Measurement of albuminuria and/or estimated glomerular filtration rate (eGFR) has a limited role in predicting future decline in kidney function. Current focus has therefore shifted to novel biomarkers, but it is unclear what benefit these add to current practice. The aim of the present study was to investigate novel circulating protein biomarkers for predicting rapid eGFR decline in a community-based cohort of individuals with type 2 diabetes (T2D).

Mass spectrometry was used to measure biomarkers at study entry in 349 participants with T2D from the Fremantle Diabetes Study Phase II. The prognostic ability of baseline biomarker concentrations to predict rapid eGFR decline over a four year follow-up period, was determined using eGFR trajectories defined by eGFR measured at three time-points. Three linear trajectories of eGFR change (‘low’, ‘medium’ and ‘high’) as well as a 'rapid declining' eGFR trajectory were identified. Multiple logistic regression modelling was used to identify conventional clinical predictors of rapid decline, followed by inclusion of each biomarker. The incremental benefit of biomarkers to clinical prediction models was determined.

Of the 349 participants, 52.4% were male, mean±SD age of 67.0±9.3 years, median [IQR] diabetes duration of 9.0 [3.0-15.3] years, 37.4% had albuminuria and 12.9% had an eGFR<60ml/min/1.73m²/yr. Based on trajectory analysis, 10% of individuals were defined as ‘rapid decliners’ with a mean±SD decrease in eGFR of 2.9±3.0ml/min/1.73m²/yr. The remaining individuals had a mean eGFR decline of 1.6±2.4ml/min/1.73m²/yr. Rapid decliners were older, had longer diabetes duration, lower HDL-cholesterol, and more diuretic use compared to non-rapid decliners. The addition of biomarkers to the clinical model significantly improved model fit, discrimination and risk classification (all P<0.05).

This study identified novel plasma biomarkers that could predict rapid decline in eGFR in patients with T2D independently of known clinical variables. The clinical usefulness of these biomarkers warrants further investigation.