Acute kidney injury associated with dengue virus infection: a review

Abstract

Acute kidney injury (AKI) is one of the least studied complications of dengue, but it carries high mortality rates and prolonged hospital stay. Due to the severity of this complication, the risk of developing chronic kidney disease (CKD) and the increasing number of dengue cases reported worldwide, particularly in the tropical and subtropical regions of Africa, Southeast Asia and South America, including Brazil, we embarked on this narrative review, aimed to update the epidemiology of AKI associated with dengue, elucidate the main pathophysiological mechanisms of AKI caused by the dengue virus infection, as well as discuss useful information on the prevention and management of AKI in patients with dengue.

Primary infection of BALB/c mice with a dengue virus type 4 strain leads to kidney injury

“…Overall, the results described in this study are in line with what is seen in human cases of dengue presenting renal manifestations. Histopathological alterations observed fit the descriptions of dengue-induced AKI published in the related literature, 13 , 16 albeit milder, and non-lethal.…”

“… 12 , 13 , 14 More severe manifestations, such as acute kidney injury (AKI), rhabdomyolysis, glomerulonephritis, haemolytic uremic syndrome, and acute renal failure, are often associated to lethal cases of SD. 11 , 15 , 16 Histopathological alterations described in renal tissue include congestion of the glomerular capillary, focal haemorrhage, oedema, inflammatory cell infiltration, hydropic degeneration, formation of micro abscesses, thrombus formation in the glomeruli, glomerular congestion and acute necrosis of proximal and distal tubules. 6 , 17 - 22 On an ultrastructural level, these necrotic tubular cells were shown to be undergoing pyknosis, with dilated endoplasmic reticulum.…”

“… 31 Although the mechanisms that lead to AKI are not yet fully understood, its appearance is hypothesised to be due to a series of factors, such as the direct cytopathic viral action, cytokine induced haemodynamical alterations, deposition of antigen-antibody immune complexes, rhabdomyolysis, haemolysis and acute glomerular injury. 13 , 16 , 27 , 32 …”

Transcriptomics of Marburg virus-infected primary proximal tubular cells reveals negative correlation of immune response and energy metabolism

“…Hantavirus-induced AKI is mainly associated to infection of endothelial cells, tubulointerstitial nephritis and dysregulated cytokine release ( Krautkrämer et al, 2013 ; Mir, 2022 ). The pathophysiology of DENV-associated AKI is seen in dysregulated cytokine release and primarily glomerular injury ( Bignardi et al, 2022 ; Lima et al, 2007 ). On the contrary, renal epithelial cells infected with ZIKV exhibit NLRP3 inflammasome activation ( Chen et al, 2017 ; Liu et al, 2019 ).…”

Severe dengue in the intensive care unit

“…[ 135 ] Although not yet fully understood, some mechanisms suggested as causes of AKI in severe dengue are hypotension – leading to hypoperfusion and tubular necrosis – direct injury caused by the virus, indirect injury via the immune system, and rhabdomyolysis. [ 136 , 137 ] Immunohistochemical studies performed on kidney specimens from fatal human cases of dengue infection found viral RNA and observed an accumulation of immune cells and intense acute congestion, suggesting that a combination of high viral load, exacerbated immune response, and increased permeability play a role in renal damage during dengue infection. [ 138 , 139 ]…”