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Kidney dysfunction associated with severe P. vivax malaria
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In a retrospective analysis of malaria infections caused by Plasmodium vivax, researchers found that severe cases were often associated with abnormal creatinine increases, especially among patients who died from the mosquito-borne disease.
“These findings reinforce the hypothesis that renal dysfunction is a key component in P. vivax malaria associated with clinical severity and mortality, possibly through intense inflammation and immune imbalance,” Bruno B. Andrade, MD, PhD, from the Oswaldo Cruz Foundation in Brazil, and colleagues wrote in PLoS Neglected Tropical Diseases. “Our study argues for systematic evaluation of kidney function as part of the clinical assessment in vivax malaria patients and warrants additional studies in experimental models for further mechanism investigations.”
According to WHO, at least 216 million people were infected with malaria in 2016 and around 445,000 died. Five Plasmodium species can cause malaria in humans. P. vivax is the dominant parasite in most countries outside of sub-Saharan Africa and has historically been associated with milder diseases than infections caused by P. falciparum, the most prevalent and deadliest malaria parasite in Africa.
Andrade and colleagues said severe clinical presentations of P. vivax infection have increased in recent years but are not well-understood and that multiorgan involvement has been reported in some severe cases, although there is not much evidence linking it to kidney dysfunction.
For their study, they assessed data from 179 patients with P. vivax monoinfection — including 18 severe infections, six of them fatal — from a databank of 572 people recruited in 2006 to 2007 for a malaria study in the Brazilian Amazon. They analyzed data based on levels of creatinine, a marker of kidney function, as well as indicators of inflammation, according to a news release, and compared the results with 165 healthy controls from the same databank.
According to their analysis, 16.85% of patients with P. vivax infection and elevated creatinine presented with severe disease compared with just 3.33% of patients with normal values.
“Following a similar pattern, frequency of hospitalization was also elevated in patients with elevated creatinine levels vs. those with normal values,” Andrade and colleagues wrote.
“Moreover,” they continued, “all [six] patients who did not survive were among the group of individuals presenting with the highest creatinine levels; two of them presented with anuric renal failure while the other four presented respiratory failure as the major presentation at admission. Furthermore, within the group of patients with abnormally high creatinine values, nonsurvivors presented with even higher levels when compared with survivors.”
Andrade and colleagues also found that a particular ratio of proteins and C-reactive protein values “could distinguish subjects with elevated creatinine levels who did not survive from those who did.”
“We predict that the systemic inflammation observed in more severely ill malaria patients could be contributing to kidney dysfunction through different mechanisms,” they concluded. “In addition, the overall evaluation of biomarkers suggests that liver abnormalities and hyperbilirubinemia could also play a role in severe vivax malaria-associated kidney dysfunction. The identification of key factors driving the pathogenesis of this type of disease presentation and experimental models still are necessary to guide future studies and approaches.” – by Gerard Gallagher
Disclosures: The authors report no relevant financial disclosures.
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