Serum dipeptidyl peptidase-4 as an adjunctive biomarker in diabetic kidney disease: A multicentre case-control study from Iraq

Objective: Conventional renal indices for diabetic kidney disease (DKD) have limitations. This study compared serum dipeptidyl peptidase-4 (DPP-4) levels among Iraqi adults with type 2 diabetes mellitus (T2DM) with DKD, T2DM without DKD, and healthy controls, and evaluated its association with DKD. Methods: This multicentre case-control study (November 2025 - April 2026) enrolled 171 participants: T2DM with DKD (n=51), T2DM without DKD (n=60), and healthy controls (n=60). DKD was classified using KDIGO 2024 criteria (eGFR by CKD-EPI 2021, UACR). Serum DPP-4 was quantified by ELISA. Logistic regression and ROC analysis were performed. Results: Serum DPP-4 showed stepwise elevation (controls 203.6±44.4, T2DM 502.6±93.1, DKD 587.2±97.6 ng/mL; all P<0.001). DPP-4 correlated with creatinine (ρ=+0.374), eGFR (ρ=−0.405), CKD stage (ρ=+0.437), and albuminuria (ρ=+0.429). Per 100 ng/mL increase, DPP-4 was independently associated with DKD (aOR 3.00, 95% CI 1.00–8.03; P=0.044), alongside hypertension and diabetes duration. ROC-AUC was 0.779 (cutoff >554 ng/mL; sensitivity 80%, specificity 75%). SGLT-2 inhibitor association with DPP-4 was attenuated after adjustment (P=0.089). Conclusion: Serum DPP-4 was independently associated with DKD and showed modest discriminative ability. It may serve as an adjunctive biomarker in Iraqi patients but should not replace standard indices.