 예후가 나쁘지만, 병력의 세밀한 검토, 임상소견 및 조직검사, 유전자 분석을 통한 정확한 진단이 빠르게 이루어져 조기 투석 및 신이식 등 적극적인 치료를 한다면 생존률의 향상을 기대할 수 있을 것이다. 대부분의 1세 이전 진단받는 신증후군은 유전적 신질환으로 추후 이들 환아들에 대한 유전형-표현형의 상관관계에 대한 추가 연구가 필요하다.

Keywords

References

  1. Vogt BA, Avner ED. Nephrotic syndrome. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Textbook of Pediatrics. 18th ed. Philadephia: W.B. Saunders Co. 2007:2190-5.
  2. Papez KE, Smoyer WE. Recent advances in congenital nephrotic syndrome. Curr Opin Pediatr 2004;16:165-70. https://doi.org/10.1097/00008480-200404000-00009
  3. Habib R. Nephrotic syndrome in the first year of life. Pediatr Nephrol 1993;7:347-53. https://doi.org/10.1007/BF00857534
  4. Lee YK, Cha ES, Kwon MJ, Lee JS, Kim PK, Jeong HJ. Congenital nephrotic syndrome. Korean J Nephrol 1997;16:136-41.
  5. Motoyama O, Arai K, Kawamura T, Aikawa A, Ohara T, Iitaka K, et al. Clinical course of congenital nephrotic syndrome and Denys-Drash syndrome in Japan. Pediatr Int 2005;47:607-11. https://doi.org/10.1111/j.1442-200x.2005.02139.x
  6. Choi HJ, Lee BH, Kang JH, Jeong HJ, Moon KC, Ha IS, et al. Variable phenotype of Pierson syndrome. Pediatr Nephrol 2008;23:995-1000. https://doi.org/10.1007/s00467-008-0748-7
  7. Ismaili K, Pawtowski A, Boyer O, Wissing KM, Janssen F, Hall M. Genetic forms of nephrotic syndrome: a single-center experience in Brussels. Pediatr Nephrol 2009;24:287-94. https://doi.org/10.1007/s00467-008-0953-4
  8. Vachvanichsanong P, Mitarnun W, Tungsinmunkong K, Dissaneewate P. Congenital and infantile nephrotic syndrome in Thai infants. Clin Pediatr (Phila) 2005;44:169-74. https://doi.org/10.1177/000992280504400209
  9. Hahn H, Cho YM, Park YS, You HW, Cheong HI. Two cases of isolated diffuse mesangial sclerosis with WT1 mutations. J Korean Med Sci 2006;21:160-4. https://doi.org/10.3346/jkms.2006.21.1.160
  10. Lee BH, Ahn YH, Choi HJ, Kang HK, Kim SD, Cho BS, et al. Two korean infants with genetically confirmed congenital nephrotic syndrome of finnish type. J Korean Med Sci 2009;24:210-4. https://doi.org/10.3346/jkms.2009.24.S1.S210
  11. Yu JJ, Cheong HI, Lee HS, Choi Y, Jin DK. A case of congenital nephrotic syndrome due to diffuse mesangial sclerosis. J Korean Pediatr Soc 1998;41:415-9.
  12. Hinkes BG, Mucha B, Vlangos CN, Gbadegesin R, Liu J, Hasselbacher K, 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 2007;119:907-19. https://doi.org/10.1542/peds.2006-2164
  13. Jung HS, Cho EY, Lim JY, Seo JH, Choi MB, Park CH, et al. Galloway-Mowat syndrome in two siblings. J Korean Pediatr Soc 2001;44:1081-4.
  14. Choi HJ, Lee BH, Kang JH, Jeong HJ, Moon KC, Ha IS, et al. Variable phenotype of Pierson syndrome. Pediatr Nephrol 2008;23:995-1000. https://doi.org/10.1007/s00467-008-0748-7
  15. Yoo BW, Cho SM, Kie JH, Jung HJ, Kim KH. A Case of microcephaly and early-onset nephrotic syndrome: Galloway-Mowat syndrome. J Korean Soc Pediatr Nephrol 2003;7:197-203.
  16. Lee YK, Cha ES, Kwon MJ, Lee JS, Kim PK, Jeong HJ. Congenital nephrotic syndrome. Korean J Nephrol 1997;16:136-41.
  17. Ira DD, Ellis DA. Introduction to glomerular disease. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Textbook of Pediatrics. 18th ed. Philadephia: W.B. Saunders Co. 2007:2163-6.
  18. Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS. Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability. J Clin Invest 2003;112:209-21.
  19. Lee YK, Kwon TG, Kim DJ, Kim MK, Yoon SJ, Lee HR, et al. Expression of nephrin in puromycin arninonucleoside nephrosis in rat. Korean J Nephrol 2002;21:382-90.
  20. Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Trryggvson K, et al. Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephritic syndrome advocate a functional inter-relationship in glomerular filtration. Hum Mol Genet 2002;11:379-88. https://doi.org/10.1093/hmg/11.4.379
  21. Heeringa SF, Vlangos CN, Chernin G, Hinkes B, Gbadegesin R, Liu J, et al. Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome. Nephrol Dial Transplant 2008;23:3527-33. https://doi.org/10.1093/ndt/gfn271
  22. Dietrich A, Matejas V, Bitzan M, Hashmi S, Kiraly-Borri C, Lin SP, et al. Analysis of genes encoding laminin beta2 and related proteins in patients with Galloway-Mowat syndrome. Pediatr Nephrol 2008 ;23: 1779-86. https://doi.org/10.1007/s00467-008-0880-4
  23. Schumacher V, Scharer K, Wuhl E, Altrogge H, Bonzel K, Guschmann M, et al. Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations. Kidney Int 1998;53:1594-600. https://doi.org/10.1046/j.1523-1755.1998.00948.x
  24. Kestila M, Lenkkeri U, Mannikko M, Lamrdin J, McCready P, Putaala H, et al. Positionally cloned gene for a novel glomerular proteinnephrin-is mutated in congenital nephritic syndrome. Mol Cell 1998;1:575-82. https://doi.org/10.1016/S1097-2765(00)80057-X
  25. Beltcheva OJ, Martin P, Lenkkeri U, Tryggvason K. Mutation spectrum in the nephrin gene (NPHS1) in congenital nephritic syndrome. Hum Mutat 2001;17:368-73. https://doi.org/10.1002/humu.1111
  26. Hasselbacher K, Wiggins RC, Matejas V, Hinkes BG, Mucha B, Hoskins BE, et al. Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. Kidney Int 2006;70:1008-12. https://doi.org/10.1038/sj.ki.5001679
  27. Winn MP, Daskalakis N, Spurney RF, Middleton JP. Unexpected role of TRPC6 channel in familial nephritic syndrome: Dose in have clinical implications? J Am Soc Nephrol 2006;17:378-87. https://doi.org/10.1681/ASN.2005090962
  28. Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephritic syndrome variant that maybe reversible. Nat Genet 2006;38:1397-405. https://doi.org/10.1038/ng1918
  29. Choi HJ, Lee BH, Cho HY, Moon KC, Ha S, Nagata M, et al. Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosacism. Am J Kidney Dis 2008;51:834-8. https://doi.org/10.1053/j.ajkd.2008.01.018
  30. Patrakka J, Kestila M, Wartiovaara J, Ruotsalainen V, Tissari P, Lenkkeri U, et al. Congenital nephrotic syndrome (NPHS1): Features resulting from different mutations in Finnish patients. Kidney Int 2000;58:972-80. https://doi.org/10.1046/j.1523-1755.2000.00254.x
  31. Su W, Chen J, Yang H, You L, Xu L, Wang X, et al. Expression of nestin in the podocytes of normal and diseased human kidneys. Am J Physiol Regul Integr Comp Physiol 2007;292:1761-7. https://doi.org/10.1152/ajpregu.00319.2006
  32. Kohsaka T, Tagawa M, Yamada M. Denys-Drash syndrome. Nippon Rinsho 2006;3:457-64.
  33. Hurber TB, Benzing T. The slit diaphragm: a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens 2005;14:211-6. https://doi.org/10.1097/01.mnh.0000165885.85803.a8
  34. Habio R, Loirat C, Gubler MC, Niaudet P, Bensman A, Levy M, et al. The nephropathy associated with male pseudohermaphrodism and Wilms' tumor (Drash syndrome): a distinctive glomerular lesion, report of 10 cases. Clin Nephrol 1985;24:269-78.