Abstract
Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.
Highlights
Dengue virus (DENV) has four related but antigenically distinct serotypes (DENV-1 to 4)
In the proximal convoluted tubules (PCT), loss of the apical cell portion and cytoplasmic remains in light were observed in cases 2 and 4 (Figure 1D,F), and congestion of peritubular capillaries was found in cases 1, 2, and 4 (Figure 1B,E,H)
In addition to the changes described in the renal glomerulus, a focus of interstitial fibroedema and tubular atrophy with discrete mononuclear inflammatory infiltrate, focal cell necrosis, granular material in the fibrous endarteritis lumen into the intertubular arteries, and focal hemorrhage were observed only in case 3 (Figure 1C)
Summary
Dengue virus (DENV) has four related but antigenically distinct serotypes (DENV-1 to 4). In Brazil, the first DENV-4 cases leading to this serotype spread nationwide, occurring in Roraima and Amazonas in 2010, about 30 years after its first detection in the country [6]. In 2012, DENV-4 was prevalent and detected in 63% of the cases reported in Brazil [7]. 2013 (1,452,289 cases), DENV-4 circulation was associated with mild cases [8,9], but severe and fatal cases due to DENV-4 were reported [10]. There has been no definitive association of the different DENV serotypes within the clinical course of the disease, it has been suggested that DENV-2 and DENV-3 are more frequently associated with severe disease [11]
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