Circulating GDF-15 in relation to the progression and prognosis of chronic kidney disease: A systematic review and dose-response meta-analysis

Background: Patients with chronic kidney disease (CKD) typically exhibit circulating growth differentiation factor-15 (GDF-15) at high levels. This meta-analysis aimed to evaluate the potential value of GDF-15 in pre-dicting CKD progression and prognosis. Furthermore, when sufficient information was provided, the dose -response correlation was studied. Methods: Studies were searched in Web of Science, Embase, and PubMed from inception until November 2022. By using random-or fixed-effects models, the pooled effect size was estimated in accordance with heterogeneity in existing research. Results: This study covered 14 studies from 12 articles with 7813 subjects participating in the research. CKD patients in the top GDF-15 tertile had notably higher risks of CKD progression (HR 2.60, 95% CI 2.06-3.27), all -cause mortality (HR 2.05, 95% CI 1.44-2.92), cardiovascular mortality (HR 2.82, 95% CI 1.85-4.30), and car-diovascular events (HR 2.74, 95% CI 2.21-3.40), as compared to CKD patients in the bottom tertile. In the dose -response study, the risks for CKD progression, all-cause death, cardiovascular death, and cardiovascular events were increased by 31% (HR 1.31, 95% CI 1.06-1.61), 44% (HR 1.44, 95% CI 1.08-1.92), 67% (HR 1.67, 95% CI 1.37-2.03), and 55% (HR 1.55, 95% CI 1.31-1.83), respectively, with per 1 ng/mL increase in GDF-15. The positive linear correlations between GDF-15 and CKD progression and prognosis in a certain GDF-15 concen-tration range of approximately 0-3 ng/mL were indicated by the dose-response curve. Conclusions: Circulating GDF-15 independently predicted CKD progression and worse prognosis; however, the predicted correlations may fall into a specific range of GDF-15 concentrations.