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REDUCTION OF GLOMERULAR HYPERFILTRATION IN NORMOALBUMINURIC IDDM PATIENTS BY 6 MO OF ALDOSE REDUCTASE INHIBITION
Author(s): PEDERSEN MM, CHRISTIANSEN JS, MOGENSEN CE
Source: DIABETES    Volume: 40    Issue: 5    Pages: 527-531    Published: MAY 1991  
Times Cited: 71     References: 41     
Abstract: Hyperglycemia causes enhanced glucose metabolism by the polyol pathway in tissues not requiring insulin for glucose uptake. It has been suggested that the high level of aldose reductase activity may cause functional and structural abnormalities in diabetes and may be involved in the development of late complications. To elucidate the effect of an aldose reductase inhibitor (ponalrestat) on kidney function in uncomplicated insulin-dependent diabetes mellitus (IDDM), 20 normoalbuminuric IDDM patients were randomized to follow either 6 mo of treatment with ponalrestat (n = 11, mean +/- SD age 30 +/- 8 yr, diabetes duration 10 +/- 6 yr) or 6 mo of placebo (age 33 +/- 7 yr, diabetes duration 12 +/- 6 yr). The glomerular filtration rate (clearance of [I-125]iothalamate) was significantly reduced from 140 +/- 18 to 129 +/- 10 ml. min-1. 1.73 m-2, 2P = 0.02) in the ponalrestat-treated patients, whereas no change was seen after placebo (142 +/- 12 vs. 141 +/- 12 ml. min-1. 1.73 m-2). The renal plasma flow (clearance of I-131-labeled hippuran), urinary albumin excretion rate (radioimmunoassay), fractional albumin clearance, and renal vascular resistance were unchanged in both groups. HbA1c showed a modest increase during ponalrestat (7.9 +/- 1.8 vs. 8.7 +/- 1.5%, 2P = 0.01) but was unchanged during placebo. No side effects of ponalrestat were observed. Thus, inhibition of aldose reductase may reduce the characteristic hyperfiltration in uncomplicated IDDM.
Document Type: Article
Language: English
Reprint Address: PEDERSEN, MM (reprint author), AARHUS UNIV, AARHUS KOMMUNEHOSP, INTERNAL MED CLIN 2, DK-8000 AARHUS, DENMARK
Publisher: AMER DIABETES ASSOC, 1660 DUKE ST, ALEXANDRIA, VA 22314
Subject Category: Endocrinology & Metabolism
IDS Number: FL179
ISSN: 0012-1797
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