title: Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy.
abstract: We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and urinary albumin excretion in incipient diabetic nephropathy (defined as urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) in two out of three sterile ketone-free 24-h urine collections in patients having insulin-dependent diabetes mellitus (IDDM) without hypertension or other kidney disease). The urinary excretion of prostaglandin E2 was significantly elevated in 8 insulin-dependent diabetic patients with incipient nephropathy as compared with 9 normoalbuminuric IDDM patients and 11 healthy controls: 317 (182-1273); 95 (67-225); 132 (54-263) pg/min, respectively (2p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within 2 weeks in 8 females having IDDM with incipient nephropathy. The study design was a randomized double-blind trial with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%) (2p less than 0.01), urinary albumin excretion rate diminished from 207 (63-253) to 87 (49-147) mg/24 h (2p less than 0.01), fractional clearance of albumin declined (70%) (2p less than 0.01). Glomerular filtration rate remained stable (108 (88-133) versus 110 (95-142) ml/min). Blood glucose and blood pressure were comparable during the placebo and indomethacin treatment (12.6 +/- 3 versus 13.4 +/- 5 mmol/l and 122/79 +/- 3/9 versus 122/82 +/- 4/10 mmHg, respectively). Our results suggest that enhanced glomerular synthesis of vasodilating prostaglandins may accelerate microalbuminuria in incipient diabetic nephropathy.
authors.affiliation: Hvidøre Hospital, Klampenborg, Denmark.
authors.forename: E R
authors.initials: ER
authors.lastname: Mathiesen
authors.forename: E
authors.initials: E
authors.lastname: Hommel
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 / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D015232:Dinoprostone; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008875:Middle Aged; D011453:Prostaglandins / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000502:physiology / Q000652:urine*; D011458:Prostaglandins E / Q000652:urine
chemical_list: D011453:Prostaglandins; D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin