Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection
Article first published online: 14 MAY 2014
© 2014 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 276, Issue 4, pages 387–395, October 2014
How to Cite
Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection. J Intern Med 2014; 276: 387–395., , , , , , , (Tampere University Hospital, Tampere; School of Medicine, University of Tampere, Tampere; Fimlab Laboratories, Tampere, Finland; University of Massachusetts Medical School, Worcester, MA, USA; and Haartman Institute, University of Helsinki, Helsinki, Finland).
- Issue published online: 20 SEP 2014
- Article first published online: 14 MAY 2014
- Accepted manuscript online: 9 APR 2014 11:00PM EST
- Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital. Grant Number: 9P031
- Fimlab. Grant Number: X50000
- Diagnosis and control of rodent-borne viral zoonoses in Europe. Grant Number: QLK2-CT-2002-01358
- National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID). Grant Number: U19 AI57319
- Academy of Finland
- Sigrid Jusélius Foundation
- Finnish Kidney Foundation
- Orion-Farmos Research Foundation
- acute kidney injury;
- soluble urokinase-type plasminogen activator receptor;
- tubulointerstitial nephritis
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.
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.
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).
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.