Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment

Abstract

Malaria remains a important global disease with more than 200 million cases and 600 000 deaths each year. Malaria-associated acute kidney injury (MAKI) may occur in up to 40% of patients with severe malaria and is associated with increased mortality. Histopathological characteristics of AKI in malaria are acute tubular injury, interstitial nephritis, focal segmental glomerulosclerosis, collapsing glomerulopathy and glomerulonephritis. We observed that C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) develop MAKI in parallel with malaria-associated acute respiratory distress syndrome (MA-ARDS). MAKI pathology was associated with proteinuria, acute tubular injury and collapse of glomerular capillary tufts, which resolved rapidly after treatment with antimalarial drugs. Importantly, parasite sequestration was not detected in the kidneys in this model. Furthermore, with the use of skeleton binding protein-1 (SBP-1) KO PbNK65 parasites, we found that parasite sequestration in other organs and its subsequent high parasite load are not required for the development of experimental MAKI. Similar proteinuria, histopathological features, and increases in kidney expression of interferon-γ, TNF-α, kidney injury molecule-1 (KIM-1) and heme oxygenase-1 (HO-1) was observed in both infected groups despite a significant difference in parasite load. Taken together, we introduce a model of experimental AKI in malaria with important similarities to AKI in malaria patients. Therefore, this mouse model might be important to further study the pathogenesis of AKI in malaria.

Exchange transfusion combined with artesunate (ET-AS) as a safe and effective therapy in severe P. falciparum malaria: a case series

“…The length of ICU stay range from 2 ~ 10 days, and all patients treated with ET-AS remained in the hospital for 3 ~ 19 days, significantly shorter than the findings reported by previous studies [30,31]. Malaria-associated acute kidney injury with severe malaria is associated with increased mortality [32]. Renal replacement therapy has been found to be associated with improved survival rate and recovery of renal function [33].…”

Exchange Transfusion combined with Artesunate (ET-AS) as a safe and effective Therapy in Severe P. falciparum Malaria: A retrospective case series

“…The median length of ICU and hospital treatments stay is 3 days and 6 days, signi cantly shorter than the ndings reported by previous studies [19,20] . Malaria-associated acute kidney injury with severe malaria is associated with increased mortality [21] . Renal replacement therapy has been found to be associated with improved survival rate and recovery of renal function [22] .…”

Effect of moringa extract on parasitemia, monocyte activation and organomegaly among Mus musculus infected by Plasmodium berghei ANKA

“…Renal enlargement can be caused by obstruction of blood circulation in glomerular, tubular necrosis and hydronephrosis [22,23] and is linked to the localization of host monocytes in the kidney as well as sequestration of parasitized erythrocyte [23]. Malaria-associated acute kidney injury is characterized by elevated levels of acute kidney injury (AKI) biomarkers, including urinary neutrophil gelatinase-associated lipocalin, serum cystatin C, and blood urea nitrogen [24][25]. Deposit of malarial pigment in the glomerular area also contributes to worsening renal destruction and results in renal failure in severe malaria infection [23,25].…”

“…Malaria-associated acute kidney injury is characterized by elevated levels of acute kidney injury (AKI) biomarkers, including urinary neutrophil gelatinase-associated lipocalin, serum cystatin C, and blood urea nitrogen [24][25]. Deposit of malarial pigment in the glomerular area also contributes to worsening renal destruction and results in renal failure in severe malaria infection [23,25]. Sequestration by Plasmodium infection disturbed the microcirculation and blood filtration of waste products [24,26]…”