Urine soluble urokinase‐type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection

• Published in: Journal of internal medicine Vol. 276; no. 4; pp. 387 - 395
• Main Authors: Outinen, T. K., Mäkelä, S., Huttunen, R., Mäenpää, N., Libraty, D., Vaheri, A., Mustonen, J., Aittoniemi, J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2014
• Subjects: acute kidney injury; Adult; Aged; Albuminuria; Convalescence; Correlation; Creatinine; Creatinine - blood; Creatinine - urine; Endothelial cells; Excretion; Female; Hantavirus; Hemorrhagic Fever with Renal Syndrome - blood; Hemorrhagic Fever with Renal Syndrome - urine; Humans; Infections; Integrins; Iron; Kidneys; Male; Middle Aged; Prospective Studies; Proteinuria; Puumala virus; Receptors; Receptors, Urokinase Plasminogen Activator - blood; Receptors, Urokinase Plasminogen Activator - metabolism; soluble urokinase‐type plasminogen activator receptor; suPAR; Thrombolytic drugs; tubulointerstitial nephritis; U-Plasminogen activator; Urine; Urokinase; Young Adult; soluble urokinase-type plasminogen activator receptor; acute kidney injury; hantavirus; suPAR; tubulointerstitial nephritis
• ISSN: 0954-6820; 1365-2796; 1365-2796
• DOI: 10.1111/joim.12257

Objectives Urokinase‐type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to β3‐integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3‐integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection. Design A single‐centre, prospective cohort study. Subjects and methods Urinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) was calculated. Results The FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8–52.0%, vs. median 1.9%, range 1.0–5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001) and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001) and an inverse correlation with minimum urinary output (r = −0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324). Conclusion Urinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection.