Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients

Soon Hyo Kwon, John R. Woollard, Ahmed Saad, Vesna D Garovic, Ladan Zand, Kyra L. Jordan, Stephen C Textor, Lilach O Lerman

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin- angiotensin blockade). After isolation fromurine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.46 6.4, 6.8 6 3.4 and 6.3 6 3.7%, respectively; P 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target.

Original languageEnglish (US)
Pages (from-to)800-807
Number of pages8
JournalNephrology Dialysis Transplantation
Volume32
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Podocytes
Renovascular Hypertension
Kidney
Healthy Volunteers
Multidetector Computed Tomography
Renal Circulation
Angiotensins
Wounds and Injuries
Renin
Flow Cytometry
Therapeutics
Perfusion
Sodium
Pressure
Essential Hypertension
Extracellular Vesicles

Keywords

  • CKD
  • extracellular vesicles
  • hypertension
  • podocyte
  • renovascular hypertension

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients. / Kwon, Soon Hyo; Woollard, John R.; Saad, Ahmed; Garovic, Vesna D; Zand, Ladan; Jordan, Kyra L.; Textor, Stephen C; Lerman, Lilach O.

In: Nephrology Dialysis Transplantation, Vol. 32, No. 5, 01.05.2017, p. 800-807.

Research output: Contribution to journalArticle

@article{cd14add48c0c4134af59acac26761a1d,
title = "Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients",
abstract = "Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin- angiotensin blockade). After isolation fromurine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.46 6.4, 6.8 6 3.4 and 6.3 6 3.7{\%}, respectively; P 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target.",
keywords = "CKD, extracellular vesicles, hypertension, podocyte, renovascular hypertension",
author = "Kwon, {Soon Hyo} and Woollard, {John R.} and Ahmed Saad and Garovic, {Vesna D} and Ladan Zand and Jordan, {Kyra L.} and Textor, {Stephen C} and Lerman, {Lilach O}",
year = "2017",
month = "5",
day = "1",
doi = "10.1093/ndt/gfw077",
language = "English (US)",
volume = "32",
pages = "800--807",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients

AU - Kwon, Soon Hyo

AU - Woollard, John R.

AU - Saad, Ahmed

AU - Garovic, Vesna D

AU - Zand, Ladan

AU - Jordan, Kyra L.

AU - Textor, Stephen C

AU - Lerman, Lilach O

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin- angiotensin blockade). After isolation fromurine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.46 6.4, 6.8 6 3.4 and 6.3 6 3.7%, respectively; P 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target.

AB - Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin- angiotensin blockade). After isolation fromurine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.46 6.4, 6.8 6 3.4 and 6.3 6 3.7%, respectively; P 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target.

KW - CKD

KW - extracellular vesicles

KW - hypertension

KW - podocyte

KW - renovascular hypertension

UR - http://www.scopus.com/inward/record.url?scp=85020236475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020236475&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfw077

DO - 10.1093/ndt/gfw077

M3 - Article

VL - 32

SP - 800

EP - 807

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 5

ER -