Effect of varied protein intake on the nephropathy of the diabetic mouse (C57BL/s J db/db).

Protein intake has been suggested to influence progression of renal disease by affecting intraglomerular pressures and flows. The renal disease of the diabetic mouse (C57BL/Ks/db/db) has been proposed as a suitable model of human diabetic nephropathy. Ten diabetic mice and ten non-diabetic controls were placed on 1 of 3 protein intakes, 4%, 27% and 50%, and serial functional measurements were made at 2 to 3 week intervals until week 20. All diabetic animals showed similar degrees of hyperglycemia. The creatinine clearances were generally higher in the diabetic mice than the controls, except the 4% protein intake diabetic group, until week 20 when the 27% db/db mice showed a significant decline (p less than 0.05) compared to the control mice. Albumin excretion was significantly higher in the 27% and 50% protein intake db/db mice than the controls. Again the 4% group showed albuminuria not different from the control animals. Histologic studies at 20 weeks showed minimal abnormalities in the normal and 4% protein intake diabetic group. The 27% and 50% intake diabetic mice showed a progressive increase in severity of mesangial matrix expansion with segmental sclerosis. Electron microscopy confirmed these findings. Immunofluorescence microscopy showed a marked increase in mesangial immunoglobulin G and M. With similar degree of hyperglycemia, higher protein intake was associated with more severe histologic changes, greater albuminuria and early decline in GFR. Thus protein intake can markedly affect the progression of renal disease in the diabetic mouse.