Glomerular filtration barrier dysfunction in an RNA virus-induced glomerulopathy resembles findings of common nephrotic syndromes

Background: Virally induced kidney dysfunction is highlighted by the alarming incidence of SARS-CoV-2 associated acute renal disease including nephrotic syndrome (NS) Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) are elevated in COVID patients and provide prognostic insights SuPAR is also involved in proteinuric kidney diseases such as focal segmental glomerulosclerosis in which podocytes effacement/injury is a common feature Hantavirus-induced hemorrhagic fever with renal syndrome (HFRS) represents another RNA virus-induced disease with acute kidney injury and NS The exact pathophysiology of proteinuria is, however, unclear We hypothesized that hantavirus infection results in podocyte injury and a dysfunctional glomerular filtration barrier (GFB), similar to findings in common NS Methods: Renal biopsy specimens were analyzed by light and electron microscopy Urinary nephrin and serum suPAR were measured over time in 26 patients with HFRS and 18 healthy controls Results: Hantavirus patients showed significantly increased urinary nephrin, immunoglobulin G (IgG), a1-microglobulin (a1-MG) and serum suPAR concentrations compared to healthy controls Furthermore, nephrin and IgG levels were significantly higher in patients with severe than with mild proteinuria Differences in a1-MG levels, however, disappeared after normalization to urinary creatinine Urinary nephrin levels as a marker for podocyte damage correlated strongly with biomarkers of non-selective glomerular proteinuria Interestingly, suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a potential pathophysiological mediator in GFB dysfunction in response to RNA virus infection The main finding in microscopy analyses was a focal foot process effacement Proteinuria and kidney dysfunction recovered autonomously in all patients Conclusions: Hantavirus infection causes a podocyte injury leading to GFB dysfunction A better understanding of transient virally induced proteinuria syndromes and their often self-limiting disease character may generate new therapeutic approaches for NS