Rapidly Progressive Acute Kidney Injury Associated with Nivolumab Treatment

Abstract

A 63-year-old man with pulmonary adenocarcinoma was treated with nivolumab. High fever developed within several hours after the first administration of nivolumab; subsequently, serum creatinine levels kept increasing daily. We diagnosed acute kidney injury (AKI) as an immune-related adverse event; the patient was initially treated with 50 mg prednisolone, and the dose was then tapered. Renal biopsy pathologically revealed tubulointerstitial inflammation with strong infiltration of only T cells that were CD3⁺, CD4⁺, and CD8⁺. The infiltration of CD163⁺ M2 macrophage was also observed. AKI within 1 week after the administration of nivolumab seems to be rare; therefore, the present case provides important findings useful in daily clinical practice.

Keywords: Acute kidney injury; Acute tubular necrosis; Immune checkpoint inhibitors; Nivolumab; Renal biopsy.

Fig. 1

Clinical course after the first dose of nivolumab. High fever occurred immediately after the administration of nivolumab, and the patient's serum creatinine level rapidly increased within several days. Corticosteroid therapy was effective for treating renal failure. The high fever resolved, and serum creatinine levels improved remarkably.

Fig. 2

Hematoxylin and eosin stain (a, b), and periodic acid methenamine silver stain (c). Pathological findings of the biopsied specimen obtained from the left kidney showed acute tubulointerstitial nephritis. Severe tubulointerstitial inflammation, tubular atrophy, and an area of interstitial edema with mononuclear cells and eosinophils were observed.

Fig. 3

Immunohistochemical staining showed the infiltration of CD3⁺ T cells, CD4⁺ helper T cells, and CD8⁺ cytotoxic T cells without CD20⁺ B cell infiltration. The infiltration of CD68⁺ and CD163⁺ macrophage was also observed. Only T cell response and macrophage growth were microscopically evident on immunostaining.

Fig. 4

Computed tomography scan of the chest before treatment with nivolumab showed a mass in the right upper lobe of the lung (a). The tumor shrunk with cavity formation and maintained regressing on day 45 after the first dose of nivolumab (b).