title: 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 m(2) 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 m(2) among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.73 m(2) among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥ 90 ml per minute per 1.73 m(2)) 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 m(2), 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.).
authors.affiliation: From the Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine (S.S.H., Y.-A.K., M.A., L.S.S., S.L., A.A.Q.), and the Department of Biostatistics and Bioinformatics, Emory University (Y.-A.K.) - both in Atlanta; the Department of Medicine, Harvard Medical School, Boston, and Division of Nephrology, Massachusetts General Hospital, Charlestown - both in Massachusetts (S.S.); the Department of Pediatrics, NYU Langone Medical Center, New York (H.T.); and the Department of Medicine, Rush University Medical Center (S.W., M.M.A., C.W., A.L.F., J.R.), and the Women's Interagency HIV Study/CORE Center of Cook County (A.L.H., A.L.F.) - both in Chicago.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Hayek
authors.forename: Sanja
authors.initials: S
authors.lastname: Sever
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Ko
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: Mosaab
authors.initials: M
authors.lastname: Awad
authors.forename: Shikha
authors.initials: S
authors.lastname: Wadhwani
authors.forename: Mehmet M
authors.initials: MM
authors.lastname: Altintas
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.forename: Anna L
authors.initials: AL
authors.lastname: Hotton
authors.forename: Audrey L
authors.initials: AL
authors.lastname: French
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Sperling
authors.forename: Stamatios
authors.initials: S
authors.lastname: Lerakis
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator