Rodent Models of AKI and AKI-CKD Transition: an Update in 2024

Overview

Journal Am J Physiol Renal Physiol

Publisher American Physiological Society

Specialties Nephrology
Physiology

Date 2024 Feb 1

PMID 38299215

Authors

Ying Fu

Yu Xiang

Qingqing Wei

Daria Ilatovskaya

Zheng Dong

Affiliations

Soon will be listed here.

Abstract

Despite known drawbacks, rodent models are essential tools in the research of renal development, physiology, and pathogenesis. In the past decade, rodent models have been developed and used to mimic different etiologies of acute kidney injury (AKI), AKI to chronic kidney disease (CKD) transition or progression, and AKI with comorbidities. These models have been applied for both mechanistic research and preclinical drug development. However, current rodent models have their limitations, especially since they often do not fully recapitulate the pathophysiology of AKI in human patients, and thus need further refinement. Here, we discuss the present status of these rodent models, including the pathophysiologic compatibility, clinical translational significance, key factors affecting model consistency, and their main limitations. Future efforts should focus on establishing robust models that simulate the major clinical and molecular phenotypes of human AKI and its progression.

Citing Articles

Oxidative stress and NRF2 signaling in kidney injury.

Ng C, Kim M, Yanti , Kwak M Toxicol Res. 2025; 41(2):131-147.

PMID: 40013079 PMC: 11850685. DOI: 10.1007/s43188-024-00272-x.

Leucine-rich alpha-2-glycoprotein 1 deficiency suppresses ischemia-reperfusion injury-induced renal fibrosis.

Okami N, Wakui H, Azushima K, Miyazawa T, Kubo E, Tsukamoto S Sci Rep. 2025; 15(1):1259.

PMID: 39779883 PMC: 11711393. DOI: 10.1038/s41598-024-84798-y.

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts.

Rudman-Melnick V, Vanhoutte D, Stowers K, Sargent M, Adam M, Ma Q Sci Rep. 2024; 14(1):29307.

PMID: 39592775 PMC: 11599588. DOI: 10.1038/s41598-024-80930-0.

Recent advances in extracellular matrix manipulation for kidney organoid research.

Wang R, Sui Y, Liu Q, Xiong Y, Li S, Guo W Front Pharmacol. 2024; 15:1472361.

PMID: 39568581 PMC: 11576200. DOI: 10.3389/fphar.2024.1472361.

VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition.

Melchinger I, Guo K, Li X, Guo J, Cantley L, Xu L Am J Physiol Renal Physiol. 2024; 327(4):F610-F622.

PMID: 39116349 PMC: 11483080. DOI: 10.1152/ajprenal.00076.2024.

References

Tu Y, Wang H, Sun R, Ni Y, Ma L, Xv F . Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury. Ren Fail. 2014; 36(10):1559-63. DOI: 10.3109/0886022X.2014.949764. View

Harwood R, Bridge J, Ressel L, Scarfe L, Sharkey J, Czanner G . Murine models of renal ischemia reperfusion injury: An opportunity for refinement using noninvasive monitoring methods. Physiol Rep. 2022; 10(5):e15211. PMC: 8907719. DOI: 10.14814/phy2.15211. View

Landau S, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R . Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney Int. 2019; 95(4):797-814. PMC: 6543531. DOI: 10.1016/j.kint.2018.11.042. View

Schentag J, PLAUT M, Cerra F . Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients. Antimicrob Agents Chemother. 1981; 19(5):859-66. PMC: 181535. DOI: 10.1128/AAC.19.5.859. View

Solez K, MOREL-MAROGER L, Sraer J . The morphology of "acute tubular necrosis" in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore). 1979; 58(5):362-76. View

Danelli L, Madjene L, Madera-Salcedo I, Gautier G, Pacreau E, Ben Mkaddem S . Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury. J Immunol. 2017; 198(6):2374-2382. DOI: 10.4049/jimmunol.1601282. View

Mohamed A, Hosney M, Bassiony H, Hassanein S, Soliman A, Fahmy S . Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats. Sci Rep. 2020; 10(1):378. PMC: 6962368. DOI: 10.1038/s41598-019-57252-7. View

Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw S, Bell M . Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013; 17(1):R25. PMC: 4057242. DOI: 10.1186/cc12503. View

Humphreys B, Valerius M, Kobayashi A, Mugford J, Soeung S, Duffield J . Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008; 2(3):284-91. DOI: 10.1016/j.stem.2008.01.014. View

10.

Ravichandran K, Wang Q, Ozkok A, Jani A, Li H, He Z . CD4 T cell knockout does not protect against kidney injury and worsens cancer. J Mol Med (Berl). 2015; 94(4):443-55. DOI: 10.1007/s00109-015-1366-z. View

11.

Ramesh G, Ranganathan P . Mouse models and methods for studying human disease, acute kidney injury (AKI). Methods Mol Biol. 2014; 1194:421-36. DOI: 10.1007/978-1-4939-1215-5_24. View

12.

Skrypnyk N, Siskind L, Faubel S, de Caestecker M . Bridging translation for acute kidney injury with better preclinical modeling of human disease. Am J Physiol Renal Physiol. 2016; 310(10):F972-84. PMC: 4889323. DOI: 10.1152/ajprenal.00552.2015. View

13.

Mittwede P, Xiang L, Lu S, Clemmer J, Hester R . A novel experimental model of orthopedic trauma with acute kidney injury in obese Zucker rats. Physiol Rep. 2013; 1(5):e00097. PMC: 3841033. DOI: 10.1002/phy2.97. View

14.

Jama H, R Muralitharan R, Xu C, ODonnell J, Bertagnolli M, Broughton B . Rodent models of hypertension. Br J Pharmacol. 2021; 179(5):918-937. DOI: 10.1111/bph.15650. View

15.

Espandiari P, Rosenzweig B, Zhang J, Zhou Y, Schnackenberg L, Vaidya V . Age-related differences in susceptibility to cisplatin-induced renal toxicity. J Appl Toxicol. 2009; 30(2):172-82. PMC: 2829343. DOI: 10.1002/jat.1484. View

16.

Infante B, Conserva F, Pontrelli P, Leo S, Stasi A, Fiorentino M . Recent advances in molecular mechanisms of acute kidney injury in patients with diabetes mellitus. Front Endocrinol (Lausanne). 2023; 13:903970. PMC: 9849571. DOI: 10.3389/fendo.2022.903970. View

17.

Miura K, Goldstein R, Morgan D, Pasino D, Hewitt W, Hook J . Age-related differences in susceptibility to renal ischemia in rats. Toxicol Appl Pharmacol. 1987; 87(2):284-96. DOI: 10.1016/0041-008x(87)90290-0. View

18.

Sharp C, Siskind L . Developing better mouse models to study cisplatin-induced kidney injury. Am J Physiol Renal Physiol. 2017; 313(4):F835-F841. PMC: 5668582. DOI: 10.1152/ajprenal.00285.2017. View

19.

Adler S, Schwartz S, Williams M, Arauz-Pacheco C, Bolton W, Lee T . Phase 1 study of anti-CTGF monoclonal antibody in patients with diabetes and microalbuminuria. Clin J Am Soc Nephrol. 2010; 5(8):1420-8. PMC: 2924405. DOI: 10.2215/CJN.09321209. View

20.

Baatarjav C, Komada T, Karasawa T, Yamada N, Sampilvanjil A, Matsumura T . dsDNA-induced AIM2 pyroptosis halts aberrant inflammation during rhabdomyolysis-induced acute kidney injury. Cell Death Differ. 2022; 29(12):2487-2502. PMC: 9750976. DOI: 10.1038/s41418-022-01033-9. View