CASE OF NON-SEVERE CONGENITAL NEPHROTIC SYNDROME

Nephrotic syndrome is a severe renal disease that may result in the end-stage renal failure despite the extent of proteinuria. Prognosis and tactics of therapy of nephrotic syndrome depend both on the morphological diagnosis and on the cause of the disease. It ought to be considered that congenital nephrotic syndrome is resistant to immunosuppressive therapy. However, several foreign authors demonstrate cases of immunosuppressive therapy effectiveness (steroids and cyclosporine A) in a range of familial cases of nephrotic
syndrome. Timely detection of children with genetically caused nephrotic syndrome allows to define the patient management tactics in each case on time. This clinical case represents non-severe course of congenital nephrotic syndrome caused by an NPHS2 gene mutation, which had not before been described neither in Russian nor in foreign literature. The authors deem introduction of the molecular genetic analysis to the routine clinical practice for all cases of congenital nephrotic syndrome and steroid-resistant nephrotic syndrome reasonable.

1. Loimann E., Tsygin A.N., Sarkisyan A.A. Detskaya nefrologiya: prakticheskoe rukovodstvo [Pediatric Nephrology: Practical Guide]. Moscow, Litterra, 2010. pp. 123–141.

2. Sajantila A., Salem A.-H., Savolainen P., Bauer K., Gierig C., Paabo S. Paternal and maternal DNA linkages reveal a bottleneck in the founding of the Finnish population. Proc Nat Acad Sci. 1996; 93: 12035–12039.

3. Weber S., Gribouval O., Esquivel E.L., Moriniere V., Tete M.J., Legendre C., Niaudet P., Antignac C. NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant NS and low post-transplant recurrence. Kidney Int. 2004; 66: 571–579.

4. Proesmans W., Van Dyck M., Devriendt K. Nail-patella syndrome, infantile nephrotic syndrome: complete remission with antiproteinuric treatment. Nephrol Dial Transplant. 2009; 24: 1335–1338.

5. Takahashi A., Fukusumi Y., Yamazaki M., Kayaba M., Kitazawa Y., Tomita M., Kawachi H. Angiotensin II type 1 receptor blockade ameliorates proteinuria in puromycin aminonucleoside nephropathy by inhibiting the reduction of NEPH1 and nephrin. J Nephrol. 2014.

6. Caridi G., Bertelli R., Di Duca M., Dagnino M., Emma F., Onetti Muda A., Scolari F., Miglietti N., Mazzucco G., Murer L., Carrea A., Massella L., Rizzoni G., Perfumo F., Ghiggeri G.M. Broadening the spectrum of diseases related to podocin mutations. J Am Soc Nephrol. 2003; 14: 1278–1286.

7. Ruf R.G., Lichtenberger A., Karle S.M., Haas J.P., Anacleto F.E., Schultheiss M., Zalewski I., Imm A., Ruf E.M., Mucha B., Bagga A., Neuhaus T., Fuchshuber A., Bakkaloglu A., Hildebrandt F. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of NS. J Am Soc Nephrol. 2004; 15: 722–732.

8. Gellermann J., Stefanidis C.J., Mitsioni A., Querfeld U. Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr Nephrol. 2010; 25 (7): 1285–1289.

9. Gessler M., Konig A., Bruns G.A.P. The genomic organization and expression of the WT1 gene. Genomics. 1992; 12 (4): 807–813.

10. Sabnis S.G., Antonovych T.T., Argy W.P. Nail-patella syndrome. Clinical Nephrology. 1980; 14 (3): 148–153.

11. Zenker M., Tralau T., Lennert T. et al. Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome. American Journal of Medical Genetics. 2004; 130 (2): 138–145.

12. Sachs N., Kreft M., van den Bergh Weerman M.A. et al. Kidney failure in mice lacking the tetraspanin CD151. Journal of Cell Biology. 2006; 175 (1): 33–39.

13. Clewing J.M., Antalfy B.C., Lücke T. et al. Schimke immuno-osseous dysplasia: a clinicopathological correlation. Journal of Medical Genetics. 2007; 44 (2): 122–130.

14. Kambham N., Tanji N., Seigle R.L. et al. Congenital focal segmental glomerulosclerosis associated withβ4 integrin mutation and epidermolysis bullosa. American Journal of Kidney Diseases. 2000; 36 (1): 190–196.

15. Stefanidis C.J., Querfeld U. The podocyte as a target: cyclosporin A in the management of the nephrotic syndrome caused by WT1 mutations. Eur J Pediatr. 2011; 170 (11): 1377–1383.

16. Büscher A.K., Kranz B., Büscher R., Hildebrandt F., Dworniczak B., Pennekamp P., Kuwertz-Bröking E., Wingen A.M., John U., Kemper M., Monnens L., Hoyer P.F., Weber S., Konrad M. Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2012; 7 (8): 1372–1374.

17. Benetti E., Caridi G., Centi S., Vella M.D., Ghiggeri G.M., Artifoni L., Murer L. mRNA sequencing of a novel NPHS2 intronic mutation in a child with focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl. 2014; 25 (4): 854–857.

18. Malina M., Cinek O., Janda J., Seeman T. Partial remission with cyclosporine A in a patient with nephrotic syndrome due to NPHS2 mutation. Pediatr Nephrol. 2009; 24 (10): 2051–2053.

19. Mishra O.P., Kakani N., Singh A.K., Narayan G., Abhinay A., Prasad R., Batra V.V. NPHS2 R229Q polymorphism in steroid resistant nephrotic syndrome: is it responsive to immunosuppressive therapy? J Trop Pediatr. 2014; 60 (3): 231–237.