Efficacy and Safety of Immunosuppressive Monotherapy Agents for IgA Nephropathy: A Network Meta-Analysis

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.

Efficacy and safety of tacrolimus-based treatment for non-rapidly progressive IgA nephropathy

“…For example, TAC was reported to effectively decrease proteinuria in a prospective cohort study of 50 patients with IgAN (24 hUTP ≥ 2.0 g, estimated GFR ≥50 mL/min/1.73 m 2 ) (Yan et al, 2022) and a retrospective observational study of 34 patients with refractory IgAN (Hu et al, 2018). A network meta-analysis revealed that TAC improved the remission of proteinuria (RR = 3.67; 95% CI = 1.06-12.63) in patients with IgAN better than that in patients receiving supportive care alone (Han et al, 2020), and the proteinuria remission rate of TAC treatment showed no significant differences (p = 0.7) with full-dose GCs (Yan et al, 2022). In our study, TAC treatment led to a significantly higher Frontiers in Pharmacology frontiersin.org decrease in proteinuria at 3, 9 and 12 months and significantly higher total remission and CR rates than non-TAC treatment (including immunosuppressive agents CTX and MMF), which has not been reported in previous studies.…”

Recent advances of gut microbiota in chronic kidney disease patients

“…IgA nephropathy is usually considered to be an immune complex-induced or polymerized IgA1-induced glomerulonephritis [57][58][59][60]. Zhong et al [61] reported that although α-diversity exhibited no significant differences in taxon richness and evenness, there was a clear separation in the composition of gut microbiota between patients with IgA nephropathy and healthy controls, indicating that the diversity of gut microbiota was altered in patients with IgA nephropathy.…”

Literature Review: The Efficacy of Glucocorticoids in IgA Nephropathy Patients

“…In addition, long-term steroid therapy has higher efficacy than short-term therapy and standard therapy in reducing ESRD risks, urinary protein excretion, and urinary protein excretion [18]. Corticosteroids were also found to significantly improve clinical remission rates and the risk of ESRD compared to supportive management alone [20]. Another meta-analysis also demonstrated superior efficacy of corticosteroid compared to standard therapy, particularly impairment of renal function occurs in patients with hypertension or older people [21].…”

“…Similarly, steroids treatment has statistically significant impacts in preventing the decline in renal function, even though this result was not altered by steroids type [22]. Nonetheless, corticosteroids use was linked with several high-risk adverse events [19][20][21]. For instance, diabetes mellitus or impaired glucose intolerance, high blood pressure, gastrointestinal bleeding, cushingoid features, insomnia, headache, increased weight, and significant infection [19][20][21].…”

“…Nonetheless, corticosteroids use was linked with several high-risk adverse events [19][20][21]. For instance, diabetes mellitus or impaired glucose intolerance, high blood pressure, gastrointestinal bleeding, cushingoid features, insomnia, headache, increased weight, and significant infection [19][20][21]. The frequency of gastrointestinal symptoms, such as gastrointestinal bleeding, enhanced appetite, and dyspepsia, represent vital antagonistic impacts, and these effects increased by 105% within the steroid group [22].…”