Do trandolapril and indomethacin influence renal function and renal functional reserve in hypertensive patients?
OBJECTIVE
To assess the effect of trandolapril (2 mg once daily) and indomethacin (25 mg three times daily), alone and in combination, on renal function and renal functional reserve in hypertensive patients (DBP 95-115 mmHg) requiring regular non-steroidal anti-inflammatory drugs (NSAIDs).


METHODS
Randomized, double-blind, placebo-controlled, four way crossover design. After 3 weeks treatment renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured using the p-aminohippurate (PAH) and inulin methods. Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1) and 10% amino acid solution.


RESULTS
There was no significant difference in RPF between treatments: -22.79 ml min(-1) (95% CI -54.82, 9.24) for placebo and trandolapril, -10.37 ml min(-1) (95% CI -30.7, 9.96) for placebo and indomethacin, -14.78 ml min(-1) (95% CI -50.33, 20.77) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve RPF between treatments: -34.96 ml min(-1) (95% CI -119.8, 49.88) for placebo and trandolapril, 29.78 ml min(-1), -15.18, 74.74) for placebo and indomethacin, and -25.84 ml min(-1) (95% CI -87.62, 35.94) for placebo and trandolapril with indomethacin. There was no significant difference in GFR between treatments: -1.01 ml min(-1) (95% CI -7.45, 5.42) for placebo and trandolapril, -7.88 ml min(-1) (95% CI -15.08, -0.68) for placebo and indomethacin, and -0.36 ml min(-1) (95% CI -7.58, 6.86) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve GFR between treatments: 5.13 ml min(-1) (95% CI -4.97, 15.23) for placebo and trandolapril, 6.31 ml min(-1) (95% CI -1.88, 14.5) for placebo and indomethacin, 7.21 ml min(-1) (95% CI 1.26, 13.16) for placebo and trandolapril with indomethacin.


CONCLUSIONS
In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR.
Pritchard
G
G
Clinical Pharmacology Unit, University of Aberdeen, Foresterhill, UK.
Lyons
D
D
Webster
J
J
Petrie
J C
JC
MacDonald
T M
TM
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007444:Inulin / Q000652:urine; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012039:Regional Blood Flow / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D010919:Placebos; C052035:trandolapril; D007444:Inulin; D007213:Indomethacin; D010130:p-Aminohippuric Acid