Checkmate: kidney injury associated with targeted cancer immunotherapy

Area of Science:

• Oncology
• Immunology
• Nephrology

Background:

• Immune checkpoint inhibitors (ICIs) are a cornerstone of modern cancer immunotherapy, targeting pathways like CTLA-4 and PD-1.
• These therapies harness the immune system to eliminate cancer cells but can disrupt self-tolerance, leading to immune-related adverse events (irAEs).
• Common irAEs include pneumonitis, colitis, and endocrinopathies, impacting various organ systems.

Purpose of the Study:

• To identify and characterize acute kidney injury (AKI) as a potential immune-related adverse event associated with immune checkpoint inhibitors.
• To investigate the primary renal pathology underlying ICI-induced AKI.

Main Methods:

• Review of clinical data and renal biopsies from patients experiencing AKI during ICI therapy.
• Histopathological analysis focusing on inflammatory infiltrates and tubular damage.

Main Results:

• AKI is increasingly recognized as an irAE of ICI therapy.
• Acute tubulointerstitial nephritis (ATIN) is the predominant cause of ICI-induced AKI.
• Specific patterns of immune cell infiltration in ATIN are observed.

Conclusions:

• Acute kidney injury, particularly ATIN, should be considered in patients on immune checkpoint inhibitors presenting with renal dysfunction.
• Understanding the mechanisms of ICI-induced ATIN is crucial for timely diagnosis and management.
• Further research is needed to elucidate the precise immunopathogenesis and develop targeted treatments for ICI-related nephrotoxicity.