Acute Interstitial Nephritis and Checkpoint Inhibitor Therapy: Single Center Experience of Management and Drug Rechallenge

Abstract

Background: The objective of this case cohort study was to describe our experience in the care of patients with immune checkpoint inhibitor-related acute interstitial nephritis (ICI-AIN) including rechallenge.

Methods: A descriptive case series of patients that received an ICI and had an AKI (defined as a ≥1.5-fold increase in serum creatinine) as an immune-related adverse event (irAE), with biopsy-proven or clinically suspected ICI-AIN from January 1, 2014 to December 1, 2018 at Mayo Clinic, Rochester. We studied details regarding diagnosis, clinical course, management, and outcomes of rechallenge of immunotherapy. Complete response (CR) was defined as return of kidney function back to baseline or <0.3 mg/dl above baseline creatinine; partial response (PR) was defined as creatinine >0.3 mg/dl from baseline, but less than twofold above the baseline by the end of steroid course.

Results: A total of 14 cases of biopsy-proven (35%) or clinically suspected (65%) ICI-AIN was identified. All patients had their ICI withheld and 12 patients received steroids. Steroid regimens were highly variable. The starting equivalent dose of prednisone was higher in those that had a CR versus a PR (median 0.77 mg/kg versus 0.66 mg/kg). Proton pump inhibitors (PPIs) were used in 11 patients and were stopped in eight (73%) patients at the time of the AKI event. A CR was seen in five (63%) of the eight patients who discontinued PPIs. Rechallenge was attempted in four of the 14 patients: three were successful with no recurrence of AKI, but one patient had recurrent AKI and fatal pneumonitis.

Conclusions: Careful review, withholding ICI and concomitant known AIN-inducing medications, along with prompt initial steroid management were the key in complete renal kidney recovery. A kidney biopsy should be strongly considered. Rechallenge of immunotherapy after a kidney irAE, although challenging, is possible and would need careful evaluation on an individual basis.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_01_30_KID0000152019.mp3.

Keywords: Acute Interstitial Nephritis; Acute Kidney Injury; Acute Kidney Injury and ICU Nephrology; Biopsy; Cohort Studies; Creatinine; Immune check point-rechallenge; Immune checkpoint inhibitors; Immune-related adverse event; Immunotherapy; Kidney Function Tests; Pneumonia; Prednisone; Proton Pump Inhibitors.