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Published on: February 5, 2020
Nephrotoxicity in patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies: a systematic review
Han Li1, Jinsheng Xu2, Yaling Bai1
1Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People's Republic of China.
Abstract:
Background Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) have dramatically improved cancer therapy for many patients. Adverse kidney effects have been found to be an important complication but have unclear mechanisms. Methods We searched Embase, PubMed, and the Cochrane Library to identify potential eligible studies. All included studies were randomized controlled trials (RCTs) examining patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) and/or chemotherapy. The relative risk (RR) was used to assess the risk of nephrotoxic events. Results We included 27 clinical trials (15,063 patients). Compared with chemotherapy, the RR of all-grade nephritis was significantly increased with anti-PD-1/PD-L1 mAbs (RR = 2.77, 95% CI: 1.09-6.99, P = 0.03). Furthermore, anti-PD-1/PD-L1 mAbs plus chemotherapy can significantly increase the RR of all-grade nephritis (RR = 2.99, 95% CI: 1.07-8.35, P = 0.04). There was also a significant increase in the RRs of all-grade increased blood creatinine (RR = 1.88, 95% CI: 1.24-2.86, P = 0.003) and acute kidney injury (AKI) (RR =3.35, 95% CI: 1.48-7.60, P = 0.004). Conclusions Anti-PD-1/PD-L1 mAbs can significantly increase nephrotoxicity in patients with solid tumors, especially when combined with chemotherapy. During the application of these drugs, we should remain aware of nephrotoxicity for better efficacy. Trial registration number and date of registration Not applicable.
Insights
Programmed death-1 (PD-1) and PD-L1 inhibitors significantly increase the risk of kidney damage, including nephritis and acute kidney injury, in cancer patients. This risk is elevated when these immunotherapies are combined with chemotherapy.
Area of Science:
- Oncology
- Nephrology
- Immunotherapy
Background:
- Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) immunotherapies have revolutionized cancer treatment.
- However, adverse kidney effects are a known complication with unclear mechanisms.
Purpose of the Study:
- To systematically evaluate the risk of nephrotoxicity associated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) in patients with solid tumors.
- To compare the incidence of kidney adverse events between anti-PD-1/PD-L1 mAbs and chemotherapy.
Main Methods:
- A comprehensive literature search was conducted across Embase, PubMed, and the Cochrane Library.
- Included studies were randomized controlled trials (RCTs) involving solid tumor patients treated with anti-PD-1/PD-L1 mAbs and/or chemotherapy.
- Relative risk (RR) was calculated to assess nephrotoxic events.
Main Results:
- Twenty-seven RCTs comprising 15,063 patients were analyzed.
- Anti-PD-1/PD-L1 mAbs significantly increased the risk of all-grade nephritis compared to chemotherapy (RR = 2.77).
- Combination therapy (mAbs + chemotherapy) also significantly elevated nephritis risk (RR = 2.99), alongside increased risks of elevated creatinine and acute kidney injury (AKI).
Conclusions:
- Anti-PD-1/PD-L1 mAbs significantly increase nephrotoxicity in solid tumor patients.
- The risk of kidney adverse events is particularly heightened when these agents are used in combination with chemotherapy.
- Clinical awareness of potential nephrotoxicity is crucial for optimizing the use of these immunotherapies.
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