Severe hyperglycemia: a determinant factor for hypofiltration in alloxan diabetic rats

The relationships among glomerular filtration rate, renal plasma flow and extracellular fluid volume were investigated in control and severely hyperglycemic (442+/-33 mg/dl) untreated, alloxan diabetic ats. Most of diabetic animals showed significant lower values of inulin clearance (diabetics, 0.55+/-0.07 ml/min.100 g; controls, 0.97+/-0.04) and p-aminohippurate clearance (diabetics, 2.11+/-0.39 ml/min.100 g; controls, 3.93+/-0.25). Diabetic rats exhibited reduced efficiency in tubular Na(+) reabsorption, increased urinary Na(+) excretion (diabetics, 3.12+/-0.27 mEq/day; controls, 1.25+/-0.14) and diminished values of plasma renin activity (diabetics, 3.34+/-0.44 ng/ml.h; controls, 8.64+/-0.79). Significant negative correlations were found between glycemia and renal hemodynamic variables. Acute overload with glucose further decreased these variables in both groups: inulin clearance in diabetics vs. controls, 0.26+/-0.04 vs. 0.44+/-0.05 ml/min.100 g; p-aminohippuric acid clearance in diabetics vs. controls, 1.09+/-0.20 vs. 1.55+/-0.21 ml/min.100 g. We conclude that chronically hyperglycemic alloxan diabetic rats showed diminished glomerular filtration rates (inulin clearance), renal plasma flow ( p-aminohippurate clearance) and extracellular fluid volume associated with urinary Na(+) losses and alterations in the renin-angiotensin system. Decreased renin-angiotensin system activity might reduce aldosterone secretion, which in turn could result in (successively) urinary sodium loss, extracellular fluid volume contraction and reductions in glomerular filtration and renal plasma flow.