Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury
Cisplatin is a widely used chemotherapeutic agent used to treat solid tumours, such as ovarian, head and neck, and testicular germ cell. A known complication of cisplatin administration is acute kidney injury (AKI). The development of effective tumour interventions with reduced nephrotoxicity relies...
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doaj-c5d6a497150248cfa219e233e93c16112020-11-25T01:14:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-06-012012301110.3390/ijms20123011ijms20123011Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney InjurySara J. Holditch0Carolyn N. Brown1Andrew M. Lombardi2Khoa N. Nguyen3Charles L. Edelstein4Division of Renal Diseases and Hypertension, University of Colorado at Denver, Box C281, 12700 East, 19th Ave, Aurora, CO 80045, USADivision of Renal Diseases and Hypertension, University of Colorado at Denver, Box C281, 12700 East, 19th Ave, Aurora, CO 80045, USADivision of Renal Diseases and Hypertension, University of Colorado at Denver, Box C281, 12700 East, 19th Ave, Aurora, CO 80045, USADivision of Renal Diseases and Hypertension, University of Colorado at Denver, Box C281, 12700 East, 19th Ave, Aurora, CO 80045, USADivision of Renal Diseases and Hypertension, University of Colorado at Denver, Box C281, 12700 East, 19th Ave, Aurora, CO 80045, USACisplatin is a widely used chemotherapeutic agent used to treat solid tumours, such as ovarian, head and neck, and testicular germ cell. A known complication of cisplatin administration is acute kidney injury (AKI). The development of effective tumour interventions with reduced nephrotoxicity relies heavily on understanding the molecular pathophysiology of cisplatin-induced AKI. Rodent models have provided mechanistic insight into the pathophysiology of cisplatin-induced AKI. In the subsequent review, we provide a detailed discussion of recent advances in the cisplatin-induced AKI phenotype, principal mechanistic findings of injury and therapy, and pre-clinical use of AKI rodent models. Cisplatin-induced AKI murine models faithfully develop gross manifestations of clinical AKI such as decreased kidney function, increased expression of tubular injury biomarkers, and tubular injury evident by histology. Pathways involved in AKI include apoptosis, necrosis, inflammation, and increased oxidative stress, ultimately providing a translational platform for testing the therapeutic efficacy of potential interventions. This review provides a discussion of the foundation laid by cisplatin-induced AKI rodent models for our current understanding of AKI molecular pathophysiology.https://www.mdpi.com/1422-0067/20/12/3011cisplatinacute kidney injuryAKIapoptosisinflammationoxidative stress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sara J. Holditch Carolyn N. Brown Andrew M. Lombardi Khoa N. Nguyen Charles L. Edelstein |
spellingShingle |
Sara J. Holditch Carolyn N. Brown Andrew M. Lombardi Khoa N. Nguyen Charles L. Edelstein Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury International Journal of Molecular Sciences cisplatin acute kidney injury AKI apoptosis inflammation oxidative stress |
author_facet |
Sara J. Holditch Carolyn N. Brown Andrew M. Lombardi Khoa N. Nguyen Charles L. Edelstein |
author_sort |
Sara J. Holditch |
title |
Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury |
title_short |
Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury |
title_full |
Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury |
title_fullStr |
Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury |
title_full_unstemmed |
Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury |
title_sort |
recent advances in models, mechanisms, biomarkers, and interventions in cisplatin-induced acute kidney injury |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-06-01 |
description |
Cisplatin is a widely used chemotherapeutic agent used to treat solid tumours, such as ovarian, head and neck, and testicular germ cell. A known complication of cisplatin administration is acute kidney injury (AKI). The development of effective tumour interventions with reduced nephrotoxicity relies heavily on understanding the molecular pathophysiology of cisplatin-induced AKI. Rodent models have provided mechanistic insight into the pathophysiology of cisplatin-induced AKI. In the subsequent review, we provide a detailed discussion of recent advances in the cisplatin-induced AKI phenotype, principal mechanistic findings of injury and therapy, and pre-clinical use of AKI rodent models. Cisplatin-induced AKI murine models faithfully develop gross manifestations of clinical AKI such as decreased kidney function, increased expression of tubular injury biomarkers, and tubular injury evident by histology. Pathways involved in AKI include apoptosis, necrosis, inflammation, and increased oxidative stress, ultimately providing a translational platform for testing the therapeutic efficacy of potential interventions. This review provides a discussion of the foundation laid by cisplatin-induced AKI rodent models for our current understanding of AKI molecular pathophysiology. |
topic |
cisplatin acute kidney injury AKI apoptosis inflammation oxidative stress |
url |
https://www.mdpi.com/1422-0067/20/12/3011 |
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