title: Do non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors have different renal effects?
abstract: The main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cyclooxygenase (COX), the enzyme involved in prostaglandin synthesis. NSAID nephrotoxicity is linked to this, since prostaglandins act not only in response to inflammatory stimuli, but also as modulators of physiological functions. When blood volume is compromised, prostaglandins play a role in the renal circulation including vasodilatation, renin secretion, and sodium and water excretion. If vasoconstrictive forces stimulated to maintain the filtration fraction are not balanced by prostaglandin-induced vasodilatation, renal failure may occur. The identification of two isoforms of COX (COX-1 or the "constitutive" isoform and COX-2 or the "inducible" isoform) led to the hypothesis that COX-1-derived prostaglandins were involved in regulating physiological functions, whereas COX-2-derived prostaglandins played a major role in inflammation or tissue damage. It was assumed that the pharmacological effects of NSAIDs depend on the inhibition of COX-2, whereas the toxic organ-specific effects are linked to the inhibition of COX-1. Therefore, rofecoxib and celecoxib, selective inhibitors of COX-2, at least in vitro, were introduced. However, COX-2 plays a physiological role in many tissues and organs, and COX-1 is also involved in inflammatory reactions. In the kidney, "constitutive" expression has been demonstrated for both isoforms. COX-2 inhibitor drugs, such as NSAIDs, reduce sodium excretion, and may cause acute renal failure in patients in whom the maintenance of adequate renal perfusion is "prostaglandin-dependent". Therefore, COX-2 inhibitors, like other NSAIDs, must be used cautiously or not at all in patients with predisposing diseases.
authors.affiliation: Nephrology and Dialysis Unit, Trieste, Italy. giovanni.galli@aots.sanita.fvg.it
authors.forename: Galli
authors.initials: G
authors.lastname: Giovanni
authors.forename: Panzetta
authors.initials: P
authors.lastname: Giovanni
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000502:physiology; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases