Serum Uric Acid (SUA), Urinary Albumin Excretion (UAE), and Hypertension (HTN) in Adolescents with Type 2 Diabetes (T2D) in the TODAY Study

Abstract

Elevated SUA is increasingly recognized as a risk factor for kidney disease in adults with diabetes, yet there are limited data in youth. We hypothesized that elevated SUA would predict development of elevated UAE and HTN over time in teens with T2D. Serum creatinine, cystatin C, SUA, and urine albumin to creatinine ratio (ACR) were assessed in 539 youth, ages 12-17 with T2D duration <2 years at baseline in the TODAY study. Estimated GFR (eGFR) was calculated using creatinine and cystatin C. HTN was defined as systolic (SBP) or diastolic blood pressure (DBP) ≥130/80 mm Hg and elevated albumin excretion (UAE) as ACR ≥30mg/g. Mean arterial pressure (MAP) was calculated ([SBP + 2 (DBP)]/3). Generalized estimating equations and Cox proportional hazard models evaluated the relationship between SUA and outcome variables longitudinally over 7 years, adjusting for age, sex, race/ethnicity, BMI, A1c, eGFR, ACEi/ARB use, and TODAY treatment group assignment. Hyperuricemia (≥6.8 mg/dL) was present in 25.6%, HTN in 18.7%, and elevated UAE in 6.1% at baseline, and boys had higher baseline SUA than girls (6.7±1.4 vs. 5.4±1.2 mg/dl, p<0.0001). Over 7 years, 37.4% developed HTN and 18.0% elevated UAE. Baseline SUA correlated with increase in SBP (β±SE: 0.66±0.16, p<.0001), DBP (0.37±0.15, p=0.01), MAP (0.47±0.14, p=0.001), and log UAE (0.05±0.02, p=0.01) over time in multivariable models. Higher baseline SUA increased risk of incident HTN (HR: 1.20, 95% CI 1.05-1.36, p=0.007, per 1 mg/dL increase in SUA) and incident elevated UAE (HR: 1.23, 95% CI 1.03-1.47, p=0.02, per 1 mg/dL increase in SUA) in fully adjusted models. Hyperuricemia was common in youth with T2D; higher baseline SUA independently increased risk for onset of HTN and elevated UAE over 7 years. Therapies lowering SUA may hold promise to impede development of diabetic kidney disease and HTN in T2D youth.