Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period
Importância da avaliação de biomarcadores e parâmetros fisiológicos da hipóxia tecidual induzida por anemia no período perioperatório
Kyle Chin, Hannah Joo, Helen Jiang, Chloe Lin, Iryna Savinova, Sarah Joo, Ahmad Alli, Michael C. Sklar, Fabio Papa, Jeremy Simpson, Andrew J. Baker, C. David Mazer, William Darrah, Gregory M.T. Hare
Abstract
Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2 = 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93806*10−0.02, r2 = 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.
Keywords
Resumo
A anemia está associada ao aumento do risco de lesão renal aguda (LRA), acidente vascular cerebral e mortalidade em pacientes perioperatórios. Procuramos entender o(s) mecanismo(s) avaliando as respostas fisiológicas integrativas à anemia (rim, cérebro), os graus de hipóxia tecidual induzida pela anemia e os biomarcadores e parâmetros fisiológicos associados. Medidas experimentais demonstram uma relação linear entre o teor de oxigênio no sangue (CaO2) e a PO2 microvascular renal (y = 0,30x + 6,9, r2 = 0,75), demonstrando que a hipóxia renal é proporcional ao grau de anemia. Isso define o rim como um potencial sensor de oxigênio durante a anemia. Evidência adicional de detecção de oxigênio renal é demonstrada pelo aumento proporcional na eritropoietina sérica (EPO) durante a anemia (y = 93,806*10−0,02, r2 = 0,82). Esses dados implicam os níveis sistêmicos de EPO como um biomarcador de hipóxia tecidual renal induzida por anemia. Por outro lado, a entrega de oxigênio cerebral (DO2) é defendida por um profundo aumento proporcional no fluxo sanguíneo cerebral (FSC), minimizando a hipóxia tecidual no cérebro, até que ocorram níveis mais graves de anemia. Nossa hipótese é que o rim experimenta profunda hipóxia tecidual induzida por anemia precoce que contribui para mecanismos adaptativos para preservar a perfusão cerebral. Em níveis graves de anemia, a hipóxia renal se intensifica e ocorre hipóxia cerebral, possivelmente contribuindo para o(s) mecanismo(s) de LRA e acidente vascular cerebral quando os mecanismos adaptativos para preservar a perfusão dos órgãos são sobrecarregados. Métodos clínicos para detectar hipóxia do tecido renal (um sinal de alerta precoce) e hipóxia cerebral (uma consequência posterior da anemia grave) podem informar a prática clínica e apoiar a avaliação de biomarcadores clínicos (ou seja, EPO) e parâmetros fisiológicos (ou seja, PO2 urinário) de hipóxia tecidual induzida por anemia. Esta informação pode direcionar estratégias de tratamento direcionadas para prevenir resultados adversos associados à anemia.
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Submitted date:
08/24/2022
Accepted date:
10/17/2022
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