NSAIDs and Kidney
P Ejaz, K Bhojani, VR Joshi*
NSAIDs are commonly used drugs. Even with the advent of selective COX-2 inhibitors, nephrotoxicity still remains a concern. The adverse effects of NSAIDs are mediated via inhibition of prostaglandin synthesis from arachidonic acid by non-specific blocking of the enzyme cyclooxygenase leading to vasoconstriction and reversible mild renal impairment in volume contracted states. When unopposed, this may lead to acute tubular necrosis and acute renal failure. NSAIDs also produce interstitial nephritis with or without nephrotic syndrome secondary to minimal change disease. Although this presents as acute renal failure, it can progress in some cases to chronic renal failure. Papillary necrosis has been incriminated in the development of chronic renal failure secondary to NSAIDs. In patients on long term NSAIDs without acute or chronic renal failure, subclinical renal dysfunction such as reduced creatinine clearance and impaired urine concentrating ability has been shown to be present. Although this sub-clinical dysfunction is reversible on withdrawal of NSAIDs, some reports have suggested a persistent residual dysfunction. Even with a wide range of NSAIDs at our disposal, a renal safe NSAID is yet to be discovered. ©
on steroidal anti-inflammatory drugs (NSAIDs) are amongst the most commonly prescribed medication. Some are available over the counter and likely to be abused. Serious gastrointestinal side effects have been minimized with the advent of selective and specific COX-2 inhibitors and misoprostol. However, the newer NSAIDs continue to be nephrotoxic much like the conventional NSAIDs.1 Nephrotoxicity attributed to NSAIDS has been reviewed in the past.2-8 The spectrum of nephrotoxicity includes acute tubular necrosis, acute tubulointerstitial nephritis, glomerulonephritis, renal papillary necrosis, chronic renal failure, salt and water retention, hypertension, hyperkalaemia and hypereninaemic hypoaldosteronism.9 There are reports of sub- clinical renal dysfunction due to NSAIDs.10 NSAID induced chronic renal failure remains a debatable issue.11 This article reviews relevant English literature on acute and chronic renal failure and sub-clinical renal impairment due to NSAIDs (Medline search from 1990 to 2002 using key words – NSAIDs, acute renal failure, chronic renal failure, interstitial nephritis and subclinical nephrotoxicity)
Prostaglandins maintain renal blood flow (RBF) and
*Director Research, Consultant Physician and Rheumatologist, PD Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai – 400 016. Received : 23.12.2003; Accepted : 14..5.2004
glomerular filtration rate (GFR) especially in fluid depleted states. Locally synthesised prostaglandins PGI2 (prostacyclin), PGE2, and PGD2 cause vascular dilatation, diminish vascular resistance and enhance renal perfusion with redistribution of blood flow from the renal cortex to nephrons in the juxta-medullary region.12 PGE2 and to a lesser degree PGF2µ cause diuresis and natriuresis by inhibiting the transport of sodium and chloride in the thick ascending limb of loop of Henle and the collecting ducts.13,14 PGE1 tends to antagonize the action of antidiuretic hormone (vasopressin).15,16 Lastly, prostacyclin in concert with PGE2, serves to maintain the glomerular filtration rate.7 In volume contracted states renin-angiotensin-aldosterone axis is stimulated with increased renin, angiotensin II, and aldosterone production resulting in renal vasoconstriction and increased sodium and chloride reabsorption. There is increased sympathetic outflow, which further increases the vascular tone. In this setting, prostaglandins provide compensatory vasodilatation of renal vascular bed and ensure adequate renal blood supply precluding acute renal functional deterioration. PGE2, PGD2, and to a lesser degree prostacyclin, cause...