Preliminary Study for New Markers of Early Tubuloglomerular Injury and Renal Inflammation in Patients with Visceral Leishmaniasis Receiving Liposomal Amphotericin B Treatment.

Visceral leishmaniasis is treated with liposomal amphotericin B (L-AMB), which is associated with nephrotoxicity. Thus, we aimed to investigate nephrotoxicity through novel renal biomarkers in patients with visceral leishmaniasis during L-AMB use. Ours was a prospective study with 17 patients with visceral leishmaniasis treated with L-AMB during their hospital stay. Laboratory tests, renal parameters, urinary biomarkers (urinary kidney injury molecule 1, urinary monocyte chemoattractant protein 1 [uMCP-1], sodium-potassium-2 chloride cotransporter, sodium-hydrogen exchanger 3), and serum inflammatory biomarkers (MCP-1, interferon-γ, and IL-6) were evaluated in two periods: before and during L-AMB use. Glomerular filtration rate, creatinine, proteinuria, and albuminuria were similar before and during L-AMB use. IL-6 levels, aquaporin 2, and sodium-hydrogen exchanger 3 expression decreased, whereas uMCP-1 and urinary kidney injury molecule 1 levels increased during L-AMB treatment. In patients who developed acute kidney injury, uMCP-1 showed higher levels. L-AMB aggravated tubuloglomerular lesions, inflammation, and renal tubular disorders. Thus, patients treated with L-AMB need to be monitored for inflammatory and electrolyte disturbances to prevent acute kidney injury, longer length of hospital stay, higher public costs, and mortality.

Involvement of NADPH-oxidase enzyme in the nephroprotective effect of (-)-α-bisabolol on HK2 cells exposed to ischemia - Reoxygenation.

Acute Kidney Injury (AKI) is associated with high morbidity and mortality. Ischemia and reperfusion (I/R) are events that lead to AKI through hypoxia, reactive oxygen species (ROS) production, oxidative stress and apoptosis. We aimed to evaluate the mechanism of nephroprotection mediated by Bisabolol in human tubular kidney cells after injury by I/R in vitro. HK2 cells were exposed to I/R and treated with Bisabolol. Cell viability was accessed by MTT assay. Cells were submitted to flow cytometry to evaluate necrotic/apoptotic cells, reactive oxygen species production and mitochondrial transmembrane depolarization. TBARS and GSH were used as parameters of redox balance. Also, KIM-1 supernatant levels were measured. In order to identify an interaction between bisabolol and NOX4, molecular docking and enzymatic assays were performed. Expression of isoform NOX4 on treated cells was examined by western-blot. Finally, cells were visualized by scanning electron microscopy. Bisabolol improved cell viability and prevented cell death by apoptosis, indicated also by the decreased levels of KIM-1. It was observed a decrease on reactive oxygen species production and mitochondrial depolarization, with antioxidant regulation by increased GSH and decreased lipid peroxidation. It was also demonstrated that bisabolol treatment can inhibit NOX4. Finally, SEM images showed that bisabolol reduced I/R-induced cell damage. Bisabolol treatment protects HK2 cells against oxidative damage occasioned by I/R. This effect is related to inhibition of apoptosis, decrease on KIM-1 release, reactive oxygen species accumulation and mitochondrial dysfunction. Bisabolol inhibited NOX4 activity in the tubular cells, impairing reactive oxygen species synthesis.