An unusual form of crystal-forming chronic interstitial nephritis following long-term exposure to tosufloxacin tosilate

Abstract

Fluoroquinolones are known to cause acute renal failure because of interstitial nephritis with or without epithelioid granulomas. We report the first case of slowly progressive renal failure caused by crystal-forming chronic interstitial nephritis with non-Langerhans’ cell histiocytosis after long-term exposure to a fluoroquinolone, tosufloxacin tosilate. Lesions consisted of spindle- to cuboidal-shaped histiocytes with minimal collagenous matrix and low-level lymphocyte infiltration replacing normal tubulointerstitial structure of the kidney. Histiocytes were positive for CD68, but negative for S-100, suggesting they were derived from macrophages. There were numerous rhomboid- to needle-shaped crystal deposits in the cytoplasm of histiocytes, which showed bright birefringence under polarized light. No immunoglobulin deposits were seen in the kidney, and no evidence of paraproteinemia/lymphoproliferative diseases was identified in this patient. Despite a negative drug lymphocyte-stimulating test result using tosufloxacin tosilate, withdrawal of the drug and treatment with steroids gradually improved renal function. In this report, we describe the clinical course and histopathologic findings of this patient and discuss the possible pathogenesis. Fluoroquinolones are known to cause acute renal failure because of interstitial nephritis with or without epithelioid granulomas. We report the first case of slowly progressive renal failure caused by crystal-forming chronic interstitial nephritis with non-Langerhans’ cell histiocytosis after long-term exposure to a fluoroquinolone, tosufloxacin tosilate. Lesions consisted of spindle- to cuboidal-shaped histiocytes with minimal collagenous matrix and low-level lymphocyte infiltration replacing normal tubulointerstitial structure of the kidney. Histiocytes were positive for CD68, but negative for S-100, suggesting they were derived from macrophages. There were numerous rhomboid- to needle-shaped crystal deposits in the cytoplasm of histiocytes, which showed bright birefringence under polarized light. No immunoglobulin deposits were seen in the kidney, and no evidence of paraproteinemia/lymphoproliferative diseases was identified in this patient. Despite a negative drug lymphocyte-stimulating test result using tosufloxacin tosilate, withdrawal of the drug and treatment with steroids gradually improved renal function. In this report, we describe the clinical course and histopathologic findings of this patient and discuss the possible pathogenesis.