Glomerular dysfunction in diabetic nephropathy.

In the early stages of insulin-dependent diabetes mellitus (IDDM) in humans and in animals the renal plasma flow (RPF) and the glomerular filtration rate (GFR) have often been found higher than normal. Moreover, in a subset of IDDM patients, early abnormalities in protein excretion, termed 'subclinical proteinuria' or 'microalbuminuria' have been found. This finding is thought to be a predictor of clinically overt diabetic nephropathy. Hence, it has been proposed that high glomerular hydraulic pressure and/or plasma flow rate may be responsible for causing both proteinuria and the progression of diabetic nephropathy. However, other abnormalities such as the impaired synthesis of prostaglandins, an abnormal production of cationic polyamino-acids found in IDDM, may cause both proteinuria and nephropathy. So the role of increased glomerular pressure in initiating diabetic nephropathy is being debated. To verify whether increased GFR and proteinuria are causally linked, we have randomly allocated 12 IDDM patients (age range 25-58, mean 35 years; six males, six females) with increased GFR (131-165 ml/min, mean 145 ml/min), microalbuminuria above the normal range (range 35-130 micrograms/min, mean 80 micrograms/min) and moderate hypertension (mean blood pressure above 110 mmHg) to take a low protein diet with their standard antihypertensive therapy or their usual diet together with captopril administration (25-50 mg/day) for 4 weeks each. After low protein diet we found a significant decrease in GFR (P less than 0.05) and also in albuminuria (P less than 0.01). After captopril administration we found a small, statistically insignificant decrease in GFR with a moderate increase in filtration fraction and a significant decrease in albuminuria (P = 0.05). No correlation was found between the GFR and albuminuria variations during the low protein diet or during captopril administration. In conclusion, both the low protein diet and the captopril administration significantly decrease protein excretion. However, our data suggest that the proteinuria decrease does not correlate with the decrease in GFR, so other mechanisms besides hyperfiltration seem to be involved in the proteinuria of IDDM patients.