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Clinical Characteristics and Outcomes of Immune Checkpoint Inhibitor Associated Renal Toxicities: A Retrospective
Charmi Trivedi1, Julia Contini2, MacKenzie Adams1
1Department of Internal Medicine, Brown University Health, Providence, Rhode Island.
Abstract:
The mechanism of immune checkpoint inhibitors lead to off-target inflammation that results in a broad spectrum of toxicities. The aim of this study was evaluate risk factors, management, and outcomes of immune checkpoint inhibitor-related nephritis. We performed a retrospective review of 2,723 patients treated with ICIs (2015-2024) at a tertiary center. Patients who developed immune-mediated nephritis were identified and analyzed for demographics, cancer type, treatment, nephritis severity (ASCO grading), and outcomes. Fisher's exact tests assessed associations with renal cell carcinoma (RCC) and baseline chronic kidney disease (CKD). Thirty-seven patients (1.36%) developed ICI-related nephritis, with a median onset at 16.5 weeks. RCC was associated with a higher risk (OR: 5.9, p < 0.001), while baseline CKD was not associated with increased severity of ICI nephritis. Most patients (65%) did not recover renal function despite holding ICIs. Among those treated with steroids, 62% were refractory. Rechallenge led to recurrent AKI in 78% of patients, and nearly one-third transitioned to hospice. ICI-related nephritis is rare but associated with poor renal recovery and high recurrence on rechallenge. Improved risk stratification and optimization of management strategies are needed.
Insights
Immune checkpoint inhibitor-related nephritis is a rare but serious toxicity. Renal function often does not recover, and rechallenging patients leads to high recurrence rates.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) can cause off-target inflammation, leading to various toxicities.
- Immune-mediated nephritis is a significant adverse event associated with ICI therapy.
Purpose of the Study:
- To evaluate the risk factors, management strategies, and outcomes of nephritis in patients treated with ICIs.
- To identify patient demographics, cancer types, and treatment details associated with ICI-related nephritis.
Main Methods:
- Retrospective review of 2,723 patients treated with ICIs between 2015 and 2024.
- Analysis of patients who developed immune-mediated nephritis, assessing demographics, cancer type, treatment, severity (ASCO grading), and outcomes.
- Fisher's exact tests used to assess associations with renal cell carcinoma (RCC) and baseline chronic kidney disease (CKD).
Main Results:
- 37 patients (1.36%) developed ICI-related nephritis, with a median onset of 16.5 weeks.
- Renal cell carcinoma (RCC) was associated with a significantly higher risk (OR: 5.9, p < 0.001).
- Most patients (65%) did not recover renal function, 62% of those treated with steroids were refractory, and 78% experienced recurrent acute kidney injury (AKI) upon rechallenge.
Conclusions:
- ICI-related nephritis is rare but linked to poor renal recovery and high recurrence rates after rechallenge.
- Current management strategies, including steroid treatment and ICI withdrawal, show limited efficacy in restoring renal function.
- There is a critical need for improved risk stratification and optimized management protocols for ICI-induced nephritis.
