Analysis of Serum Creatinine Data from Long-tailed and Rhesus Macaques to Assess Malaria-associated Acute Kidney Injury

Abstract

Malaria caused by the protozoan parasite Plasmodium is associated with vast morbidity and mortality worldwide. Among the serious clinical complications of this disease are acute kidney injury (AKI) and acute kidney disease (AKD), characterized by a decline in kidney function measurable by changes in serum creatinine. Research using nonhuman primates (NHPs) has revealed commonalities between NHPs and humans in malaria pathogenesis. Here, we perform a reanalysis of serum creatinine data from published studies on P. knowlesi malaria infections of long-tailed (natural host) and rhesus (nonnatural host) macaques to assess AKI and AKD. In rhesus macaques, despite receiving antimalarial treatment to reduce parasitemia, delayed onset of AKD occurred days to weeks post-treatment, showing a disconnect between parasitemia and AKD. While the high mortality of rhesus macaques prohibited a prolonged experimental design, the use of long-tailed macaques, naturally resistant to P. knowlesi, enabled longer time series studies and revealed more details about disease progression. Most long-tailed macaques, despite having a natural ability to control parasitemia, also exhibited a delayed onset of AKD in the period following peak parasitemia. Altogether, this study shows that both rhesus and long-tailed macaques exhibit a delayed onset of AKD during malaria, as has been reported in humans.