Renal Toxicity of the Nonsteroidal Anti-Inflammatory Drugs

Abstract

NSAIDs pose little threat of renal insult in normal, healthy persons at therapeutic dosages. However, NSAID administration to susceptible persons may cause decrements in renal plasma flow and glomerular filtration rate within hours. Such acute noxious renal effects are mediated by products of arachidonic acid metabolism. Precipitous decrements in glomerular filtration and renal ischemia, manifested by increased serum creatinine and urea nitrogen, are possible. However, these effects are usually fully reversible with prompt discontinuation of the offending NSAID. Risk factors for the development of these acute renal effects are known. Acute interstitial nephritis with or without nephrotic syndrome is a rare form of renal toxicity that typically occurs between 2-18 months of use. Renal impairment may be so severe as to require temporary hemodialysis; however, renal function usually returns to normal upon discontinuation of the NSAID. The mechanism of acute interstitial nephritis is presumed to be of allergic origin but could also be caused by a reactive metabolite. Fenoprofen use appears to be associated with a much higher risk for its development. In contrast to the acute effects of NSAIDs, irreversible, analgesic-associated nephropathy manifested by papillary necrosis and chronic interstitial nephritis may occur following months to years of high doses of analgesic mixtures. The mechanism by which combination analgesics produce this form of renal injury is unknown and could be either a result of medullary ischemia or a direct effect of a reactive metabolite. An important issue to be resolved is the relationship between the acute, reversible, prostaglandin-mediated renal effects of the NSAIDs and chronic, irreversible destruction, if such a relationship exists. Theoretically, continual or repeated decrements in renal function in patients with predisposing risk factors could cause or contribute to progressive deterioration in renal function. Elevations in blood pressure or interference with the effects of antihypertensive medications could theoretically also contribute to long-term renal deterioration. In addition to renal syndromes caused by NSAIDs that result in renal impairment, other transient effects on electrolyte and water metabolism may also occur. Reduced secretion of sodium may result in formation of edema, exacerbation of heart failure, or increased blood pressure. Hyporeninemic-hypoaldosteronism may produce hyperkalemia. Finally, reduced excretion of water has rarely caused hyponatremia. It has been suggested that NSAIDs may be renoprotective in patients with nephrotic syndrome. Others have suggested that sulindac is "renal-sparing" because of a unique metabolic pathway that supposedly limits the exposure of the kidney to the active sulfide metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute kidney injury following total joint arthroplasty: retrospective analysis

“…These medications affect renal autoregulation via impaired synthesis of renal prostaglandins, which reduces renal plasma flow and GFR. 36,37 In surgical patients with normal renal function, a transient decrement in renal function is observed but considered to be clinically irrelevant, 38 but in the setting of stressed kidneys, continued NSAID administration should be avoided. 36,39 Nevertheless, it is unknown if withholding NSAIDS from patients at higher risk of injury would affect the rate or magnitude of AKI.…”

A Maladaptive Role for EP4 Receptors in Podocytes

“…9,10 Although many factors undoubtedly contribute to the initiation and progression of podocyte injury and dysfunction, nonsteroidal anti-inflammatory drugs reduce proteinuria, suggesting that prostanoids derived from cyclooxygenase 1 and 2 (COX-1 and COX-2) activity may compose a portion of the causative mosaic. 11,12 Unfortunately, widespread use of COX inhibitors is not feasible, because they diminish vasodilatory prostanoid levels, resulting in reduced GFR and renal blood flow (RBF) 13,14 ; however, inhibition of either COX-1 or COX-2 isoforms attenuates the synthesis of at least five distinct prostanoids (PGE 2 , PGD2, PGI2, PGF2␣, and TxA2) that interact with their respective Gprotein-coupled receptors (prostanoid E-type 1 through type 4 [EP-1 through -4], and prostanoid D-, I-, F-and T-type [TP]) to provoke a variety of physiologic actions in the kidney and elsewhere. Targeting those prostanoid receptors that are pro-proteinuric while avoiding those that regulate GFR/RBF may represent a potential therapy for preserving GFB function in renal disease.…”

Massive Naproxen Overdose with Serial Serum Levels

“…This was followed by polyuria for a short period the next day; this latter finding might have been due to the extra volume of fluid he received or due to post acute tubular necrosis effect; polyuria has been reported previously in an ibuprofen overdose [16]. Other reported adverse renal effects reported in chronic NSAID use include tubulointerstitial nephritis, minimal change disease, membranous nephropathy, and papillary necrosis [17]. Acute papillary necrosis causing bilateral ureteral obstruction has been reported after acute therapeutic use of ibuprofen [18].…”