Tissue hypoxia, inflammation, and loss of glomerular filtration rate in human atherosclerotic renovascular disease

Abdelrhman Abumoawad, Ahmed Saad, Christopher M. Ferguson, Alfonso Eirin, John R. Woollard, Sandra Herrmann, LaTonya Hickson, Emily C. Bendel, Sanjay Misra, James Glockner, Lilach O Lerman, Stephen C Textor

Research output: Contribution to journalArticle

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Abstract

The relationships between renal blood flow (RBF), tissue oxygenation, and inflammatory injury in atherosclerotic renovascular disease (ARVD) are poorly understood. We sought to correlate RBF and tissue hypoxia with glomerular filtration rate (GFR) in 48 kidneys from patients with ARVD stratified by single kidney iothalamate GFR (sGFR). Oxygenation was assessed by blood oxygenation level dependent magnetic resonance imaging (BOLD MRI), which provides an index for the levels of deoxyhemoglobin within a defined volume of tissue (R2*). sGFR correlated with RBF and with the severity of vascular stenosis as estimated by duplex velocities. Higher cortical R2* and fractional hypoxia and higher levels of renal vein neutrophil-gelatinase-associated-lipocalin (NGAL) and monocyte-chemoattractant protein-1 (MCP-1) were observed at lower GFR, with an abrupt inflection below 20 ml/min. Renal vein MCP-1 levels correlated with cortical R2* and with fractional hypoxia. Correlations between cortical R2* and RBF in the highest sGFR stratum (mean sGFR 51 ± 12 ml/min; R = –0.8) were degraded in the lowest sGFR stratum (mean sGFR 8 ± 3 ml/min; R = –0.1). Changes in fractional hypoxia after furosemide were also absent in the lowest sGFR stratum. These data demonstrate relative stability of renal oxygenation with moderate reductions in RBF and GFR but identify a transition to overt hypoxia and inflammatory cytokine release with severely reduced GFR. Tissue oxygenation and RBF were less correlated in the setting of reduced sGFR, consistent with variable oxygen consumption or a shift to alternative mechanisms of tissue injury. Identifying transitions in tissue oxygenation may facilitate targeted therapy in ARVD.

Original languageEnglish (US)
Pages (from-to)948-957
Number of pages10
JournalKidney international
Volume95
Issue number4
DOIs
StatePublished - Apr 1 2019

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Renal Circulation
Glomerular Filtration Rate
Inflammation
Renal Veins
Chemokine CCL2
Kidney
Iothalamic Acid
Furosemide
Wounds and Injuries
Oxygen Consumption
Blood Vessels
Hypoxia
Pathologic Constriction
Magnetic Resonance Imaging
Cytokines

Keywords

  • BOLD MR
  • cortical
  • GFR
  • hypertension
  • hypoxia
  • medullary
  • NGAL
  • renal artery stenosis
  • renal blood flow
  • renovascular disease
  • revascularization
  • VEGF-A

ASJC Scopus subject areas

  • Nephrology

Cite this

Tissue hypoxia, inflammation, and loss of glomerular filtration rate in human atherosclerotic renovascular disease. / Abumoawad, Abdelrhman; Saad, Ahmed; Ferguson, Christopher M.; Eirin, Alfonso; Woollard, John R.; Herrmann, Sandra; Hickson, LaTonya; Bendel, Emily C.; Misra, Sanjay; Glockner, James; Lerman, Lilach O; Textor, Stephen C.

In: Kidney international, Vol. 95, No. 4, 01.04.2019, p. 948-957.

Research output: Contribution to journalArticle

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AU - Abumoawad, Abdelrhman

AU - Saad, Ahmed

AU - Ferguson, Christopher M.

AU - Eirin, Alfonso

AU - Woollard, John R.

AU - Herrmann, Sandra

AU - Hickson, LaTonya

AU - Bendel, Emily C.

AU - Misra, Sanjay

AU - Glockner, James

AU - Lerman, Lilach O

AU - Textor, Stephen C

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AB - The relationships between renal blood flow (RBF), tissue oxygenation, and inflammatory injury in atherosclerotic renovascular disease (ARVD) are poorly understood. We sought to correlate RBF and tissue hypoxia with glomerular filtration rate (GFR) in 48 kidneys from patients with ARVD stratified by single kidney iothalamate GFR (sGFR). Oxygenation was assessed by blood oxygenation level dependent magnetic resonance imaging (BOLD MRI), which provides an index for the levels of deoxyhemoglobin within a defined volume of tissue (R2*). sGFR correlated with RBF and with the severity of vascular stenosis as estimated by duplex velocities. Higher cortical R2* and fractional hypoxia and higher levels of renal vein neutrophil-gelatinase-associated-lipocalin (NGAL) and monocyte-chemoattractant protein-1 (MCP-1) were observed at lower GFR, with an abrupt inflection below 20 ml/min. Renal vein MCP-1 levels correlated with cortical R2* and with fractional hypoxia. Correlations between cortical R2* and RBF in the highest sGFR stratum (mean sGFR 51 ± 12 ml/min; R = –0.8) were degraded in the lowest sGFR stratum (mean sGFR 8 ± 3 ml/min; R = –0.1). Changes in fractional hypoxia after furosemide were also absent in the lowest sGFR stratum. These data demonstrate relative stability of renal oxygenation with moderate reductions in RBF and GFR but identify a transition to overt hypoxia and inflammatory cytokine release with severely reduced GFR. Tissue oxygenation and RBF were less correlated in the setting of reduced sGFR, consistent with variable oxygen consumption or a shift to alternative mechanisms of tissue injury. Identifying transitions in tissue oxygenation may facilitate targeted therapy in ARVD.

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KW - GFR

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KW - hypoxia

KW - medullary

KW - NGAL

KW - renal artery stenosis

KW - renal blood flow

KW - renovascular disease

KW - revascularization

KW - VEGF-A

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