Growth-Differentiation Factor 15 Predicts Worsening of Albuminuria in Patients With Type 2 Diabetes

Abstract

OBJECTIVE Development of micro- or macroalbuminuria is associated with increased risk of cardiorenal complications, particularly in diabetes. For prevention of transition to micro- or macroalbuminuria, more accurate prediction markers on top of classical risk markers are needed. We studied a promising new marker, growth-differentiation factor (GDF)-15, to predict transition to increasing stage of albuminuria in type 2 diabetes mellitus (T2DM). In addition, we looked at the GDF-15 potential in nondiabetic subjects with hypertension (HT). RESEARCH DESIGN AND METHODS Case and control subjects were selected from the PREVEND cohort, a large (n = 8,592), prospective general population study on the natural course of albuminuria, with >10 years of follow-up and repeated albuminuria measurements. We found 24 T2DM and 50 HT case subjects transitioning from normo- to macroalbuminuria and 9 T2DM and 25 HT case subjects transitioning from micro- to macroalbuminuria (average follow-up 2.8 years). Control subjects with stable albuminuria were pair matched for age, sex, albuminuria status, and diabetes duration. GDF-15 was measured in samples prior to albuminuria transition. RESULTS Prior to transition, GDF-15 was significantly higher in case subjects with T2DM than in control subjects (median [IQR] 1,288 pg/mL [885–1,546] vs. 948 pg/mL [660–1,016], P < 0.001). The odds ratio for transition in albuminuria increased significantly per SD of GDF-15 (2.9 [95% CI 1.1–7.5], P = 0.03). GDF-15 also improved prediction of albuminuria transition, with significant increases in C statistic (from 0.87 to 0.92, P = 0.03) and integrated discrimination improvement (0.148, P = 0.001). In HT, GDF-15 was also independently associated with transition in albuminuria stage (2.0 [1.1–3.5], P = 0.02) and improved prediction significantly. CONCLUSIONS We identified GDF-15 as a clinically valuable marker for predicting transition in albuminuria stage in T2DM beyond conventional risk markers. These findings were confirmed in nondiabetic HT subjects.