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Immune Checkpoint Inhibitor-Associated AKI: Debates in Diagnosis, Management, and Rechallenge
Harish Seethapathy1, Sandra M Herrmann2, Arash Rashidi3
1Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Abstract:
Immune checkpoint inhibitors (ICIs) are now established treatments for advanced cancer and their use is now ubiquitous. The high upside of ICIs is tempered by their toxicity profile affecting almost every organ, including the kidneys. Although acute interstitial nephritis is the major kidney-related adverse effect of checkpoint inhibitors, other manifestations such as electrolyte abnormalities and renal tubular acidosis have been described. With increasing awareness and recognition of these events, the focus has shifted to non-invasive identification of ICI-acute interstitial nephritis, with sophisticated approaches involving biomarkers and immunologic signatures being studied. Although the management of immune-related adverse events with corticosteroids is straightforward, there now are more data to help guide immunosuppressive regimens, ICI rechallenge, and delineate risk and efficacy in special populations such as individuals on dialysis or those who have received a transplant.
Insights
Immune checkpoint inhibitors (ICIs) treat advanced cancers but can harm kidneys. Research focuses on identifying ICI-induced kidney damage non-invasively and managing these toxicities, even in special patient groups.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) are vital for advanced cancer treatment.
- ICI use is widespread, but significant renal toxicities are a concern.
- Acute interstitial nephritis is a primary kidney adverse effect, alongside electrolyte disturbances and renal tubular acidosis.
Purpose of the Study:
- To review the spectrum of kidney-related adverse events from ICIs.
- To discuss advancements in non-invasive identification of ICI-induced acute interstitial nephritis using biomarkers and immunologic signatures.
- To provide guidance on managing ICI-related kidney toxicities, including immunosuppression, rechallenge, and special populations.
Main Methods:
- Literature review and synthesis of current research on ICI nephrotoxicity.
- Analysis of diagnostic approaches, including emerging non-invasive biomarkers.
- Evaluation of management strategies for immune-related adverse events affecting the kidneys.
Main Results:
- Acute interstitial nephritis is the most common kidney issue with ICIs.
- Non-invasive diagnostic methods, including biomarkers, are under investigation.
- Corticosteroids are standard, but further data guide other immunosuppressants, ICI rechallenge, and risk stratification in specific populations.
Conclusions:
- ICI nephrotoxicity is a significant clinical challenge requiring careful monitoring and management.
- Advances in diagnostics and understanding of management protocols are crucial for optimizing patient outcomes.
- Further research is needed to refine risk-benefit assessments in diverse patient populations, including those with renal impairment or on dialysis.
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