Nonproteinuric progressive diabetic kidney disease.

We will summarize recent epidemiological observations on the risk for overt diabetic kidney disease (DKD) in nonproteinuric patients, will focus on novel studies based on a proteomic biomarker of DKD and will discuss the possibility of preventing the progression of DKD in nonproteinuric patients by sodium glucose transporter 2 (SGLT2) inhibitors. Although less frequently than in type 2 diabetes, DKD may develop also in nonproteinuric type 1 diabetes. However, the progression rate to kidney failure in nonproteinuric diabetic people is much lower than in proteinuric ones. A new proteomic biomarker, the chronic kidney disease (CKD)273, reliably predicts the risk of incident micro and macroalbuminuria and of CKD in nonalbuminuric diabetic people. SGLT2 inhibition markedly reduces albuminuria in macro and microalbuminuric patients and discernibly mitigates albumin excretion also in those with albuminuria in the normal range. Studies focusing on risk factors for DKD in nonproteinuric patients are a clinical research priority. The CKD273 classifier is a promising biomarker for the early identification of nonproteinuric patients at high risk for progressive DKD. Empagliflozin and SGLT2 inhibitors may have a favorable impact on the progression of DKD in nonalbuminuric diabetic people, a hypothesis to be tested in specific clinical trials.