Non-steroidal anti-inflammatory drugs and the continuum of renal dysfunction.
Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat diverse inflammatory diseases because of their ability to inhibit cyclooxygenase (COX), which constitutes the rate-limiting enzyme in the biosynthetic cascade of prostaglandin (PG). However, NSAID therapy is associated with adverse changes in renal function. Most prominent are changes in electrolyte homeostasis and impaired renal perfusion. PGs such as PGE2, PGF2a, and PGI2 (prostacyclin) modulate many renal physiologic effects, including renal haemodynamics and renal tubular function. Consequently, one would anticipate that impairment of the synthesis of such PGs would adversely affect renal function. About one fourth of NSAID-treated patients have sodium retention, regardless of the type of NSAID being used. NSAID therapy may also cause blood pressure destabilization. This destabilization is attributable to the well defined ability of NSAIDs to attenuate the antihypertensive effects of several agents including diuretics and angiotensin-converting enzyme inhibitors. Because an estimated 14 million Americans are treated with both anti-hypertensive drugs and NSAIDs, the public health implications are clear. Finally, NSAIDs may occasionally produce acute renal failure. The pathogenesis is believed to be renal vasoconstriction secondary to inhibition of vasodilatory PGs with unopposed vasoconstrictor forces including angiotensin II, catecholamines and enhanced sympathetic activity.
Epstein
Murray
M
Department of Medicine, University of Miami School of Medicine, Miami, Florida, USA.
D058186:Acute Kidney Injury / Q000139:chemically induced; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced*; D012079:Renal Circulation / Q000187:drug effects; D012307:Risk Factors; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D014867:Water; D012964:Sodium