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

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 predicting CKD progression and prognosis. Furthermore, when sufficient information was provided, the dose-response correlation was studied.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.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 cardiovascular 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 concentration range of approximately 0-3 ng/mL were indicated by the dose-response curve.Circulating GDF-15 independently predicted CKD progression and worse prognosis; however, the predicted correlations may fall into a specific range of GDF-15 concentrations.