NSAIDs are a well-recognized cause of renal dysfunction. Their inhibition of COX-1 diminishes the production of prostaglandins that mediate renal vascular tone, natriuresis, and ADH responsiveness. Acute effects of NSAID intake, usually in high doses, include:
- Decreased glomerular filtration (renal ischemia that often develops in the setting of compromised renal perfusion, e.g. volume depletion or CHF)
- Salt and water retention (COX-1 mediated prostaglandins inhibit Na transport in the TAL and collecting duct; they also antagonize ADH function)
- Hyperkalemia (by blunting prostaglandin-related renin release, which decreases aldosterone formation; also, without prostaglandins to diminish Na reabsorption the loop of Henle, less sodium arrives at the distal nephron, meaning less Na-K exchange takes place)
- Interstitial nephritis
- Nephrotic syndrome
- Acute renal papillary necrosis (a severe sequela of renal ischemia)
While NSAID-induced chronic renal papillary necrosis (also called analgesic-abuse nephropathy) was a common occurrence several decades ago, it was largely due to use of phenacetin-containing analgesic compounds. Phenacetin has been off the market since 1983 in the United States, and has been banned in most countries*. Chronic papillary necrosis has been reported with other NSAIDS, but extremely rarely, and the incidence has not been determined.
So it seems I can’t hang my hat on my patient’s NSAID use as a cause of her CKD, although I am curious to see what happens to her creatinine after she stops taking them. If her renal function continues to decline, she may be headed for a biopsy.
*A web search for phenacetin yielded multiple internet retailers of phenacetin, most from mainland China. It looks like it is only sold in bulk (i.e. 25 kg drums)—an amount to make any nephrologist shudder.