Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT).

Abstract

OBJECTIVE Baseline data from the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-creatinine ratios (ACR) in the normal range at age 10-16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR tertile remained associated with DN and CVD risk over the 2-4 year AdDIT study. RESEARCH DESIGN AND METHODS 150 adolescents (mean[SD] age: 14.1[1.6]years) with baseline ACR in the upper tertile (high-ACR group) recruited to the AdDIT trial, who remained untreated, and 396 (age: 14.3[1.6]years) with ACR in the middle and lower tertiles (low-ACR group), who completed the parallel AdDIT observational study, were evaluated prospectively with assessments of ACR, renal and CVD markers, combined with carotid intima-media thickness (cIMT) at baseline and end of study. RESULTS After a median follow-up of 3.9 years, the cumulative incidence of microalbuminuria was 16.3% in the high- vs 5.5% in the low-ACR group (log-rank p<0.001). Cox models showed independent contributions of the high-ACR group (hazard ratio [95%CI]: 4.29[2.08; 8.85]) and HbA1c (1.37[1.10; 1.72]) to microalbuminuria risk. cIMT change from baseline was significantly greater in the high vs low-ACR group (mean difference: 0.010[0.079]mm, p=0.006). Changes in estimated GFR, systolic blood pressure and hs-C-Reactive Protein were also significantly greater in the high-ACR group (p<0.05). CONCLUSIONS ACR at the higher end of the normal range at the age of 10-16 years is associated with an increased risk of progression to microalbuminuria and future CVD risk, independently of HbA1c.