Effects of indomethacin on kidney function in Type 1 (insulin-dependent) diabetic patients with nephropathy

Abstract

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albumimiria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95pg/min) and 11 non-diabetic women (132 pg/min), respectively (p<0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized doubleblind trial, with the patients receiving either indomethacin (150mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%, p<0.01), glomerular filtration rate diminished from 120±18 to 106±17ml/min/1.73m2 (p<0.05), albuminuria declined from 148 to 69 μg/min (median and range) (p<0.05) and fractional clearance of albumin diminished 42% (p<0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4±4 versus 14.2±3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins. © 1987 Springer-Verlag.