Virus-Associated Nephropathies: A Narrative Review

Abstract

While most viral infections cause mild symptoms and a spontaneous favorable resolution, some can lead to severe or protracted manifestations, specifically in immunocompromised hosts. Kidney injuries related to viral infections may have multiple causes related to the infection severity, drug toxicity or direct or indirect viral-associated nephropathy. We review here the described virus-associated nephropathies in order to guide diagnosis strategies and treatments in cases of acute kidney injury (AKI) occurring concomitantly with a viral infection. The occurrence of virus-associated nephropathy depends on multiple factors: the local epidemiology of the virus, its ability to infect renal cells and the patient's underlying immune response, which varies with the state of immunosuppression. Clear comprehension of pathophysiological mechanisms associated with a summary of described direct and indirect injuries should help physicians to diagnose and treat viral associated nephropathies.

Keywords: acute kidney injury; glomerulopathy; nephropathy; viral infection.

Figure 1

Main representative direct (a,d) and indirect (b,c) mechanisms observed in viral nephropathies. (a) Podocyte infection by HIV leads to expression of HIV transgenes which promote dedifferentiation and vacuolization of podocytes. Abnormal podocytes detach from the glomerular basement membrane, leading to collapse of the capillary coves and flocculus. (b) The B cell-mediated reaction to viral infection, especially during HCV, can lead to the production of immune complexes consisting of specific IgG and IgM that fix viral particles, possibly with a cryoglobulinemic property. These complexes will further disseminate through the whole organism, and notably throughout the glomerular capillaries where they induce neutrophil and T cell recruitment, leading to the MPGN pattern. (c) Patients with the APOL-1 at-risk polymorphism carry a risk of collapsing glomerulopathy, especially if a “second” hit occurs involving the interferon pathway. The APOL-1 variant transcript is thus increased, leading to podocyte differentiation and progression to collapsing glomerulopathy. (d) Epithelial renal tubular cells are infected with BKPyV, leading to intranuclear viral inclusions (Stage 1), further evolving towards cytoplasmic modifications with a local immune reaction (Stage 2) and finally cell apoptosis and fibrosis (Stage 3).