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Predictors of Acute Kidney Injury in Patients Prescribed Immune Checkpoint Inhibitor Therapy and Their Association
Jingying Sun1, Xiyou Zhang1, Yang Luo1
1Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Abstract:
Immune checkpoint inhibitors (ICIs) are a novel and promising anti-cancer therapy. We conducted this systematic review to precisely quantify the occurrence and development for actue kidney injury(AKI) following ICIs treatment for cancer. We conducted a search of the PubMed, Embase, Web of Science, and Cochrane Library databases. Twenty-nine studies, comprising 24,953 cancer patients who received ICIs were finally eligible. The incidence of AKI was 16.2% (95%CI:12.8%-19.8%); the incidence of immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) was 3.1%(95%CI:2.4%-4%); the incidence of non-ICPi-AKI was 11.2%(95%CI:8.4%-14.3%), and the incidence of sustained AKI was 14.9%(95%CI:7.5%-24.3%). Patients who developed AKI (HR = 1.521(95%CI:1.208-1.916)) and ICPi-AKI (HR = 1.407(95%CI:1.059-1.869)) exhibited an elevated risk of all-cause mortality. An increased risk for AKI was observed with preexisting chronic kidney disease (CKD) and combined with other extrarenal immune-related adverse events (irAEs). The use of nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitor (PPI), diuretic, renin-angiotensin-aldosterone system (RAASi), antibiotics and fluidone was also significantly associated with incident AKI. Combined therapy had a greater impact on renal injury compared to monotherapy. Patients using ipilimumab were more prone to developing AKI, compared to those using nivoluma. CTLA4 (ref'PD-1) was associated with a higher likelihood of sustained AKI. The use of PDL-1(ref='PD-1) was linked to an increased susceptibility to ICPi-AKI. The occurrence of AKI was intricately linked to specific complications, the concomitant use of certain medications, and the specific regimen of ICIs. This deserves our attention.
Insights
Immune checkpoint inhibitors (ICIs) can cause acute kidney injury (AKI) in cancer patients. This review found AKI incidence at 16.2%, with higher mortality risk and associations with specific medications and ICI types.
Area of Science:
- Oncology
- Nephrology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) represent a significant advancement in cancer therapy.
- Acute kidney injury (AKI) is a potential adverse event associated with ICI treatment.
- Understanding the incidence and risk factors for ICI-related AKI is crucial for patient management.
Purpose of the Study:
- To systematically review and quantify the occurrence of AKI in cancer patients treated with ICIs.
- To identify risk factors and patient characteristics associated with ICI-induced AKI.
- To assess the impact of AKI on mortality in patients receiving ICIs.
Main Methods:
- A systematic search of major biomedical databases (PubMed, Embase, Web of Science, Cochrane Library) was performed.
- Twenty-nine studies including 24,953 cancer patients treated with ICIs were included in the analysis.
- Incidence rates, hazard ratios for mortality, and associations with risk factors were calculated.
Main Results:
- The overall incidence of AKI was 16.2%, with immune checkpoint inhibitor-associated AKI (ICPi-AKI) at 3.1%.
- Patients with AKI and ICPi-AKI showed an increased risk of all-cause mortality (HR=1.521 and HR=1.407, respectively).
- Preexisting chronic kidney disease (CKD), combined immune-related adverse events (irAEs), and concomitant use of NSAIDs, PPIs, diuretics, RAAS inhibitors, antibiotics, and certain ICIs (ipilimumab, CTLA4, PDL-1) were associated with increased AKI risk.
Conclusions:
- AKI is a significant concern in patients receiving ICIs, associated with increased mortality.
- Specific patient comorbidities, concomitant medications, and ICI regimens influence AKI development.
- Close monitoring and risk factor management are essential for patients undergoing ICI therapy.
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