Epidemiology and mechanistic basis of analgesic-associated nephropathy

Renal Changes Associated with Naproxen Sodium Administration in Cynomolgus Monkeys

“…Our findings are consistent with the current view that medullary changes are the primary event in NSAID/analgesic-related renal disease in humans (4,8,9,16,33,39 (24,37,41,43). Progressive loss of these cells may be an underlying mechanism involved in NSAIDrelated interstitial changes and renal toxicity, as interstitial fibroblasts appear to be involved in the production of beneficial vasoactive prostaglandins and in the production and modeling of the extracellular matrix, including ground substance (4,27,31,37,40 (4) have been suggested as causes of tubular dilatation. In the 2-wk study, tubular dilatation was not attributed to physical obstruction by casts and/or crystals, because casts were observed infrequently relative to tubular dilatation, crystalline-like spaces were even more infrequent, and tubular dilatation occurred in kidneys lacking crystals or casts.…”

“…In most human cases, the infiltrate consists primarily of lymphocytes, although infiltrates that include neutrophils and eosinophils have been described (5,23,34,50 (47). In humans, the recommended prescription dose of naproxen is 1,000 mg/day divided into 2 doses (15-20 mg/kg/day), although 1,500 mg/day (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) mg/kg/ day) may be used for 2 wk (36,52), and 1,800 mg/day of naproxen was administered for 1 mo without any side effects (48). Thus, on a milligram per kilogram basis, renal toxicity occurs at much lower doses in cynomolgus monkeys than in rhesus monkeys and occurs at doses that are only 2-to 3-fold higher than the human prescription dose.…”

“…Papillary necrosis and secondary chronic nephritis, termed analgesic nephropathy, have been more frequently associated with consumption of other aspirin-like drugs that lack significant anti-inflammatory activity, such as phenacetin (4,9,17,30). While adverse renal effects related to NSAIDs and other aspirin-like drugs are considered uncommon in humans, there is concern that these effects may occur more frequently than is currently recognized (27,39), and it was recently recommended that prolonged, regular use of NSAIDs should be avoided (17). Administration of NSAIDs to laboratory animals has not proven to be a good model of NSAID-related renal disease, because the spectrum of disease observed in humans is not seen in laboratory animals, and these animals often develop significant extrarenal toxicity (4,6,27).…”

Clinical relevance

“…Solvents have been implicated as inducers of glomerulonephritis [72], while the association between chronic interstitial nephritis and analgesic abuse is acknowledged [73] and the association between hypertensive renal disease (nephrosclerosis) and lead nephropathy continues to be explored [74,75]. According to data provided by USRDS for 1994 through 1998, glomerulonephritis accounted for 9.1% of ESRD, hypertensive renal disease was present in 25.2%, secondary glomerulonephritis and vasculitis involved 2.2%, 3.6% were unknown etiology and interstitial nephritis/pyelonephritis accounted for 3.8% of all cases of ESRD being treated in USA [61].…”

Radiologische Diagnostik der Nieren bei Dialysepatienten

“…Bei der durch Analgetika bedingten terminalen Niereninsuffizienz ist darüber hinaus noch ein erhöhtes Risiko eines Urothelkarzinoms beschrieben [14,15]. Sekundäre Zeichen wie ein intrarenaler Aufstau werden hierbei durch den stark verminderten Urinfluß kaum zu sehen sein.…”