To evaluate the role of glomerular hyperfiltration in the development and progression of
diabetic nephropathy, we performed clearance and histopathologic studies in 24 rats with
streptozocin-induced diabetes after 3 months of diets with different
protein compositions.
Calcium phosphate was added to an 8%
protein diet in group I (nine rats), and
calcium carbonate to a 24%
protein diet in group II (nine rats) to equalize
calcium and
phosphate contents in these diets. Group I and II rats also received small doses of
insulin to reduce the excessive
hyperglycemia induced by the high
sucrose content of the diets. In group III, six rats given an 8%
protein diet, no
calcium, phosphate, or
insulin was added. In groups I and III, low
dietary protein significantly reduced glomerular filtration rate and renal plasma flow per gram of kidney weight as compared with rates observed in group II rats with a higher
protein intake. Features of diabetic glomerulopathy including mesangial hypercellularity and mesangial matrix expansion were also significantly milder in the groups with a
low protein diet. On the other hand, medullary calcification and interstitial changes were most prominent in group I, given
calcium phosphate supplement; the increase in the kidney weight was greater in groups I and II, which received
insulin, than in group III, which did not. It was concluded that
low protein diet significantly ameliorates diabetic glomerulopathy but that supplementation with
inorganic phosphate in an amount equal to organic
phosphate contained in the higher
protein diet causes medullary calcification and
interstitial nephritis. Also, administration of suboptimal doses of
insulin in diabetic animals greatly enhances renal growth, more than that induced by diabetes alone.