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Elevated Urinary Prostaglandin Excretion and the Effect of Indomethacin on Renal Function in Incipient Diabetic Nephropathy
Author(s) -
Mathiesen E. R.,
Hommel E.,
Olsen U. B.,
Parving H.H.
Publication year - 1988
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.1988.tb00961.x
Subject(s) - medicine , microalbuminuria , endocrinology , renal function , albuminuria , excretion , diabetic nephropathy , nephropathy , kidney disease , diabetes mellitus , urology
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 E 2 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 (2 p <0.01). Glomerular filtration rate (single bolus 51 Cr‐EDTA technique) and albuminuria (radioimmuno‐assay) 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 E 2 excretion (73%) (2 p <0.01), urinary albumin excretion rate diminished from 207 (63–253) to 87 (49–147) mg/24 h (2 p <0.01), fractional clearance of albumin declined (70%) (2 p <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.