title: Inflammatory and injury signals released from the post-stenotic human kidney.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  Essential 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.
  
  
  CONCLUSIONS
  Renal 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.
authors: Division of Nephrology and Hypertension, Department of Internal Medicine,  Mayo Clinic, 200 First Street SW, Rochester, MN 55905,  USA.
authors: Alfonso
authors: A
authors: Eirin
authors: Monika L
authors: ML
authors: Gloviczki
authors: Hui
authors: H
authors: Tang
authors: Mario
authors: M
authors: Gössl
authors: Kyra L
authors: KL
authors: Jordan
authors: John R
authors: JR
authors: Woollard
authors: Amir
authors: A
authors: Lerman
authors: Joseph P
authors: JP
authors: Grande
authors: Stephen C
authors: SC
authors: Textor
authors: Lilach O
authors: LO
authors: Lerman
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000503:physiopathology; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001167:Arteritis / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012078:Renal Artery Obstruction / Q000378:metabolism* / Q000503:physiopathology; D012082:Renal Veins / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014682:Vena Cava, Inferior / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016207:Cytokines; D019040:E-Selectin; D019089:Stem Cell Factor; D019010:Vascular Cell Adhesion Molecule-1