Characterization of Renal Damage Associated with Oncologic Immunotherapy
Abstract Immune checkpoint inhibitors (IPCIs) are a remarkable pharmacological group on cancer immunotherapy. IPCIs are administered in monotherapy or in combination therapy with chemotherapeutics such as cisplatin, showing excellent clinical results. However, they are not exempt from adverse reactions such as IPCI-induced renal injury, which has been minimally studied and worsens the patient’s prognosis. The aim of the study was the functional characterization of renal damage associated with IPCIs (anti-CTLA-4 and anti-PD-1), and their combination with cisplatin, by means of a battery of renal injury biomarkers. In the study, male C57BL/6 mice were divided into experimental groups. Each group received correspondingly; anti-PD-1, anti-CTLA-4, cisplatin, or the combined therapy of cisplatin+anti-CTLA-4+anti-PD-1. Biomarker analysis was performed using colorimetric and immunoassay techniques. The data were subjected to statistical analysis using IBM SPSS® Statistics software. Plasma biomarkers (creatinine and urea) did not show renal injury in any treatment group, whereas urinary biomarkers (NGAL, KIM-1 and albumin) increased in the combined therapy groups showing subclinical renal damage. Therefore, urinary biomarkers could be advantageous in the early diagnosis of renal damage associated with IPCIs in oncology patients.
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Perazella MA, Shirali AC. Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do? Kidney Int. enero de 2020; 97(1):62-74. DOI: 10.1016/j.kint.2019.07.022
Quimby FW, Luong RH. Clinical Chemistry of the Laboratory Mouse. Mouse Biomed Res. 2007; 171-216. DOI: 10.1016/B978-012369454-6/50060-1
Sharp CN, Siskind LJ. Developing better mouse models to study cisplatin-induced kidney injury. Am J Physiol-Ren Physiol. 1 de octubre de 2017; 313(4):F835-841. DOI: 10.1152/ajprenal.00285.2017
Smertka M, Chudek J. Using NGAL as an Early Diagnostic Test of Acute Kidney Injury. Ren Fail. febrero de 2012; 34(1):130-133. DOI: 10.3109/0886022X.2011.623500
Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008; 48:463-493. DOI: 10.1146/annurev.pharmtox.48.113006.094615
Wu H, Huang J. Drug-Induced Nephrotoxicity: Pathogenic Mechanisms, Biomarkers and Prevention Strategies. Curr Drug Metab. 2018; 19(7):559-567. DOI: 10.2174/1389200218666171108154419
Agrawal S, Smoyer WE. Role of albumin and its modifications in glomerular injury. Pflüg Arch - Eur J Physiol. 1 de agosto de 2017; 469(7):975-982. DOI: 10.1007/s00424-017-2029-4
Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec; 13(6):638-644. DOI: 10.1097/MCC.0b013e3282f07570
Centanni M, Moes DJAR, Trocóniz IF, Ciccolini J, van Hasselt JGC. Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors. Clin Pharmacokinet. 2019 Jul; 58(7):835-857. DOI: 10.1007/s40262-019-00748-2
Cortazar FB, Marrone KA, Troxell ML, Ralto KM, Hoenig MP, Brahmer JR et al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int. septiembre de 2016; 90(3):638-647. DOI: 10.1016/j.kint.2016.04.008
Flynn MJ, Larkin JMG. Novel combination strategies for enhancing efficacy of immune checkpoint inhibitors in the treatment of metastatic solid malignancies. Expert Opin Pharmacother. 2017 Oct; 18(14):1477-1490. DOI: 10.1080/14656566.2017.1369956
Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury. Kidney Int. julio de 2002 [citado 12 de marzo de 2022]; 62(1):237-244. DOI: 10.1046/j.1523-1755.2002.00433.x
Izzedine H, Mateus C, Boutros C, Robert C, Rouvier P, Amoura Z, Mathian A. Renal effects of immune checkpoint inhibitors. Nephrol Dial Transplant. 2017 Jun 1; 32(6):936-942. DOI: 10.1093/ndt/gfw382
Hryniewicki AT, Wang C, Shatsky RA, Coyne CJ. Management of Immune Checkpoint Inhibitor Toxicities: A Review and Clinical Guideline for Emergency Physicians. J Emerg Med. octubre de 2018; 55(4):489-502. DOI: 10.1016/j.jemermed.2018.07.005
Perazella MA, Shirali AC. Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do? Kidney Int. enero de 2020; 97(1):62-74. DOI: 10.1016/j.kint.2019.07.022
Quimby FW, Luong RH. Clinical Chemistry of the Laboratory Mouse. Mouse Biomed Res. 2007; 171-216. DOI: 10.1016/B978-012369454-6/50060-1
Sharp CN, Siskind LJ. Developing better mouse models to study cisplatin-induced kidney injury. Am J Physiol-Ren Physiol. 1 de octubre de 2017; 313(4):F835-841. DOI: 10.1152/ajprenal.00285.2017
Smertka M, Chudek J. Using NGAL as an Early Diagnostic Test of Acute Kidney Injury. Ren Fail. febrero de 2012; 34(1):130-133. DOI: 10.3109/0886022X.2011.623500
Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008; 48:463-493. DOI: 10.1146/annurev.pharmtox.48.113006.094615
Wu H, Huang J. Drug-Induced Nephrotoxicity: Pathogenic Mechanisms, Biomarkers and Prevention Strategies. Curr Drug Metab. 2018; 19(7):559-567. DOI: 10.2174/1389200218666171108154419
Abril, A., Tascón, J., Vicente-Vicente, L., Casanova, A. G., Prieto, M., & Morales, A. I. (2023). Characterization of Renal Damage Associated with Oncologic Immunotherapy. FarmaJournal, 8(1), 7–19. https://doi.org/10.14201/fj202381719
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