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

Sandhya Manohar, Panagiotis Kompotiatis, Charat Thongprayoon, Wisit Cheungpasitporn, Joerg Herrmann, Sandra Herrmann

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: The 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. Methods: We 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. Results: A 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%). Conclusions: Treatment 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.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Programmed Cell Death 1 Receptor
Hypocalcemia
Acute Kidney Injury
Meta-Analysis
Confidence Intervals
Electrolytes
Odds Ratio
Therapeutics
Clinical Trials
Interstitial Nephritis
Incidence
MEDLINE
Databases
Calcium
Kidney

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

@article{5cbc7ef4d1e8442ab3fd9680d83a7408,
title = "Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis",
abstract = "Background: The 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. Methods: We 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. Results: A 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{\%}). Conclusions: Treatment 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.",
author = "Sandhya Manohar and Panagiotis Kompotiatis and Charat Thongprayoon and Wisit Cheungpasitporn and Joerg Herrmann and Sandra Herrmann",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/ndt/gfy105",
language = "English (US)",
volume = "34",
pages = "108--117",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia

T2 - meta-analysis

AU - Manohar, Sandhya

AU - Kompotiatis, Panagiotis

AU - Thongprayoon, Charat

AU - Cheungpasitporn, Wisit

AU - Herrmann, Joerg

AU - Herrmann, Sandra

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The 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. Methods: We 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. Results: A 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%). Conclusions: Treatment 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.

AB - Background: The 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. Methods: We 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. Results: A 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%). Conclusions: Treatment 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.

UR - http://www.scopus.com/inward/record.url?scp=85058648086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058648086&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfy105

DO - 10.1093/ndt/gfy105

M3 - Article

C2 - 29762725

AN - SCOPUS:85058648086

VL - 34

SP - 108

EP - 117

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 1

ER -