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Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis

Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and... ABSTRACTBackgroundThe aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors.MethodsWe conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579.ResultsA total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95–3.64] and 1.67 (95% CI 0.89–3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57–11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40–84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5–3.0%) and 1.0% (95% CI 0.6–1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2–26.0%).ConclusionsTreatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nephrology Dialysis Transplantation Oxford University Press

Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
ISSN
0931-0509
eISSN
1460-2385
DOI
10.1093/ndt/gfy105
Publisher site
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Abstract

ABSTRACTBackgroundThe aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors.MethodsWe conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579.ResultsA total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95–3.64] and 1.67 (95% CI 0.89–3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57–11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40–84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5–3.0%) and 1.0% (95% CI 0.6–1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2–26.0%).ConclusionsTreatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring.

Journal

Nephrology Dialysis Transplantation – Oxford University Press

Published: Jan 1, 2019

Keywords: acute kidney injury; hypocalcemia; nivolumab; PD-1 inhibitor; pembrolizumab

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