Off-label Use of Mycophenolate Mofetil in Immunoglobulin A Nephropathy: A Systematic Review and Meta-analysis.

Abstract

Introduction: Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety.

Methods: We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause.

Results: Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (RR, 0.32; 95%CI, 0.13 to 0.77), reducing proteinuria (RR, 1.41; 95%CI, 1.22 to 1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14 to 0.72). No significant differences were detected in the incidence of ESRD (RR: 0.87, 95% CI: 0.38 to 2.03), or progression of chronic kidney disease (RR, 1.01; 95%CI, 0.22 to 4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95%CI, 1.21 to 4.00).

Conclusion: MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still needs need further cross-regional and cross-ethnical verification.