Short term effect of an aldose reductase inhibitor on urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) in type 1 diabetic patients with incipient nephropathy.

Abstract

OBJECTIVE: Increased activity of the enzyme aldose reductase in the polyol pathway, occurring with hyperglucaemia, has been implicated in the development of late diabetic complications. The effect of an aldose reductase inhibitor (Ponalrestat) on renal function in type 1 diabetes with incipient nephropathy (urinary albumin excretion rate > 20 micrograms.min-1) was evaluated. RESEARCH DESIGN AND METHODS: Thirty Type 1 diabetic patients (age: 34.4 +/- 3.1 yrs; diabetes duration 13.1 +/- 1.3 yrs) were treated with 600 mg of Ponalrestat per day for 3 months using a randomized double blind placebo controlled crossover design. Urinary albumin excretion rate and glomerular filtration rate were measured. RESULTS: Twenty three patients completed the entire study. Compared to placebo, there was no significant change in urinary albumin excretion rate and glomerular filtration rate during the Ponalrestat treatment period. Blood pressure and HbA1 were also unchanged during the placebo and Ponalrestat periods. Treatment with Ponalrestat appeared to be safe and there were no side effects. CONCLUSION: We conclude that three months aldose reductase inhibition with Ponalrestat had no effect on urinary albumin excretion rate and glomerular filtration rate in Type 1 diabetic patients with incipient nephropathy.