Drug-induced acute interstitial nephritis with granulomas.

To shed more light on the immunopathogenesis of drug-induced acute interstitial nephritis, a combined histologic, immunopathologic, and ultrastructural study of renal biopsy specimens from nine patients with drug-induced renal disease was performed. None of the patients had pre-existing renal disease or evidence of sarcoidosis or tuberculosis. The principal drugs included a hydrochlorothiazide-triamterene combination (Dyazide), hydrochlorothiazide, fenoprofen, and furosemide and triamterene. Renal insufficiency developed approximately four to ten weeks after initiation of drug therapy. In all cases, withdrawal of the drug(s) with or without steroid therapy resulted in restoration of normal or near-normal renal function. Histologically, all biopsy specimens showed acute interstitial nephritis characterized by an intense but patchy mononuclear cell interstitial infiltrate consisting of lymphocytes, monocytes, and plasma cells, modest numbers of eosinophils, patchy tubular atrophy, interstitial edema, and normal glomeruli. All biopsy specimens contained interstitial (and, in two cases, perivascular) non-caseating granulomas, which were numerous in one case, moderate in four cases, and rare in the remainder. Direct immunofluorescence was negative for IgG, IgM, IgA, C1q, C4, and C3 along glomerular and tubular basement membranes. Immunoperoxidase staining for lysozyme (performed in three cases) demonstrated many positive cells in the infiltrate. In two cases in which granulomas were present in prepared sections, the epithelioid and multinucleated giant cells did not stain for lysozyme. Electron microscopy of the granulomas in two cases revealed that the epithelioid and giant cells had "secretory" features characteristic of hypersensitivity granulomas. These findings provide further evidence for the participation of cell-mediated immunity in the pathogenesis of at least some cases of drug-induced acute interstitial nephritis.