Visceral leishmaniasis-associated nephropathy in hospitalised Brazilian patients: new insights based on kidney injury biomarkers

Abstract

Objective: To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis. Methods: Prospective study with 50 hospitalised VL patients. AKI biomarkers, that is, serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL, uNGAL, respectively), urinary kidney injury molecule-1 (uKIM-1) and urinary monocyte chemotactic protein-1 (uMCP-1), were quantified by immunoassay (ELISA). Also, interferon-gamma (INF-y) and C-reactive protein (CRP) were evaluated as inflammatory biomarkers possibly related to VL severity. Results: VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, haematologic and hepatic disorders. AKI was found in 46%, and one death (2%) occurred. The AKI group had significant longer hospital stay, lower levels of IFN-y and higher levels of CRP, more clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM-1 and uMCP-1. Overall, sNGAL, uKIM-1 and uMCP-1 showed correlations with important clinical renal abnormalities, such as proteinuria, albuminuria, serum creatinine and glomerular filtration rate using adjusted correlations with CRP and IFN-y. Only sNGAL showed an early association with AKI development (OR = 2.78, 95% CI = 1.429–5.428, per each increase of 50 ng/ml), even after adjusting for clinical signals of VL severity and for immune biomarkers. Moreover, sNGAL showed a better performance in predicting AKI development (AUC-ROC = 0.81, 95% CI = 0.69–0.93; cut-off = 154 ng/ml, sensitivity = 82.6%, specificity = 74.1%, P < 0.001). Conclusions: Visceral leishmaniasis-associated nephropathy showed important proximal tubular injury and glomerular inflammation. Serum NGAL showed an early association with VL-associated nephropathy and may be used to improve clinical management strategies and decrease morbimortality in VL patients.