Abstract: Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever
with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia,
and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to
characterize associations of serum immunological, hemostatic or kidney injury markers to disease
severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic
patients (<100 × 109 platelets/L) compared to patients with higher platelet counts, RANTES was
significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was
used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like
growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in
patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below
30 m/min/1.73 m2
. The increased expression of these markers specifically indicates pathology in
glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon
gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney
dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central
role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this
cytokine in the pathogenesis of kidney dysfunction.
