Association of growth differentiation factor-15 with renal disease outcomes and all-cause death in type 1 and type 2 diabetic patients: a meta-analysis

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OBJECTIVE: The association of growth differentiation factor-15 (GDF-15) with renal disease outcomes is conflicting and its linkage with all-cause death is uncertain in diabetic patients. Hence, this meta-analysis analyzed associations of GDF-15 with poor renal outcomes, diabetic kidney disease (DKD), and all-cause death in diabetic patients. METHODS: Web of Science, PubMed, and EMBASE databases were searched until October 2025. Randomized controlled trials (RCTs) and non-RCTs (observational studies, and cross-sectional studies) that reported associations between GDF-15 and renal disease outcomes or all-cause death with an extractable hazard ratio (HR) or odds ratio (OR) and 95% confidence interval (CI) were eligible and separated for meta-analysis. Poor renal outcomes were defined as end-stage renal disease, doubling of the serum creatinine level, > 30% estimated glomerular filtration rate decline, and/or renal death. Quality of studies was assessed using Risk Of Bias In Nonrandomized Studies-of Interventions for observational studies, Cochrane ROB tool for RCTs, and Joanna Briggs Institute criterion for cross-sectional studies. RESULTS: Two RCTs with 4,410 diabetic patients and 6 non-RCTs with 7,341 diabetic patients were included. Pooled analyses showed that higher GDF-15 was related to increased risks of poor renal outcomes [2 RCTs, N = 4,410, HR (95% CI) = 1.549 (1.226, 1.957); 4 non-RCTs, N = 4,356, HR (95% CI): 1.669 (1.419, 1.963)], DKD in patients without previous nephropathy [6 non-RCTs, N = 3,623, OR (95% CI): 1.223 (1.054, 1.418)], and all-cause death [4 non-RTCTs, N = 4,356, HR (95% CI): 2.168 (1.769, 2.656)]. The included studies were at low or moderate risk of bias. CONCLUSION: Higher GDF-15 may be related to increased risks of poor renal outcomes and all-cause death in diabetic patients, as well as an elevated DKD risk in patients without previous nephropathy, but further studies are needed to confirm these findings. PROSPERO Registration Number: CRD420251165958. CLINICAL TRIAL NUMBER: Not applicable.

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