Childhood Nephrotic Syndrome--current and Future Therapies

Overview

Journal Nat Rev Nephrol

Specialty Nephrology

Date 2012 Jun 13

PMID 22688744

Citations 53

Authors

Larry A Greenbaum

Rainer Benndorf

William E Smoyer

Affiliations

Soon will be listed here.

Abstract

The introduction of corticosteroids more than 50 years ago dramatically improved the prognosis of children with nephrotic syndrome. Corticosteroids remain the standard initial treatment for children with this disease, but a considerable proportion of patients do not respond and are therefore at risk of progressing to end-stage renal disease. Because of this risk, new therapeutic strategies are needed for steroid-resistant nephrotic syndrome. These strategies have historically focused on identifying effective alternative immunosuppressive agents, such as ciclosporin and tacrolimus, yet evidence now indicates that nephrotic syndrome results from podocyte dysfunction. Even conventional immunosuppressive agents, such as glucocorticoids and ciclosporin, directly affect podocyte structure and function, challenging the 'immune theory' of the pathogenesis of childhood nephrotic syndrome in which disease is caused by T cells. This Review summarizes the currently available treatments for childhood nephrotic syndrome, and discusses selected novel pathways in podocytes that could be targeted for the development of next-generation treatments for children with this syndrome.

Citing Articles

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References

Tang S, Tang A, Wong S, Leung J, Ho Y, Lai K . Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 2009; 77(6):543-9. DOI: 10.1038/ki.2009.499. View

Gaestel M, Mengel A, Bothe U, Asadullah K . Protein kinases as small molecule inhibitor targets in inflammation. Curr Med Chem. 2007; 14(21):2214-34. DOI: 10.2174/092986707781696636. View

Machuca E, Benoit G, Antignac C . Genetics of nephrotic syndrome: connecting molecular genetics to podocyte physiology. Hum Mol Genet. 2009; 18(R2):R185-94. DOI: 10.1093/hmg/ddp328. View

Souto M, Teixeira A, Russo R, Penido M, Silveira K, Teixeira M . Immune mediators in idiopathic nephrotic syndrome: evidence for a relation between interleukin 8 and proteinuria. Pediatr Res. 2008; 64(6):637-42. DOI: 10.1203/PDR.0b013e318186ddb2. View

Alvarez B, Carballal S, Turell L, Radi R . Formation and reactions of sulfenic acid in human serum albumin. Methods Enzymol. 2010; 473:117-36. DOI: 10.1016/S0076-6879(10)73005-6. View

Tahzib M, Frank R, Gauthier B, Valderrama E, Trachtman H . Vitamin E treatment of focal segmental glomerulosclerosis: results of an open-label study. Pediatr Nephrol. 1999; 13(8):649-52. DOI: 10.1007/s004670050674. View

Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-LE Camus C, Afanetti M . Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008; 23(8):1269-79. DOI: 10.1007/s00467-008-0814-1. View

Candiano G, Petretto A, Bruschi M, Santucci L, Dimuccio V, Prunotto M . The oxido-redox potential of albumin methodological approach and relevance to human diseases. J Proteomics. 2009; 73(2):188-95. DOI: 10.1016/j.jprot.2009.06.006. View

Niaudet P . Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone. French Society of Pediatric Nephrology. J Pediatr. 1994; 125(6 Pt 1):981-6. DOI: 10.1016/s0022-3476(05)82020-7. View

10.

Gargah T, Lakhoua M . Mycophenolate mofetil in treatment of childhood steroid-resistant nephrotic syndrome. J Nephrol. 2011; 24(2):203-7. DOI: 10.5301/jn.2011.6327. View

11.

Moudgil A, Bagga A, Jordan S . Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions. Pediatr Nephrol. 2005; 20(10):1376-81. DOI: 10.1007/s00467-005-1964-z. View

12.

Nakakura H, Ashida A, Hirano K, Tamai H . Oxidative stress in a rat model of nephrosis can be quantified by electron spin resonance. Pediatr Nephrol. 2004; 19(3):266-70. DOI: 10.1007/s00467-003-1332-9. View

13.

Sheryanna A, Bhangal G, McDaid J, Smith J, Manning A, Foxwell B . Inhibition of p38 mitogen-activated protein kinase is effective in the treatment of experimental crescentic glomerulonephritis and suppresses monocyte chemoattractant protein-1 but not IL-1beta or IL-6. J Am Soc Nephrol. 2007; 18(4):1167-79. DOI: 10.1681/ASN.2006010050. View

14.

Yang H, Ma L, Ma J, Fogo A . Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis. Kidney Int. 2006; 69(10):1756-64. DOI: 10.1038/sj.ki.5000336. View

15.

Garcia C, Bittencourt V, Tumelero A, Antonello J, Malheiros D, Garcia V . Plasmapheresis for recurrent posttransplant focal segmental glomerulosclerosis. Transplant Proc. 2006; 38(6):1904-5. DOI: 10.1016/j.transproceed.2006.06.069. View

16.

Peters H, van de Kar N, Wetzels J . Rituximab in minimal change nephropathy and focal segmental glomerulosclerosis: report of four cases and review of the literature. Neth J Med. 2008; 66(10):408-15. View

17.

Sharda S, Gulati S, Tripathi G, Jafar T, Kumar A, Sharma R . Do glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic nephrotic syndrome?. Pediatr Nephrol. 2008; 23(11):2001-6. DOI: 10.1007/s00467-008-0883-1. View

18.

Eddy A, Symons J . Nephrotic syndrome in childhood. Lancet. 2003; 362(9384):629-39. DOI: 10.1016/S0140-6736(03)14184-0. View

19.

Pavlova E, Lilova M, Savov V . Oxidative stress in children with kidney disease. Pediatr Nephrol. 2005; 20(11):1599-604. DOI: 10.1007/s00467-005-1990-x. View

20.

Rydel J, Korbet S, Borok R, Schwartz M . Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment. Am J Kidney Dis. 1995; 25(4):534-42. DOI: 10.1016/0272-6386(95)90120-5. View