Naheed Ali, MD, PhD

Acute kidney injury (AKI) and blackwater fever (BWF) have some relationship, but both of these are separate complications of acute febrile illness involving the kidneys. It was inferred from an observational cohort-based study that BWF is closely related to AKI in children who were hospitalized because of acute febrile illness [1]. In order to decrease mortality in these children, we need to understand the association between BWF and AKI more closely with increased access to technology for prompt and accurate diagnosis.

AKI is quite common in children and is an important cause of increased deaths. About eighty-five percent of cases of AKI are seen in countries with low and middle-income economies, and most of these cases are community-acquired. If not diagnosed and managed early, AKI may lead to chronic and irreversible kidney damage. The leading causes of AKI are malaria and sepsis in African children. Studies suggest that twenty-four to fifty-nine percent of children suffering from a severe form of malaria develop AKI as well [2].

An increase in AKI is being recognized in children with the severe complication of malaria known as BWF, in which hemolysis takes place, resulting in the accumulation of hemoproteins that overpower the ability of innate hemoprotein scavenger systems. These hemoproteins have renal excretion via PCT, and excess exposure to these proteins results in cellular injury, thereby increasing oxidative stress, endothelial activation, and inflammation of the interstitium of tubules, leading to AKI. But still, any systemic relationship between BWF and AKI hasn’t been established.

Various prospective cohort-based studies were done to examine the link between AKI and BWF with consequent mortality, and it was found that the rate of AKI in patients with BWF was 29%, whereas in those without BWF it was 9.5% [3]. The relationship between BWF, gender, and age was also studied, and it was concluded that males with BWF had about four times the increased risk of developing severe AKI. On the contrary, females with BWF or males without BWF didn’t have an increased risk.

It was also inferred that children who had RDT + (positive) for HRP-2 had a higher incidence of BWF as compared to those who didn’t have malaria. Antimalarials like artemisinins also cause increased hemolysis and may lead to AKI, but no clear evidence has been reported in this regard. Similarly, G6PD deficiency is not reported to have any effect on the pathogenesis of hemolysis in BWF.

Further studies need to be done to establish a proper relationship between AKI and BWF by investigating the prognostic and pathophysiologic factors. It should be determined what the mechanism of development of AKI is. Whether BWF diminishes the immune response or it is basically an alerting symptom that indicates the worsening of the situation is rather unclear.

Advancements in diagnostics and understanding will be required to timely manage the cases before they develop into life-threatening conditions. Early kidney protective measures are often required to preserve life in most cases. The most suitable time to initiate them is another question that needs to be addressed by establishing more research-based longitudinal studies.

References:

[1] Van Driest SL, Wang L, McLemore MF, et al. Acute kidney injury risk-based screening in pediatric inpatients: a pragmatic randomized trial. Pediatr Res. 2020;87(1):118-124.

[2] Batte A, Berrens Z, Murphy K, et al. Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges. Int J Nephrol Renovasc Dis. 2021;14:235-253. Published 2021 Jul 8.

[3] Conroy AL, Hawkes MT, Leligdowicz A, et al. Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: Pathophysiology and prognostic significance. BMC Medicine. 2022;20(1).