Biomarkers of kidney injury and klotho in patients with atherosclerotic renovascular disease

Clin J Am Soc Nephrol. 2015 Mar 6;10(3):443-51. doi: 10.2215/CJN.07290714. Epub 2014 Dec 26.

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Keywords: biomarkers; kidney injury; renovascular hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / complications
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Essential Hypertension
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Glomerular Filtration Rate
  • Glucuronidase / blood*
  • Humans
  • Hypertension / blood
  • Hypertension, Renovascular / blood*
  • Hypertension, Renovascular / etiology
  • Klotho Proteins
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood*
  • Prospective Studies
  • Receptors, Urokinase Plasminogen Activator / blood*
  • Renal Artery Obstruction / blood*
  • Renal Artery Obstruction / etiology
  • Renal Circulation
  • Renal Veins
  • Thromboplastin / metabolism
  • Vena Cava, Inferior

Substances

  • Biomarkers
  • FGF23 protein, human
  • Lipoproteins
  • Plasminogen Activator Inhibitor 1
  • Receptors, Urokinase Plasminogen Activator
  • lipoprotein-associated coagulation inhibitor
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Thromboplastin
  • Glucuronidase
  • Klotho Proteins