Effects of acute and chronic dosing of NSAIDs in patients with renal insufficiency

Abstract

Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to patients with chronically impaired renal function has been reported to cause abrupt and sustained reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), and solute and water excretion in association with decreased renal prostanoid production. However, the time course of these acute effects and whether they are sustained during chronic exposure to the NSAIDs are unknown. Accordingly, using standard clearance and balance techniques, we investigated the effects of acute (zero to four hours) and chronic (five days) oral administration of two different NSAIDs on renal function in patients with stable, mild to moderate chronic renal insufficiency (CRI) and in normal subjects. In patients, acute oral administration of ketoprofen (K) and indomethacin (I) resulted in significant decreases in GFR (K: from 36 +/- 3 to 20 +/- 4 ml/min, P = 0.001; I: from 37 +/- 6 to 30 +/- 7 ml/min, P = 0.032; in RPF (K: from 194 +/- 21 to 146 +/- 21 ml/min, P = 0.002; I: from 222 +/- 33 to 147 +/- 18 ml/min, P = 0.016); and in urinary PGE2 excretion (K: from 0.60 +/- 0.25 to 0.08 +/- 0.02 ng/min, P = 0.05; I: from 0.34 +/- 0.06 to 0.18 +/- 0.06 ng/min, P = 0.042). Fractional excretion of sodium chloride and fractional free water clearance (CH2O/CIn) also decreased significantly after both agents. In normal subjects, GFR and RPF were not significantly decreased after acute dosing, whereas urinary PGE2 and fractional excretions of NaCl and free water decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)