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Updated: Aug 1, 2025
Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
Novel Experimental Mouse Model to Study Malaria-Associated Acute Kidney Injury
Johanna Bensalel1,2, Alexandra Roberts1, Kiara Hernandez1
1Department of Biological Sciences, Bronx, Lehman College, The City University of New York, New York, NY 10468, USA.
Abstract:
The impact of malaria-associated acute kidney injury (MAKI), one of the strongest predictors of death in children with severe malaria (SM), has been largely underestimated and research in this area has been neglected. Consequently, a standard experimental mouse model to research this pathology is still lacking. The purpose of this study was to develop an in vivo model that resembles the pathology in MAKI patients. In this study, unilateral nephrectomies were performed on wild-type mice prior to infection with Plasmodium berghei NK65. The removal of one kidney has shown to be an effective approach to replicating the most common findings in humans with MAKI. Infection of nephrectomized mice, compared to their non-nephrectomized counterparts, resulted in the development of kidney injury, evident by histopathological analysis and elevated levels of acute kidney injury (AKI) biomarkers, including urinary neutrophil gelatinase-associated lipocalin, serum Cystatin C, and blood urea nitrogen. Establishment of this in vivo model of MAKI is critical to the scientific community, as it can be used to elucidate the molecular pathways implicated in MAKI, delineate the development of the disease, identify biomarkers for early diagnosis and prognosis, and test potential adjunctive therapies.
Insights
Researchers developed a novel mouse model for malaria-associated acute kidney injury (MAKI) by performing unilateral nephrectomies before infection. This model effectively replicates human MAKI pathology, aiding future research into this critical condition.
Area of Science:
- Nephrology
- Infectious Diseases
- Experimental Pathology
Background:
- Malaria-associated acute kidney injury (MAKI) is a severe complication of malaria, significantly increasing mortality in children.
- Research and effective experimental models for MAKI are lacking, hindering understanding and treatment development.
Purpose of the Study:
- To develop a standardized in vivo mouse model that accurately reflects the pathology observed in human MAKI patients.
- To provide a crucial tool for investigating the mechanisms, diagnosis, and treatment of MAKI.
Main Methods:
- Wild-type mice underwent unilateral nephrectomy (surgical removal of one kidney).
- Mice were subsequently infected with *Plasmodium berghei* NK65.
- Kidney injury was assessed through histopathological analysis and measurement of AKI biomarkers (urinary NGAL, serum Cystatin C, BUN).
Main Results:
- Nephrectomized mice infected with *P. berghei* NK65 exhibited significant kidney injury compared to non-nephrectomized controls.
- Elevated levels of key AKI biomarkers were observed in the infected, nephrectomized mice.
- The model successfully replicated common pathological findings seen in human MAKI.
Conclusions:
- The established unilateral nephrectomy and *P. berghei* NK65 infection model is a viable tool for studying MAKI.
- This model will facilitate research into MAKI's molecular pathways, disease progression, and the evaluation of potential adjunctive therapies.
