Serum uric acid to creatinine ratio as marker of early vascular damage and renal tubular injury in non-albuminuric diabetic kidney disease

Purpose: Serum uric acid to creatinine ratio (SUA/sCr) has emerged as potential biomarker for non-albuminuric diabetic kidney disease (NA-DKD), a recently recognized high-prevalence DKD phenotype. However, the relationship between SUA/sCr and cardiovascular and renal injury profile in this population is not well established. This study aimed to evaluate SUA/sCr across the spectrum of DKD, particularly focusing on NA-DKD, and to test its association with subclinical vascular damage, urinary biomarkers and ultrasound features of kidney damage. Methods: Presence of carotid plaques, pulse wave velocity (PWV), renal resistive index (RRI), and urinary biomarkers of tubular injury were assessed in 207 individuals with type 2 diabetes. Participants were split based on estimated-glomerular-filtration-rate (eGFR) and urinary-albumin-to-creatinine-ratio (UACR) into four groups: controls (UACR < 30 mg/g, eGFR ≥ 60 ml/min/1.73m2), A-DKD (Albuminuric-DKD; UACR ≥ 30 mg/g, eGFR ≥ 60 ml/min/1.73m2), NA-DKD (Non-albuminuric-DKD; UACR < 30 mg/g, eGFR < 60 ml/min/1.73m2), A&L-DKD (Albuminuric-and-Low-eGFR-DKD; UACR ≥ 30 mg/g, eGFR < 60 ml/min/1.73m2). Results: Participants with NA-DKD showed a lower SUA/sCr than those with A-DKD and controls (4.71 ± 1.52 vs 6.06 ± 1.70 vs 6.67 ± 1.87, both P < 0.0001). A lower SUA/sCr was independently correlated with NA-DKD (β = -1.63, P < 0.0001) and A&L-DKD (β = -2.01, P < 0.0001). SUA/sCr was inversely and independently associated with urinary β2-microglobulin (β = -0.21, P = 0.0082). Moreover, lower SUA/sCr was associated with PWV > 10 m/s (OR 0.77, 95%CI 0.63–0.95, P = 0.014), the presence of carotid plaques (OR 0.78, 95%CI 0.63–0.96, P = 0.020), and higher RRI (β = -0.18, P = 0.0082). Conclusion: In T2D, lower SUA/sCr correlated with NA-DKD, but not with A-DKD. Lower SUA/sCr was associated with subclinical vascular and tubular damage. Future studies are needed to test SUA/sCr as candidate biomarker to improve DKD risk stratification.