Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jul 16;2008(3):CD003233.
doi: 10.1002/14651858.CD003233.pub2.

Immunosuppressive treatment for focal segmental glomerulosclerosis in adults

Norbert Braun  1 , Frank Schmutzler, Catalina Lange, Annalisa Perna, Giuseppe Remuzzi, Teut Risler, Narelle S Willis
Affiliations

Immunosuppressive treatment for focal segmental glomerulosclerosis in adults

Norbert Braun et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Corticosteroids remain the mainstay of treatment in idiopathic nephrotic syndrome, including focal and segmental glomerulosclerosis (FSGS). However, only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome despite treatment.

Objectives: To assess the effects of different immunomodulatory and immunosuppressive regimes in adults with FSGS.

Search strategy: We searched MEDLINE, EMBASE and CENTRAL and handsearched congress reports of the American Society of Nephrology and the European Dialysis and Transplantation Association. Date of search: 31 January 2007.

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs which examined the effects of different doses, dose strategies and duration of treatment of steroids, alkylating agents, cyclosporin A and antimetabolites in the treatment of FSGS in adults, where included.

Data collection and analysis: At least two authors independently assessed abstracts and/or full text articles to determine which studies satisfied the inclusion criteria. Information was entered onto a separate data sheet for each identified study. Data relevant to outcomes (complete or partial remission of nephrotic syndrome, doubling of serum creatinine, adverse effects) from identified studies were included. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI).

Main results: Four studies (108 participants) were included. Three studies investigated cyclosporin A (CSA) with or without prednisone versus prednisone or no treatment and one compared chlorambucil plus prednisone versus no treatment. Outcome data was only available for complete or partial remission and doubling of serum creatinine. There was a significant increase in the number of participants who obtained complete or partial remission with CSA plus low dose prednisone versus prednisone alone (one study, 49 participants: RR 8.85, 95% CI 1.22 to 63.92). Pooled analyses were not performed due to the heterogeneity of the data.

Authors' conclusions: Adult patients treated with CSA at an initial dose of 3.5-5 mg/kg/d in two divided doses perhaps in combination with oral prednisolone 0.15 mg/kg/d are more likely to achieve a partial remission of the nephrotic syndrome compared with symptomatic treatment or prednisolone alone. However, there is a probability of deterioration of kidney function due to the nephrotoxic effect of CSA in the long term. For CSA, a larger controlled trial with longer follow-up should be performed to prove the benefit of this regimen not only on proteinuria but also on the preservation of kidney function. Present available data do not support the general use of alkylating substances for the treatment of FSGS in adults.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

1.1
1.1. Analysis
Comparison 1 Remission of proteinuria, Outcome 1 Complete remission.
1.2
1.2. Analysis
Comparison 1 Remission of proteinuria, Outcome 2 Partial remission.
1.3
1.3. Analysis
Comparison 1 Remission of proteinuria, Outcome 3 Complete or partial remission (combined end‐point).
1.4
1.4. Analysis
Comparison 1 Remission of proteinuria, Outcome 4 Complete or partial remission ‐ CSA versus any or no treatment.
2.1
2.1. Analysis
Comparison 2 Deterioration of kidney function, Outcome 1 Doubling of serum creatinine.
See this image and copyright information in PMC

References

References to studies included in this review

Bhamik 2002 {published data only}
    1. Bhamik SK, Majumdar A, Barman SC. Comparison of pulse methylprednisolone vs cyclosporin based therapy in steroid resistant focal segmental glomerulosclerosis [abstract]. Indian Journal of Nephrology 2002;12(4):190. [CENTRAL: CN‐00460392]
Cattran 1999 {published data only}
    1. Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, et al. A randomized trial of cyclosporine in patients with steroid‐resistant focal segmental glomerulosclerosis. Kidney International 1999;56(6):2220‐6. [MEDLINE: ] - PubMed
Imbasciati 1980 {published data only}
    1. Imbasciati E, Cagnoli L, Case N, Pasquali S, Filippo G, Limido D, et al. Controlled study of treatment of steroids and chlorambucil, in alternate months, for membranous nephropathy and focal glomerulosclerosis. Preliminary evaluation of the results. Minerva Nefrologica 1980;27(4):571‐5. [MEDLINE: ] - PubMed
Ponticelli 1993 {published data only}
    1. Ponticelli C, Rizzoni G, Edefonti A, Altieri P, Rivolta E, Rinaldi S, et al. A randomized trial of cyclosporine in steroid‐resistant idiopathic nephrotic syndrome. Kidney International 1993;43(6):1377‐84. [MEDLINE: ] - PubMed

References to studies excluded from this review

Bagga 2003 {published data only}
    1. Bagga A, Pankaj H, Moudgil A, Jordan SC. Mycophenolate Mofetil and Prednisolone therapy in children with steroid‐dependent nephrotic syndrome. American Journal of Kidney Diseases 2003;42(6):1114‐20. [MEDLINE: ] - PubMed
Bakir 1996 {published data only}
    1. Bakir AA, Share DS, Levy PS, Arruda JAL, Dunea G. Focal segmental glomerulosclerosis in adult African Americans. Clinical Nephrology 1996;46(5):306‐11. [MEDLINE: ] - PubMed
Banfi 1991 {published data only}
    1. Banfi G, Moriggi M, Sabadini E, Fellin G, D´Amico G, Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal‐segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. Clinical Nephrology 1991;36(2):53‐9. [MEDLINE: ] - PubMed
Beaufils 1978 {published data only}
    1. Beaufils H, Alphonse JC, Guedon J, Legrain M. Focal glomerulosclerosis: natural history and treatment. A report of 70 cases. Nephron 1978;21(2):75‐85. [MEDLINE: ] - PubMed
Bolton 1977 {published data only}
    1. Bolton WK, Atuk NO, Sturgill BC, Westervelt Jr FB. Therapy of the idiopathic nephrotic syndrome with alternate day steroids. American Journal of Medicine 1977;62(1):60‐70. [MEDLINE: ] - PubMed
Chan 1991 {published data only}
    1. Chan PC, Chan KW, Cheng IK, Chan MK. Focal sclerosing glomerulopathy. Risk factors of progression and optimal mode of treatment. International Urology & Nephrology 1991;23(6):619‐29. [MEDLINE: ] - PubMed
Crenshaw 1999 {published data only}
    1. Crenshaw G, Bigler S, Salem M, Crook ED. Focal segmental glomerulosclerosis in African Americans: Effects of steroids and angiotensin converting enzyme inhibitors. American Journal of Medical Sciences 2000;319(5):320‐5. [MEDLINE: ] - PubMed
Dantal 1998 {published data only}
    1. Dantal J, Godfrin Y, Koll R, Perretto S, Naulet J, Bouhours JF, et al. Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome. Journal of the American Society of Nephrology 1998;9(9):1709‐15. [MEDLINE: ] - PubMed
Dudar 2004 {published and unpublished data}
    1. Dudar I, Kolesnik N, Velichko M, Vinnicova L. The result of pulse dose cyclophosphamide and ACE‐inhibitor of focal segmental glomerulosclerosis/hyalinosis (FSGS/G) of patients with glomerulonephritis [abstract]. 41st Congress. European Renal Association. European Dialysis and Transplantation Association; 2004 May 15‐18; Lisbon (Portugal). 2004:39‐40. [CENTRAL: CN‐00509166]
El‐Reshaid 1995 {published data only}
    1. El‐Reshaid K, Amer E, Madda JP, Kapoor M. Long‐term cyclosporin A treatment in adults with refractory nephrotic syndrome. Renal Failure 1995;17(6):695‐703. [MEDLINE: ] - PubMed
Emre 2001 {published data only}
    1. Emre S, Oktem F, Denizem Y. Long term pulse methylprednisolone infusion therapy in patients with focal segmental glomerulosclerosis [abstract]. Pediatric Nephrology 2001;16(8):C115. [CENTRAL: CN‐00445227]
Garin 1988 {published data only}
    1. Garin EH, Orak JK, Hiott KL, Sutherland SE. Cyclosporine therapy for steroid‐resistant nephrotic syndrome. A controlled study. American Journal of Diseases of Children 1988;142(9):985‐8. [MEDLINE: ] - PubMed
Goumenos 2006 {published data only}
    1. Goumenos DS, Tsagalis G, Meguid El Nahas A, Shortland JR, Davlouros P, Vlachojannis JG, et al. Immunosuppressive treatment of idiopathic focal segmental glomerulosclerosis: a five‐year follow‐up study. Nephron 2006;104(2):c75‐82. [MEDLINE: ] - PubMed
Grcevska 2006 {published data only}
    1. Grcevska L, Dzikova S, Petrusevska G, Polenakovic M. Prednisone/cyclophosphamide treatment in adult‐onset autosomal dominant familial focal segmental glomerulosclerosis (FSGS 1). Clinical Nephrology 2006;65(6):461‐2. [MEDLINE: ] - PubMed
Gulati 2000 {published data only}
    1. Gulati S, Kher V. Intravenous pulse cyclophosphamide ‐ a new regime for steroid resistant focal segmental glomerulosclerosis. Indian Pediatrics 2000;37(2):141‐8. [MEDLINE: ] - PubMed
Heering 2004 {published data only}
    1. Heering P, Braun N, Müllejans R, Ivens K, Zäuner I, Fünfstück R, et al. Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis. American Journal of Kidney Diseases 2004;43(1):10‐18. [MEDLINE: ] - PubMed
Ittel 1995 {published data only}
    1. Ittel TH, Clasen W, Fuhs M, Kindler J, Mihatsch MJ, Sieberth HG. Long‐term ciclosporine A treatment in adults with minimal change nephrotic syndrome or focal segmental glomerulosclerosis. Clinical Nephrology 1995;44(3):156‐62. [MEDLINE: ] - PubMed
Lee 1995 {published data only}
    1. Lee HY, Kim HS, Kang CM, Kim SG, Kim MJ. The efficacy of cyclosporine A in adult nephrotic syndrome with minimal change disease and focal‐segmental glomerulosclerosis: a multicenter study in Korea. Clinical Nephrology 1995;43(6):375‐81. [MEDLINE: ] - PubMed
Lieberman 1996 {published data only}
    1. Lieberman KV, Tejani A. A randomized double‐blind placebo‐controlled trial of Cyclosporine in steroid‐resistant idiopathic focal segmental glomerulosclerosis in children. Journal of the American Society of Nephrology 1996;7(1):56‐63. [MEDLINE: ] - PubMed
Medizábal 2005 {published data only}
    1. Mendizábal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J. Mycophenolate mofetil in steroid/cyclosporine‐dependent/resistant nephrotic syndrome. Pediatric Nephrology 2005;20(7):914‐9. [MEDLINE: ] - PubMed
Meyrier 1986 {published data only}
    1. Meyrier A, Simon P, Perret G, Condamin‐Meyrier MC. Remission of idiopathic nephrotic syndrome after treatment with cyclosporin A. British Medical Journal (Clinical Research Ed.) 1986;292(6523):789‐92. [MEDLINE: ] - PMC - PubMed
Meyrier 1989 {published data only}
    1. Meyrier A, Bacri JL, Bagros P, Lebranchu Y, Bataille P, Baumelou A, et al. Ciclosporin in the treatment of nephrosis. Minimal change disease and focal‐segmental glomerulosclerosis. American Journal of Nephrology 1989;9 Suppl 1:65‐71. [MEDLINE: ] - PubMed
Meyrier 1994 {published data only}
    1. Meyrier A, Noel LH, Auriche P, Callard P. Long‐term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Societe de Nephrologie. Kidney International 1994;45(5):1446‐56. [MEDLINE: ] - PubMed
Mowry 1993 {published data only}
    1. Mowry J, Marik J, Cohen A, Hogg R, Sahney S, Ettenger R. Treatment of recurrent focal segmental glomerulosclerosis with high‐dose cyclosporine A and plasmapheresis. Transplantation Proceedings 1993;25(1 Pt 2):1345‐6. [MEDLINE: ] - PubMed
Nagai 1994 {published data only}
    1. Nagai R, Cattran DC, Pei Y. Steroid therapy and prognosis of focal segmental glomerulosclerosis in the elderly. Clinical Nephrology 1994;42(1):18‐21. [MEDLINE: ] - PubMed
Pei 1987 {published data only}
    1. Pei Y, Cattran D, Delmore T, Katz A, Lang A, Rance P. Evidence suggesting under‐treatment in adults with idiopathic focal segmental glomerulosclerosis. Regional Glomerulonephritis Registry Study. American Journal of Medicine 1987;82(5):938‐44. [MEDLINE: ] - PubMed
Ponticelli 1999 {published data only}
    1. Ponticelli C, Villa M, Banfi G, Cesana B, Pozzi C, Pani A, et al. Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?. American Journal of Kidney Diseases 1999;34(4):618‐25. [MEDLINE: ] - PubMed
Raafat 2004 {published data only}
    1. Raafat RH, Kalia A, Travis LB, Diven SC. High‐dose oral cyclosporin therapy for recurrent focal segmental glomerulosclerosis in children. American Journal of Kidney Diseases 2004;44(1):50‐6. [MEDLINE: ] - PubMed
Rydel 1995 {published data only}
    1. Rydel JJ, Korbet SM, Borok RZ, Schwartz MM. Focal segmental glomerular sclerosis in adults: presentation, course and response to treatment. American Journal of Kidney Diseases 1995;25(4):534‐42. [MEDLINE: ] - PubMed
Tarshish 1996 {published data only}
    1. Tarshish P, Tobin, JN, Bernstein J, Edelmann Jr CM. Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. Pediatric Nephrology 1996;10(5):590‐3. [MEDLINE: ] - PubMed
Walker 1990 {published data only}
    1. Walker RG, Kincaid‐Smith P. The effect of treatment of corticosteroid‐resistant idiopathic (primary) focal and segmental hyalinosis and sclerosis (focal glomerulosclerosis) with ciclosporin. Nephron 1990;54(2):117‐21. [MEDLINE: ] - PubMed
Xia 2003 {published data only}
    1. Xia ZK, Liu GL, Gao YF, Fu J, Fu YF, Zhang LF, et al. Cyclosporin A treatment of 83 children with nephrotic syndrome of different pathological types. Zhonghua Erke Zazhi 2003;41(11):813‐6. [MEDLINE: ] - PubMed

References to ongoing studies

Chan 2003 {published data only}
    1. Chan D. Mycophenolate mofetil in membranous nephropathy and focal segmental. ClinicalTrials.Gov, National Institutes of Health [http://www.clinicaltrials.gov] 2003. [NCT00404833]
Friedman 2004 {published data only}
    1. Friedman A, Gassmann J. Focal segmental glomerulosclerosis clinical trial (FSGS‐CT). ClinicalTrials.Gov, National Institutes of Health [http://www.clinicaltrials.gov] 2004. [NCT00135811]
Liu 2006 {published data only}
    1. Liu Z. Tacrolimus treatment of patients with idiopathic focal segmental glomerulosclerosis. ClinicalTrials.Gov, National Institutes of Health [http://www.clinicaltrials.gov] 2006. [CENTRAL: CN‐00583312; NCT00302536]
NIDDK 2003 {published data only}
    1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Pulse dexamethasone over 48 weeks for podocyte disease. ClinicalTrials.Gov, National Institutes of Health [http://www.clinicaltrials.gov] 2003. [NCT00065611]
Trachtman 2005 {published data only}
    1. Trachtman H, Gipson D, Greene T. Pilot studies of novel therapies to treat resistant focal segmental glomerulosclerosis (FSGS). ClinicalTrials.Gov, National Institutes of Health [http://www.clinicaltrials.gov] 2005. [NCT00193648]

Additional references

Bohle 1986
    1. Bohle, GHV. Die Niere. Stuttgart: Schattauer, 1986.
Burgess 1999
    1. Burgess E. Management of focal segmental glomerulosclerosis: evidence based recommendations. Kidney International ‐ Supplement 1999;70:S26‐32. [MEDLINE: ] - PubMed
Glassock 1993
    1. Glassock RJ. Therapy of idiopathic nephrotic syndrome in adults. A conservative or aggressive therapeutic approach?. American Journal of Nephrology 1993;13(5):422‐8. [MEDLINE: ] - PubMed
Kincaid‐Smith 1978
    1. Kincaid‐Smith P, Yeung CK. Focal and segmental proliferative glomerulonephritis, focal and segmental hyalinosis and sclerosis, and focal sclerosis in the adult. Glomerulonephritis. New York: John Wiley & Sons, 1978:231‐45.
Korbet 1994
    1. Korbet S, Schwartz M, Lewis E. Primary focal segmental glomerulosclerosis: clinical course and response to therapy. American Journal of Kidney Diseases 1994;23(6):773‐83. [MEDLINE: ] - PubMed
Meyrier 1999
    1. Meyrier A. Treatment of primary focal segmental glomerulosclerosis. Nephrology, Dialysis, Transplantation 1999;14 Suppl 3:74‐8. [MEDLINE: ] - PubMed
Schulman 1988
    1. Schulman SL, Kaiser BA, Polinsky MS, Srinivasan R, Baluarte HJ. Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: Superiority of response to corticosteroid therapy over histopathologic patterns. Journal of Pediatrics 1988;133(3):996‐1001. [MEDLINE: ] - PubMed
Thomas 2006
    1. Thomas DB, Franceschini N, Hogan SL, Holder S, Jennette CE, Falk RJ, et al. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney International 2006;69(5):920‐6. [MEDLINE: ] - PubMed
Tune 1995
    1. Tune BM, Kirpekar R, Sibley RK, Reznuk VM, Grisworld WR, Mendoza SA. Intravenous methylprednisolone and oral alkylating agent therapy of prednisone‐resistant pediatric focal segmental glomerulosclerosis: a long‐term follow‐up. Clinical Nephrology 1995;43(2):84‐8. [MEDLINE: ] - PubMed
Valeri 1996
    1. Valeri A, Barisoni L, Appel GB, Seigle R, D´Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney International 1996;50(5):1734‐46. [MEDLINE: ] - PubMed
Velosa 1983
    1. Velosa JA, Holley KE, Torres VE, Offord KP. Significance of proteinuria on the outcome of renal function in patients with focal segmental glomerulosclerosis. Mayo Clinic Proceedings 1983;58(9):568‐77. [MEDLINE: ] - PubMed
Von Graffenried 1991
    1. Graffenried B, Feutren G, Schiess W, Rohrmann C, Brodehl J Meyrier A, et al. Safety and tolerability of cyclosporin A (Sandimmun) in idiopathic nephrotic syndrome. Clinical Nephrology 1991;35 Suppl 1:S48‐60. [MEDLINE: ] - PubMed

Publication types

MeSH terms

LinkOut - more resources