Hantavirus is a genus of the virus family Bunyaviridae, has manysub-species, and is endemic in several parts of the world. Human disease is caused by viral transmission from the excreta of infected rodents. Outside of endemic areas, which may be enlarging, nephrologists frequently know little about the disease.
The classic presentation is with influenza–like symptoms followed by a hypotensive phase with an often severe inflammatory response. Infection of endothelial cells cause increased vascular permeability, with lung and kidney involvement depending on the virus type. Old World Hantaviruses tend to cause hemorrhagic fever with renal syndrome (HFRS) while New World viruses classically cause human pulmonary syndrome (HPS), although some overlap may be observed. Kidney involvement with Hantavirus infection traditionally involves a tubulointerstitial injury with low levels of proteinuria but cases of overt proteinuria have been described in <25% of cases. A dense mononuclear infiltrate is typical, with tubular injury and medullary hemorrhage often seen.
In an article recently published in AJKD, Boehlke et al present a case of acute Hantavirus infection with concomitant nephrotic syndrome and acute kidney injury, which reversed following resolution of the infection. Light microscopy of the kidney biopsy revealed usual tubulointerstitial changes. Electron microscopy demonstrated widespread podocyte foot process effacement, and immunofluorescence showed disrupted podocyte morphology with mislocalization of the slit diaphragm protein podocin and the tight junction protein ZO-1. Podocytes express αvβ3-integrin which the Hantavirus may use to enter the cell, but why only certain viruses and equally important only certain individuals manifest severe glomerular involvement remains unclear. Genetic susceptibility has been described, with HLA B8, C4A*Q0, and DRB1*0301 alleles associated with particularly aggressive disease, but exact pathogenesis is yet to be determined. It must be noted that podocyte foot process effacement may occur with many insults, including viral infections (i.e. Parvovirus B19 and cytomegalovirus). Moreover HIV infection causes a collapsing glomerulopathy in genetically primed individuals, notably African Americans with APOL1 risk polymorphisms. This raises the possibility of modifier genes interacting with certain viral genotypes to produce alternative phenotypes in viral nephropathies.
To summarize, this report emphasizes that Hantavirus infection may cause a podocytopathy, as well as the classic tubulointerstitial nephritis pattern. It may occur rapidly and be fully reversible, suggesting that podocyte foot process effacement may be a functional and reversible reaction to glomerular epithelial cell stress.
Dr. Paul Phelan
Royal Infirmary of Edinburgh