Soluble Urokinase Receptor and Chronic Kidney Disease

Abstract

BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.)

SuPAR, an emerging biomarker in kidney and inflammatory diseases

“…Hence, suPAR affects the αvβ3 integrins pathway, resulting in the inability of podocytes to adapt to physiological events 9. This highlights a proposed mechanism behind which suPAR is involved in the development of different pathologies including chronic kidney diseases (CKD), focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) 10. Two major studies with several thousands of individuals showed that plasma suPAR is associated with new onset kidney disease 10.…”

“…This highlights a proposed mechanism behind which suPAR is involved in the development of different pathologies including chronic kidney diseases (CKD), focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) 10. Two major studies with several thousands of individuals showed that plasma suPAR is associated with new onset kidney disease 10. Higher suPAR level at baseline was associated with a greater decline in the estimated glomerular filtration rate (eGFR) during subsequent visits and was associated with incident CKD 10.…”

Soluble Urokinase Plasminogen Activator Receptor is Associated with Coronary Artery Calcification and Cardiovascular Disease in Patients Undergoing Hemodialysis

“…suPAR is also a novel indicator of risk in the CKD population. A recent large study involving 3683 patients demonstrated that elevated suPAR levels were independently associated with the incidence of CKD and predicted an accelerated decline in the estimated glomerular filtration rate in groups [22]. …”

What is the Role of Soluble Urokinase-Type Plasminogen Activator in Renal Disease?

“…Following the description of suPAR as a potential FSGS “circulating factor” came the publication of a major paper delineating a relationship between suPAR levels at baseline assessment and progression of CKD [37]. …”