Non-steroidal Antiinflamatory Drugs (NSAIDs) and the Kidney

Non-steroidal antiinflammatory drugs (NSAIDs) are among the most widely utilized thera­peutic agents today. The main mechanism of their action is via inhibition of cyclooxygenase, the enzyme involved in prostaglandin synthesis. Prostaglandins play a crucial role in the renal circulation when systemic circulation is destabilized or when the blood volume and effec­tive arterial blood volume are compromised. They enable vasodilatation of the renal circulation, renin secretion, and sodium and water excretion. There are two isoforms of cyclooxygenase (COX) (COX-1 or the »constitutive« isoform and COX-2 or the »inducible« isoform). The inhi­bition of COX-2, which is normally expressed in activated macrophages and induced by proinflammatory substances, accounts for antiinflammatory, analgesic and antipyretic effects whereas COX-1 suppression causes most side effects, for example gastrointestinal bleed­ing and ulceration, and platelet dysfunction. It was assumed that selective inhibition of COX-2 would diminish the wide range of toxic organ effects of nonselective NSAIDs. In the kidney, constitutive expression has been demonstrated for both isoforms. Renal toxicity is therefore similar in nonselective and selective COX-2 inhibitors. Moreover, a number of analyses have suggested that prolonged exposure to selective COX-2 inhibitors increases the risk of car­diovascular disease. Renal toxicity associated with the use of NSAIDs can be classified in several distinct clinical syndromes: acute hemodynamic renal failure, acute tubulointerstitial nephri­tis with nephrotic syndrome and chronic kidney disease. They differ in the time of drug use that is required for its development, pathogenesis and treatment