Adiponectin and All-Cause Mortality in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Background/Objectives: Elevated levels of adiponectin in chronic kidney disease (CKD) have been paradoxically associated with increased mortality. This meta-analysis aimed to evaluate the association between circulating adiponectin levels and all-cause mortality in patients with CKD, in total and various subgroups. Methods: We systematically searched PubMed, Embase, and Cochrane Library from their inception to December 2024 for studies examining baseline adiponectin levels and observed mortality outcomes in patients with CKD. Studies were included if they evaluated CKD stages 2-5 patients, measured baseline circulating adiponectin levels, and reported hazard ratios (HRs) for all-cause mortality. We excluded non-original research, studies of acute conditions, normal kidney function, kidney transplantation, and those using log-transformed or standardized HRs. HRs with a 95% confidence interval (CI) for all-cause mortality risk per 1 µg/mL increase in adiponectin were extracted and analyzed using the Comprehensive Meta-Analysis Version 4. Study quality was assessed using the Newcastle-Ottawa Scale. Results: Twelve studies with 2523 subjects were included. The pooled unadjusted HR was 1.003 (95% CI: 0.981-1.025) using a random-effects model (I² = 79%). Subgroup analyses demonstrated increased mortality risk with elevated adiponectin levels in non-Asia (HR 1.021 [95% CI: 1.006-1.037], p = 0.006), studies with female proportion <47% (HR 1.021 [95% CI: 1.009-1.033], p < 0.001), and studies with body mass index ≥25 kg/m² (HR 1.023 [95% CI: 1.008-1.038], p = 0.003). In contrast, higher adiponectin levels were associated with decreased mortality risk in the peritoneal dialysis group (HR 0.956 [95% CI: 0.934-0.979], p < 0.001) and female proportion ≥47% group (HR 0.929 [95% CI: 0.874-0.988], p = 0.019). Discussion/Conclusions: This meta-analysis revealed that elevated adiponectin levels have varying associations with the risk of all-cause mortality across CKD patient subgroups. These findings suggest that the prognostic value of adiponectin levels in CKD may be modulated by demographic and clinical factors. Limitations include poor generalizability with underrepresentation of early-stage CKD. This research received no external funding and was not registered.