Blood levels of the soluble urokinase plasminogen activator receptor (suPAR) protein may be a helpful tool for assessing disease severity and prognosis in people with ANCA-associated vasculitis (AAV), a new study reports.
The study, “The Plasma Soluble Urokinase Plasminogen Activator Receptor Is Related to Disease Activity of Patients with ANCA-Associated Vasculitis,” was published in the journal Mediators of Inflammation.
Although ANCA vasculitis involves multiple organs in the body, the kidneys are the most susceptible and their function can worsen rapidly. Identifying biomarkers that predict kidney disease and survival in these patients is needed to improve their clinical management.
The suPAR protein is involved in several inflammatory diseases and its levels in blood and urine appear to be associated with worse kidney function in people with kidney diseases. A study also has suggested this protein might be linked with clinical severity in AAV patients.
Researchers at Huazhong University of Science and Technology, China, set out to investigate the relationship between blood suPAR levels and clinical parameters of ANCA vasculitis. They also tested the value of suPAR as a prognostic tool.
The study included 90 AAV patients diagnosed at their facility from September 2014 to September 2016. Their average age was 53.8 years, most were female (58.9%), had kidney damage (63%), and autoantibodies targeting the myeloperoxidase (MPO) protein (88.9%).
Participants were compared with a control group of 35 healthy people matched to patients in sex and age.
Results showed that blood suPAR levels were significantly higher in ANCA vasculitis patients than in healthy people. Levels also were significantly higher in patients with active disease compared with those in partial remission.
Statistical analysis then demonstrated that suPAR blood levels were significantly associated with Birmingham Vasculitis Activity Score, a measure of disease activity, and with C-reactive protein, C3 protein, and procalcitonin, which denotes increased inflammation.
Finally, suPAR blood levels were associated significantly with worse kidney function, as measured with the biomarkers creatinine blood levels, blood urea nitrogen, and estimated Glomerular Filtration Rate (eGFR).
In fact, patients with higher suPAR levels (above 5,683 picograms per milliliter) were more likely to die or achieve end-stage renal disease (ESRD) — when the kidneys no longer work to meet the body’s needs, and patients need dialysis or a transplant — during the follow-up.
Additional analysis found that suPAR levels were able to significantly predict kidney survival in these patients. In a model adjusted for age and sex, an increase in suPAR levels by 500 picograms per milliliter (pg/mL) increased the risk of death or ESRD by 5%.
“Results indicate that plasma [blood] suPAR levels are associated with renal involvement and disease activity in patients with AAV,” the researchers wrote.
Researchers then established a concentration of 6,662.2 pg/mL as the optimal threshold for identifying patients more likely to die or achieve ESRD. This model had an accuracy of 82%, being able to identify about 62% of patients at risk, and 88% of patients who would not develop ESRD or die.
“suPAR has a promising prognostic value … indicating a relationship between elevated suPAR levels and high risk of poor outcomes and revealing a potential pathophysiological significance for suPAR,” the researchers concluded.