Effect of maximal hydration on the renal responses to pretreatment with nonsteroidal anti-inflammatory drugs and probenecid in man.

The renal response to a challenge of maximal water diuresis has been studied in seven subjects pretreated over 48 h with either placebo, probenecid, indomethacin or piroxicam. Probenecid did not alter the excretion of water and sodium chloride when compared with placebo responses, but increased both phosphate and urate clearances. Indomethacin reduced significantly both water and sodium chloride clearances by approximately 40%. Piroxicam reduced water excretion to a similar extent but did not influence salt output. In parallel with these changes, both drugs caused significant phosphaturia. It is concluded that the renal actions of nonsteroidal anti-inflammatory drugs (NSAIDs) are individually distinct and involve direct effects on tubular transport of ions and water to differing extents within both the proximal and distal portions of the nephron.