ACUTE KIDNEY INJURY WITH KARYOMEGALIC INTERSTITIAL NEPHRITIS AFTER NIVOLUMAB TREATMENT - TWO CASE REPORTS. (June 2018)

• Record Type: Journal Article
• Authors: Ryuzaki, M.; Miyashita, K.; Tokuyama, H.; Uchiyama, K.; Nakaya, H.; Hasegawa, K.; Wakino, S.; Itoh, H.
• Is Part Of: Journal of hypertension. Volume 36(2018)Supplement 1
• Publication Date: 2018-06
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000539510.74234.61
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Background: Acute kidney injury (AKI) caused by immune checkpoint inhibitors are poorly described. Herein, we present 2 cases of AKI in patients under nivolumab treatment. Each case displayed acute interstitial nephritis (AIN) with karyomegalic interstitial nephritis (KIN), which was successfully treated with the discontinuation of nivolumab or the administration of corticosteroid. Design and method: Case 1: A 76-year old male with pancreatic cancer was admitted for AKI (serum creatinine (SCr) level from 0.84 to 3.08 mg/dL) after a series of nivolumab treatment. Five months after the initiation of nivolumab, he suffered from edema in his lower extremities along with the elevation of blood pressure (BP) to 170/97 mmHg. Kidney biopsy showed AIN where tubular epithelial cells with variably sized nuclei that were massively enlarged, irregularly shaped, and abnormally hyperchromatic, which findings were indicative of KIN. Approximately one year after quitting nivolumab treatment, his renal function improved to SCr level of 1.42 mg/dL, Results: Case 2: A 76-year old female with non-small cell lung cancer started treatment by nivolumab. Two months later, she exhibited AKI (SCr level from 0.81 to 1.54 mg/dL). Kidney biopsy revealed tubular injury with interstitial infiltration of inflammatory cells. Of note, tubular epithelial cells were focally enlarged with hyperchromatic nuclei, which finding was consistent with that of KIN. Since most of the enlarged tubular epithelial cells were positive for Ki-67, karyomegalic changes of tubular epithelia are suggested to be associated with the cell cycle abnormalities of tubular cells. The patient was administrated high dose of corticosteroid, and SCr level returned to that of her baseline. Conclusions: Conclusion: This is the first report of characteristic histological findings of KIN in nivolumab-associated AIN. The association of nivolumab-induced AIN with cell cycle derangement in our patients suggests that the activation of effector T cell by nivolumab may affect the proliferation of tubular epithelial cells, thereby leading to karyomegalic changes. In addition to the discontinuation of nivolumab, the administration of corticosteroid successfully improved renal function.