GDF-15 and FGF-23 are associated with mortality in type 2 diabetic patients with microalbuminuria

Background and aims: We evaluated two biomarkers (growth differentiation factor 15 (GDF-15) and (FGF-23) reflecting different aspects of renal pathophysiology as determinants of decline in estimated glomerular filtration rate (eGFR), incident cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D) and microalbuminuria, but without clinical coronary artery disease. Materials and methods: Prospective study including 200 patients. GDF-15 and FGF-23 were measured at baseline and were available in 191 patients. Adjusted Cox models included sex, age, LDL cholesterol, smoking, HbA1c, creatinine, systolic blood pressure and urine albumin excretion rate (UAER). A decline in eGFR of >30%, which has recently been suggested as a valid renal outcome, at any time point during follow-up was the predefined endpoint of CKD progression. Hazard ratios (HR) are provided per 1 SD increment of log-transformed values of the urinary biomarkers. Results: Patients were (± SD) 59 ± 9 years old, eGFR 91.1 ± 18.3 ml/min/1.73m2 and UAER (IQR) 103 (39-230) mg/24-h. During a median 6.1 years follow-up, there were 40 incident CVD events and 26 deaths and a total of 42 patients reached the predefined CKD progression endpoint after 4.9 years (median). Higher GDF-15 was a determinant of decline in eGFR >30% in unadjusted (HR (95% CI) 1.7 (1.3-2.4); p=0.001) and adjusted (HR 1.7 (1.1-2.5); p=0.018) models, a predictor of CVD in the unadjusted model (HR 1.4 (1.0-1.9); p=0.034) but not in the adjusted model (HR 1.3 (0.9-1.8); p=0.25) and of all-cause mortality in unadjusted (HR 1.8 (1.3-2.6); p<0.001) and adjusted (HR 1.9 (1.2-2.9); p=0.003) models. Higher FGF-23 was not associated with decline in eGFR >30% or CVD, but was associated with all-cause mortality in unadjusted (HR 1.5 (1.1-2.0); p=0.010) and adjusted (HR 1.6 (1.1-2.2); p=0.011) models. Conclusion: In patients with T2D and microalbuminuria, GDF-15 was independently associated with decline in kidney function and all-cause mortality, and higher FGF-23 was associated with all-cause mortality.