Pediatric Nephrology

, Volume 26, Issue 6, pp 881–892

New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

Educational Review

Abstract

Although many children with idiopathic nephrotic syndrome (INS) respond initially to steroid therapy, repeated courses for patients with relapses often cause significant steroid toxicity. Patients with frequent relapses who develop steroid dependency thus require alternative treatment. The first such options have been considered to be cyclophosphamide or levamisole, although the latter is no longer available in many countries. There is also an increasing body of data indicating that mycophenolic acid (MPA) may be an alternative for these patients. Calcineurin inhibitors (cyclosporine A or tacrolimus) are usually effective and often used after cytotoxic treatment, but long-term treatment with these agents is necessary, raising concerns of a possible accumulation of side effects. Some patients show a tendency to relapse even on such maintenance regimens, and some even have a refractory course that creates a medical dilemma. For this situation, recent data indicate that monoclonal antibodies directed to B-cells (e.g. rituximab) may have some effect and that such drugs may also prove to be a therapeutic option in less complicated cases. Patients that do not respond to steroid treatment need genetic testing and a renal biopsy since focal segmental glomerulosclerosis (FSGS) may be present. Treatment options include pulse methylprednisolone, often in addition to calcineurin inhibitors, mainly in the form of cyclosporine, but tacrolimus has also come into recent favor. Some studies have found cytotoxic treatment, especially intravenous cyclophosphamide, to be effective in steroid resistant nephrotic syndrome, but it seems to be inferior to calcineurin inhibitors. MPA and rituximab have also been used in children with primary FSGS, but the response seems to be inferior to that in patients with steroid sensitive nephrotic syndrome. Taken together, INS in both steroid-sensitive and steroid-resistant patients is a potentially complicated disorder, and despite a wide arsenal of immunological interventions, some patients have a treatment refractory course. Prospective studies or at least standardized treatment for complicated cases is urgently needed.

Keywords

Nephrotic syndrome Steroid sensitive Steroid resistant Immunosuppression Minimal change glomerulonephritis Focal segmental glomerulosclerosis 

References

  1. 1.
    International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165Google Scholar
  2. 2.
    Murnaghan K, Vasmant D, Bensman A (1984) Pulse methylprednisolone therapy in severe idiopathic childhood nephrotic syndrome. Acta Paediatr Scand 73:733–739PubMedCrossRefGoogle Scholar
  3. 3.
    Hodson EM, Alexander SI (2008) Evaluation and management of steroid-sensitive nephrotic syndrome. Curr Opin Pediatr 20:145–150PubMedCrossRefGoogle Scholar
  4. 4.
    Hoyer PF, Brodehl J (2006) Initial treatment of idiopathic nephrotic syndrome in children: prednisone versus prednisone plus cyclosporine A: a prospective, randomized trial. J Am Soc Nephrol 17:1151–1157PubMedCrossRefGoogle Scholar
  5. 5.
    Hiraoka M, Tsukahara H, Matsubara K, Tsurusawa M, Takeda N, Haruki S, Hayashi S, Ohta K, Momoi T, Ohshima Y, Suganuma N, Mayumi M (2003) A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children. Am J Kidney Dis 41:1155–1162PubMedCrossRefGoogle Scholar
  6. 6.
    MacHardy N, Miles PV, Massengill SF, Smoyer WE, Mahan JD, Greenbaum L, Massie S, Yao L, Nagaraj S, Lin JJ, Wigfall D, Trachtman H, Hu Y, Gipson DS (2009) Management patterns of childhood-onset nephrotic syndrome. Pediatr Nephrol 24:2193–2201PubMedCrossRefGoogle Scholar
  7. 7.
    International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564CrossRefGoogle Scholar
  8. 8.
    Ehrich JH, Brodehl J (1993) Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Eur J Pediatr 152:357–361PubMedCrossRefGoogle Scholar
  9. 9.
    Rüth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202–207PubMedCrossRefGoogle Scholar
  10. 10.
    Niaudet P (2009) Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. Clin J Am Soc Nephrol 4:1547–1548PubMedCrossRefGoogle Scholar
  11. 11.
    Davin JC, Merkus MP (2005) Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise? Pediatr Nephrol 20:10–14PubMedCrossRefGoogle Scholar
  12. 12.
    Kemper MJ, Altrogge H, Ludwig K, Timmermann K, Muller-Wiefel DE (2000) Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 14:772–775PubMedCrossRefGoogle Scholar
  13. 13.
    Vester U, Kranz B, Zimmermann S, Hoyer PF (2003) Cyclophosphamide in steroid-sensitive nephrotic syndrome: outcome and outlook. Pediatr Nephrol 18:661–664PubMedGoogle Scholar
  14. 14.
    Sharda SV, Gulati S, Tripathi G, Jafar T, Kumar A, Sharma RK, Agrawal S (2008) Do glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic nephrotic syndrome? Pediatr Nephrol 23:2001–2006PubMedCrossRefGoogle Scholar
  15. 15.
    Kyrieleis HA, Levtchenko EN, Wetzels JF (2007) Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome. Am J Kidney Dis 49:592–597PubMedCrossRefGoogle Scholar
  16. 16.
    Kyrieleis HA, Lowik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ, van den Heuvel BL, Wetzels JF, Levtchenko EN (2009) Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol 4:1593–1600PubMedCrossRefGoogle Scholar
  17. 17.
    Prasad N, Gulati S, Sharma RK, Singh U, Ahmed M (2004) Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 19:494–498PubMedCrossRefGoogle Scholar
  18. 18.
    Kemper MJ, Kuwertz-Broeking E, Bulla M, Mueller-Wiefel DE, Neuhaus TJ (2004) Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome. Nephrol Dial Transplant 19:1136–1141PubMedCrossRefGoogle Scholar
  19. 19.
    Hulton SA, Neuhaus TJ, Dillon MJ, Barratt TM (1994) Long-term cyclosporin A treatment of minimal-change nephrotic syndrome of childhood. Pediatr Nephrol 8:401–403PubMedCrossRefGoogle Scholar
  20. 20.
    Nozu K, Iijima K, Sakaeda T, Okumura K, Nakanishi K, Yoshikawa N, Honda M, Ikeda M, Matsuo M (2005) Cyclosporin A absorption profiles in children with nephrotic syndrome. Pediatr Nephrol 20:910–913PubMedCrossRefGoogle Scholar
  21. 21.
    Hodson EM, Willis NS, Craig JC (2008) Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev CD002290Google Scholar
  22. 22.
    Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, Zacchello G, Confalonieri R, Altieri P, Altieri P, Bettinelli A, Maschio G, Cinotti GA, Fuiano G, Schena FP, Castellani A, Casa-Alberighi OD (1993) Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 8:1326–1332PubMedGoogle Scholar
  23. 23.
    Sumegi V, Haszon I, Bereczki C, Papp F, Turi S (2008) Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome. Pediatr Nephrol 23:1085–1092PubMedCrossRefGoogle Scholar
  24. 24.
    Kengne-Wafo S, Massella L, Diomedi-Camassei F, Gianviti A, Vivarelli M, Greco M, Stringini GR, Emma F (2009) Risk factors for cyclosporin A nephrotoxicity in children with steroid-dependant nephrotic syndrome. Clin J Am Soc Nephrol 4:1409–1416PubMedCrossRefGoogle Scholar
  25. 25.
    Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670PubMedCrossRefGoogle Scholar
  26. 26.
    Sinha MD, MacLeod R, Rigby E, Clark AG (2006) Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant 21:1848–1854PubMedCrossRefGoogle Scholar
  27. 27.
    Dötsch J, Dittrich K, Plank C, Rascher W (2006) Is tacrolimus for childhood steroid-dependent nephrotic syndrome better than ciclosporin A? Nephrol Dial Transplant 21:1761–1763PubMedCrossRefGoogle Scholar
  28. 28.
    Dittrich K, Knerr I, Rascher W, Dötsch J (2006) Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment. Pediatr Nephrol 21:958–961PubMedCrossRefGoogle Scholar
  29. 29.
    Bagga A, Hari P, Moudgil A, Jordan SC (2003) Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 42:1114–1120PubMedCrossRefGoogle Scholar
  30. 30.
    Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104PubMedCrossRefGoogle Scholar
  31. 31.
    Hogg RJ, Fitzgibbons L, Bruick J, Bunke M, Ault B, Baqi N, Trachtman H, Swinford R (2006) Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 1:1173–1178PubMedCrossRefGoogle Scholar
  32. 32.
    Fujinaga S, Ohtomo Y, Hirano D, Nishizaki N, Someya T, Ohtsuka Y, Kaneko K, Shimizu T (2009) Mycophenolate mofetil therapy for childhood-onset steroid dependent nephrotic syndrome after long-term cyclosporine: extended experience in a single center. Clin Nephrol 72:268–273PubMedGoogle Scholar
  33. 33.
    Ulinski T, Dubourg L, Said MH, Parchoux B, Ranchin B, Cochat P (2005) Switch from cyclosporine A to mycophenolate mofetil in nephrotic children. Pediatr Nephrol 20:482–485PubMedCrossRefGoogle Scholar
  34. 34.
    Dorresteijn EM, Kist-van Holthe JE, Levtchenko EN, Nauta J, Hop WC, van der Heijden AJ (2008) Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome. Pediatr Nephrol 23:2013–2020PubMedCrossRefGoogle Scholar
  35. 35.
    Mendizabal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J (2005) Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome. Pediatr Nephrol 20:914–919PubMedCrossRefGoogle Scholar
  36. 36.
    de Mello VR, Rodrigues MT, Mastrocinque TH, Martins SP, de Andrade OV, Guidoni EB, Scheffer DK, Martini Filho D, Toporovski J, Benini V (2010) Mycophenolate mofetil in children with steroid/cyclophosphamide-resistant nephrotic syndrome. Pediatr Nephrol 25:453–460PubMedCrossRefGoogle Scholar
  37. 37.
    Kawasaki Y, Suzuki J, Takahashi A, Isome M, Nozawa R, Suzuki H (2005) Mizoribine oral pulse therapy for steroid-dependent nephrotic syndrome. Pediatr Nephrol 20:96–98PubMedCrossRefGoogle Scholar
  38. 38.
    Durkan A, Hodson EM, Willis NS, Craig JC (2005) Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev CD002290Google Scholar
  39. 39.
    Kemper MJ, Meyer-Jark T, Lilova M, Muller-Wiefel DE (2003) Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol 60:242–247PubMedGoogle Scholar
  40. 40.
    Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279PubMedCrossRefGoogle Scholar
  41. 41.
    Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M, Iijima K (2009) Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol 24:1321–1328PubMedCrossRefGoogle Scholar
  42. 42.
    Prytula A, Iijima K, Kamei K, Geary D, Gottlich E, Majeed A, Taylor M, Marks SD, Tuchman S, Camilla R, Ognjanovic M, Filler G, Smith G, Tullus K (2010) Rituximab in refractory nephrotic syndrome. Pediatr Nephrol 25:461–468PubMedCrossRefGoogle Scholar
  43. 43.
    Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, Srivastava RN, Moudgil A, Bagga A (2010) Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol. doi:10.2215/CJN.03470410 Google Scholar
  44. 44.
    Kemper MJ, Moeller C, Rink N, van Husen M, Mueller-Wiefel DE (2007) Treatment of refractory steroid sensitive nephrotic syndrome with rituximab. Pediatr Nephrol 22:1445Google Scholar
  45. 45.
    Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschenes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755PubMedCrossRefGoogle Scholar
  46. 46.
    Bitzan M, Anselmo M, Carpineta L (2009) Rituximab (B-cell depleting antibody) associated lung injury (RALI): a pediatric case and systematic review of the literature. Pediatr Pulmonol 44:922–934PubMedCrossRefGoogle Scholar
  47. 47.
    Park SS, Hahn WH, Kim SD, Cho BS (2009) Remission of refractory minimal change nephrotic syndrome after basiliximab therapy. Pediatr Nephrol 24:1403–1407PubMedCrossRefGoogle Scholar
  48. 48.
    Clark AG, Amlot P (1995) Anti-CD25 monoclonal antibody induces remission of steroid responsive nephrotic syndrome-a case report. Pediatr Nephrol 9:C86CrossRefGoogle Scholar
  49. 49.
    Francois H, Daugas E, Bensman A, Ronco P (2007) Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic syndrome in the adult: first case report and pathophysiological considerations. Am J Kidney Dis 49:158–161PubMedCrossRefGoogle Scholar
  50. 50.
    Raveh D, Shemesh O, Ashkenazi YJ, Winkler R, Barak V (2004) Tumor necrosis factor-alpha blocking agent as a treatment for nephrotic syndrome. Pediatr Nephrol 19:1281–1284PubMedCrossRefGoogle Scholar
  51. 51.
    Kausman JY, Yin L, Jones CL, Johnstone L, Powell HR (2005) Vincristine treatment in steroid-dependent nephrotic syndrome. Pediatr Nephrol 20:1416–1419PubMedCrossRefGoogle Scholar
  52. 52.
    Krishnan RG, Coulthard MG, Moghal NE (2006) Is there a role for vincristine in nephrotic syndrome? Pediatr Nephrol 21:597PubMedCrossRefGoogle Scholar
  53. 53.
    Vehaskari VM (1999) Treatment practices of FSGS among North American pediatric nephrologists. Pediatr Nephrol 13:301–303PubMedCrossRefGoogle Scholar
  54. 54.
    Gipson DS, Chin H, Presler TP, Jennette C, Ferris ME, Massengill S, Gibson K, Thomas DB (2006) Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol 21:344–349PubMedCrossRefGoogle Scholar
  55. 55.
    Buescher AK, Kranz B, Buscher R, Hildebrandt F, Dworniczak B, Pennekamp P, Kuwertz-Broking E, Wingen AM, John U, Kemper M, Monnens L, Hoyer PF, Weber S, Konrad M (2010) Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. doi: 10.2215/​CJN.01190210
  56. 56.
    Bhimma R, Adhikari M, Asharam K (2006) Steroid-resistant nephrotic syndrome: the influence of race on cyclophosphamide sensitivity. Pediatr Nephrol 21:1847–1853PubMedCrossRefGoogle Scholar
  57. 57.
    El-Husseini A, El-Basuony F, Mahmoud I, Sheashaa H, Sabry A, Hassan R, Taha N, Hassan N, Sayed-Ahmad N, Sobh M (2005) Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience. Nephrol Dial Transplant 20:2433–2438PubMedCrossRefGoogle Scholar
  58. 58.
    Tune BM, Kirpekar R, Sibley RK, Reznik VM, Griswold WR, Mendoza SA (1995) Intravenous methylprednisolone and oral alkylating agent therapy of prednisone-resistant pediatric focal segmental glomerulosclerosis: a long-term follow-up. Clin Nephrol 43:84–88PubMedGoogle Scholar
  59. 59.
    Ehrich JH, Geerlings C, Zivicnjak M, Franke D, Geerlings H, Gellermann J (2007) Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrol Dial Transplant 22:2183–2193PubMedCrossRefGoogle Scholar
  60. 60.
    Plank C, Kalb V, Hinkes B, Hildebrandt F, Gefeller O, Rascher W (2008) Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie. Pediatr Nephrol 23:1483–1493PubMedCrossRefGoogle Scholar
  61. 61.
    Shenoy M, Plant ND, Lewis MA, Bradbury MG, Lennon R, Webb NJ (2010) Intravenous methylprednisolone in idiopathic childhood nephrotic syndrome. Pediatr Nephrol 25:899–903PubMedCrossRefGoogle Scholar
  62. 62.
    Meyrier AY (2009) Treatment of focal segmental glomerulosclerosis with immunophilin modulation: when did we stop thinking about pathogenesis? Kidney Int 76:487–491PubMedCrossRefGoogle Scholar
  63. 63.
    Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14:931–938PubMedCrossRefGoogle Scholar
  64. 64.
    Bensman A, Niaudet P (2010) Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies. Pediatr Nephrol 25:1197–1199PubMedCrossRefGoogle Scholar
  65. 65.
    Ingulli E, Singh A, Baqi N, Ahmad H, Moazami S, Tejani A (1995) Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis. J Am Soc Nephrol 5:1820–1825PubMedGoogle Scholar
  66. 66.
    Cattran DC, Alexopoulos E, Heering P, Hoyer PF, Johnston A, Meyrier A, Ponticelli C, Saito T, Choukroun G, Nachman P, Praga M, Yoshikawa N (2007) Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int 72:1429–1447PubMedCrossRefGoogle Scholar
  67. 67.
    Hamasaki Y, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ishikura K, Yata N, Kaneko T, Honda M (2009) Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 24:2177–2185PubMedCrossRefGoogle Scholar
  68. 68.
    Segarra A, Vila J, Pou L, Majo J, Arbos A, Quiles T, Piera LL (2002) Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or -dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 17:655–662PubMedCrossRefGoogle Scholar
  69. 69.
    Duncan N, Dhaygude A, Owen J, Cairns TD, Griffith M, McLean AG, Palmer A, Taube D (2004) Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 19:3062–3067PubMedCrossRefGoogle Scholar
  70. 70.
    Westhoff TH, van der Giet M (2007) Tacrolimus in the treatment of idiopathic nephrotic syndrome. Expert Opin Investig Drugs 16:1099–1110PubMedCrossRefGoogle Scholar
  71. 71.
    Li X, Li H, Ye H, Li Q, He X, Zhang X, Chen Y, Han F, He Q, Wang H, Chen J (2009) Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR. Am J Kidney Dis 54:51–58PubMedCrossRefGoogle Scholar
  72. 72.
    Loeffler K, Gowrishankar M, Yiu V (2004) Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. Pediatr Nephrol 19:281–287PubMedCrossRefGoogle Scholar
  73. 73.
    Gulati S, Prasad N, Sharma RK, Kumar A, Gupta A, Baburaj VP (2008) Tacrolimus: a new therapy for steroid-resistant nephrotic syndrome in children. Nephrol Dial Transplant 23:910–913PubMedCrossRefGoogle Scholar
  74. 74.
    Butani L, Ramsamooj R (2009) Experience with tacrolimus in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 24:1517–1523PubMedCrossRefGoogle Scholar
  75. 75.
    Roberti I, Vyas S (2010) Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 25:1117–1124PubMedCrossRefGoogle Scholar
  76. 76.
    Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A (2009) Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial. Am J Kidney Dis 53:760–769PubMedCrossRefGoogle Scholar
  77. 77.
    Rennert WP, Kala UK, Jacobs D, Goetsch S, Verhaart S (1999) Pulse cyclophosphamide for steroid-resistant focal segmental glomerulosclerosis. Pediatr Nephrol 13:113–116PubMedCrossRefGoogle Scholar
  78. 78.
    Gulati S, Kher V (2000) Intravenous pulse cyclophosphamide–a new regime for steroid resistant focal segmental glomerulosclerosis. Indian Pediatr 37:141–148PubMedGoogle Scholar
  79. 79.
    Al Salloum AA (2004) Pulse cyclophosphamide therapy for steroid-resistant focal segmental glomerulosclerosis in children. Ann Saudi Med 24:27–30PubMedGoogle Scholar
  80. 80.
    Abeyagunawardena AS, Sebire NJ, Risdon RA, Dillon MJ, Rees L, Van't Hoff W, Kumarasiri PV, Trompeter RS (2007) Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis. Pediatr Nephrol 22:215–221PubMedCrossRefGoogle Scholar
  81. 81.
    Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1996) Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. A report of the International Study of Kidney Disease in Children. Pediatr Nephrol 10:590–593PubMedCrossRefGoogle Scholar
  82. 82.
    Cattran DC, Wang MM, Appel G, Matalon A, Briggs W (2004) Mycophenolate mofetil in the treatment of focal segmental glomerulosclerosis. Clin Nephrol 62:405–411PubMedGoogle Scholar
  83. 83.
    El-Reshaid K, El-Reshaid W, Madda J (2005) Combination of immunosuppressive agents in treatment of steroid-resistant minimal change disease and primary focal segmental glomerulosclerosis. Ren Fail 27:523–530PubMedCrossRefGoogle Scholar
  84. 84.
    Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G (2003) Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 18:772–777PubMedCrossRefGoogle Scholar
  85. 85.
    Barletta GM, Smoyer WE, Bunchman TE, Flynn JT, Kershaw DB (2003) Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome. Pediatr Nephrol 18:833–837PubMedCrossRefGoogle Scholar
  86. 86.
    Gellermann J, Querfeld U (2009) Long-term outcome of idiopathic steroid resistant nephrotic syndrome-associated with focal segmental glomerulosclerosis: a single center study. Pediatr Nephrol 24:1807Google Scholar
  87. 87.
    Yabu JM, Ho B, Scandling JD, Vincenti F (2008) Rituximab failed to improve nephrotic syndrome in renal transplant patients with recurrent focal segmental glomerulosclerosis. Am J Transplant 8:222–227PubMedGoogle Scholar
  88. 88.
    Bagga A, Sinha A, Moudgil A (2007) Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 356:2751–2752PubMedCrossRefGoogle Scholar
  89. 89.
    Nakayama M, Kamei K, Nozu K, Matsuoka K, Nakagawa A, Sako M, Iijima K (2008) Rituximab for refractory focal segmental glomerulosclerosis. Pediatr Nephrol 23:481–485PubMedCrossRefGoogle Scholar
  90. 90.
    Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M (2008) Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Transl Res 151:288–292PubMedCrossRefGoogle Scholar
  91. 91.
    De Smet E, Rioux JP, Ammann H, Deziel C, Querin S (2009) FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant 24:2938–2940PubMedCrossRefGoogle Scholar
  92. 92.
    Cho ME, Hurley JK, Kopp JB (2007) Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am J Kidney Dis 49:310–317PubMedCrossRefGoogle Scholar
  93. 93.
    Tumlin JA, Miller D, Near M, Selvaraj S, Hennigar R, Guasch A (2006) A prospective, open-label trial of sirolimus in the treatment of focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 1:109–116PubMedCrossRefGoogle Scholar
  94. 94.
    Tsagalis G, Psimenou E, Iliadis A, Nakopoulou L, Laggouranis A (2009) Rapamycin for focal segmental glomerulosclerosis: a report of 3 cases. Am J Kidney Dis 54:340–344PubMedCrossRefGoogle Scholar
  95. 95.
    Hocker B, Knuppel T, Waldherr R, Schaefer F, Weber S, Tonshoff B (2006) Recurrence of proteinuria 10 years post-transplant in NPHS2-associated focal segmental glomerulosclerosis after conversion from cyclosporin A to sirolimus. Pediatr Nephrol 21:1476–1479PubMedCrossRefGoogle Scholar
  96. 96.
    Piecha G, Kokeny G, Nakagawa K, Koleganova N, Geldyyev A, Berger I, Ritz E, Schmitt CP, Gross ML (2008) Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats. Am J Physiol Renal Physiol 294:F748–F757PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2011

Authors and Affiliations

  1. 1.Pediatric NephrologyUniversity Medical Center Hamburg–EppendorfHamburgGermany

Personalised recommendations