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Nonproteinuric progressive diabetic kidney disease

Zoccali, Carminea; Mallamaci, Francescaa,b

Current Opinion in Nephrology and Hypertension: May 2019 - Volume 28 - Issue 3 - p 227–232
doi: 10.1097/MNH.0000000000000489

Purpose of review 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.

Recent findings 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.

Summary 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.

aCNR National Research Council Clinical Epidemiology and Pathophysiology of Renal Disease and Hypertension Unit

bRenal and Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy

Correspondence to Carmine Zoccali, FASN FNKF FERA, Nefrologia e CNR, Ospedali Riuniti, Reggio Calabria 89124, Italy. Tel: +0039 3407354062; e-mail:

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