Necrotizing tubulointerstitial nephritis associated with adenovirus infection

We report 10 autopsy cases of necrotizing tubulointerstitial nephritis induced by adenovirus (ADV). Hemorrhagic, necrotizing tubulitis with intranuclear inclusion bodies was observed in the kidneys of five bone marrow transplant recipients and five patients treated with intensive chemotherapy for malignancies (four cases of leukemia and one case of lung cancer). It was histopathologically demonstrated that necrobiotic tubular cells had inclusion-bearing cells of three types: "smudge cells," Cowdry A intranuclear inclusion cells, and full-type intranuclear-containing cells. Immunofluorescent examination with anti-ADV antibody demonstrated specific fluorescence on the affected tubular cells of all 10 kidneys. Specific antigens for ADV type 11 were also revealed in all but one case by an immunofluorescent test using type-specific antiserum and convalescent serum containing high titer antibody to this serotype. Electron microscopy revealed intranuclear crystalline arrays of viral particles, 75 to 80 nm in diameter, in each of the seven cases examined. Extrarenal involvement, indicated by ADV-induced cytopathologic change, was confined to bladder or prostate. Hemorrhagic cystitis was recorded in all the bone marrow transplant cases as well as in one leukemia case. Adenovirus type 11 was isolated from urine in all five cases tested during these episodes. Renal failure was ascribed to ADV infection in two of five patients who died from renal dysfunction. The presence of hemorrhagic cystitis and localization of invasive infection in urogenital organs suggested that renal infection might occur by ascending route from the bladder. We propose that ADV should be added as a viral agent to the pathogenetic list of tubulointerstitial nephritis.