Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.
BACKGROUND
Idiopathic membranous nephropathy (IMN) is the most common form of nephrotic syndrome in adults. The disease shows a benign or indolent course in the majority of patients, with a rate of spontaneous complete or partial remission of nephrotic syndrome as high as 30% or more. Despite this, 30-40% of patients progress toward end-stage renal failure (ESRF) within 5-15 years.


OBJECTIVE
To assess the benefits and harms of immunosuppressive treatment for IMN in adults.


METHODS
We searched the Cochrane Renal Group Specialised Register (December 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 4, 2003), MEDLINE and Pre-MEDLINE (1966 - December 2003), EMBASE (1980 - December 2003), reference lists of nephrology textbooks, review articles, prospective trial registers, relevant trials and abstracts from nephrology scientific meetings and the internet without language restriction. We also contacted principal investigators of controlled studies.


METHODS
Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive interventions for the treatment of IMN in adults.


METHODS
Two reviewers independently assessed and extracted information. Information was collected on method, participants, interventions and outcomes (death, ESRF, proteinuria, serum creatinine, GRF, remission, adverse events).


RESULTS
A total of 18 trials with 1025 patients were included. No differences were found when we combined data of all treatment categories as a group and compared them with placebo or no treatment. Oral glucocorticoids. No beneficial effect on any of the end points chosen for efficacy was observed. Alkylating agents showed a significant beneficial effect on complete remission (RR 2.37, 95%CI 1.32 to 4.25, P = 0.004) but not on partial remission (RR 1.22, 95%CI 0.63 to 2.35, P = 0.56) or complete or partial remission (RR 1.55, 95%CI 0.72 to 3.34, P = 0.27). Cyclophosphamide treatment resulted in significantly lower rate of discontinuations due to adverse events as compared to chlorambucil (RR 2.34, 95%CI 1.25 to 4.39, P = 0.008). There was no evidence of clinically relevant differences in favour of cyclosporin and there was insufficient data on anti-proliferative agents.


CONCLUSIONS
This review failed to show any long-term effect of immunosuppressive treatment on patient and/or renal survival. There was an increased number of discontinuations due to adverse events in immunosuppressive treatment groups. Within the class of alkylating agents there is weak evidence supporting the efficacy of cyclophosphamide as compared to chlorambucil. On the other hand, cyclophosphamide had fewer side effects leading to patient withdrawal than chlorambucil.
Schieppati
A
A
Renal Medicine, Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, Bergamo, Italy, 24125. manuelap@marionegri.it
Perna
A
A
Zamora
J
J
Giuliano
G A
GA
Braun
N
N
Remuzzi
G
G
D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009404:Nephrotic Syndrome / Q000150:complications* / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
D007166:Immunosuppressive Agents; D016572:Cyclosporine