Immunosuppressive agents versus steroids in the treatment of IgA nephropathy-induced proteinuria: A meta-analysis

Immunoglobulin A nephropathy (IgAN) is one of the most common types of primary glomerular disease. Immunosuppressive treatment for patients with IgAN remains controversial. The present meta-analysis aimed to assess the efficacy and safety of various immunosuppressive agents compared with steroids in patients with IgAN and moderate to severe proteinuria. PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Weipu, Chinese Biomedical Literature Database and Qinghuatongfang were searched for relevant randomized controlled trials (RCTs) published between 1990 and September 2013. All eligible studies (biopsy proven IgA nephropathy, use of immunosuppressive agents) measured urinary protein excretion and proteinuria remission. Data were analyzed with the random effects model using Review Manager. A total of 29 RCTs were included, involving 1,466 patients. Compared with steroids, immunosuppressive agents, including azathioprine (AZA) [complete response (CR)/partial response (PR); relative risk (RR), 3.43; 95% confidence interval (CI) 1.92–6.12; P<0.0001], mycophenolate mofetil (MMF) (CR/PR; RR, 2.19; 95% CI, 1.25–3.85; P=0.006) and leflunomide (LET) (CR/PR; RR, 2.64; 95% CI, 1.80–3.86; P<0.00001) resulted in increased partial or complete proteinuria remission. Cyclophosphamide (CTX) resulted in a higher reduction of urinary protein excretion than steroids (SMD, 0.91; 95% CI, 0.41–1.41; P=0.0004)). Compared to CTX, LET showed higher effectiveness (CR/PR; RR, 2.01; 95% CI, 1.08–3.75; P=0.03) with a lower incidence of adverse events. The present meta-analysis, which is based on IgAN patients, suggested that AZA, MMF, LET and CTX are effective in reducing proteinuria levels, with acceptable side effects. Therefore, immunosuppressive agents may be considered promising therapeutic agents for the treatment of IgAN and should be investigated further in large sample size, high-quality studies.