Abstract
Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach. Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine. Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17–1.93), MMF (RR 2.05, 95% CI 1.15–3.65), TAC (RR 3.67, 95% CI 1.06–12.63), and HCQ (RR 3.25, 95% CI 1.05–10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12–0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37–6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40–4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration. Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.
Highlights
Immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases and a leading cause of end-stage renal disease (ESRD) worldwide (Rodrigues et al, 2017)
The results showed that patients with IgAN receiving steroids had higher risks of Serious adverse event (SAE) than the control group (RR 2.90, 95% Confidence interval (CI) 1.37–6.13) and similar results were observed in the pairwise metaanalysis (RR 4.27, 95% CI 1.79–10.18)
The use of mycophenolate mofetil (MMF) in IgAN is still controversial—this study suggested higher clinical remission in MMF monotherapy groups but no beneficial effect when the follow-up time was more than 2 years in clinical remission, ESRD, or serum creatinine level
Summary
Immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases and a leading cause of end-stage renal disease (ESRD) worldwide (Rodrigues et al, 2017). Immunosuppressive monotherapy is an optional treatment for IgAN and includes calcineurin inhibitors and mycophenolate mofetil (MMF) (Zhang and Zhang, 2018). Previous pairwise meta-analyses indicated that calcineurin inhibitors and MMF could be effective in the treatment of IgAN (Peng et al, 2016; Du et al, 2017), their independent effects are controversial and their relative effects among different immunosuppressive agents are unknown. As network meta-analysis (NMA) can compare the effects of all these drugs under a coherent framework, in addition to the probability of optimal treatment, we conducted an NMA to determine the effect of monotherapy for IgAN using different immunosuppressive agents and, if possible, predicted the best candidate for treatment. The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach
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