title: 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 albuminuria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253 pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95 pg/min) and 11 non-diabetic women (132 pg/min), respectively (p less than 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 double-blind trial, with the patients receiving either indomethacin (150 mg/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 less than 0.01), glomerular filtration rate diminished from 120 +/- 18 to 106 +/- 17 ml/min/1.73 m2 (p less than 0.05), albuminuria declined from 148 to 69 micrograms/min (median and range) (p less than 0.05) and fractional clearance of albumin diminished 42% (p less than 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.
authors.forename: E
authors.initials: E
authors.lastname: Hommel
authors.forename: E
authors.initials: E
authors.lastname: Mathiesen
authors.forename: S
authors.initials: S
authors.lastname: Arnold-Larsen
authors.forename: B
authors.initials: B
authors.lastname: Edsberg
authors.forename: U B
authors.initials: UB
authors.lastname: Olsen
authors.forename: H H
authors.initials: HH
authors.lastname: Parving
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D015232:Dinoprostone; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D011458:Prostaglandins E / Q000096:biosynthesis; D011897:Random Allocation
chemical_list: D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin