The changing epidemiology of malaria-associated acute kidney injury in African children and a recap of theories of pathogenesis - a narrative review.

Background: Increased reports of malaria-associated acute kidney injury (MAKI) among African children have largely been attributed to the adoption of more sensitive diagnostic criteria. The burden, factors affecting its distribution, and the effect of changing malaria transmission patterns remain unclear. Similarly, MAKI impact on patient outcomes is not well described. The purpose of this narrative review was to describe the epidemiology and the outcomes of MAKI among African children as well as to summarize the pathogenetic pathways that may be involved in the development of MAKI. Methods: We searched databases for information on MAKI epidemiology in African children as well as theories of its pathogenesis using key search terms. Results: MAKI prevalence among children varies widely with the highest rates reported in intermediate malaria transmission intensity regions. Unlike historical cohorts, the effect of age was unclear. Dialysis access is limited probably accounting for observed high mortality rates and data on progression to CKD is scanty. Exact mechanisms of MAKI pathogenesis remain elusive but, the two most dominant theories of pathogenesis are cytoadherence and haem pigment nephrotoxicity. Amplifying factors include endothelial activation, oxidative stress, coagulopathy, and dysregulated inflammation. Furthermore, the effectiveness of haem protein scavengers and genetic polymorphisms in inflammatory and antioxidant pathways likely impact the risk of developing MAKI. Conclusion: The burden of MAKI is likely to increase as the malaria transmission intensity shifts towards intermediate levels across the continent. Mortality remains unacceptably high among MAKI cohorts, a reflection of limited access to organ support facilities. Haem-related nephrotoxicity and cytoadherence are key to MAKI pathogenesis, amplified by dysregulated inflammation, endothelial activation, and oxidative stress. More research on the impact of MAKI, factors affecting progression to CKD and improved strategies to advocate for greater access to organ support are required. Clarity on pathogenesis would help to identify possible molecules for adjuvant therapies and risk prediction.