Congenital Nephrotic Syndrome and Recurrence of Proteinuria After Renal Transplantation

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2014 Apr 1

PMID 24682440

Citations 23

Authors

Christer Holmberg

Hannu Jalanko

Affiliations

Soon will be listed here.

Abstract

Renal transplantation (RTx) is the only curative treatment for most cases of congenital and infantile nephrotic syndrome (NS) caused by genetic defects in glomerular podocyte proteins. The outcome of RTx in these children is usually excellent, with no recurrence of nephrotic syndrome. A subgroup of patients with the Finnish type of congenital nephrosis (CNF), shows, however, a clear risk for post-RTx proteinuria. Most of these patients have a homozygous truncating mutation (Fin-major mutation) in the nephrin gene (NPHS1), leading to total absence of the major podocyte protein, nephrin. After RTx, these patients develop anti-nephrin antibodies resulting in nephrotic range proteinuria. Plasma exchange combined with cyclophosphamide and anti-CD20 antibodies has proved to be successful therapy for these episodes. NS recurrence has also occurred in a few patients with mutations in the podocin gene (NPHS2). No anti-podocin antibodies have been detectable, and the pathophysiology of the recurrence remains open. While most of these episodes have resolved, the optimal therapy remains to be determined.

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References

Gondos A, Dohler B, Brenner H, Opelz G . Kidney graft survival in Europe and the United States: strikingly different long-term outcomes. Transplantation. 2012; 95(2):267-74. DOI: 10.1097/TP.0b013e3182708ea8. View

Becker-Cohen R, Bruschi M, Rinat C, Feinstein S, Zennaro C, Ghiggeri G . Recurrent nephrotic syndrome in homozygous truncating NPHS2 mutation is not due to anti-podocin antibodies. Am J Transplant. 2006; 7(1):256-60. DOI: 10.1111/j.1600-6143.2006.01605.x. View

Diomedi-Camassei F, Di Giandomenico S, Santorelli F, Caridi G, Piemonte F, Montini G . COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol. 2007; 18(10):2773-80. DOI: 10.1681/ASN.2006080833. View

Bitzan M, Babayeva S, Vasudevan A, Goodyer P, Torban E . TNFα pathway blockade ameliorates toxic effects of FSGS plasma on podocyte cytoskeleton and β3 integrin activation. Pediatr Nephrol. 2012; 27(12):2217-26. DOI: 10.1007/s00467-012-2163-3. View

Flynn J, Schulman S, DeChadarevian J, Dunn S, Kaiser B, Polinsky M . Treatment of steroid-resistant post-transplant nephrotic syndrome with cyclophosphamide in a child with congenital nephrotic syndrome. Pediatr Nephrol. 1992; 6(6):553-5. DOI: 10.1007/BF00866503. View

Patzer R, Amaral S, Klein M, Kutner N, Perryman J, Gazmararian J . Racial disparities in pediatric access to kidney transplantation: does socioeconomic status play a role?. Am J Transplant. 2012; 12(2):369-78. PMC: 3951009. DOI: 10.1111/j.1600-6143.2011.03888.x. View

Kuusniemi A, Qvist E, Sun Y, Patrakka J, Ronnholm K, Karikoski R . Plasma exchange and retransplantation in recurrent nephrosis of patients with congenital nephrotic syndrome of the Finnish type (NPHS1). Transplantation. 2007; 83(10):1316-23. DOI: 10.1097/01.tp.0000262569.27890.64. View

Chaudhuri A, Kambham N, Sutherland S, Grimm P, Alexander S, Concepcion W . Rituximab treatment for recurrence of nephrotic syndrome in a pediatric patient after renal transplantation for congenital nephrotic syndrome of Finnish type. Pediatr Transplant. 2011; 16(5):E183-7. DOI: 10.1111/j.1399-3046.2011.01519.x. View

Srivastava T, Garola R, Kestila M, Tryggvason K, Ruotsalainen V, Sharma M . Recurrence of proteinuria following renal transplantation in congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol. 2006; 21(5):711-8. DOI: 10.1007/s00467-006-0047-0. View

10.

Mehls O, Fine R . Growth hormone treatment after renal transplantation: a promising but underused chance to improve growth. Pediatr Nephrol. 2012; 28(1):1-4. DOI: 10.1007/s00467-012-2293-7. View

11.

Lane P, Schnaper H, Vernier R, Bunchman T . Steroid-dependent nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. Pediatr Nephrol. 1991; 5(3):300-3. DOI: 10.1007/BF00867484. View

12.

Jeanpierre C, Denamur E, Henry I, Cabanis M, Luce S, Cecille A . Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database. Am J Hum Genet. 1998; 62(4):824-33. PMC: 1377045. DOI: 10.1086/301806. View

13.

Kashtan C . Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore). 1999; 78(5):338-60. DOI: 10.1097/00005792-199909000-00005. View

14.

Weber S, Gribouval O, Esquivel E, Moriniere V, Tete M, Legendre C . NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int. 2004; 66(2):571-9. DOI: 10.1111/j.1523-1755.2004.00776.x. View

15.

DAgati V, Kaskel F, Falk R . Focal segmental glomerulosclerosis. N Engl J Med. 2011; 365(25):2398-411. DOI: 10.1056/NEJMra1106556. View

16.

Salvatierra Jr O, Singh T, Shifrin R, Conley S, Alexander S, Tanney D . Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow. Transplantation. 1998; 66(7):819-23. DOI: 10.1097/00007890-199810150-00001. View

17.

Kumar J, Shatat I, Skversky A, Woroniecki R, Del Rio M, Perelstein E . Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis. Pediatr Nephrol. 2012; 28(2):333-8. PMC: 3541458. DOI: 10.1007/s00467-012-2314-6. View

18.

Hocker B, Knuppel T, Waldherr R, Schaefer F, Weber S, Tonshoff B . Recurrence of proteinuria 10 years post-transplant in NPHS2-associated focal segmental glomerulosclerosis after conversion from cyclosporin A to sirolimus. Pediatr Nephrol. 2006; 21(10):1476-9. DOI: 10.1007/s00467-006-0148-9. View

19.

Tainio J, Qvist E, Vehmas R, Jahnukainen K, Holtta T, Valta H . Pubertal development is normal in adolescents after renal transplantation in childhood. Transplantation. 2011; 92(4):404-9. DOI: 10.1097/TP.0b013e3182247bd5. View

20.

Herthelius M, Celsi G, Halling S, Krmar R, Sandberg J, Tyden G . Renal transplantation in infants and small children. Pediatr Nephrol. 2011; 27(1):145-50. DOI: 10.1007/s00467-011-1962-2. View