Search

Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery. The value of a predictive biomarker is determined not only by its predictive efficacy, but also by how early this prediction can be made. For a biomarker of cardiac surgery-associated AKI, this is ideally during the intra-operative period. Therefore, in 82 adult patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), we prospectively compared the predictive efficacy of various blood and urinary biomarkers with that of continuous measurement of urinary oxygen tension (UPO2) at pre-determined intra- and post-operative time-points. None of the blood or urine biomarkers we studied showed predictive efficacy for post-operative AKI when measured intra-operatively. When treated as a binary variable (<= or > median for the whole cohort), the earliest excess risk of AKI was predicted by an increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) at 3 h after entry into the intensive care unit (odds ratio [95% confidence limits], 2.86 [1.14-7.21], p = 0.03). Corresponding time-points were 6 h for serum creatinine (3.59 [1.40-9.20], p = 0.008), and 24 h for plasma NGAL (4.54 [1.73-11.90], p = 0.002) and serum cystatin C (6.38 [2.35-17.27], p = 0.001). In contrast, indices of intra-operative urinary hypoxia predicted AKI after weaning from CPB, and in the case of a fall in UPO2 to <=10 mmHg, during the rewarming phase of CPB (3.00 [1.19-7.56], p = 0.02). We conclude that continuous measurement of UPO2 predicts AKI earlier than plasma or urinary NGAL, serum cystatin C, or early post-operative changes in serum creatinine.Copyright © 2021 John Wiley & Sons Australia, Ltd

Aim: Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure. Method(s): Cardiopulmonary bypass was established in eight instrumented sheep under isoflurane anaesthesia, at a target continuous pump flow of 80 mL.kg-1 min-1 and mean arterial pressure of 65 mmHg. We then tested the effects of simultaneously increasing target pump flow to 104 mL.kg-1 min-1 and mean arterial pressure to 80 mmHg with metaraminol (total dose 0.25-3.75 mg). We also tested the effects of transitioning from continuous flow to partially pulsatile flow (pulse pressure ~15 mmHg). Result(s): Compared with conscious sheep, at the lower target pump flow and mean arterial pressure, cardiopulmonary bypass was accompanied by reduced renal blood flow (6.8 +/- 1.2 to 1.95 +/- 0.76 mL.min-1 kg-1) and renal oxygen delivery (0.91 +/- 0.18 to 0.24 +/- 0.11 mL.O2 min-1 kg-1). There were profound reductions in cortical oxygen tension (PO2) (33 +/- 13 to 6 +/- 6 mmHg) and medullary PO2 (31 +/- 12 to 8 +/- 8 mmHg). Increasing target pump flow and mean arterial pressure increased renal blood flow (to 2.6 +/- 1.0 mL.min-1 kg-1) and renal oxygen delivery (to 0.32 +/- 0.13 mL.O2 min-1kg-1) and returned cortical PO2 to 58 +/- 60 mmHg and medullary PO2 to 28 +/- 16 mmHg; levels similar to those of conscious sheep. Partially pulsatile pump flow had no significant effects on renal perfusion or oxygenation. Conclusion(s): Renal hypoxia during experimental CPB can be corrected by increasing target pump flow and mean arterial pressure within a clinically feasible range.Copyright © 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

Introduction: The renal medulla is susceptible to hypoxia during cardiopulmonary bypass (CPB), which may contribute to the development of acute kidney injury. But the speed of onset of renal medullary hypoxia remains unknown. Method(s): We continuously measured renal medullary oxygen tension (MPO2) in 24 sheep, and urinary PO2 (UPO2) as an index of MPO2 in 92 patients, before and after induction of CPB. Result(s): In laterally recumbent sheep with a right thoracotomy (n = 20), even before CPB commenced MPO2 fell from (mean +/- SEM) 52 +/- 4 to 41 +/-5 mmHg simultaneously with reduced arterial pressure (from 108 +/- 5 to 88 +/- 5 mmHg). In dorsally recumbent sheep with a medial sternotomy (n = 4), MPO2 was even more severely reduced (to 12 +/- 12 mmHg) before CPB. In laterally recumbent sheep in which a crystalloid prime was used (n = 7), after commencing CPB, MPO2 fell abruptly to 24 +/-6 mmHg within 20-30 minutes. MPO2 during CPB was not improved by adding donor blood to the prime (n = 13). In patients undergoing cardiac surgery, UPO2 fell by 4 +/- 1 mmHg and mean arterial pressure fell by 7 +/- 1 mmHg during the 30 minutes before CPB. UPO2 then fell by a further 12 +/- 2 mmHg during the first 30 minutes of CPB but remained relatively stable for the remaining 24 minutes of observation. Conclusion(s): Renal medullary hypoxia is an early event during CPB. It starts to develop even before CPB, presumably due to a pressure-dependent decrease in renal blood flow. Medullary hypoxia during CPB appears to be promoted by hypotension and is not ameliorated by increasing blood hemoglobin concentration.Copyright © The Author(s) 2021.

Using a large national database of cardiac surgical procedures, we applied machine learning (ML) to risk stratification and profiling for cardiac surgery-associated acute kidney injury. We compared performance of ML to established scoring tools. Four ML algorithms were used, including logistic regression (LR), gradient boosted machine (GBM), K-nearest neighbor, and neural networks (NN). These were compared to the Cleveland Clinic score, and a risk score developed on the same database. Five-fold cross-validation repeated 20 times was used to measure the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Risk profiles from GBM and NN were generated using Shapley additive values. A total of 97,964 surgery events in 96,653 patients were included. For predicting postoperative renal replacement therapy using pre- and intraoperative data, LR, GBM, and NN achieved an AUC (standard deviation) of 0.84 (0.01), 0.85 (0.01), 0.84 (0.01) respectively outperforming the highest performing scoring tool with 0.81 (0.004). For predicting cardiac surgery-associated acute kidney injury, LR, GBM, and NN each achieved 0.77 (0.01), 0.78 (0.01), 0.77 (0.01) respectively outperforming the scoring tool with 0.75 (0.004). Compared to scores and LR, shapely additive values analysis of black box model predictions was able to generate patient-level explanations for each prediction. ML algorithms provide state-of-the-art approaches to risk stratification. Explanatory modeling can exploit complex decision boundaries to aid the clinician in understanding the risks specific to individual patients.Copyright © 2020

Glomerular filtration rate (GFR) is acutely increased following a high-protein meal or systemic infusion of amino acids. The mechanisms underlying this renal functional response remain to be fully elucidated. Nevertheless, they appear to culminate in preglomerular vasodilation. Inhibition of the tubuloglomerular feedback signal appears critical. However, nitric oxide, vasodilator prostaglandins, and glucagon also appear important. The increase in GFR during amino acid infusion reveals a "renal reserve,"which can be utilized when the physiological demand for single nephron GFR increases. This has led to the concept that in subclinical renal disease, before basal GFR begins to reduce, renal functional reserve can be recruited in a manner that preserves renal function. The extension of this concept is that once a decline in basal GFR can be detected, renal disease is already well progressed. This concept likely applies both in the contexts of chronic kidney disease and acute kidney injury. Critically, its corollary is that deficits in renal functional reserve have the potential to provide early detection of renal dysfunction before basal GFR is reduced. There is growing evidence that the renal response to infusion of amino acids can be used to identify patients at risk of developing either chronic kidney disease or acute kidney injury and as a treatment target for acute kidney injury. However, large multicenter clinical trials are required to test these propositions. A renewed effort to understand the renal physiology underlying the response to amino acid infusion is also warranted.Copyright © 2020 the American Physiological Society.

Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery. The value of a predictive biomarker is determined not only by its predictive efficacy, but also by how early this prediction can be made. For a biomarker of cardiac surgery-associated AKI, this is ideally during the intra-operative period. Therefore, in 82 adult patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), we prospectively compared the predictive efficacy of various blood and urinary biomarkers with that of continuous measurement of urinary oxygen tension (UPO2) at pre-determined intra- and post-operative time-points. None of the blood or urine biomarkers we studied showed predictive efficacy for post-operative AKI when measured intra-operatively. When treated as a binary variable (<= or > median for the whole cohort), the earliest excess risk of AKI was predicted by an increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) at 3 h after entry into the intensive care unit (odds ratio [95% confidence limits], 2.86 [1.14-7.21], p = 0.03). Corresponding time-points were 6 h for serum creatinine (3.59 [1.40-9.20], p = 0.008), and 24 h for plasma NGAL (4.54 [1.73-11.90], p = 0.002) and serum cystatin C (6.38 [2.35-17.27], p = 0.001). In contrast, indices of intra-operative urinary hypoxia predicted AKI after weaning from CPB, and in the case of a fall in UPO2 to <=10 mmHg, during the rewarming phase of CPB (3.00 [1.19-7.56], p = 0.02). We conclude that continuous measurement of UPO2 predicts AKI earlier than plasma or urinary NGAL, serum cystatin C, or early post-operative changes in serum creatinine.Copyright © 2021 John Wiley & Sons Australia, Ltd

Aim: Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure. Method(s): Cardiopulmonary bypass was established in eight instrumented sheep under isoflurane anaesthesia, at a target continuous pump flow of 80 mL.kg-1 min-1 and mean arterial pressure of 65 mmHg. We then tested the effects of simultaneously increasing target pump flow to 104 mL.kg-1 min-1 and mean arterial pressure to 80 mmHg with metaraminol (total dose 0.25-3.75 mg). We also tested the effects of transitioning from continuous flow to partially pulsatile flow (pulse pressure ~15 mmHg). Result(s): Compared with conscious sheep, at the lower target pump flow and mean arterial pressure, cardiopulmonary bypass was accompanied by reduced renal blood flow (6.8 +/- 1.2 to 1.95 +/- 0.76 mL.min-1 kg-1) and renal oxygen delivery (0.91 +/- 0.18 to 0.24 +/- 0.11 mL.O2 min-1 kg-1). There were profound reductions in cortical oxygen tension (PO2) (33 +/- 13 to 6 +/- 6 mmHg) and medullary PO2 (31 +/- 12 to 8 +/- 8 mmHg). Increasing target pump flow and mean arterial pressure increased renal blood flow (to 2.6 +/- 1.0 mL.min-1 kg-1) and renal oxygen delivery (to 0.32 +/- 0.13 mL.O2 min-1kg-1) and returned cortical PO2 to 58 +/- 60 mmHg and medullary PO2 to 28 +/- 16 mmHg; levels similar to those of conscious sheep. Partially pulsatile pump flow had no significant effects on renal perfusion or oxygenation. Conclusion(s): Renal hypoxia during experimental CPB can be corrected by increasing target pump flow and mean arterial pressure within a clinically feasible range.Copyright © 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

Introduction: The renal medulla is susceptible to hypoxia during cardiopulmonary bypass (CPB), which may contribute to the development of acute kidney injury. But the speed of onset of renal medullary hypoxia remains unknown. Method(s): We continuously measured renal medullary oxygen tension (MPO2) in 24 sheep, and urinary PO2 (UPO2) as an index of MPO2 in 92 patients, before and after induction of CPB. Result(s): In laterally recumbent sheep with a right thoracotomy (n = 20), even before CPB commenced MPO2 fell from (mean +/- SEM) 52 +/- 4 to 41 +/-5 mmHg simultaneously with reduced arterial pressure (from 108 +/- 5 to 88 +/- 5 mmHg). In dorsally recumbent sheep with a medial sternotomy (n = 4), MPO2 was even more severely reduced (to 12 +/- 12 mmHg) before CPB. In laterally recumbent sheep in which a crystalloid prime was used (n = 7), after commencing CPB, MPO2 fell abruptly to 24 +/-6 mmHg within 20-30 minutes. MPO2 during CPB was not improved by adding donor blood to the prime (n = 13). In patients undergoing cardiac surgery, UPO2 fell by 4 +/- 1 mmHg and mean arterial pressure fell by 7 +/- 1 mmHg during the 30 minutes before CPB. UPO2 then fell by a further 12 +/- 2 mmHg during the first 30 minutes of CPB but remained relatively stable for the remaining 24 minutes of observation. Conclusion(s): Renal medullary hypoxia is an early event during CPB. It starts to develop even before CPB, presumably due to a pressure-dependent decrease in renal blood flow. Medullary hypoxia during CPB appears to be promoted by hypotension and is not ameliorated by increasing blood hemoglobin concentration.Copyright © The Author(s) 2021.

Background: Acute kidney injury (AKI) is common after cardiac surgery requiring cardiopulmonary bypass. Renal hypoxia may precede clinically detectable AKI. We compared the efficacy of two indices of renal hypoxia, (i) intraoperative urinary oxygen tension (UPO2) and (ii) the change in plasma erythropoietin (pEPO) during surgery, in predicting AKI. We also investigated whether the performance of these prognostic markers varies with preoperative patient characteristics. Method(s): In 82 patients undergoing on-pump cardiac surgery, blood samples were taken upon induction of anesthesia and upon entry into the intensive care unit. UPO2 was continuously measured throughout surgery. Result(s): Thirty-two (39%) patients developed postoperative AKI. pEPO increased during surgery, but this increase did not predict AKI, regardless of risk of postoperative mortality assessed by EuroSCORE-II. For patients categorized at higher risk by EuroSCORE-II >1.98 (median score for the cohort), UPO2 <=10 mmHg at any time during surgery predicted a 4.04-fold excess risk of AKI (p =.04). However, UPO2 did not significantly predict AKI in lower-risk patients. UPO2 significantly predicted AKI in patients who were older, had previous myocardial infarction, diabetes, lower preoperative serum creatinine, or shorter bypass times. pEPO and UPO2 were only weakly correlated. Conclusion(s): Intraoperative change in pEPO does not predict AKI. However, UPO2 shows promise, particularly in patients with higher risk of operative mortality. The disparity between these two markers of renal hypoxia may indicate that UPO2 reflects medullary oxygenation whereas pEPO reflects cortical oxygenation.Copyright © 2021 Wiley Periodicals LLC

Using a large national database of cardiac surgical procedures, we applied machine learning (ML) to risk stratification and profiling for cardiac surgery-associated acute kidney injury. We compared performance of ML to established scoring tools. Four ML algorithms were used, including logistic regression (LR), gradient boosted machine (GBM), K-nearest neighbor, and neural networks (NN). These were compared to the Cleveland Clinic score, and a risk score developed on the same database. Five-fold cross-validation repeated 20 times was used to measure the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Risk profiles from GBM and NN were generated using Shapley additive values. A total of 97,964 surgery events in 96,653 patients were included. For predicting postoperative renal replacement therapy using pre- and intraoperative data, LR, GBM, and NN achieved an AUC (standard deviation) of 0.84 (0.01), 0.85 (0.01), 0.84 (0.01) respectively outperforming the highest performing scoring tool with 0.81 (0.004). For predicting cardiac surgery-associated acute kidney injury, LR, GBM, and NN each achieved 0.77 (0.01), 0.78 (0.01), 0.77 (0.01) respectively outperforming the scoring tool with 0.75 (0.004). Compared to scores and LR, shapely additive values analysis of black box model predictions was able to generate patient-level explanations for each prediction. ML algorithms provide state-of-the-art approaches to risk stratification. Explanatory modeling can exploit complex decision boundaries to aid the clinician in understanding the risks specific to individual patients.Copyright © 2020

Glomerular filtration rate (GFR) is acutely increased following a high-protein meal or systemic infusion of amino acids. The mechanisms underlying this renal functional response remain to be fully elucidated. Nevertheless, they appear to culminate in preglomerular vasodilation. Inhibition of the tubuloglomerular feedback signal appears critical. However, nitric oxide, vasodilator prostaglandins, and glucagon also appear important. The increase in GFR during amino acid infusion reveals a "renal reserve,"which can be utilized when the physiological demand for single nephron GFR increases. This has led to the concept that in subclinical renal disease, before basal GFR begins to reduce, renal functional reserve can be recruited in a manner that preserves renal function. The extension of this concept is that once a decline in basal GFR can be detected, renal disease is already well progressed. This concept likely applies both in the contexts of chronic kidney disease and acute kidney injury. Critically, its corollary is that deficits in renal functional reserve have the potential to provide early detection of renal dysfunction before basal GFR is reduced. There is growing evidence that the renal response to infusion of amino acids can be used to identify patients at risk of developing either chronic kidney disease or acute kidney injury and as a treatment target for acute kidney injury. However, large multicenter clinical trials are required to test these propositions. A renewed effort to understand the renal physiology underlying the response to amino acid infusion is also warranted.Copyright © 2020 the American Physiological Society.

Using a large national database of cardiac surgical procedures, we applied machine learning (ML) to risk stratification and profiling for cardiac surgery-associated acute kidney injury. We compared performance of ML to established scoring tools. Four ML algorithms were used, including logistic regression (LR), gradient boosted machine (GBM), K-nearest neighbor, and neural networks (NN). These were compared to the Cleveland Clinic score, and a risk score developed on the same database. Five-fold cross-validation repeated 20 times was used to measure the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Risk profiles from GBM and NN were generated using Shapley additive values. A total of 97,964 surgery events in 96,653 patients were included. For predicting postoperative renal replacement therapy using pre- and intraoperative data, LR, GBM, and NN achieved an AUC (standard deviation) of 0.84 (0.01), 0.85 (0.01), 0.84 (0.01) respectively outperforming the highest performing scoring tool with 0.81 (0.004). For predicting cardiac surgery-associated acute kidney injury, LR, GBM, and NN each achieved 0.77 (0.01), 0.78 (0.01), 0.77 (0.01) respectively outperforming the scoring tool with 0.75 (0.004). Compared to scores and LR, shapely additive values analysis of black box model predictions was able to generate patient-level explanations for each prediction. ML algorithms provide state-of-the-art approaches to risk stratification. Explanatory modeling can exploit complex decision boundaries to aid the clinician in understanding the risks specific to individual patients.

Pseudocyst of the pancreas extending into the thorax represents a rare but potentially catastrophic diagnosis. It can be difficult to both diagnose and manage, with only limited management suggestions within the literature. While pleural effusion is a common complication of pancreatitis, transthoracic extension of a pseudocyst is a rare phenomenon. Herein we discuss a patient with a difficult to recognize extension of pancreatic pseudocyst into the left hemithorax, with unique imaging findings. He had good response to trans-gastric and percutaneous drainage and ultimately proceeded to thoracotomy and decortication. Around this case, the options for investigation and management are discussed.Copyright © The Author(s) 2019.

Renal medullary hypoxia may contribute to the pathophysiology of acute kidney injury, including that associated with cardiac surgery requiring cardiopulmonary bypass (CPB). When performed under volatile (isoflurane) anesthesia in sheep, CPB causes renal medullary hypoxia. There is evidence that total intravenous anesthesia (TIVA) may preserve renal perfusion and renal oxygen delivery better than volatile anesthesia. Therefore, we assessed the effects of CPB on renal perfusion and oxygenation in sheep under propofol/fentanyl-based TIVA. Sheep (n = 5) were chronically instrumented for measurement of whole renal blood flow and cortical and medullary perfusion and oxygenation. Five days later, these variables were monitored under TIVA using propofol and fentanyl and then on CPB at a pump flow of 80 mL*kg-1*min-1 and target mean arterial pressure of 70 mmHg. Under anesthesia, before CPB, renal blood flow was preserved under TIVA (mean difference +/- SD from conscious state: -16 +/- 14%). However, during CPB renal blood flow was reduced (-55 +/- 13%) and renal medullary tissue became hypoxic (-20 +/- 13 mmHg versus conscious sheep). We conclude that renal perfusion and medullary oxygenation are well preserved during TIVA before CPB. However, CPB under TIVA leads to renal medullary hypoxia, of a similar magnitude to that we observed previously under volatile (isoflurane) anesthesia. Thus use of propofol/fentanyl-based TIVA may not be a useful strategy to avoid renal medullary hypoxia during CPB.Copyright © 2020 the American Physiological Society

Aim: Blood transfusion may improve renal oxygenation during cardiopulmonary bypass (CPB). In an ovine model of experimental CPB, we tested whether increasing blood haemoglobin concentration [Hb] from ~7 g dL-1 to ~9 g dL-1 improves renal tissue oxygenation. Method(s): Ten sheep were studied while conscious, under stable isoflurane anaesthesia, and during 3 hours of CPB. In a randomized cross-over design, 5 sheep commenced bypass at a high target [Hb], achieved by adding 600 mL donor blood to the priming solution. After 90 minutes of CPB, PlasmaLyte was added to the blood reservoir to achieve low target [Hb]. For the other 5 sheep, no blood was added to the prime, but after 90 minutes of CPB, 800-900 mL of donor blood was given to achieve a high target [Hb]. Result(s): Overall, CPB was associated with marked reductions in renal oxygen delivery (-50 +/- 12%, mean +/- 95% confidence interval) and medullary tissue oxygen tension (PO2, -54 +/- 29%). Renal fractional oxygen extraction was 17 +/- 10% less during CPB at high [Hb] than low [Hb] (P =.04). Nevertheless, no increase in tissue PO2 in either the renal medulla (0 +/- 6 mmHg change, P >.99) or cortex (-19 +/- 13 mmHg change, P =.08) was detected with high [Hb]. Conclusion(s): In experimental CPB blood transfusion to increase Hb concentration from ~7 g dL-1 to ~9 g dL-1 did not improve renal cortical or medullary tissue PO2 even though it decreased whole kidney oxygen extraction.Copyright © 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

Pseudocyst of the pancreas extending into the thorax represents a rare but potentially catastrophic diagnosis. It can be difficult to both diagnose and manage, with only limited management suggestions within the literature. While pleural effusion is a common complication of pancreatitis, transthoracic extension of a pseudocyst is a rare phenomenon. Herein we discuss a patient with a difficult to recognize extension of pancreatic pseudocyst into the left hemithorax, with unique imaging findings. He had good response to trans-gastric and percutaneous drainage and ultimately proceeded to thoracotomy and decortication. Around this case, the options for investigation and management are discussed.Copyright © The Author(s) 2019.

Renal medullary hypoxia may contribute to the pathophysiology of acute kidney injury, including that associated with cardiac surgery requiring cardiopulmonary bypass (CPB). When performed under volatile (isoflurane) anesthesia in sheep, CPB causes renal medullary hypoxia. There is evidence that total intravenous anesthesia (TIVA) may preserve renal perfusion and renal oxygen delivery better than volatile anesthesia. Therefore, we assessed the effects of CPB on renal perfusion and oxygenation in sheep under propofol/fentanyl-based TIVA. Sheep (n = 5) were chronically instrumented for measurement of whole renal blood flow and cortical and medullary perfusion and oxygenation. Five days later, these variables were monitored under TIVA using propofol and fentanyl and then on CPB at a pump flow of 80 mL*kg-1*min-1 and target mean arterial pressure of 70 mmHg. Under anesthesia, before CPB, renal blood flow was preserved under TIVA (mean difference +/- SD from conscious state: -16 +/- 14%). However, during CPB renal blood flow was reduced (-55 +/- 13%) and renal medullary tissue became hypoxic (-20 +/- 13 mmHg versus conscious sheep). We conclude that renal perfusion and medullary oxygenation are well preserved during TIVA before CPB. However, CPB under TIVA leads to renal medullary hypoxia, of a similar magnitude to that we observed previously under volatile (isoflurane) anesthesia. Thus use of propofol/fentanyl-based TIVA may not be a useful strategy to avoid renal medullary hypoxia during CPB.Copyright © 2020 the American Physiological Society

Introduction: Urinary oxygen tension (PO2) may provide a useful estimate of renal medullary PO2 and thus risk of acute kidney injury (AKI). However, the relationship between urinary PO2 and medullary PO2 could be confounded by variations in urine flow and arterial PO2. In the current study we exploited data we had previously generated, from experimental studies in ovine septic AKI and in patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), to perform a detailed analysis of the influences of urine flow and arterial PO2 on urinary PO2. We also investigated the potential for simultaneous measurement of urine flow and urinary PO2, during CPB, to improve prediction of AKI over that provided by measurement of each variable on its own. Method(s): In ovine septic AKI urine flow, urinary PO2, arterial PO2, and medullary PO2 were measured. In human patients undergoing cardiac surgery requiring CPB urinary PO2 and arterial PO2 were measured continuously and urine flow was estimated every 5 minutes. Result(s): In 28 conscious septic sheep breathing room air, urinary PO2 was more closely correlated with medullary PO2 (r2=0.29) than with arterial PO2 (r2=0.06) or urine flow (r2=0.03). The difference between medullary PO2 and urinary PO2 varied little with urine flow or arterial PO2. In 20 patients, urine flow increased abruptly from 2.81 +/- 0.24 mL/min to 6.53 +/- 0.30 mL/min upon commencement of CPB, usually coincident with a fall in urinary PO2 (Fig. 1). During hyperoxic CPB high values of urinary PO2 were often observed at low urine flow. In 65 patients, low urinary PO2 during CPB (<10 mmHg at any time during CPB) was associated with greater (4.5-fold) risk of AKI. However, the level of urine flow on bypass was not significantly associated with risk of AKI. [Figure presented] Conclusion(s): We developed a method for virtually continuous measurement of urine flow in the operating theatre. We found that urinary PO2 provides a relatively robust estimate of

Introduction: Renal medullary hypoxia may be a pathophysiological factor in cardiac surgery-associated acute kidney injury. However, the effects of cardiopulmonary bypass (CPB) on oxygenation of the renal medulla remain poorly understood. Furthermore, whether increased pump flow or arterial pressure can improve renal medullary oxygenation has not been determined. Therefore, in the current study we tested whether CPB causes medullary hypoxia and whether medullary oxygenation during CPB varies with pump flow and mean arterial pressure. Method(s): Twelve sheep were instrumented to allow measurement of whole kidney, medullary and cortical blood flow and oxygenation. The experiment was performed five days later, under isoflurane anesthesia. Sheep were first placed on CPB at a pump flow of 80 mL/kg/min and a target mean arterial pressure of 70 mmHg. Pump flow was then set at 60 and 100 mL/kg/min while mean arterial pressure was maintained at ~70 mmHg. Mean arterial pressure was then increased by infusion of metaraminol (0.2 mg/min) at a set pump flow of 80 mL/kg/min. Result(s): Transition to CPB at a pump flow of 80 ml/kg/min was associated with reduced total renal blood flow (RBF, -61% less than the conscious state), along with reduced perfusion in the cortex (-44%) and medulla (-40%), and reduced medullary PO2 (from 43 to 21 mmHg; Figure) but not cortical PO2. Changes in pump flow and arterial pressure were associated with changes in medullary PO2 (Figure). That is, decreasing pump flow from 80 to 60 mL/kg/min further decreased RBF (-16%) and medullary PO2 (to 14 mmHg). Increasing pump flow from 80 to 100 mL/kg/min increased RBF (17%) and medullary PO2 (to 29 mmHg). Metaraminol (0.2 mg/min) increased mean arterial pressure (from 63 to 90 mmHg), RBF (47%) and medullary PO2 (from 19 to 39 mmHg). [Figure presented] Conclusion(s): The renal medulla appears to be more susceptible to hypoxia during CPB than the renal cortex. However, medullary oxygenation can be improved by i

Renal medullary hypoxia may contribute to cardiac surgery-associated acute kidney injury (AKI). However, the effects of cardiopulmonary bypass (CPB) on medullary oxygenation are poorly understood. Here we tested whether CPB causes medullary hypoxia and whether medullary oxygenation during CPB can be improved by increasing pump flow or mean arterial pressure (MAP). Twelve sheep were instrumented to measure whole kidney, medullary, and cortical blood flow and oxygenation. Five days later, under isoflurane anesthesia, CPB was initiated at a pump flow of 80 mL kg-1min-1 and target MAP of 70 mm Hg. Pump flow was then set at 60 and 100 mL kg-1min-1, while MAP was maintained at approximately 70 mm Hg. MAP was then increased by vasopressor (metaraminol, 0.2-0.6 mg/min) infusion at a pump flow of 80 mL kg-1min-1. CPB at 80 mL kg-1min-1 reduced renal blood flow (RBF), -61% less than the conscious state, perfusion in the cortex (-44%) and medulla (-40%), and medullary PO2 from 43 to 27 mm Hg. Decreasing pump flow from 80 to 60 mL kg-1min-1 further decreased RBF (-16%) and medullary PO2 from 25 to 14 mm Hg. Increasing pump flow from 80 to 100 mL kg-1min-1 increased RBF (17%) and medullary PO2 from 20 to 29 mm Hg. Metaraminol (0.2 mg/min) increased MAP from 63 to 90 mm Hg, RBF (47%), and medullary PO2 from 19 to 39 mm Hg. Thus, the renal medulla is susceptible to hypoxia during CPB, but medullary oxygenation can be improved by increasing pump flow or increasing target MAP by infusion of metaraminol.Copyright © 2019 International Society of Nephrology

Introduction: Continuous measurement of bladder urinary oxygen tension (PO2) may provide a real-time surrogate measure of oxygenation in the renal medulla. Therefore, urinary PO2 may be a useful tool for early prediction of acute kidney injury (AKI) and potentially also the management of renal oxygenation in patients with AKI. We examined the relationship between urinary PO2, measured in the intensive care unit (ICU), and development of AKI in patients who had undergone cardiac surgery requiring cardiopulmonary bypass (CPB). Method(s): In 74 patients undergoing on-pump cardiac surgery, bladder urinary PO2 was measured continuously in the ICU using a fibre optic probe placed in the patient's bladder catheter. AKI was diagnosed by modified 'Kidney Disease: Improving Global Outcomes' (KDIGO) criteria, excluding the urine flow criterion. Result(s): Twenty-eight out of 74 patients (37.8%) developed post-operative AKI (18 Stage 1, 7 Stage 2, and 3 Stage 3). The median time to first diagnosis of AKI, using serum creatinine, was 16.9 hours after entry into the ICU (interquartile range (IQR): 13, 32 h). The median duration of monitoring of urinary PO2 was 37.8 hours (IQR: 24.0, 47.3 h). During the first 3 hours after arrival in the ICU, overall mean urinary PO2 (AKI: 19.4 +/- 9.3 vs. non-AKI: 25.3 +/- 9.7 mmHg, p = 0.01), and the nadir (lowest recorded) urinary PO2 (AKI: 12.1 +/- 6.8 vs. non-AKI: 16.0 +/- 5.7 mmHg, p = 0.01) were lower in patients who developed AKI than those who did not. Furthermore, within the first 3 hours of entry to the ICU, 17 of the 28 patients (61%) who developed AKI had urinary PO2 less than or equal to 15 mmHg while this threshold was only reached in 16 of the 46 patients (35%) who did not develop AKI. Patients who developed AKI also experienced longer periods with urinary PO2 less than or equal to 15 mmHg (median time of 10.9 min per hour of measurement) than those who did not (median 0.0 min per hour), p = 0.01. If urinary PO2 fell to 10 mmHg or

Background. Acute kidney injury (AKI) is common after cardiac surgery and profoundly affects postoperative mortality and morbidity. There are no validated methods to assess risk of AKI intraoperatively. Methods. We determined the association between postoperative AKI and intraoperative urinary oxygen tension (PO2), measured via a fiber optic probe in the tip of the urinary catheter, in 65 patients undergoing high-risk cardiac surgery requiring cardiopulmonary bypass (CPB). AKI was diagnosed by modified Kidney Disease: Improving Global Outcomes criteria. Results. Urinary PO2 fell during the operation, often reaching its nadir during rewarming or after weaning from CPB. Nadir urinary PO2 was lower in the 26 patients who developed AKI (mean 6 SD, 8.9 6 5.6 mmHg) than in the 39 patients who did not (14.9 6 10.2 mmHg, P 1/4 0.008). Patients who developed AKI had longer periods of urinary PO2 15 and 10 mmHg than patients who did not. Odds of AKI increased when urinary PO2 fell to 10 mmHg {3.60 [95% confidence interval (CI) 1.27-10.21]} or 5 mmHg [3.60 (95% CI 1.04-12.42), P 1/4 0.04] during the operation. When urinary PO2 fell to 15 mmHg, for more than or equal to the median duration for all patients (4.8 min/h surgery), the odds of AKI were 4.85 (95% CI 1.64-14.40), P 1/4 0.004. The area under the receiver-operator curve for this parameter alone was 0.69, and was 0.89 when other variables with P 0.10 in univariable analysis were included in the model. Conclusion. Low urinary PO2 during adult cardiac surgery requiring CPB predicts AKI, so may identify patients in which intervention to improve renal oxygenation might reduce the risk of AKI.Copyright © The Author(s) 2018.

Introduction: Continuous measurement of urinary oxygen tension (PO2) in patients undergoing cardiac surgery may allow prediction of post-operative acute kidney injury (AKI). The predictive efficacy of urinary PO2 may be because it provides a good estimate of renal medullary PO2. Medications given during the perioperative period, particularly diuretics, could potentially alter medullary and/or urinary PO2. Thus, administration of furosemide may reduce the utility of urinary PO2 in predicting AKI. Therefore, we tested the effects of furosemide on urinary PO2 in patients recovering in the intensive care unit (ICU) after open heart surgery requiring cardiopulmonary bypass. Method(s): Bladder urinary PO2 was measured using a fibre optic probe, placed in the patient's bladder catheter at the time of induction of anaesthesia in the operating theatre. Urinary PO2 was measured in the ICU in 66 patients for up to 48 h (mean +/- SEM 38.9 +/- 2.6 h) after admission to the ICU. Of these, 39 patients received a bolus intravenous dose of furosemide (10-80 mg). Result(s): Urine flow in the hour before furosemide administration averaged 0.83 +/- 0.11 mL/min (mean +/- SEM) in the 23 patients who did not develop AKI during the five days after surgery (KDIGO criteria excluding urine flow criterion) and 0.57 +/- 0.11 mL/min in the 16 patients who did develop AKI (Figure 1A). In the two hours following administration of furosemide, urine flow increased to 2.10 +/- 0.37 mL/min in patients who did not develop AKI, and 1.97 +/- 0.44 mL/min in patients who did develop AKI. Urinary PO2 before administration of furosemide was lower in patients who developed AKI (20.2 +/- 2.0 mmHg) than those who did not (26.3 +/- 2.6 mmHg) (Figure 1B). Urinary PO2 did not change significantly in the first two hours following administration of furosemide in patients who did develop AKI (21.9 +/- 2.3 mmHg), or in patients who did not develop AKI (25.9 +/- 1.8 mmHg). There was also no significant relationship bet

Objectives: Acute kidney injury (AKI) develops in ~30% of patients following cardiac surgery on cardiopulmonary bypass (CPB). There are no interventions to prevent post-operative AKI, because its pathophysiology remains unclear. Our aims are (1) to determine the effects of CPB on the renal macro-and micro-circulation and (2) to determine the effects of altering pump flow on global and regional-kidney perfusion and oxygenation during CPB. Method(s): We implanted a flow probe on the renal artery and laser Doppler/oxygen-sensing probes in the cortex and medulla in sheep (N = 10). After baseline recordings in conscious sheep, animals were anesthetized, then placed on CPB with inspired oxygen fraction (FiO2) maintained at 0.6. From a baseline level of 80 mL/kg/min, pump flow was altered to 60, 80 and 100 mL/kg/min in random order. Result(s): During CPB, renal blood flow (RBF; 287 +/- 21 to 109 +/- 19 mL/ min), medullary perfusion (720 +/- 127 to 222 +/- 42 BPU) and medullary oxygenation (48 +/- 5 to 22 +/- 7 mmHg) were all reduced, compared with conscious sheep. Cortical oxygenation increased during CPB (46 +/- 3 to 70 +/- 17 mmHg), despite reduced perfusion (1954 +/- 378 to 872 +/- 112 BPU). Reducing pump flow exacerbated medullary hypoxia (to 11 +/- 3 mmHg), while increasing pump flow tended to improve medullary oxygenation (to 29 +/- 7 mmHg). Conclusion(s): CPB had detrimental effects on RBF, medullary and cortical perfusion and medullary oxygenation. Cortical oxygenation was maintained by the high FiO2. Medullary hypoxia may be a crucial mediator of post-CPB AKI. Thus, avoiding medullary hypoxia, by optimizing perfusion conditions on CPB, may be a feasible strategy to mitigate post-operative AKI.

Aim: Urinary oxygen tension (uPO2) may provide an estimate of renal medullary PO2 (mPO2) and thus risk of acute kidney injury (AKI). We assessed the potential for variations in urine flow and arterial PO2 (aPO2) to confound these estimates. Method(s): In 28 sheep urine flow, uPO2, aPO2 and mPO2 were measured during development of septic AKI. In 65 human patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) uPO2 and aPO2 were measured continuously during CPB, and in a subset of 20 patients, urine flow was estimated every 5 minutes. Result(s): In conscious sheep breathing room air, uPO2 was more closely correlated with mPO2 than with aPO2 or urine flow. The difference between mPO2 and uPO2 varied little with urine flow or aPO2. In patients, urine flow increased abruptly from 3.42 +/- 0.29 mL min-1 to 6.94 +/- 0.26 mL min-1 upon commencement of CPB, usually coincident with reduced uPO2. During hyperoxic CPB high values of uPO2 were often observed at low urine flow. Low urinary PO2 during CPB (<10 mm Hg at any time during CPB) was associated with greater (4.5-fold) risk of AKI. However, low urine flow during CPB was not significantly associated with risk of AKI. Conclusion(s): uPO2 provides a robust estimate of mPO2, but this relationship is confounded by the simultaneous presence of systemic hyperoxia and low urine flow. Urine flow increases and uPO2 decreases during CPB. Thus, CPB is probably the best time to use uPO2 to detect renal medullary hypoxia and risk of post-operative AKI.Copyright © 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

Renal medullary hypoxia may contribute to cardiac surgery-associated acute kidney injury (AKI). However, the effects of cardiopulmonary bypass (CPB) on medullary oxygenation are poorly understood. Here we tested whether CPB causes medullary hypoxia and whether medullary oxygenation during CPB can be improved by increasing pump flow or mean arterial pressure (MAP). Twelve sheep were instrumented to measure whole kidney, medullary, and cortical blood flow and oxygenation. Five days later, under isoflurane anesthesia, CPB was initiated at a pump flow of 80 mL kg-1min-1 and target MAP of 70 mm Hg. Pump flow was then set at 60 and 100 mL kg-1min-1, while MAP was maintained at approximately 70 mm Hg. MAP was then increased by vasopressor (metaraminol, 0.2-0.6 mg/min) infusion at a pump flow of 80 mL kg-1min-1. CPB at 80 mL kg-1min-1 reduced renal blood flow (RBF), -61% less than the conscious state, perfusion in the cortex (-44%) and medulla (-40%), and medullary PO2 from 43 to 27 mm Hg. Decreasing pump flow from 80 to 60 mL kg-1min-1 further decreased RBF (-16%) and medullary PO2 from 25 to 14 mm Hg. Increasing pump flow from 80 to 100 mL kg-1min-1 increased RBF (17%) and medullary PO2 from 20 to 29 mm Hg. Metaraminol (0.2 mg/min) increased MAP from 63 to 90 mm Hg, RBF (47%), and medullary PO2 from 19 to 39 mm Hg. Thus, the renal medulla is susceptible to hypoxia during CPB, but medullary oxygenation can be improved by increasing pump flow or increasing target MAP by infusion of metaraminol.Copyright © 2019 International Society of Nephrology

Background. Acute kidney injury (AKI) is common after cardiac surgery and profoundly affects postoperative mortality and morbidity. There are no validated methods to assess risk of AKI intraoperatively. Methods. We determined the association between postoperative AKI and intraoperative urinary oxygen tension (PO2), measured via a fiber optic probe in the tip of the urinary catheter, in 65 patients undergoing high-risk cardiac surgery requiring cardiopulmonary bypass (CPB). AKI was diagnosed by modified Kidney Disease: Improving Global Outcomes criteria. Results. Urinary PO2 fell during the operation, often reaching its nadir during rewarming or after weaning from CPB. Nadir urinary PO2 was lower in the 26 patients who developed AKI (mean 6 SD, 8.9 6 5.6 mmHg) than in the 39 patients who did not (14.9 6 10.2 mmHg, P 1/4 0.008). Patients who developed AKI had longer periods of urinary PO2 15 and 10 mmHg than patients who did not. Odds of AKI increased when urinary PO2 fell to 10 mmHg {3.60 [95% confidence interval (CI) 1.27-10.21]} or 5 mmHg [3.60 (95% CI 1.04-12.42), P 1/4 0.04] during the operation. When urinary PO2 fell to 15 mmHg, for more than or equal to the median duration for all patients (4.8 min/h surgery), the odds of AKI were 4.85 (95% CI 1.64-14.40), P 1/4 0.004. The area under the receiver-operator curve for this parameter alone was 0.69, and was 0.89 when other variables with P 0.10 in univariable analysis were included in the model. Conclusion. Low urinary PO2 during adult cardiac surgery requiring CPB predicts AKI, so may identify patients in which intervention to improve renal oxygenation might reduce the risk of AKI.Copyright © The Author(s) 2018.

Introduction: Renal medullary hypoxia may be a pathophysiological factor in cardiac surgery-associated acute kidney injury. However, the effects of cardiopulmonary bypass (CPB) on oxygenation of the renal medulla remain poorly understood. Furthermore, whether increased pump flow or arterial pressure can improve renal medullary oxygenation has not been determined. Therefore, in the current study we tested whether CPB causes medullary hypoxia and whether medullary oxygenation during CPB varies with pump flow and mean arterial pressure. Method(s): Twelve sheep were instrumented to allow measurement of whole kidney, medullary and cortical blood flow and oxygenation. The experiment was performed five days later, under isoflurane anesthesia. Sheep were first placed on CPB at a pump flow of 80 mL/kg/min and a target mean arterial pressure of 70 mmHg. Pump flow was then set at 60 and 100 mL/kg/min while mean arterial pressure was maintained at ~70 mmHg. Mean arterial pressure was then increased by infusion of metaraminol (0.2 mg/min) at a set pump flow of 80 mL/kg/min. Result(s): Transition to CPB at a pump flow of 80 ml/kg/min was associated with reduced total renal blood flow (RBF, -61% less than the conscious state), along with reduced perfusion in the cortex (-44%) and medulla (-40%), and reduced medullary PO2 (from 43 to 21 mmHg; Figure) but not cortical PO2. Changes in pump flow and arterial pressure were associated with changes in medullary PO2 (Figure). That is, decreasing pump flow from 80 to 60 mL/kg/min further decreased RBF (-16%) and medullary PO2 (to 14 mmHg). Increasing pump flow from 80 to 100 mL/kg/min increased RBF (17%) and medullary PO2 (to 29 mmHg). Metaraminol (0.2 mg/min) increased mean arterial pressure (from 63 to 90 mmHg), RBF (47%) and medullary PO2 (from 19 to 39 mmHg). [Figure presented] Conclusion(s): The renal medulla appears to be more susceptible to hypoxia during CPB than the renal cortex. However, medullary oxygenation can be improved by i

Introduction: Urinary oxygen tension (PO2) may provide a useful estimate of renal medullary PO2 and thus risk of acute kidney injury (AKI). However, the relationship between urinary PO2 and medullary PO2 could be confounded by variations in urine flow and arterial PO2. In the current study we exploited data we had previously generated, from experimental studies in ovine septic AKI and in patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), to perform a detailed analysis of the influences of urine flow and arterial PO2 on urinary PO2. We also investigated the potential for simultaneous measurement of urine flow and urinary PO2, during CPB, to improve prediction of AKI over that provided by measurement of each variable on its own. Method(s): In ovine septic AKI urine flow, urinary PO2, arterial PO2, and medullary PO2 were measured. In human patients undergoing cardiac surgery requiring CPB urinary PO2 and arterial PO2 were measured continuously and urine flow was estimated every 5 minutes. Result(s): In 28 conscious septic sheep breathing room air, urinary PO2 was more closely correlated with medullary PO2 (r2=0.29) than with arterial PO2 (r2=0.06) or urine flow (r2=0.03). The difference between medullary PO2 and urinary PO2 varied little with urine flow or arterial PO2. In 20 patients, urine flow increased abruptly from 2.81 +/- 0.24 mL/min to 6.53 +/- 0.30 mL/min upon commencement of CPB, usually coincident with a fall in urinary PO2 (Fig. 1). During hyperoxic CPB high values of urinary PO2 were often observed at low urine flow. In 65 patients, low urinary PO2 during CPB (<10 mmHg at any time during CPB) was associated with greater (4.5-fold) risk of AKI. However, the level of urine flow on bypass was not significantly associated with risk of AKI. [Figure presented] Conclusion(s): We developed a method for virtually continuous measurement of urine flow in the operating theatre. We found that urinary PO2 provides a relatively robust estimate of

Introduction: Continuous measurement of bladder urinary oxygen tension (PO2) may provide a real-time surrogate measure of oxygenation in the renal medulla. Therefore, urinary PO2 may be a useful tool for early prediction of acute kidney injury (AKI) and potentially also the management of renal oxygenation in patients with AKI. We examined the relationship between urinary PO2, measured in the intensive care unit (ICU), and development of AKI in patients who had undergone cardiac surgery requiring cardiopulmonary bypass (CPB). Method(s): In 74 patients undergoing on-pump cardiac surgery, bladder urinary PO2 was measured continuously in the ICU using a fibre optic probe placed in the patient's bladder catheter. AKI was diagnosed by modified 'Kidney Disease: Improving Global Outcomes' (KDIGO) criteria, excluding the urine flow criterion. Result(s): Twenty-eight out of 74 patients (37.8%) developed post-operative AKI (18 Stage 1, 7 Stage 2, and 3 Stage 3). The median time to first diagnosis of AKI, using serum creatinine, was 16.9 hours after entry into the ICU (interquartile range (IQR): 13, 32 h). The median duration of monitoring of urinary PO2 was 37.8 hours (IQR: 24.0, 47.3 h). During the first 3 hours after arrival in the ICU, overall mean urinary PO2 (AKI: 19.4 +/- 9.3 vs. non-AKI: 25.3 +/- 9.7 mmHg, p = 0.01), and the nadir (lowest recorded) urinary PO2 (AKI: 12.1 +/- 6.8 vs. non-AKI: 16.0 +/- 5.7 mmHg, p = 0.01) were lower in patients who developed AKI than those who did not. Furthermore, within the first 3 hours of entry to the ICU, 17 of the 28 patients (61%) who developed AKI had urinary PO2 less than or equal to 15 mmHg while this threshold was only reached in 16 of the 46 patients (35%) who did not develop AKI. Patients who developed AKI also experienced longer periods with urinary PO2 less than or equal to 15 mmHg (median time of 10.9 min per hour of measurement) than those who did not (median 0.0 min per hour), p = 0.01. If urinary PO2 fell to 10 mmHg or

Introduction: Continuous measurement of urinary oxygen tension (PO2) in patients undergoing cardiac surgery may allow prediction of post-operative acute kidney injury (AKI). The predictive efficacy of urinary PO2 may be because it provides a good estimate of renal medullary PO2. Medications given during the perioperative period, particularly diuretics, could potentially alter medullary and/or urinary PO2. Thus, administration of furosemide may reduce the utility of urinary PO2 in predicting AKI. Therefore, we tested the effects of furosemide on urinary PO2 in patients recovering in the intensive care unit (ICU) after open heart surgery requiring cardiopulmonary bypass. Method(s): Bladder urinary PO2 was measured using a fibre optic probe, placed in the patient's bladder catheter at the time of induction of anaesthesia in the operating theatre. Urinary PO2 was measured in the ICU in 66 patients for up to 48 h (mean +/- SEM 38.9 +/- 2.6 h) after admission to the ICU. Of these, 39 patients received a bolus intravenous dose of furosemide (10-80 mg). Result(s): Urine flow in the hour before furosemide administration averaged 0.83 +/- 0.11 mL/min (mean +/- SEM) in the 23 patients who did not develop AKI during the five days after surgery (KDIGO criteria excluding urine flow criterion) and 0.57 +/- 0.11 mL/min in the 16 patients who did develop AKI (Figure 1A). In the two hours following administration of furosemide, urine flow increased to 2.10 +/- 0.37 mL/min in patients who did not develop AKI, and 1.97 +/- 0.44 mL/min in patients who did develop AKI. Urinary PO2 before administration of furosemide was lower in patients who developed AKI (20.2 +/- 2.0 mmHg) than those who did not (26.3 +/- 2.6 mmHg) (Figure 1B). Urinary PO2 did not change significantly in the first two hours following administration of furosemide in patients who did develop AKI (21.9 +/- 2.3 mmHg), or in patients who did not develop AKI (25.9 +/- 1.8 mmHg). There was also no significant relationship bet

Objectives: Acute kidney injury (AKI) develops in ~30% of patients following cardiac surgery on cardiopulmonary bypass (CPB). There are no interventions to prevent post-operative AKI, because its pathophysiology remains unclear. Our aims are (1) to determine the effects of CPB on the renal macro-and micro-circulation and (2) to determine the effects of altering pump flow on global and regional-kidney perfusion and oxygenation during CPB. Method(s): We implanted a flow probe on the renal artery and laser Doppler/oxygen-sensing probes in the cortex and medulla in sheep (N = 10). After baseline recordings in conscious sheep, animals were anesthetized, then placed on CPB with inspired oxygen fraction (FiO2) maintained at 0.6. From a baseline level of 80 mL/kg/min, pump flow was altered to 60, 80 and 100 mL/kg/min in random order. Result(s): During CPB, renal blood flow (RBF; 287 +/- 21 to 109 +/- 19 mL/ min), medullary perfusion (720 +/- 127 to 222 +/- 42 BPU) and medullary oxygenation (48 +/- 5 to 22 +/- 7 mmHg) were all reduced, compared with conscious sheep. Cortical oxygenation increased during CPB (46 +/- 3 to 70 +/- 17 mmHg), despite reduced perfusion (1954 +/- 378 to 872 +/- 112 BPU). Reducing pump flow exacerbated medullary hypoxia (to 11 +/- 3 mmHg), while increasing pump flow tended to improve medullary oxygenation (to 29 +/- 7 mmHg). Conclusion(s): CPB had detrimental effects on RBF, medullary and cortical perfusion and medullary oxygenation. Cortical oxygenation was maintained by the high FiO2. Medullary hypoxia may be a crucial mediator of post-CPB AKI. Thus, avoiding medullary hypoxia, by optimizing perfusion conditions on CPB, may be a feasible strategy to mitigate post-operative AKI.

Aim: Urinary oxygen tension (uPO2) may provide an estimate of renal medullary PO2 (mPO2) and thus risk of acute kidney injury (AKI). We assessed the potential for variations in urine flow and arterial PO2 (aPO2) to confound these estimates. Method(s): In 28 sheep urine flow, uPO2, aPO2 and mPO2 were measured during development of septic AKI. In 65 human patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) uPO2 and aPO2 were measured continuously during CPB, and in a subset of 20 patients, urine flow was estimated every 5 minutes. Result(s): In conscious sheep breathing room air, uPO2 was more closely correlated with mPO2 than with aPO2 or urine flow. The difference between mPO2 and uPO2 varied little with urine flow or aPO2. In patients, urine flow increased abruptly from 3.42 +/- 0.29 mL min-1 to 6.94 +/- 0.26 mL min-1 upon commencement of CPB, usually coincident with reduced uPO2. During hyperoxic CPB high values of uPO2 were often observed at low urine flow. Low urinary PO2 during CPB (<10 mm Hg at any time during CPB) was associated with greater (4.5-fold) risk of AKI. However, low urine flow during CPB was not significantly associated with risk of AKI. Conclusion(s): uPO2 provides a robust estimate of mPO2, but this relationship is confounded by the simultaneous presence of systemic hyperoxia and low urine flow. Urine flow increases and uPO2 decreases during CPB. Thus, CPB is probably the best time to use uPO2 to detect renal medullary hypoxia and risk of post-operative AKI.Copyright © 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

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.Copyright © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

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.

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.Copyright © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

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.

Renal medullary hypoxia may be a common pathway in the development of acute kidney injury (AKI). There are no validated methods to detect medullary hypoxia in patients. However, experimental findings indicate that changes in urinary oxygen tension (UPO2) reflect changes in medullary PO2. Therefore, we evaluated the relationship between intra-operative UPO2 and the development of AKI after cardiac surgery requiring cardiopulmonary bypass (CPB). From January 2015 to July 2016, thirty-five adult patients undergoing on-pump cardiac surgery were prospectively enrolled. UPO2 was continuously recorded intra-operatively via a fiber-optic probe deployed through the lumen of the urinary catheter, with the end of the probe at the catheter tip, where it was in contact with bladder urine. UPO2 fell during surgery, particularly during CPB. The lowest (nadir) UPO2 was most frequently observed during the rewarming phase of CPB, or shortly after weaning from CPB (n=25, 71%). Fourteen patients (40%) developed AKI as defined by an increase in serum creatinine from baseline of either > 26.5 mumol/L (0.3 mg/dL) within 48 hours or > 50% within 5 days. Nadir intra-operative UPO2 was lower in patients who later developed AKI (8.5 +/- 1.6 mmHg, mean +/- SE) than in those who did not (16.5 +/- 4.2 mmHg, P = 0.02). UPO2 below 10 mmHg at any time during surgery was associated with a 4.5-fold [95% confidence limits 1.6 - 19.1] greater risk of AKI (P = 0.03). Furthermore, urinary PO2 below 15 mmHg for longer than the median time for all patients (5.6 min per hour of surgery) was associated with a 7.3-fold [1.8 - 35.1] greater risk of AKI (P = 0.01) and an area under the receiver operator curve of 0.73 [0.56 - 0.90] (P = 0.03). We conclude that low UPO2 during cardiac surgery requiring CPB is strongly associated with later development of AKI. Continuous intra-operative monitoring of UPO2 is simple and relatively noninvasive. It may provide a real-time biomarker of risk of AKI. Early detection of

Introduction: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart defect with limited data on long-term outcomes after surgery. We sought to determine outcomes of patients operated for ALCAPA at the Royal Children's Hospital. Method(s): All patients who underwent repair of ALCAPA were identified from the hospital database and retrospectively reviewed. Result(s): From November 1972 to March 2014, forty four patients were operated for ALCAPA at the Royal Children's Hospital. Median age at operation was 141 days (range 49 days to 26 years) and median weight at operation was 5.8 kilograms (range 2.3 kilograms to 64 kilograms). Four (4/44, 9%) patients had associated anomalies. Twenty nine (29/44, 66%) patients underwent reimplantation technique, 13 (13/ 44, 30%) had intrapulmonary baffle repair (Takeuchi repair) and 2 patients (2/44, 4%) had ligation of the anomalous artery. Eight (8/44, 18%) patients had associated mitral valve (MV) repair and 1 patient (1/44, 3%) had aMV replacement at time of initial surgery. Fifteen (15/44, 34%) patients required left ventricular assistdevice (LVAD) support at the completion of surgery. LVADwas removed at amean 4 days (range 2 days to 8 days) after surgery. Early mortality was 2.3% (1/44). Follow-up was 100% complete for local patients. Mean follow-upwas 12.3 years (range 4months to 31 years). Therewere no late deaths. Survival was 97% at 20 years. Ten patients underwent 13 reoperations at amean 7 years (range 2months to 25 years) after surgery. Freedomfromreoperationwas 81%, 77% and 66% at 5, 10 and 20 years after surgery, respectively. Seven patients underwent late MV repair or replacement at a mean 8 years (range 2 months to 25 years) after surgery. Freedom from late MV repair or replacement was 83%, 83% and 77% at 5, 10 and 20 years after surgery, respectively. Eleven (11/44, 25%) patients had severe mitral regurgitation (MR) preoperatively. Of those 11 patients, 5 (5/11, 45%) had MVrepai

Renal medullary hypoxia may be a common pathway in the development of acute kidney injury (AKI). There are no validated methods to detect medullary hypoxia in patients. However, experimental findings indicate that changes in urinary oxygen tension (UPO2) reflect changes in medullary PO2. Therefore, we evaluated the relationship between intra-operative UPO2 and the development of AKI after cardiac surgery requiring cardiopulmonary bypass (CPB). From January 2015 to July 2016, thirty-five adult patients undergoing on-pump cardiac surgery were prospectively enrolled. UPO2 was continuously recorded intra-operatively via a fiber-optic probe deployed through the lumen of the urinary catheter, with the end of the probe at the catheter tip, where it was in contact with bladder urine. UPO2 fell during surgery, particularly during CPB. The lowest (nadir) UPO2 was most frequently observed during the rewarming phase of CPB, or shortly after weaning from CPB (n=25, 71%). Fourteen patients (40%) developed AKI as defined by an increase in serum creatinine from baseline of either > 26.5 mumol/L (0.3 mg/dL) within 48 hours or > 50% within 5 days. Nadir intra-operative UPO2 was lower in patients who later developed AKI (8.5 +/- 1.6 mmHg, mean +/- SE) than in those who did not (16.5 +/- 4.2 mmHg, P = 0.02). UPO2 below 10 mmHg at any time during surgery was associated with a 4.5-fold [95% confidence limits 1.6 - 19.1] greater risk of AKI (P = 0.03). Furthermore, urinary PO2 below 15 mmHg for longer than the median time for all patients (5.6 min per hour of surgery) was associated with a 7.3-fold [1.8 - 35.1] greater risk of AKI (P = 0.01) and an area under the receiver operator curve of 0.73 [0.56 - 0.90] (P = 0.03). We conclude that low UPO2 during cardiac surgery requiring CPB is strongly associated with later development of AKI. Continuous intra-operative monitoring of UPO2 is simple and relatively noninvasive. It may provide a real-time biomarker of risk of AKI. Early detection of