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Combination therapy with immune check point inhibitors and acute kidney injury
Amalie Valentin1, Anne Kirstine Hundahl Møller1, Jesper Andreas Palshof1
1Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Background:
Immune checkpoint inhibitors have revolutionized the treatment of metastatic renal cell carcinoma and malignant melanoma but are also associated with a risk of severe side effects. Nephrotoxicity is an immune checkpoint inhibitor-related adverse effect, but acute kidney injury (AKI) can also be caused by other more common conditions. This study aimed to describe the incidence and causes of AKI in patients treated with combination therapy of immune checkpoint inhibitors.
Material And Methods:
This retrospective cohort study included 200 patients receiving ipilimumab and nivolumab for either metastatic renal cell carcinoma or malignant melanoma at the Department of Oncology at Copenhagen University Hospital, Herlev between 1 January 2019 and 31 December 2020. The incidence and cause of AKI within 6 months after treatment was determined.
Results:
In the 96 patients treated for malignant melanoma 15 patients (16%) had an episode of AKI. Two of these patients had potential immune checkpoint inhibitor-related AKI both of which received treatment with a proton pump inhibitor (PPI). Of the 104 included patients with metastatic renal cell carcinoma 26 patients (25%) developed AKI. Five of these patients had potential immune checkpoint inhibitor-related AKI. Treatment with PPI before the development of AKI occurred in 4 out of these 5 patients.
Conclusion:
Patients receiving combination therapy with checkpoint inhibitors are at high risk of AKI, but different causes of AKI should always be considered. Use of PPI concurrently with ICIs is likely to increase the risk of AKI.
Insights
Patients receiving immune checkpoint inhibitors (ICIs) for cancer treatment face a high risk of acute kidney injury (AKI). Concurrent use of proton pump inhibitors (PPIs) may further elevate this risk, necessitating careful consideration of AKI causes.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but carry risks of severe side effects, including nephrotoxicity.
- Acute kidney injury (AKI) is a known adverse effect of ICIs, but other common conditions can also cause AKI.
- Understanding AKI causes in patients on ICI combination therapy is crucial for patient safety.
Purpose of the Study:
- To determine the incidence of AKI in patients receiving combination ICI therapy.
- To investigate the causes of AKI in this patient population.
- To assess the potential role of proton pump inhibitors (PPIs) in ICI-related AKI.
Main Methods:
- Retrospective cohort study of 200 patients with metastatic renal cell carcinoma or malignant melanoma.
- Patients received ipilimumab and nivolumab between January 2019 and December 2020.
- AKI incidence and causes were assessed within 6 months of treatment initiation.
Main Results:
- 16% of melanoma patients (15/96) and 25% of renal cell carcinoma patients (26/104) developed AKI.
- Potential ICI-related AKI occurred in 2 melanoma patients and 5 renal cell carcinoma patients.
- Proton pump inhibitor (PPI) use was noted in 2/2 patients with ICI-related AKI in the melanoma group and 4/5 in the renal cell carcinoma group.
Conclusions:
- Combination ICI therapy is associated with a high risk of AKI.
- Diverse causes of AKI must be considered in patients on ICI therapy.
- Concurrent PPI use with ICIs appears to increase the risk of AKI.
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