Glomerular, tubular and interstitial nephritis associated with non‐steroidal antiinflammatory drugs. Evidence of a common mechanism

Abstract

Aims To study the mechanisms behind NSAID-associated nephropathy. Methods Analysis of published case reports satisfying strict criteria for NSAID nephropathy. Results Ninety-seven cases with acute nephritis (AN; 19 patients), minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN; 19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis subgroups (8 patients) were identified. Hypersensitivity reactions were seen in all groups, most often in AN. Proteinuria was more severe in MC and FS than in MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely associated with hypersensitivity, interstitial damage and renal failure. Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had discontinued NSAID treatment had improved, 57 with normal renal function. Conclusions NSAID nephropathy may be caused by hypersensitivity. The reaction is milder than in drug-induced acute tubulointerstitial nephritis, probably because the offending drug inhibits the inflammatory reaction it has started itself. Heavy proteinuria is probably due to lymphokines produced as a result of the immunological response. If the allergic reaction is strong, AN is produced rapidly with severe renal failure but little proteinuria; if it is less violent, immunocompetent cells may develop to produce lymphokines and proteinuria. Immune complexes may be formed eventually, secondary to the increased glomerular permeability, more easily in patients with a hyperactive immune system and with little consequence for renal function.

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA# and GA2LEN/HANNA*

“…Clinical symptoms of acute renal failure, proteinuria and nephrotic syndrome develop usually 2-3 weeks after starting the medication. NSAIDs may also produce glomerulopathies including minimal change nephropathy, membranous glomerulonephritis and focal sclerosis (88). Peripheral blood eosinophilia is present in almost half of patients.…”

Minimal-change Nephrotic Syndrome Associated with Isoniazid in Anti-tuberculosis Chemoprophylaxis for a Patient with Rheumatoid Arthritis

“…NSAID-induced MCNS is believed to originate in a hypersensitivity reaction to the drug. The increased glomerular permeability is probably due to the production of cytokines as an immunological response (21). In lithium-induced MCNS, the drug may stimulate T-cell activation and cytokine production, which may increase glomerular permeability to protein (22).…”

The crucial role of tubulotoxic chemicals in renal failure

“…The crucial role of the tubulointerstitial changes is also illustrated by a meta-analysis of nephritis caused by treatment with non-steroidal anti-inflammatory drugs (NSAID) 24 .…”