NEPHROTOXICITIES OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS

While the relative incidence of serious nephrotoxicities in the popula tion consuming nonsteroidal anti-inflammatory drugs (NSAIDs) is very l ow, the frequency of adverse events in patients at risk has considerab ly increased due to the rising popularity of the use of the drugs in r ecent years. Under normal conditions, NSAIDs have relatively little ef fect on the kidney because of low renal production of prostaglandins. However, in the presence of renal hypoperfusion in which local synthes is of vasodilator prostaglandins is increased to protect the glomerula r hemodynamics and to maintain appropriate renal tubular transport of fluid and electrolytes, inhibition of prostaglandin synthesis by NSAID s can lead to vasoconstrictive acute renal failure as well as fluid an d electrolyte disorders such as sodium retention and resistance to diu retics, hyponatremia and hyperkalemia. Conditions that increase the ri sk for NS;VD-induced nephrotoxicities include volume depletion from di uretics and other causes, edematous stales such as congestive heart fa ilure and cirrhosis of the liver, old age and underlying renal disease , especially in the presence of renal functional impairment. In additi on, renal parenchymal diseases may develop in susceptible patients tak ing NSAIDs. These include acute tubulointerstitial nephritis, frequent ly associated with nephrotic syndrome, and chronic progressive renal d isease, with or without renal papillary necrosis. Rare cases of vascul itis and glomerulonephritis have also been reported. Finally, NSAIDs m ay aggravate hypertension by interacting with antihypertensive drugs, especially with diuretics and beta-blockers. Withdrawal of NSAIDs in p atients at risk can frequently reverse or improve the nephrotoxicities . It is recommended that physicians be aware of the clinical settings that increase the risk for NSAID-induced nephrotoxicities and take pre ventive or therapeutic measures accordingly.