Intraoperative hyperglycemia augments ischemia reperfusion injury in renal transplantation: a prospective study.

Background. Diabetes is a risk factor for delayed graft function in kidney transplantation, and hyperglycemia increases ischemia reperfusion injury in animal models. Methods. To explore the role of perioperative hyperglycemia in ischemia reperfusion injury, we conducted a prospective study of 40 patients undergoing living donor renal transplantation. Blood glucose levels were monitored intraoperatively, and serum samples were obtained at the time anesthesia was induced and one hour after allograft reperfusion. The percentage change in neutrophil gelatinase-associated lipocalin (NGAL), a protein whose expression is increased with renal ischemia, was then used to determine the extent of injury. Results. In a multivariate model including recipient, donor, and transplant factors, recipient blood glucose >160 mg/dL at the time of allograft reperfusion (β 0.19, P-value < 0.01), warm ischemia time >30 minutes (β 0.11, P-value 0.13), and recipient age (β 0.05, P-value 0.05) were associated with percentage change in NGAL. These same predictors were associated with the percentage change in creatinine on postoperative day 2. Conclusions. Hyperglycemia is associated with increased ischemic injury in renal transplantation. Both creatinine and NGAL, a marker of ischemic injury and renal function, fall less rapidly in patients with elevated blood glucose

Acute Hyperglycemia Worsens Hepatic Ischemia/Reperfusion Injury in Rats

Acute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R. Rats were pretreated with an intraperitoneal injection of 25% glucose or 0.9% sodium chloride (10 ml/kg BW). Subsequently, rats underwent partial (70%) hepatic ischemia for 45 min. After 4 h of reperfusion, hepatic injury, oxidative stress, inflammation, and heat shock protein expression were assessed. Liver injury was increased in the hyperglycemic group with alanine aminotransferase (ALT) and aspartate aminotransferease (AST) serum concentrations of 7,832 ± 3,374 and 10,677 ± 4,110 U/L compared to 3,245 ± 2,009 and 5,386 ± 3,393 U/L (p < 0.05 vs. control). Hyperglycemic I/R was associated with increased liver nitrotyrosine concentrations and increased neutrophil infiltration. I/R upregulated the protective heat shock proteins HSP32 and HSP70 in control animals, but this protective mechanism was inhibited by hyperglycemia: HSP32 expression decreased from 1.97 ± 0.89 (control) to 0.46 ± 0.13 (hyperglycemia), HSP70 expression decreased from 18.99 ± 11.55 (control) to 3.22 ± 0.56 (hyperglycemia), (expression normalized to sham, both p < 0.05 vs. control I/R). Acute hyperglycemia worsens hepatic I/R injury by amplifying oxidative stress and the inflammatory response to I/R. The increase in injury is associated with a downregulation of the protective heat shock proteins HSP32 and HSP70

Systemic inflammation, coagulopathy, and acute renal insufficiency following endovascular thoracoabdominal aortic aneurysm repair

ObjectiveTo characterize the inflammatory and coagulopathic response after endovascular thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the effect of the response on postoperative renal function.MethodsFrom July 2005 to June 2008, 42 patients underwent elective endovascular repair of a TAAA using custom designed multi-branched stent-grafts at a single academic institution. Four patients were excluded from the analysis. White blood cell count (WBC), platelet count, prothrombin time (PT), and creatinine were measured in all patients. In the last nine patients, interleukin-6 (IL-6), protein C, Factor V, d-dimers, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) levels were also measured. Change in lab values were expressed as a percentage of baseline values.ResultsThe 30-day mortality rate was 5% (2/38). All patients (n = 38) had a higher WBC (mean ± SD: 139 ± 80%, P < .0001), lower platelet count (56 ± 15%, P < .0001), and higher PT (median: 17%, Interquartile range (IQR) 12%-22%, P < .0001) after stent-graft insertion. Twelve of 38 patients (32%) developed postoperative acute renal insufficiency (>50% rise in creatinine). Patients with renal insufficiency had significantly larger changes in WBC (178 ± 100% vs 121 ± 64%, P = .04) and platelet count (64 ± 17% vs 52 ± 12%, P = .02) compared with those without renal insufficiency. All patients (n = 9) had significant increases in NGAL (182 ± 115%, P = .008) after stent-graft insertion. Six of nine patients (67%) had increased cystatin C (35 ± 43%, P = .04) after stent-graft insertion, with a greater rise in those with postoperative renal insufficiency (87 ± 32% vs 8 ± 13%, P = .02). IL-6 levels were markedly increased in all patients (n = 9) after repair (9840 ± 6160%, P = .008). Protein C (35 ± 10%, P = .008) and Factor V levels (28 ± 20%, P = .008) were uniformly decreased, while d-dimers were elevated after repair in all patients (310 ± 213%, P = .008).ConclusionsLeukocytosis and thrombocytopenia were uniform following endovascular TAAA repair, and the severity of the response correlated with post-operative renal dysfunction. Elevation of a sensitive marker of renal injury (NGAL) suggests that renal injury may occur in all patients after stent-graft insertion

Acute hyperglycemia worsens hepatic ischemia/reperfusion injury in rats.

Background/aimsAcute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R.MethodsRats were pretreated with an intraperitoneal injection of 25% glucose or 0.9% sodium chloride (10 ml/kg BW). Subsequently, rats underwent partial (70%) hepatic ischemia for 45 min. After 4 h of reperfusion, hepatic injury, oxidative stress, inflammation, and heat shock protein expression were assessed.ResultsLiver injury was increased in the hyperglycemic group with alanine aminotransferase (ALT) and aspartate aminotransferease (AST) serum concentrations of 7,832 +/- 3,374 and 10,677 +/- 4,110 U/L compared to 3,245 +/- 2,009 and 5,386 +/- 3,393 U/L (p &lt; 0.05 vs. control). Hyperglycemic I/R was associated with increased liver nitrotyrosine concentrations and increased neutrophil infiltration. I/R upregulated the protective heat shock proteins HSP32 and HSP70 in control animals, but this protective mechanism was inhibited by hyperglycemia: HSP32 expression decreased from 1.97 +/- 0.89 (control) to 0.46 +/- 0.13 (hyperglycemia), HSP70 expression decreased from 18.99 +/- 11.55 (control) to 3.22 +/- 0.56 (hyperglycemia), (expression normalized to sham, both p &lt; 0.05 vs. control I/R).ConclusionsAcute hyperglycemia worsens hepatic I/R injury by amplifying oxidative stress and the inflammatory response to I/R. The increase in injury is associated with a downregulation of the protective heat shock proteins HSP32 and HSP70

Enhanced recovery for liver transplantation:recommendations from the 2022 International Liver Transplantation Society consensus conference

There is much controversy regarding enhanced recovery for recipients of liver transplants from deceased and living donors. The objectives of this Review were to summarise current knowledge on individual enhanced recovery elements on short-term outcomes, identify key components for comprehensive pathways, and create internationally accepted guidelines on enhanced recovery for liver-transplant recipients. The ERAS4OLT.org collaborative partnered by the International Liver Transplantation Society performed systematic literature reviews on the effect of 32 relevant enhanced perioperative recovery elements on short-term outcomes, and global specialists prepared expert statements on deceased and living donor liver transplantation. The Grading Recommendations, Assessment, Development and Evaluations approach was used for rating of quality of evidence and grading of recommendations. A virtual international consensus conference was held in January, 2022, in which results were presented, voted on by the audience, and discussed by an independent international jury of eight members, applying the Danish model of consensus. 273 liver transplantation specialists from 30 countries prepared expert statements on elements of enhanced recovery for liver transplantation based on the systematic literature reviews. The consensus conference yielded 80 final recommendations, covering aspects of enhanced recovery for preoperative assessment and optimisation, intraoperative surgical and anaesthetic conduct, and postoperative management for the recipients of liver transplants from both deceased and living donors, and for the living donor. The recommendations represent a comprehensive overview of the relevant elements and areas of enhanced recovery for liver transplantation. These internationally established guidelines could direct the development of enhanced recovery programmes worldwide, allowing adjustments according to local resources and practices.</p

Enhanced recovery for liver transplantation: recommendations from the 2022 International Liver Transplantation Society consensus conference

There is much controversy regarding enhanced recovery for recipients of liver transplants from deceased and living donors. The objectives of this Review were to summarise current knowledge on individual enhanced recovery elements on short-term outcomes, identify key components for comprehensive pathways, and create internationally accepted guidelines on enhanced recovery for liver-transplant recipients. The ERAS4OLT.org collaborative partnered by the International Liver Transplantation Society performed systematic literature reviews on the effect of 32 relevant enhanced perioperative recovery elements on short-term outcomes, and global specialists prepared expert statements on deceased and living donor liver transplantation. The Grading Recommendations, Assessment, Development and Evaluations approach was used for rating of quality of evidence and grading of recommendations. A virtual international consensus conference was held in January, 2022, in which results were presented, voted on by the audience, and discussed by an independent international jury of eight members, applying the Danish model of consensus. 273 liver transplantation specialists from 30 countries prepared expert statements on elements of enhanced recovery for liver transplantation based on the systematic literature reviews. The consensus conference yielded 80 final recommendations, covering aspects of enhanced recovery for preoperative assessment and optimisation, intraoperative surgical and anaesthetic conduct, and postoperative management for the recipients of liver transplants from both deceased and living donors, and for the living donor. The recommendations represent a comprehensive overview of the relevant elements and areas of enhanced recovery for liver transplantation. These internationally established guidelines could direct the development of enhanced recovery programmes worldwide, allowing adjustments according to local resources and practices

Impact of a Quality Improvement Project on Deceased Organ Donor Management

CONTEXT: Donors showed poor glucose control in the period between declaration of brain death and organ recovery. The level of hyperglycemia in the donors was associated with a decline in terminal renal function. OBJECTIVE: To determine whether implementation of a quality improvement project improved glucose control and preserved renal function in deceased organ donors. METHODS: Data collected retrospectively included demographics, medical history, mechanism of death, laboratory values, and data from the United Network for Organ Sharing. RESULTS: After implementation of the quality improvement project, deceased donors had significantly lower mean glucose concentrations (mean [SD], 162 [44] vs 212 [42] mg/dL; P < .001) and prerecovery glucose concentration (143 [66] vs 241 [69] mg/dL; P < .001). When the donor cohorts from before and after the quality improvement project were analyzed together, mean glucose concentration remained a significant predictor of terminal creatinine level (P < .001). Multivariate analysis of delayed graft function in kidney recipients matched to donors indicated that higher terminal creatinine level was associated with delayed graft function in recipients (P < .001). CONCLUSION: The quality improvement project improved donor glucose homeostasis, and the data confirm that poor glucose homeostasis is associated with worsening terminal renal function