Grading T Lymphocyte-Mediated Acute Interstitial Nephritis Following Checkpoint Inhibitor Therapy.

Abstract

Objective: Immuno-checkpoint inhibitors (CPIs) such as PD-1/PD-L1 inhibitors have shown positive effects in treating various metastatic carcinomas but can cause complications like kidney dysfunction. This study aimed to determine if T lymphocytes were the dominant inflammatory cells in CPI-associated acute interstitial nephritis (AIN), graded using a modified Banff criteria for renal transplant cellular rejection.

Methods: 20 renal biopsies from 18 patients with acute kidney injury following CPI treatment for metastatic carcinomas were evaluated. Infiltrating lymphocytes were stained for CD3 (T lymphocytes) and CD20 (B lymphocytes). AIN was graded using a modified Banff criteria for borderline changes and acute cellular rejection (ACR).

Results: In 14 biopsies, typical AIN was dominated by CD3-positive T lymphocytes and a small percentage of B lymphocytes, with minimal eosinophils or plasma cells. There were one grade 3 AIN, four grade 2 AIN, and nine grade 1 AIN cases. Six biopsies without AIN showed either chronic thrombotic microangiopathy (TMA, n=1) or acute tubular injury (ATN, n=5). Following renal biopsies diagnosing AIN, nine out of 14 patients (64.3 %) experienced clinical improvement with steroid treatment.

Conclusion: This study indicates that nephrotoxicity due to CPI treatment is characterized by T lymphocyte-mediated AIN, with the majority being grade 1 AIN according to the modified Banff criteria. Most patients showed some renal functional recovery in response to steroid treatment.