Grading and Follow-Up of T Lymphocyte-Mediated Acute Interstitial Nephritis following Checkpoint Inhibitor Therapy

Background: Immuno-check point inhibitors (CPI) such as PD-1/PD-L1 inhibitors have been used to treat a variety of metastatic carcinoma with positive effects. However, there are complications such as gastrointestinal symptoms and/or kidney dysfunction. This study was determine what dominant inflamatory cells were involved in the CPI-associated acute interstitial nephritis (AIN) and if the AIN can be gradred using a modified Banff criteria for the cellular rejection of renal transplants. Methods: Totally 20 renal biopsies from 18 patients were performed to evaluate renal pathology due to acute kidney injury following CPI treatment for various metastatic carcinomas. Infiltrating lymphocytes were stained for CD3 to highlight T lymphocytes and for CD20 to identify B lymphocytes. Then the AIN was graded by modifying the popular Banff criteria for borderline changes and acute cellular rejection (ACR) (see Table below). Results: The identified cases represented 0.7 % of all our renal biopsies. In 15 biopsies, typical AIN was dominated by CD3-positive T lymphocytes and a small percent of B lymphocytes with minimal eosinophils or plasma cells; there were 1 grade 3 AIN, 4 grade 2 AIN and 10 grade 1 AIN. No vasculitis was seen. Five patients’ biopsies without AIN had either chromic thrombotic microangiopathy (TMA, n = 1) or acute tubular injury (ATN, n = 4). Following renal biopsies with a diagnosis of AIN, 10 out of 15 patients (66.7 %) with AIN had clinical improvement with steroid treatment. Four patients were found deceased during the recent follow-up check. Conclusion: Our study indicate that the nephrotoxicity due to CPI treatment is characterized by T lymphocyte mediated AIN as CPI mainly activates T lymphocytes for attaching tumor cells and incidentally attacking normal targets such as renal tubular epithelium. Therefore, using the popular Banff criteria for borderline changes and ACR can be easily adapted for grading AIN due to CPI (the majority was grade 1 AIN). Most patients had some renal functional recovery in response to steroid treatment. Funding: Clinical Revenue Support