Novel Experimental Mouse Model to Study Malaria-Associated Acute Kidney Injury

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.

Automated summary

The impact of malaria-associated acute kidney injury (MAKI) has been underestimated and neglected in research, leading to a lack of standard mouse model for studying this pathology. This study developed an in vivo model in wild-type mice by performing unilateral nephrectomies prior to infection with Plasmodium berghei NK65. The nephrectomized mice showed kidney injury and elevated levels of acute kidney injury (AKI) biomarkers compared to non-nephrectomized mice. This model is critical for understanding the molecular pathways, disease development, biomarkers, and potential therapies for MAKI.