Validation of a protein biomarker test for predicting renal decline in type 2 diabetes: The Fremantle Diabetes Study Phase II

Aims To validate the prognostic utility of a novel plasma biomarker panel, PromarkerD, for predicting renal decline in an independent cohort of people with type 2 diabetes. Methods Models for predicting rapid estimated glomerular filtration rate (eGFR) decline defined as i) incident diabetic kidney disease (DKD), ii) eGFR decline ≥30% over four years, and iii) annual eGFR decline ≥5 mL/min/1.73 m2 were applied to 447 participants from the longitudinal observational Fremantle Diabetes Study Phase II. Model performance was assessed using discrimination and calibration. Results During 4.2 ± 0.3 years of follow-up, 5–10% of participants experienced a rapid decline in eGFR. A consensus model comprising apolipoprotein A-IV (apoA4), CD5 antigen-like (CD5L), insulin-like growth factor–binding protein 3 (IGFBP3), age, serum HDL-cholesterol and eGFR showed the best performance for predicting incident DKD (AUC = 0.88 (95% CI 0.84–0.93)); calibration Chi-squared = 5.6, P = 0.78). At the optimal score cut-off, this model provided 86% sensitivity, 78% specificity, 30% positive predictive value and 98% negative predictive value for four-year risk of developing DKD. Conclusions The combination of readily available clinical and laboratory features and the PromarkerD biomarkers (apoA4, CD5L, IGFBP3) proved an accurate prognostic test for future renal decline in an independent validation cohort of people with type 2 diabetes.