Contrasting renal functional reserve in very long-term Type I diabetic patients with and without nephropathy

AIMS: This study was to determine whether renal functional reserve (RFR) is present in patients who have suffered long-lasting Type I (insulin-dependent) diabetes mellitus. METHODS: Renal functional reserve was elicited by a 3-h amino acid infusion (4.5 mg x kg(-1) x min(-1)) in 10 patients with nephropathy (DN+) and 10 patients without nephropathy (DN-) who had lived with diabetes for 24 +/- 3 and 27 +/- 3 years, respectively and in 15 healthy control subjects. Renal functional reserve was calculated as the difference between amino acid-stimulated and baseline glomerular filtration rates (GFR). RESULTS: Baseline glomerular filtration rate in DN- patients (106 +/- 8) and control subjects (112 +/- 3 ml x min(-1) x (1.73m2)(-1)) was significantly higher (p < 0.01) than in DN+ patients (79 +/- 7 ml x min(-1) x (1.73m2)(-1)). Renal functional reserve was absent in DN+ patients, whereas it represented 26 +/- 4% of the baseline in DN- patients and 23 +/- 2% in control subjects. Renal vascular resistance decreased statistically significantly during amino acid infusion in DN- patients and control subjects but not in DN+ patients. CONCLUSIONS/HYPOTHESIS: These results indicate that very long-term Type I diabetic patients without diabetic nephropathy still have a normal renal functional reserve. In contrast, this reserve is suppressed in similarly long-term macroalbuminuric and hypertensive patients with overt nephropathy in spite of their remarkably maintained glomerular filtration rate. This opposite impairment supports the interpretation that glomerular hyperfiltration is a determining mechanism in human diabetic nephropathy.