Proteinuria Associated with Hypertension and Diabetes mellitus

Abstract

Proteinuria, a complication of both diabetes mellitus and hypertension, was compared in 2 genetically induced models: insulin-dependent diabetic BB rat (BB), and Okamoto-Aoki spontaneously hypertensive Wistar rats (SHR). Both disease states were clearly distinguished from each other and their respective age-matched controls by analysis of 24-hour urine samples for glucose, urobilinogen, bilirubin and total protein. Then individual protein components between 15,000 and 120,000 daltons were separated by molecular weight and quantitated by laser densitometric analysis. The results indicated that insulin-dependent diabetic BB rats excreted urine having elevation of glucose (100–250 mg/dl), bilirubin (0.05 ± 0.03 mg/dl) and urobilinogen (6.6 ± 3.8 Ehrlich units/dl) in contrast to all age-matched SHR and normotensive Wistar-Kyoto (WKY) and nondiabetic controls, which excreted urine having normal urobilinogen and no detectable glucose or bilirubin. Both SHR and insulin-dependent BB rats exhibited proteinuria, urinary protein excretion being increased approximately 4–5 times that of their age-matched controls. BB rats excreted 18.80 ± 2.62 mg protein/day attributed to an increase in albumin and an entire array of proteins between 30,000 and 120,000 daltons not present in controls which primarily excreted proteins below 20,000 daltons. In the SHR, proteinuria did not include an array of proteins; the increase in excreted protein (39.20 ± 16 mg/day) was primarily attributed to albumin and another protein having a higher molecular weight. The SHR urinary proteins were similar to proteins excreted by streptozocin-induced, noninsulin-dependent diabetic rats treated with the aldose reductase inhibitor sorbinil. If hypertension is associated with diabetic nephropathy, our preclinical results suggest that coadministration of sorbinil with antihypertensive therapy may promote a positive synergistic effect further diminishing proteinuria.