Urine albumin to creatinine ratio: A marker of early endothelial dysfunction in youth

Authors: BARTZ, SARA - Children'S Nutrition Research Center (CNRC); CALDAS, MARIA - Children'S Nutrition Research Center (CNRC); TOMSA, ANCA - Children'S Nutrition Research Center (CNRC); KRISHNAMURTHY, RAMKUMAR - Texas Children'S Hospital; BACHA, FIDA - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/8/2015
Publication Date: 9/1/2015
Citation: Bartz, S.K., Caldas, M.C., Tomsa, A., Krishnamurthy, R., Bacha, F. 2015. Urine albumin to creatinine ratio: A marker of early endothelial dysfunction in youth. Journal of Clinical Endocrinology and Metabolism. 100(9):3393-3399.

Interpretive Summary: Urine albumin to creatinine ratio (UACR), reflects the amount of albumin spilled in the urine, is an early sign of kidney dysfunction particularly in individuals with obesity and diabetes. UACR has also been associated with vascular inflammation. This measurement was found to be a useful predictor of cardiovascular (CV) events in adults. We investigated whether increased urine albumin excretion (UACR), is related to insulin resistance and to endothelial function, a marker of early atherosclerosis, in adolescents. We demonstrated that UACR is indeed an early marker of endothelial dysfunction in youth, independent of impairment in glucose metabolism. Our findings suggest that endothelial dysfunction may mediate the link between obesity related insulin resistance and early microalbuminuria. UACR is an easily obtainable measure, suitable for clinical studies aiming at assessment of CV disease risk in children and may constitute a biomarker for intervention studies that target changes in vascular function and cardiovascular disease risk.

Technical Abstract: The urine albumin-to-creatinine ratio (UACR) is a useful predictor of cardiovascular (CV) events in adults. Its relationship to vascular function in children is not clear. We investigated whether UACR was related to insulin resistance and endothelial function, a marker of subclinical atherosclerosis, in adolescents across the spectrum of glucose regulation. Participants were 58 adolescents: 13 normal weight (NW), 25 overweight with normal glucose tolerance (OW-NGT), and 20 overweight with prediabetes (OW-PreD). Interventions included oral glucose tolerance test, hyperinsulinemic-euglycemic clamp with determination of insulin sensitivity (IS), endothelial function assessment by peripheral arterial tonometry determination of the reactive hyperemia index (RHI), body composition (dual-energy x-ray absorptiometry), and abdominal fat distribution (magnetic resonance imaging). Fasting UACR was determined. The 3 groups did not differ with respect to age, sex, or Tanner stage. The NW group had significantly lower percent body fat, higher IS (10.4 +/- 0.9, 3.5 +/- 0.6, and 2.1 +/- 0.2 mg/kg/min per uU/mL; P < .001), and higher RHI (1.84 +/- 0.1, 1.56 +/- 0.1, and 1.56 +/- 0.1, P = .04) than the OW-NGT and OW-PreD groups, respectively. lnUACR was related to percent body fat (r = 0.4, P = .001), RHI (r = -0.33, p = .01), and IS (r = -0.27, P = .043). In multiple regression analysis with lnUACR as the dependent variable and RHI, percent body fat, age, sex, race, systolic blood pressure, cholesterol, glycated hemoglobin, and IS as independent variables, RHI (beta = -0.3, P = .045) and sex (beta= 0.31, P = .06) contributed to the variance in UACR (R**2 = 0.35, P = .02). UACR is an early marker of endothelial dysfunction in youth, independent of glycemia. Endothelial dysfunction may mediate the link between obesity-related insulin resistance and early microalbuminuria.