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

Area of Science:

• Nephrology
• Oncology
• Immunology

Background:

• Immune-checkpoint inhibitors (CPIs), including PD-1/PD-L1 inhibitors, are effective against metastatic carcinomas.
• CPIs can lead to kidney dysfunction, specifically acute interstitial nephritis (AIN).
• The specific inflammatory cell types involved in CPI-associated AIN require further elucidation.

Purpose of the Study:

• To investigate whether T lymphocytes are the predominant inflammatory cells in acute interstitial nephritis (AIN) associated with immune-checkpoint inhibitor (CPI) therapy.
• To grade the severity of CPI-associated AIN using a modified Banff criteria adapted for renal transplant cellular rejection.

Main Methods:

• Analysis of 20 renal biopsies from 18 patients with acute kidney injury post-CPI treatment for metastatic carcinomas.
• Immunohistochemical staining of infiltrating lymphocytes for CD3 (T lymphocytes) and CD20 (B lymphocytes).
• Grading of AIN using modified Banff criteria for borderline changes and acute cellular rejection (ACR).

Main Results:

• T lymphocytes (CD3-positive) were the dominant inflammatory cells in 14 out of 20 biopsies with AIN.
• The majority of AIN cases were graded as mild (Grade 1), with fewer moderate (Grade 2) and severe (Grade 3) cases.
• Nine of the 14 patients diagnosed with AIN showed clinical improvement following steroid treatment (64.3%).

Conclusions:

• Nephrotoxicity from CPI therapy is characterized by T lymphocyte-mediated acute interstitial nephritis (AIN).
• Most CPI-associated AIN cases are classified as Grade 1 using modified Banff criteria.
• Steroid treatment can lead to renal functional recovery in a majority of patients with CPI-associated AIN.