Soluble urokinase Plasminogen Activator Receptor in Critical Illness

Event start date
Event start time
12.00
Place

Finn-Medi 5, auditorium, address: Biokatu 12.

Doctoral defence of Lic.Med. Ville Jalkanen

Soluble urokinase Plasminogen Activator Receptor in Critical Illness

The field of science of the dissertation is Anaesthesiology.

The opponent is docent Asko Järvinen (University of Helsinki). Professor Arvi Yli-Hankala acts as the custos.

The language of the dissertation defence is Finnish.

Soluble urokinase Plasminogen Activator Receptor in Critical Illness
 
Soluble urokinase Plasminogen Activator Receptor (suPAR) has been suggested as a prognostic biomarker in several conditions, e.g. malignancies and severe sepsis. SuPAR levels can be measured with a commercially available ELISA kit from different body fluids e.g. plasma, serum or cerebro-spinal fluid. In critical illness, the prognostic and diagnostic value of suPAR is not well established.
 
In order to evaluate suPAR in the recognition and prognostication in the critically ill patients, we investigated suPAR in four different, critically ill patient groups. The data were obtained from national multi-center study cohorts or from Tampere university hospital patient cohorts.
 
In the first substudy, we evaluated the prognostic value of suPAR in the critically ill patients with acute respiratory failure. In the national multicenter study, serum suPAR values were determined at different time points and the correlation to organ failure and outcome was evaluated. The samples were obtained from 454 critically ill patients. The results suggest that in non-operative patients circulating suPAR was elevated in non-survivors compared to survivors. Patients who developed a need for renal-replacement therapy in the intensive care had higher suPAR concentrations. SuPAR correlated to commonly used classification score for organ failures (SOFA-score). However, the prognostic value of suPAR was only weak to moderate. In addition, suPAR was not able to discriminate patients with most severe form of acute respiratory failure (ARDS).
 
In the second substudy, suPAR was evaluated as a prognostic biomarker after out-of-hospital cardiac arrest. The neurological outcome was assessed after 12 months in resuscitated patients and serum suPAR was evaluated as a prognostic biomarker for neurological outcome. Alltogether, 287 patients suffering from out-of-hospital cardiac arrest were evaluated in a national multi-center study. SuPAR was as good in neurological prognostication as the commonly used biomarker neuron-specific enolase (NSE). However, as a single biomarker, the prognostic value of suPAR was insufficient for clinical decision making. Low suPAR was prognostic for good neurological outcome.
 
Acute aneurysmal subarachnoid hemorrhage (aSAH) causes major mortality and morbidity. In order to evaluate suPAR in patients with aSAH, we measured circulating suPAR in 47 patients admitted to Tampere university hospital intensive care unit and suffering from aSAH. SuPAR was not prognostic for neurological outcome in patients with aSAH and overall suPAR levels were low.
 
Pre-eclampsia is a major cause for maternal mortality and morbidity worldwide. There are no available biomarkers for the detection of pre-eclampsia despite vast research. We determined suPAR levels in 10 patients with clinical pre-eclampsia and compared them to healthy pregnancy and fertile-aged non-pregnant controls. SuPAR levels were higher in patients with pre-eclampsia compared to other groups.
 
In conclusion, suPAR was prognostic in patients with acute respiratory failure and after out-of-hospital cardiac arrest. However, as  a single biomarker the prognostic value for clinical decision making is insufficient. In aSAH the levels of circulating suPAR are low and suPAR does not add to prognostication after aSAH. In pre-eclampsia suPAR levels are elevated and reflect the inflammatory reaction in pre-eclampsia. The clinical value of suPAR in pre-eclampsia should be further investigated.

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The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2319, Tampere University Press, Tampere 2017. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1823, Tampere University Press 2017.

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