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PubMed: 29351418

Title
Red blood cell antibody-induced anemia causes differential degrees of tissue hypoxia in kidney and brain.
Journal
American journal of physiology. Regulatory, integrative and comparative physiology
Volume
314
Issue
None
Pages
R611-R622
Date
2018-04-01
Authors
Mistry N | Hare GMT | Brunt KR | Cahill LS | Doctor A | Fisher JA | Hare AGM | Lazarus AH | Mazer CD | Romanova N | Simpson JA | Sled JG | Solish M | Zhou YQ

Evidence 3cbd326d13
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Moderate anemia is associated with increased mortality and morbidity, including acute kidney injury (AKI), in surgical patients.

a(MESH:Morbidity) positiveCorrelation path(MESH:Anemia) View Subject | View Object

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a(MESH:Mortality) positiveCorrelation path(MESH:Anemia) View Subject | View Object

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path(MESH:"Acute Kidney Injury") positiveCorrelation path(MESH:Anemia) View Subject | View Object

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path(MESH:Anemia) positiveCorrelation a(MESH:Mortality) View Subject | View Object

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path(MESH:Anemia) positiveCorrelation a(MESH:Morbidity) View Subject | View Object

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path(MESH:Anemia) positiveCorrelation path(MESH:"Acute Kidney Injury") View Subject | View Object

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Evidence 3cabb1baf5
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Our data provided clear evidence of renal tissue hypoxia, which was in part due to a lack of increase in renal blood flow.

bp(HM:"Renal Blood Flow, limited") increases path(MESH:Hypoxia) View Subject | View Object

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Kidney
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Anemia
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Discussion

Evidence cbd69d7919
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Anemia has been associated with an increased risk of acute kidney injury (AKI) (17, 18, 20, 27, 28), stroke (17, 20, 27), myocardial events (6, 11, 20, 28, 47), and mortality (1, 2, 10, 11, 17, 20, 27, 28, 36, 45, 47) in patients undergoing surgery.

a(MESH:Mortality) positiveCorrelation path(MESH:Anemia) View Subject | View Object

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path(MESH:"Acute Kidney Injury") positiveCorrelation path(MESH:Anemia) View Subject | View Object

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path(MESH:Anemia) positiveCorrelation a(MESH:Mortality) View Subject | View Object

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path(MESH:Anemia) positiveCorrelation path(MESH:"Acute Kidney Injury") View Subject | View Object

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path(MESH:Anemia) positiveCorrelation path(MESH:Stroke) View Subject | View Object

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path(MESH:Stroke) positiveCorrelation path(MESH:Anemia) View Subject | View Object

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Evidence 405a434814
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By contrast, no or limited increases in renal blood flow are observed during acute hemodilution (15, 42), leading to earlier and more severe renal tissue hypoxia (5, 38), and an increase in the magnitude of hypoxia signaling responses, including stabilization of the transcription factor hypoxia- inducible factor- (HIF-) (42, 43).

bp(HM:"Renal Blood Flow, limited") increases path(MESH:Hypoxia) View Subject | View Object

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Kidney
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bp(HM:"Renal Blood Flow, limited") increases p(HGNC:HIF1A) View Subject | View Object

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Kidney
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Evidence 0782db24aa
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The absent or relatively small increase in renal blood flow likely contributed to the occurrence of renal tissue hypoxia in both models.

bp(HM:"Renal Blood Flow, limited") increases path(MESH:Hypoxia) View Subject | View Object

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Kidney
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Evidence 96681d0a5c
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The renal blood flow response to anemia is proportionally much smaller than the increase observed in cerebral blood flow (50–100%). This relative difference in organ blood flow likely explains why the kidney becomes profoundly hypoxic, whereas brain oxygenation is largely preserved during anemia (12, 32, 42).

bp(HM:"Renal Blood Flow, limited") increases path(MESH:Hypoxia) View Subject | View Object

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Kidney
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Anemia
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Evidence 7a1cd117c1
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However, as reviewed above, several experimental tal studies and our new data have demonstrated that both acute and subacute anemia are associated with renal tissue hypoxia (5, 38, 41, 43).

path(HM:"Anemia, acute") positiveCorrelation path(MESH:Hypoxia) View Subject | View Object

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Kidney
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Anemia
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path(HM:"Anemia, subacute") positiveCorrelation path(MESH:Hypoxia) View Subject | View Object

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Kidney
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Anemia
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path(MESH:Hypoxia) positiveCorrelation path(HM:"Anemia, acute") View Subject | View Object

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Kidney
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Anemia
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path(MESH:Hypoxia) positiveCorrelation path(HM:"Anemia, subacute") View Subject | View Object

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Kidney
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Evidence 8ed2c4e9b8
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Surprisingly, even moderate levels of preoperative anemia [hemoglobin (Hb) concentrations between 80 and 100 g/l] have been associated with an increased risk of renal injury {odds ratio (OR): 1.38 [95% confidence interval (CI) 1.18 –1.62], P  0.05} (28).

path(MESH:"Acute Kidney Injury") positiveCorrelation path(MESH:Anemia) View Subject | View Object

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path(MESH:Anemia) positiveCorrelation path(MESH:"Acute Kidney Injury") View Subject | View Object

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Evidence 3f21c8e991
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In perioperative medicine, there is a clear association between preoperative anemia and AKI in noncardiac and cardiac surgery (17, 18, 20, 28).

path(MESH:"Acute Kidney Injury") positiveCorrelation path(MESH:Anemia) View Subject | View Object

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Kidney
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Anemia
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path(MESH:Anemia) positiveCorrelation path(MESH:"Acute Kidney Injury") View Subject | View Object

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Kidney
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Anemia
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Evidence e37ed69c29
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The preferential adaptive increase in cerebral blood flow has also been demonstrated in other models of anemia, including acute hemodilution and chronic sickle cell anemia (3, 41).

path(MESH:"Anemia, Sickle Cell") increases bp(MESH:"Regional Blood Flow") View Subject | View Object

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Cerebrum
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Anemia
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Evidence 099ac66d3c
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By day 1 following injection, plasma Hb concentrations in the anemia group were reduced to 0.5  0.3 g/l, which was not significantly different from the control value of 0.5  0.3 g/l (n  6, unadjusted P  0.93; Fig. 3A).

path(MESH:Anemia) decreases p(HGNC:HBB) View Subject | View Object

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Plasma
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Evidence c93ef3ecbe
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SpO2 values increased in anemic mice (n  6) from a baseline value of 97.1  0.6% to a day 3 value of 98.1  0.2 and a day 4 value of 97.8  0.4% (n  6, unadjusted P  0.02, adjusted P  0.05; Fig. 4). Day 4 SpO2 values were higher than a control value of 97.0  0.8% (n  6; unadjusted P  0.01, adjusted P  0.05).

path(MESH:Anemia) increases a(MESH:"Blood Gas Monitoring, Transcutaneous") View Subject | View Object

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Plasma
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Evidence a0064a96ed
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Internal carotid artery flow increased from a baseline value of 0.3  0.1 ml/min to 0.6  0.1 ml/min during anemia (unadjusted P  0.001, adjusted P  0.001; Fig. 5).

path(MESH:Anemia) increases act(a(MESH:"Carotid Artery, Internal")) View Subject | View Object

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Plasma
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Evidence 8abe16f541
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During anemia, kidney PtO2 was reduced to a value of 13.1  4.3 mmHg (n  10) compared with a control value of 20.8  3.7 mmHg (n  14; P  0.001; Fig. 6).

path(MESH:Anemia) decreases a(MESH:"Partial Pressure") View Subject | View Object

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Kidney
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Evidence 57488fd3cc
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Brain PtO2 of anemic mice was 22.7  5.2 mmHg (n  13), which was not significantly different from a control value of 23.4  9.8 mmHg (n  14, P  0.59).

path(MESH:Anemia) causesNoChange a(MESH:"Partial Pressure") View Subject | View Object

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Brain
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Evidence bae515f470
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D). “Right kidney  liver region” HIF/luciferase radiance increased from a baseline value of 5.30 107  1.23 107 p/s to a day 4 value of 6.72 107  1.63 107 p/s (unadjusted P  0.01, adjusted P  0.04; Fig. 7E).

path(MESH:Anemia) increases complex(a(MESH:Luciferases), p(MGI:Hif1a)) View Subject | View Object

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Kidney
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Liver
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Evidence 2a3c61eac7
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“Gut region” HIF/luciferase radiance at the day 4 time point was 4.38 108  4.00 108 p/s, which was higher than a control value of 2.36 108  0.93 108 p/s (unadjusted P  0.001, adjusted P  0.001; Fig. 8E).

path(MESH:Anemia) increases complex(a(MESH:Luciferases), p(MGI:Hif1a)) View Subject | View Object

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Kidney
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Liver
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Evidence b2b79ba68c
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In addition, change in day 4 gut region HIF/luciferase radiance values from baseline in anemic mice was 1.68 108  3.48 108 p/s, which was higher than a control value of 1.08 108  1.28 108 p/s (P  0.02).

path(MESH:Anemia) increases complex(a(MESH:Luciferases), p(MGI:Hif1a)) View Subject | View Object

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Kidney
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Liver
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Evidence aac8bdf9fa
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During anemia (n  6), kidney EPO mRNA transcription increased 20-fold relative to control mice (n  5, P  0.001; Fig. 9A).

path(MESH:Anemia) increases act(r(MGI:Epo), ma(tscript)) View Subject | View Object

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Evidence 4a5a894091
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Heart EPO mRNA transcription was not significantly different in anemic mice relative to control mice (P  0.35).

path(MESH:Anemia) causesNoChange act(r(MGI:Epo), ma(tscript)) View Subject | View Object

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Heart
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Evidence 4b423ef4a8
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Despite the preserved tissue PO2 level during subacute anemia, we demonstrated an increase in HIF-dependent mRNA levels of EPO, HO-1, and GAPDH. This finding is consistent with other experimental studies that have also demonstrated increases in HIF-dependent mRNA expression in the absence of a clear reduction in brain PtO2 (12, 23).

path(MESH:Anemia) increases r(MGI:Epo) View Subject | View Object

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Brain
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Anemia
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path(MESH:Anemia) increases r(MGI:Hmox1) View Subject | View Object

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Brain
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Anemia
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path(MESH:Anemia) increases r(MGI:Gapdh) View Subject | View Object

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Brain
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Anemia
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Evidence ecb5270a8f
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Brain HO-1 mRNA levels increased by 38% in anemic mice relative to control mice (P  0.01), and GAPDH mRNA levels increased by 18% in anemic mice relative to control mice (P  0.002; Fig. 9B).

path(MESH:Anemia) increases r(MGI:Hmox1) View Subject | View Object

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Brain
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path(MESH:Anemia) increases r(MGI:Gapdh) View Subject | View Object

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Brain
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Evidence b9a63b7a2f
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Our experimental data provided clear evidence that moderate subacute anemia resulted in a profound level of renal tissue hypoxia, as characterized by a reduction in kidney PtO2, an increase in regional HIF/luciferase radiance in vivo, and a substantial increase in EPO mRNA level at a Hb concentration consistent with moderate anemia (90 g/l).

path(MESH:Anemia) increases path(MESH:Hypoxia) View Subject | View Object

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Kidney
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Evidence 86ff833998
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We observed a mild degree of plasma hypoxia could lead to organ injury.

path(MESH:Hypoxia) increases path(HM:"Organ Dysfunction") View Subject | View Object

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Plasma
MeSH
Anemia
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Discussion

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