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Efficacy and Safety of Immunosuppressive Treatment in IgA Nephropathy: A Meta-analysis of Randomized Controlled Trials

By Zheng Zhang, Yue Yang, Shi-min Jiang, Wen-ge Li

Posted 08 Jan 2019
bioRxiv DOI: 10.1101/515023 (published DOI: 10.1186/s12882-019-1519-3)

Background There is some controversy regarding the efficacy and safety of immunosuppressive agents for the treatment of kidney diseases. The recent STOP-IgAN and TESTING studies have focused attention on the application of immunosuppressive agents in IgA nephropathy (IgAN). This study investigated the benefits and risks of immunosuppressive agents in IgAN. Methods MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with any other non-immunosuppressive agents for treating IgAN. A meta-analysis was performed on the outcomes of proteinuria, creatinine (Cr), estimated glomerular filtration rate (eGFR), and adverse events in patients with IgAN, and trial sequential analyses were also performed for outcomes. Results Twenty-nine RCTs (1957 patients) that met our inclusion criteria were identified. Steroids (weighted mean difference [WMD] –0.70, 95% confidence interval [CI] –1.2 to –0.20), non-steroidal immunosuppressive agents (NSI) (WMD –0. 43, 95% CI –0.55 to –0.31), and combined steroidal and non-steroidal immunosuppressive agents (S&NSI) (WMD –1.46, 95% CI –2.13 to –0.79) therapy significantly reduced proteinuria levels in patients with IgAN. Steroid treatment significantly reduced the risk for end-stage renal disease (ESRD) (relative risk [RR] 0.39, CI 0.19 to 0.79). The immunosuppressive therapy group showed significant increases in gastrointestinal, hematological, dermatological, and genitourinary side effects, as well as impaired glucose tolerance or diabetes. Hyperkalemia was more common in the control group. Conclusion Immunosuppressive therapy can significantly reduce proteinuria and ESRD risk in patients with IgAN, but with a concomitant increase in adverse reactions. Therefore, care is required in the application of immunosuppressive agents in IgAN. The protocol and registration information are available at http://www.crd.york.ac.uk/PROSPERO/ (CRD42018096197).

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