Dickkopf-3 (Dkk3) and the progression of diabetic kidney disease in primary health care

Abstract

Accurate prediction of diabetic kidney disease progression is challenging, but mandatory. Urinary Dickkopf-3 (uDKK3), a tubular, epithelial-derived glycoprotein and marker of tubular injury, is a promising biomarker for kidney function decline. We explored the clinical utility of uDKK3 to predict kidney function decline and adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM) in a primary health care setting. In this cohort study, 3,232 patients with T2DM were analyzed. The primary end point was a composite of a sustained estimated glomerular filtration rate (eGFR) decline $40%; a sustained increase in albuminuria of at least 30%, including a transition in albuminuria class; progression to end-stage kidney disease; and death from kidney failure. After adjustment for confounding variables, uDKK3 values >200 pg/mg creatinine were associated with a higher risk of the composite kidney end point during a median follow-up of 4.26 years. Furthermore, uDKK3 improved the prediction of the 1-year eGFR decline on top of albuminuria. Individuals with high uDKK3 levels also had an increased risk for adverse cardiovascular events and all-cause mortality. uDKK3 identifies patients with T2DM at high risk for kidney function decline on top of established biomarkers (albuminuria and eGFR). In primary care, uDKK3 may help to identify high-risk patients who might benefit from intensified treatment and/or referrals to specialists.