Circulating metabolites improve the prediction of renal impairment in patients with type 2 diabetes

INTRODUCTION: Low glomerular filtration rate (GFR) is a leading cause of reduced lifespan in type 2 diabetes. Unravelling biomarkers capable to identify high-risk patients can help tackle this burden. We investigated the association between 188 serum metabolites and kidney function in type 2 diabetes and then whether the associated metabolites improve two established clinical models for predicting GFR decline in these patients. RESEARCH DESIGN AND METHODS: Two cohorts comprising 849 individuals with type 2 diabetes (discovery and validation samples) and a follow-up study of 575 patients with estimated GFR (eGFR) decline were analyzed. RESULTS: Ten metabolites were independently associated with low eGFR in the discovery sample, with nine of them being confirmed also in the validation sample (ORs range 1.3–2.4 per 1SD, p values range 1.9×10(−2)–2.5×10(−9)). Of these, five metabolites were also associated with eGFR decline (ie, tiglylcarnitine, decadienylcarnitine, total dimethylarginine, decenoylcarnitine and kynurenine) (β range −0.11 to −0.19, p values range 4.8×10(−2) to 3.0×10(−3)). Indeed, tiglylcarnitine and kynurenine, which captured all the information of the other three markers, improved discrimination and reclassification (all p<0.01) of two clinical prediction models of GFR decline in people with diabetes. CONCLUSIONS: Further studies are needed to validate our findings in larger cohorts of different clinical, environmental and genetic background.