Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT)

Background Urinary markers were tested as predictors of macroalbuminuria or microalbuminuria in patients with type 1 diabetes. Study Design Nested case-control of participants in the Diabetes Control and Complications Trial (DCCT). Setting & Participants 87 cases of microalbuminuria were matched to 174 controls in a 1:2 ratio, while 4 cases were matched to 4 controls in a 1:1 ratio, resulting in 91 cases and 178 controls for microalbuminuria. 55 cases of macroalbuminuria were matched to 110 controls in a 1:2 ratio. Controls were free of micro-/macroalbuminuria when their matching case first developed micro-/macroalbuminuria. Predictors Urinary N -acetyl-β- d -glucosaminidase (NAG), pentosidine, advanced glycation end product (AGE) fluorescence, and albumin excretion rate (AER). Outcomes Incident microalbuminuria (2 consecutive annual AERs > 40 but ≤ 300 mg/d) or macroalbuminuria (AER > 300 mg/d). Measurements Stored urine samples from DCCT entry and 1-9 years later when macro- or microalbuminuria occurred were measured for the lysosomal enzyme NAG and the AGE pentosidine and AGE fluorescence. AER and adjustor variables were obtained from the DCCT. Results Submicroalbuminuric AER levels at baseline independently predicted microalbuminuria (adjusted OR, 1.83; P