Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

Clin J Am Soc Nephrol. 2016 Mar 7;11(3):458-69. doi: 10.2215/CJN.03620415. Epub 2016 Jan 19.

Abstract

Background and objectives: Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization.

Design, setting, participants, & measurements: Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured.

Results: Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001).

Conclusions: These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.

Keywords: BOLD-MRI; renal artery stenosis; renal biomarkers; renal tissue oxygenation; renin; renovascular hypertension; single kidney glomerular filtration rate.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Atherosclerosis / complications
  • Atherosclerosis / diagnosis
  • Atherosclerosis / physiopathology
  • Atherosclerosis / therapy*
  • Biomarkers / blood
  • Cardiovascular Agents / therapeutic use*
  • Cell Hypoxia
  • Chemokine CCL2 / blood
  • Endovascular Procedures* / instrumentation
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Inflammation Mediators / blood
  • Kidney* / blood supply
  • Kidney* / metabolism
  • Kidney* / physiopathology
  • Lipocalin-2 / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multidetector Computed Tomography
  • Oxygen / metabolism*
  • Recovery of Function
  • Renal Artery Obstruction / complications
  • Renal Artery Obstruction / diagnosis
  • Renal Artery Obstruction / physiopathology
  • Renal Artery Obstruction / therapy*
  • Renal Circulation
  • Renin / blood
  • Stents
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • CCL2 protein, human
  • Cardiovascular Agents
  • Chemokine CCL2
  • Inflammation Mediators
  • LCN2 protein, human
  • Lipocalin-2
  • Renin
  • Oxygen