Expression of cleaved caspase-3 in renal tubular cells in Plasmodium falciparum malaria patients.

AIM: In Plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (AKI) is commonly associated with acute tubular necrosis (ATN) in the kidney tissues. Renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. To study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys. METHODS: Kidney tissues from P. falciparum malaria with AKI (10 cases), and without AKI (10 cases) were evaluated for tubular pathology. Normal kidney tissues from 10 cases served as controls. Tubular necrosis was assessed quantitatively in kidney tissues infected with P. falciparum malaria, based on histopathological evaluation. In addition, the occurrence of apoptosis was investigated using cleaved caspase-3 marker. Correlation between tubular necrosis and apoptosis was analyzed. RESULTS: Tubular necrosis was found to be highest in P. falciparum malaria patients with AKI (36.44% ± 3.21), compared to non-AKI (15.88% ± 1.63) and control groups (2.58% ± 0.39) (all p < 0.001). In the AKI group, the distal tubules showed a significantly higher degree of tubular necrosis than the proximal tubules (p = 0.021) and collecting tubules (p = 0.033). Tubular necrosis was significantly correlated with the level of serum creatinine (r = 0.596, p = 0.006), and the occurrence of apoptosis (r = 0.681, p = 0.001). CONCLUSION: In malarial AKI, the process of apoptosis occurs in ATN.

Glomerular changes and alterations of zonula occludens-1 in the kidneys of Plasmodium falciparum malaria patients.

BACKGROUND: The process of cytoadhesion in Plasmodium falciparum malaria infection causes signaling processes that lead to structural and functional changes at the cellular level. Histopathological changes of acute kidney injury (AKI) in P. falciparum malaria often involve glomerular proliferation, thickening of the glomerular basement membrane, acute tubular necrosis, and interstitial inflammation. Focusing on the glomeruli, this study aimed to investigate glomerular and tight junction-associated protein- zonula occludens-1 (ZO-1) changes in P. falciparum malaria patients. METHODS: Kidney tissues were grouped into P. falciparum with AKI (Cr ≥ 265 µmol/L or 3 mg/dl), P. falciparum without AKI (Cr < 265 µmol/L), and normal kidney tissues (control group). Glomerular cells and the glomerular area were quantified and compared in three experimental groups. The tight junction was investigated immunohistochemically using tight junction-associated protein, ZO-1, protein marker. A further immunofluorescence study was performed in an endothelial cell (EC)-parasitized red blood cell (PRBC) co-culture system, to evaluate the tight junction protein. RESULTS: Glomerular cell proliferation was significant in P. falciparum with AKI (Cr ≥ 265 µmol/L). By contrast, the glomerular area decreased significantly. ZO-1 expression was significantly decreased in the AKI group compared with normal kidneys, and in kidney tissues without AKI (p < 0.05). This was further confirmed by the depletion in ZO-1 localization in ECs co-cultured with PRBCs. CONCLUSIONS: In P. falciparum malaria with AKI, the decrease in glomerular area, despite glomerular cell proliferation, could be due to the collapse of cellular structures secondary to damaged tight junction-associated protein, ZO-1.