title: Biomarkers of kidney injury and klotho in patients with atherosclerotic renovascular disease.
abstract: OBJECTIVE
  Occlusive renovascular disease and hypertension may progress to CKD. Circulating levels of several biomarkers, including fibroblast growth factor (FGF)-23, Klotho, and soluble urokinase plasminogen activator receptor (suPAR), are altered in patients with CKD, but their role in essential hypertension (EH) and renovascular hypertension (RVH) remains unclear.
  
  
  METHODS
  Levels of FGF-23, Klotho, suPAR, plasminogen activator inhibitor (PAI)-1, tissue factor, and tissue factor pathway inhibitor (TFI) were measured in the inferior vena cava and renal vein of hypertensive patients with atherosclerotic renal artery stenosis (n=12) or age-matched participants with EH (n=12) and relatively preserved renal function. Single-kidney blood flow was measured to calculate renal release of markers. For control, peripheral vein levels were measured in healthy volunteers (HVs; n=12).
  
  
  RESULTS
  FGF-23 levels did not differ among the groups, whereas Klotho levels were lower in participants with RVH and EH than in HVs, and suPAR levels were elevated in patients with RVH compared with HVs and patients with EH (6.1±1.5 versus 4.4±1.9 and 3.2±1.2 ng/ml, P<0.05). PAI-1 levels were higher in patients with RVH than in patients with EH, but tissue factor and TFI levels were not statistically significantly different. After adjustment for GFR, Klotho levels remained decreased in both RVH and EH, and suPAR and PAI-1 levels remained elevated in RVH. eGFR correlated inversely with systemic and renal vein suPAR levels, and directly with systemic Klotho levels.
  
  
  CONCLUSIONS
  Klotho levels are low in hypertensive patients, whereas suPAR and PAI-1 levels are specifically elevated in RVH, correlating with GFR. Klotho, PAI-1, and suPAR may be markers of kidney injury in hypertensive patients.
authors.affiliation: Divisions of Nephrology and Hypertension and Department of Internal Medicine, Soonchunhyang University, College of Medicine, Bucheon, Korea.
authors.forename: Moo Yong
authors.initials: MY
authors.lastname: Park
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Herrmann
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Saad
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
authors.affiliation: Divisions of Nephrology and Hypertension and Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; and lerman.lilach@mayo.edu.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000150:complications; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D000075222:Essential Hypertension; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood; D006978:Hypertension, Renovascular / Q000097:blood* / Q000209:etiology; D000090265:Klotho Proteins; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012078:Renal Artery Obstruction / Q000097:blood* / Q000209:etiology; D012079:Renal Circulation; D012082:Renal Veins; D013925:Thromboplastin / Q000378:metabolism; D014682:Vena Cava, Inferior
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D055293:Receptors, Urokinase Plasminogen Activator; C051928:lipoprotein-associated coagulation inhibitor; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D013925:Thromboplastin; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: biomarkers; kidney injury; renovascular hypertension