Renal aspects of treatment with conventional nonsteroidal anti-inflammatory drugs versus cyclooxygenase-2-specific inhibitors.

In the clinical setting of reduced renal perfusion, as seen in patients with renal, cardiac, or liver disease, dehydration, or aging kidneys, renal prostaglandin production (mediated primarily by cyclooxygenase [COX]-1 and possibly by COX-2) plays a major role in compensatory renal hemodynamics. Inhibition of the synthesis of renal prostaglandins by conventional nonsteroidal anti-inflammatory drugs (NSAIDs) may result in several nephrotoxic syndromes, including fluid and electrolyte abnormalities, acute renal failure, nephrotic syndrome, and renal papillary necrosis. Moreover, NSAIDs may adversely influence blood pressure control in treated hypertensive individuals and also may decompensate the clinical stability of diuretic-treated patients with chronic heart failure. The recently approved COX-2–specific inhibitors celecoxib and rofecoxib offer the potential for sparing homeostatic COX-1 activity in the kidney while inhibiting COX-2–mediated pain and inflammation. Emerging clinical data are helping to quantify the renal and related cardiovascular risks associated with the use of COX-2–specific versus conventional NSAIDs. Although the risk of serious toxicity associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) is relatively low, nonetheless, up to approximately 5% of individuals exposed to NSAIDs may develop one or more forms of diverse “nephrotoxic” renal side effect syndromes. The number of at-risk individuals is high as a consequence of the fast consumption of these compounds either used at prescription strength or at over-the-counter dosing regimens. Hence, 500,000 to 2,500,000 individuals in the United States are estimated, on an annual basis, to potentially manifest an NSAID-related renal side-effect syndrome. The relevance of these clinical problems is particularly important in those NSAID users who become particularly “at risk” for nephrotoxic effects as a result of the clinical presence of volume-contracted states, low cardiac output, or other conditions that tend to compromise renal perfusion. The various NSAID-related renal syndromes that may become clinically apparent, after as little drug use as a single ingestion through to several weeks or months of drug consumption, will vary from the commonly encountered problems of edema formation through to the development of acute renal failure and the rare complication of acute papillary necrosis. –10 On the other hand, there are frequently encountered clinical NSAID-induced side effects that represent drug– drug– disease interactions and are manifest in treated hypertensive patients as an increase in blood pressure or seen in otherwise stable diuretic-treated individuals with chronic heart failure as a destabilization of their cardiac function. This review will summarize the known information defining the mechanisms by which these renal syndromes and related cardiovascular NSAID-induced side effects evolve and will characterize the “at-risk” NSAID consumer populations, together with approaches to the prevention and management of these diverse NSAID-related side effects. It will also summarize the currently available clinical information contrasting the development of renal and related cardiovascular NSAID-induced side effects in conventional versus COX-2–specific NSAID exposed individuals. It is clear that in conventional NSAID-treated individuals most of the nephrotoxic and related cardiovascular side effects are mediated as a result of the inhibition of renal prostaglandin synthesis.