EVOLUTION OF RENAL-FUNCTION ABNORMALITIES IN THE DB DB MOUSE THAT PARALLELS THE DEVELOPMENT OF HUMAN DIABETIC NEPHROPATHY/

The db/db mutant mouse is a rodent model of genetic diabetes that deve lops renal glomerular lesions with striking mesangial matrix accumulat ion by the age of 16 weeks, after 8-10 weeks of sustained hyperglycemi a. However, abnormalities in renal function that antedate or accompany the appearance of these pathologic changes, which resemble those foun d in human diabetes, have not been delineated. We therefore examined r enal function in young db/db mice and their nondiabetic db/m littermat es from the age of 8 through 15 weeks. Serum creatinine and blood urea nitrogen concentrations at the onset of diabetes in db/db mice did no t differ significantly from mean concentrations in db/m controls. An e levated creatinine clearance, due in large part to increased body weig ht, and increased urinary albumin excretion were observed in db/db com pared with db/m mice soon after establishment of sustained hyperglycem ia. A relative reduction in creatinine clearance was demonstrable in d b/db mice at the age of 15 weeks, coincident with the appearance of ov ert compromise in renal function manifested by frank increases in the serum creatinine and blood urea nitrogen. The findings indicate that t he well-documented glomerular pathology in db/db mice is accompanied b y definable alterations in renal function, which are similar in chrono logy and nature to those found in human diabetes.