Association of urinary dipeptidyl peptidase 4 activity with clinical outcomes in people with chronic kidney disease

Abstract

Abstract Experimental studies have shown that urinary dipeptidyl peptidase 4 (uDPP4), unlike serum DPP4 (sDPP4) activity, correlates with proteinuria, serum creatinine, and left ventricular (LV) hypertrophy in chronic kidney disease (CKD) models, suggesting a potential role for uDPP4 in CKD progression. This study examined the relationship of uDPP4 and sDPP4 activities with renal, cardiovascular, and metabolic markers, along with mortality and initiation of kidney replacement therapy (KRT) events in individuals with CKD. DPP4 activity was measured in the urine and serum of 426 participants from the Brazilian CKD cohort, PROGREDIR. Participants were stratified into tertiles based on uDPP4 and sDPP4 activities. Multivariable linear regression, Kaplan–Meier analysis, Cox hazards, and competing risk models (cause-specific and Fine–Gray) were used. uDPP4 activity was positively associated with albuminuria, urinary retinol-binding protein 4, LV mass, and type 2 diabetes but inversely associated with body mass index and use of renin-angiotensin system blockers. In contrast, sDPP4 activity correlated only with age and biological sex. Higher uDPP4 activity was associated with a higher incidence rate of all-cause mortality (p < 0.0001). Participants in the second and third uDPP4 activity tertiles had greater mortality risk compared to the lowest tertile (HR 2.03, 95% CI 1.36–3.04 and HR 2.48, 95% CI 1.67–3.67, respectively), even after controlling for potential confounders. No independent association was found between sDPP4 activity and mortality or initiation of KRT. These findings support uDPP4’s involvement in CKD progression and its association with increased mortality risk in individuals with CKD.