scholarly journals Cisplatin Effects in Lung Adenocarcinoma-bearing Mice, Alone and in Combination with Erlotinib

2018 ◽  
Vol 46 (8) ◽  
pp. 1049-1050
Author(s):  
Cierra N. Sharp
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Dose Regimen ◽  
Low Dose ◽  
Kidney Injury ◽  
Transgenic Mouse Model ◽  
Cisplatin Nephrotoxicity

Cisplatin causes nephrotoxicity that can lead to the development of acute kidney injury or chronic kidney disease. However, the current mouse model of cisplatin nephrotoxicity is neither physiologically nor clinically relevant. Our goal was to improve upon these deficits by developing a repeated, low-dose regimen of cisplatin and combining it with a transgenic mouse model of lung adenocarcinoma. This overview details how addressing these deficits have improved our understanding of cisplatin-induced kidney injury.

scholarly journals Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury–to–chronic kidney disease progression

2017 ◽  
Vol 91 (1) ◽  
pp. 157-176 ◽  
Author(s):  
Björn Tampe ◽  
Ulrike Steinle ◽  
Désirée Tampe ◽  
Julienne L. Carstens ◽  
Peter Korsten ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Disease Progression ◽  
Murine Model ◽  
Low Dose ◽  
Kidney Injury ◽  
Chronic Kidney Disease Progression ◽  
Kidney Disease Progression

scholarly journals Cyclophilin D Promotes Acute, but Not Chronic, Kidney Injury in a Mouse Model of Aristolochic Acid Toxicity

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 700
Author(s):  
Khai Gene Leong ◽  
Elyce Ozols ◽  
John Kanellis ◽  
Frank Y. Ma ◽  
David J. Nikolic-Paterson
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Cell Death ◽  
Kidney Disease ◽  
Low Dose ◽  
Aristolochic Acid ◽  
Chinese Herb ◽  
Kidney Injury ◽  
High Dose ◽  
Cyclophilin D

The plant-derived toxin, aristolochic acid (AA), is the cause of Chinese Herb Nephropathy and Balkan Nephropathy. Ingestion of high dose AA induces acute kidney injury, while chronic low dose ingestion leads to progressive kidney disease. Ingested AA is taken up by tubular epithelial cells of the kidney, leading to DNA damage and cell death. Cyclophilin D (CypD) participates in mitochondrial-dependent cell death, but whether this mechanism operates in acute or chronic AA-induced kidney injury is unknown. We addressed this question by exposing CypD-/- and wild type (WT) mice to acute high dose, or chronic low dose, AA. Administration of 5 mg/kg AA to WT mice induced acute kidney injury 3 days later, characterised by loss of kidney function, tubular cell damage and death, and neutrophil infiltration. All of these parameters were significantly reduced in CypD-/- mice. Chronic low dose (2 mg/kg AA) administration in WT mice resulted in chronic kidney disease with impaired renal function and renal fibrosis by day 28. However, CypD-/- mice were not protected from AA-induced chronic kidney disease. In conclusion, CypD facilitates AA-induced acute kidney damage, but CypD does not contribute to the transition of acute kidney injury to chronic kidney disease during ongoing AA exposure.

scholarly journals The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation

2020 ◽  
Vol 97 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Katsuyuki Matsushita ◽  
Turgay Saritas ◽  
Mahaba B. Eiwaz ◽  
Nicholas McClellan ◽  
Ian Coe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Mouse Model ◽  
Kidney Injury ◽  
Cardiorenal Syndrome

scholarly journals Subclinical kidney injury induced by repeated cisplatin administration results in progressive chronic kidney disease

2018 ◽  
Vol 315 (1) ◽  
pp. F161-F172 ◽  
Author(s):  
Cierra N. Sharp ◽  
Mark A. Doll ◽  
Judit Megyesi ◽  
Gabrielle B. Oropilla ◽  
Levi J. Beverly ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Mouse Model ◽  
Chronic Inflammation ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Dosing Regimen ◽  
Repeated Dosing

Cisplatin is used to treat many solid cancers, but its dose-limiting side effect is nephrotoxicity, causing acute kidney injury in 30% of patients. Previously, we have developed a mouse model that better recapitulates the cisplatin dosing regimen humans receive and found that repeated dosing of cisplatin induces interstitial renal fibrosis. Chronic kidney disease is progressive and is characterized by chronic inflammation, worsening interstitial fibrosis, development of glomerulosclerosis, and endothelial dysfunction. To determine if damage caused by repeated cisplatin dosing results in bona fide chronic kidney disease, mice were treated with our repeated dosing regimen and then aged for 6 mo. These mice had progressive, chronic inflammation and worsened interstitial fibrosis compared with mice euthanized after day 24. Mice aged for 6 mo developed glomerular pathologies, and endothelial dysfunction was persistent. Mice treated with only two doses of cisplatin had little inflammation or kidney damage. Thus repeated dosing of cisplatin causes long-term effects that are characteristic of chronic kidney disease. This translational mouse model of cisplatin injury may better represent the 70% of patients that do not develop clinical acute kidney injury and can be used to identify both biomarkers for early injury, as well as novel therapeutic targets for the prevention of cisplatin-induced chronic kidney disease.

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