Investigação de novos biomarcadores renais em pacientes com Leishmaniose visceral

Abstract

Background: Visceral leishmaniasis (VL) is an important parasitic neglected tropical disease that affects million people in many countries. VL is deadly if untreated, mostly in acute kidney injury (AKI) development. Aims: to evaluate the role of novel kidney biomarkers in pathophysiology of renal injury and in predict AKI diagnosis of VL patients. Methods: Was performed a prospective study with 50 VL patients between April 2015 and January 2017 in a reference hospital of infectious disease, Ceará, Brazil. At admission and after VL diagnostic, random urine samples and blood were collected. AKI development in VL patients during hospital stay was defined according to KDIGO criteria. Were evaluated clinical and renal parameters associated with severity of VL. The novel kidney biomarkers: serum and urinary NGAL (sNGAL, uNGAL), serum cystatin C, urinary KIM-1 (uKIM-1) and urinary MCP-1 (uMCP-1) were quantified using immunoassay method (ELISA). Also, INF-y and CRP were measured as inflammatory biomarkers in VL pathophysiology. Statitical correlations, logistic regression and ROC curve analysis were performed to evaluated the role of novel kidney biomarkers in kidney abnormalities and diagnostic of AKI in VL patients Results: VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia and important hematologic and hepatic disorders. The AKI development was present in 46% and one case died (2%). The “AKI” group had significant more hospital stay, lower levels of IFN-y and higher CRP and IL-6 levels, clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM-1 and uMCP-1. sNGAL, uKIM-1 and uMCP-1 had important correlations with various clinical renal abnormalities as proteinuria, albuminuria, serum creatinine and glomerular filtration rate, including when using adjusted correlations with IFN-y and CRP. Only sNGAL was significantly associated with AKI development (O.R.= 1.227, 95% CI: 1.074-1.403 per each increase of 10 ng/mL), even after adjust for VL severity and immune biomarkers. sNGAL presented better performance in AKI diagnosis (AUC-ROC=0.814, 95% CI: 0.692-0.936) and with cut-off=154 ng/mL had a sensitivity = 82.6% and specificity = 74.1% (p<0.001). Conclusion: VL patients had important proximal tubular injury and glomerular inflammation associated with proteinuria and albuminuria. sNGAL was the most reliable biomarker to predict the risk for AKI development in VL patients, even after excluding the host’s immune response influence.