Inflammatory and injury signals released from the post-stenotic human kidney

Alfonso Eirin, Monika L. Gloviczki, Hui Tang, Mario Gössl, Kyra L. Jordan, John R. Woollard, Amir Lerman, Joseph Peter Grande, Stephen C Textor, Lilach O Lerman

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Aims The mechanisms mediating kidney injury and repair in humans with atherosclerotic renal artery stenosis (ARAS) remain poorly understood. We hypothesized that the stenotic kidney releases inflammatory mediators and recruits progenitor cells to promote regeneration.Methods and resultsEssential hypertensive (EH) and ARAS patients (n= 24 each) were studied during controlled sodium intake and antihypertensive treatment. Inferior vena cava (IVC) and renal vein (RV) levels of CD34+/KDR+ progenitor cells, cell adhesion molecules, inflammatory biomarkers, progenitor cell homing signals, and pro-angiogenic factors were measured in EH and ARAS, and their gradient and net release compared with systemic levels in matched normotensive controls (n= 24). Blood pressure in ARAS was similar to EH, but the glomerular filtration rate was lower. Renal vein levels of soluble E-Selectin, vascular cell adhesion molecule-1, and several inflammatory markers were higher in the stenotic kidney RV vs. normal and EH RV (P< 0.05), and their net release increased. Similarly, stem-cell homing factor levels increased in the stenotic kidney RV. Systemic CD34+/KDR+ progenitor cell levels were lower in both EH and ARAS and correlated with cytokine levels. Moreover, CD34+/KDR+ progenitor cells developed a negative gradient across the ARAS kidney, suggesting progenitor cell retention. The non-stenotic kidney also showed signs of inflammatory processes, which were more subtle than in the stenotic kidney.ConclusionRenal vein blood from post-stenotic human kidneys has multiple markers reflecting active inflammation that portends kidney injury and reduced function. CD34+/KDR+ progenitor cells sequestered within these kidneys may participate in reparative processes. These inflammation-related pathways and limited circulating progenitor cells may serve as novel therapeutic targets to repair the stenotic kidney.

Original languageEnglish (US)
Pages (from-to)540-548
Number of pages9
JournalEuropean Heart Journal
Volume34
Issue number7
DOIs
StatePublished - Feb 14 2013

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Renal Artery Obstruction
Kidney
Stem Cells
Wounds and Injuries
Renal Veins
Inflammation
Stem Cell Factor
E-Selectin
Vascular Cell Adhesion Molecule-1
Angiogenesis Inducing Agents
Cell Adhesion Molecules
Inferior Vena Cava
Glomerular Filtration Rate
Antihypertensive Agents
Regeneration
Veins
Biomarkers
Sodium
Cytokines
Blood Pressure

Keywords

  • Cytokines
  • Inflammatory biomarkers
  • Progenitor cells
  • Renal artery stenosis
  • Renovascular hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Inflammatory and injury signals released from the post-stenotic human kidney. / Eirin, Alfonso; Gloviczki, Monika L.; Tang, Hui; Gössl, Mario; Jordan, Kyra L.; Woollard, John R.; Lerman, Amir; Grande, Joseph Peter; Textor, Stephen C; Lerman, Lilach O.

In: European Heart Journal, Vol. 34, No. 7, 14.02.2013, p. 540-548.

Research output: Contribution to journalArticle

Eirin, Alfonso ; Gloviczki, Monika L. ; Tang, Hui ; Gössl, Mario ; Jordan, Kyra L. ; Woollard, John R. ; Lerman, Amir ; Grande, Joseph Peter ; Textor, Stephen C ; Lerman, Lilach O. / Inflammatory and injury signals released from the post-stenotic human kidney. In: European Heart Journal. 2013 ; Vol. 34, No. 7. pp. 540-548.
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abstract = "Aims The mechanisms mediating kidney injury and repair in humans with atherosclerotic renal artery stenosis (ARAS) remain poorly understood. We hypothesized that the stenotic kidney releases inflammatory mediators and recruits progenitor cells to promote regeneration.Methods and resultsEssential hypertensive (EH) and ARAS patients (n= 24 each) were studied during controlled sodium intake and antihypertensive treatment. Inferior vena cava (IVC) and renal vein (RV) levels of CD34+/KDR+ progenitor cells, cell adhesion molecules, inflammatory biomarkers, progenitor cell homing signals, and pro-angiogenic factors were measured in EH and ARAS, and their gradient and net release compared with systemic levels in matched normotensive controls (n= 24). Blood pressure in ARAS was similar to EH, but the glomerular filtration rate was lower. Renal vein levels of soluble E-Selectin, vascular cell adhesion molecule-1, and several inflammatory markers were higher in the stenotic kidney RV vs. normal and EH RV (P< 0.05), and their net release increased. Similarly, stem-cell homing factor levels increased in the stenotic kidney RV. Systemic CD34+/KDR+ progenitor cell levels were lower in both EH and ARAS and correlated with cytokine levels. Moreover, CD34+/KDR+ progenitor cells developed a negative gradient across the ARAS kidney, suggesting progenitor cell retention. The non-stenotic kidney also showed signs of inflammatory processes, which were more subtle than in the stenotic kidney.ConclusionRenal vein blood from post-stenotic human kidneys has multiple markers reflecting active inflammation that portends kidney injury and reduced function. CD34+/KDR+ progenitor cells sequestered within these kidneys may participate in reparative processes. These inflammation-related pathways and limited circulating progenitor cells may serve as novel therapeutic targets to repair the stenotic kidney.",
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T1 - Inflammatory and injury signals released from the post-stenotic human kidney

AU - Eirin, Alfonso

AU - Gloviczki, Monika L.

AU - Tang, Hui

AU - Gössl, Mario

AU - Jordan, Kyra L.

AU - Woollard, John R.

AU - Lerman, Amir

AU - Grande, Joseph Peter

AU - Textor, Stephen C

AU - Lerman, Lilach O

PY - 2013/2/14

Y1 - 2013/2/14

N2 - Aims The mechanisms mediating kidney injury and repair in humans with atherosclerotic renal artery stenosis (ARAS) remain poorly understood. We hypothesized that the stenotic kidney releases inflammatory mediators and recruits progenitor cells to promote regeneration.Methods and resultsEssential hypertensive (EH) and ARAS patients (n= 24 each) were studied during controlled sodium intake and antihypertensive treatment. Inferior vena cava (IVC) and renal vein (RV) levels of CD34+/KDR+ progenitor cells, cell adhesion molecules, inflammatory biomarkers, progenitor cell homing signals, and pro-angiogenic factors were measured in EH and ARAS, and their gradient and net release compared with systemic levels in matched normotensive controls (n= 24). Blood pressure in ARAS was similar to EH, but the glomerular filtration rate was lower. Renal vein levels of soluble E-Selectin, vascular cell adhesion molecule-1, and several inflammatory markers were higher in the stenotic kidney RV vs. normal and EH RV (P< 0.05), and their net release increased. Similarly, stem-cell homing factor levels increased in the stenotic kidney RV. Systemic CD34+/KDR+ progenitor cell levels were lower in both EH and ARAS and correlated with cytokine levels. Moreover, CD34+/KDR+ progenitor cells developed a negative gradient across the ARAS kidney, suggesting progenitor cell retention. The non-stenotic kidney also showed signs of inflammatory processes, which were more subtle than in the stenotic kidney.ConclusionRenal vein blood from post-stenotic human kidneys has multiple markers reflecting active inflammation that portends kidney injury and reduced function. CD34+/KDR+ progenitor cells sequestered within these kidneys may participate in reparative processes. These inflammation-related pathways and limited circulating progenitor cells may serve as novel therapeutic targets to repair the stenotic kidney.

AB - Aims The mechanisms mediating kidney injury and repair in humans with atherosclerotic renal artery stenosis (ARAS) remain poorly understood. We hypothesized that the stenotic kidney releases inflammatory mediators and recruits progenitor cells to promote regeneration.Methods and resultsEssential hypertensive (EH) and ARAS patients (n= 24 each) were studied during controlled sodium intake and antihypertensive treatment. Inferior vena cava (IVC) and renal vein (RV) levels of CD34+/KDR+ progenitor cells, cell adhesion molecules, inflammatory biomarkers, progenitor cell homing signals, and pro-angiogenic factors were measured in EH and ARAS, and their gradient and net release compared with systemic levels in matched normotensive controls (n= 24). Blood pressure in ARAS was similar to EH, but the glomerular filtration rate was lower. Renal vein levels of soluble E-Selectin, vascular cell adhesion molecule-1, and several inflammatory markers were higher in the stenotic kidney RV vs. normal and EH RV (P< 0.05), and their net release increased. Similarly, stem-cell homing factor levels increased in the stenotic kidney RV. Systemic CD34+/KDR+ progenitor cell levels were lower in both EH and ARAS and correlated with cytokine levels. Moreover, CD34+/KDR+ progenitor cells developed a negative gradient across the ARAS kidney, suggesting progenitor cell retention. The non-stenotic kidney also showed signs of inflammatory processes, which were more subtle than in the stenotic kidney.ConclusionRenal vein blood from post-stenotic human kidneys has multiple markers reflecting active inflammation that portends kidney injury and reduced function. CD34+/KDR+ progenitor cells sequestered within these kidneys may participate in reparative processes. These inflammation-related pathways and limited circulating progenitor cells may serve as novel therapeutic targets to repair the stenotic kidney.

KW - Cytokines

KW - Inflammatory biomarkers

KW - Progenitor cells

KW - Renal artery stenosis

KW - Renovascular hypertension

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