Effects of anti-inflammatory agents on clinical outcomes in people with chronic kidney disease: a systematic review and meta-analysis of randomized control trials

Background: Chronic kidney disease (CKD) is characterized by chronic inflammation, which is strongly linked to risk of cardiovascular disease. Anti-inflammatory agents present a novel strategy to reduce the burden of cardiovascular disease in people with CKD, but their effects on clinical outcomes are uncertain. Methods: A systematic review and meta-analysis was performed to assess the efficacy and safety of anti-inflammatory agents in CKD (PROSPERO CRD42021238755). Medline, Embase and Cochrane databases were searched up to 8 October 2024 for randomized controlled trials of anti-inflammatory agents in CKD with at least 100 patient-years follow-up per treatment arm. The primary study outcome was major adverse cardiovascular events (MACE; defined as myocardial infarction, stroke or cardiovascular death). Other outcomes included CKD progression, malignancy and infection. Results: Nine trials of 12 042 participants and six different anti-inflammatory classes were identified. Overall, anti-inflammatory agents did not reduce the risk of MACE [risk ratio (RR) 1.01, 95% confidence interval (CI) 0.81-1.24], although there was significant heterogeneity across studies (P-heterogeneity =. 001; I² = 72%). Anti-inflammatory agents did not have a clear effect on the composite kidney outcome (RR 0.82, 95% CI 0.55-1.22), although there were few events and some trials suggested improvements in the rate of decline in kidney function. Infections were increased with anti-inflammatory agents compared with placebo (RR 1.35, 95% CI 1.01-1.82). Conclusion: There is currently insufficient evidence to support the use of anti-inflammatory agents to reduce cardiovascular risk or CKD progression in people with CKD, and further dedicated studies in this population are warranted. The potential increased risk of infection with anti-inflammatory agents is an important consideration in the evaluation of these therapies in CKD.