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

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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 patientswith 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 (6.161.5 versus 4.461.9 and 3.261.2 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.

Original languageEnglish (US)
Pages (from-to)443-451
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number3
DOIs
StatePublished - 2015

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Renovascular Hypertension
Urokinase Plasminogen Activator Receptors
Biomarkers
Plasminogen Activator Inhibitor 1
Kidney
Wounds and Injuries
Renal Veins
Thromboplastin
Renal Artery Obstruction
Inferior Vena Cava
Essential Hypertension
Veins
Healthy Volunteers

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

@article{3743de0ebd4c4d86a25b5cec55231dda,
title = "Biomarkers of kidney injury and klotho in patients with atherosclerotic renovascular disease",
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 patientswith 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 (6.161.5 versus 4.461.9 and 3.261.2 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.",
author = "Park, {Moo Yong} and Sandra Herrmann and Ahmed Saad and Alfonso Eirin and Hui Tang and Amir Lerman and Textor, {Stephen C} and Lerman, {Lilach O}",
year = "2015",
doi = "10.2215/CJN.07290714",
language = "English (US)",
volume = "10",
pages = "443--451",
journal = "Clinical Journal of the American Society of Nephrology",
issn = "1555-9041",
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T1 - Biomarkers of kidney injury and klotho in patients with atherosclerotic renovascular disease

AU - Park, Moo Yong

AU - Herrmann, Sandra

AU - Saad, Ahmed

AU - Eirin, Alfonso

AU - Tang, Hui

AU - Lerman, Amir

AU - Textor, Stephen C

AU - Lerman, Lilach O

PY - 2015

Y1 - 2015

N2 - 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 patientswith 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 (6.161.5 versus 4.461.9 and 3.261.2 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.

AB - 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 patientswith 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 (6.161.5 versus 4.461.9 and 3.261.2 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.

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