Interstitial Nephritis, Proteinuria, and Renal Failure Caused by Nonsteroidal Anti-Inflammatory Drugs. Immunologic Characterization of the Inflammatory Infiltrate

Renal Changes Associated with Naproxen Sodium Administration in Cynomolgus Monkeys

“…The consistent observation of renal toxicity after 2 wk of administration in the monkeys contrasts with the NSAID-associated nephrotoxicity seen in humans, which is considered to be an uncommon effect in healthy individuals and of highly variable onset; it may occur within days or years after initiation of NSAID therapy (39). In addition, the syndrome of nephritis in humans may be related to an allergic/immunologic reaction, which may explain the sporadic incidence of the syndrome (5,23,39,50). Another difference was the nature of the inflammatory infiltrate in the tubulointerstitial nephritis.…”

“…Tubular atrophy was considered to be secondary to chronic tubular obstruction and fibrosis. Tubular dilatation and atrophy are features of renal disease that are associated with consumption of NSAIDs and other analgesics (4,5,7,9,12,23,24 (11,39,53 (22,32). The cause of the elevated triglyceride concentrations was not clear; however, similar elevations occurred following administration of the NSAID L5418 to rhesus monkeys (21).…”

“…Another difference was the nature of the inflammatory infiltrate in the tubulointerstitial nephritis. 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).…”

Characterization of Inflammatory Cells in Drug-Induced Tubulointerstitial Nephritis

“…Similar results have been previously observed by Benderst al. [5] in a group of 9 patients with tubulointerstitial nephritis and exposure to nonsteroidal anti-inflammatory agents. In the remain ing 50% of our cases receiving a heterogeneous treatment (diuretics, anticolinergics, antipiretics, etc.…”

“…Additionally, a prevalence of OKT8 + cells in those cases with tubulointerstitial nephritis induced by antibiotics and nonsteroidal anti-inflammatory agents [5] also indi cates that cytotoxic T cells may play an important role in this renal kind of tissue damage.…”