Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts

Hypoxia as a biomarker of kidney disease

All established (e.g., serum creatinine, albuminuria) and emerging (e.g., neutrophil gelatinase-associated lipocalin, cystatin C) biomarkers of kidney disease suffer from the disadvantage that they are markers of damage to the kidney or loss of renal function. Tissue hypoxia is believed to be an initiating factor, in both chronic kidney disease (CKD) and acute kidney injury (AKI), so may provide a physiological biomarker for early diagnosis of both conditions. Currently blood oxygen dependent magnetic resonance imaging (BOLD MRI) appears to have little diagnostic value in human CKD. On the other hand, the measurement of urinary oxygen tension (PO2) has potential as a biomarker of risk of AKI in a hospital setting because: (i) Hypoxia in the renal medulla plays a central role in AKI of multiple causes; (ii) The vasa recta are closely associated with collecting ducts in the medulla so that pelvic urinary PO2 would be expected to equilibrate with medullary tissue PO2; (iii) The PO2 of urine in both the renal pelvis and the bladder varies in response to stimuli that would be expected to alter medullary tissue PO2; and (iv) New fibre-optic methods make it feasible to measure bladder urine PO2 in patients with a bladder catheter. But translation of this approach to hospital practice requires: (i) A quantitative understanding of the impact of oxygen transport across the epithelium of the ureter and bladder on urinary PO2 measured from the bladder, (ii) confirmation that changes in urinary PO2 parallel those in medullary PO2 in physiology and pathology, and (iii) Studies of the prognostic utility of urinary PO2 in hospital settings associated with risk of AKI, such as in patients undergoing cardiac surgery with cardiopulmonary bypass, those at risk of sepsis, and those undergoing imaging procedures requiring administration of radiocontrast agents

Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats*

Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer’s lactate solution (RS) or 5% (w/v) albumin (ALB), and the left lower lobes of the lungs were resected. Results: Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling (TUNEL)-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor κB (NF-κB), and phosphorylated p38 mitogen-activated protein kinase (MAPK) in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion: Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB