Efficacy and safety of calcineurin inhibitor treatment for IgA nephropathy: a meta-analysis

Background: IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant widely used in organ transplantation. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain. Methods: We performed a systematic literature search using the PubMed, Embase, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature (CBM) and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang) for randomized, controlled trials of CNIs therapy of IgA nephropathy. Complete remission rate (CR) was defined as proteinuria less than 0.5 or 0.3 g/d. Partial remission rate (PR) was defined as proteinuria reduced to at least half of the baseline measurement and an absolute value of >0.5 or 0.3 g/d. Results: Seven relevant trials were conducted with 374 patients enrolled. CNIs plus medium/low-dose steroid had a higher CR (RR = 2.51 [95% CI, 1.25 to 5.04], P = 0.02) compared to therapy with steroid alone or placebo, but were not significant on PR (RR = 0.87 [95% CI, 0.32 to 2.38]; P = 0.78). Also, significant alterations were observed in proteinuria (weighted mean difference, -0.46 g/d,[95% CI:-0.55 to -0.24], P < 0.01) with no differences were found in serum creatinine (SCr) (weighted mean difference, 0.57,95% CI:-4.05 to 5.19; P = 0.78) and estimated glomerular filtration rate (eGFR) (weighted mean difference, 1.13,95% CI:-4.05 to 6.32; P = 0.34) level between the two groups. CNI therapy was associated with an increased risk for adverse events (RR = 2.21,95% CI: 1.52 to 3.21, P < 0.01), such as gastrointestinal and neurological symptoms or hirsutism. Conclusions: CNIs might provide renal protection in patients with IgAN, but at an increased risk of adverse events. Reliably defining the efficacy and safety of CNIs in IgAN requires a high-quality trial with a large sample size.