Limited non-linear impact of warm ischemia time on renal functional decline after partial nephrectomy: a propensity score-matched study.

OBJECTIVE: To quantificationally illustrate the impact of ischemia time (IT) on renal function decline after partial nephrectomy (PN), especially for patients with compromised baseline renal function (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2). METHODS: Patients undergoing PN during 2014-2021 from a prospectively maintained database were reviewed. Propensity score matching (PSM) was employed to balance the possible covariates between patients with or without baseline compromised renal function. Specifically, the relationship of IT with postoperative renal function was illustrated. Two machine learning methods (logistic least absolute shrinkage and selection operator [LASSO] logistic regression and random forest) were applied to quantify the relative impact of each covariables. RESULTS: The average drop percent of eGFR was -10.9% (- 12.2%, - 9.0%). Multivariable Cox proportional regression and linear regression analyses identified five risk factors for renal function decline, namely RENAL Nephrometry Score (RNS), age, baseline eGFR, diabetes and IT (all p < 0.05). Specifically, the relationship of IT with postoperative functional decline emerged as non-linear, with an increase from 10-30 min and a plateau afterwards among patients with normal function (eGFR ≥ 90 mL/min/1.73 m2), whereas with an increase from 10 to 20 min and a plateau afterwards among patients with compromised function (eGFR < 90 mL/min/1.73 m2). Furthermore, the coefficient's path and random forest analysis revealed that the top two most important features were RNS and age. CONCLUSION: IT exhibits the secondarily non-linear relationship with postoperative renal function decline. Patients with compromised baseline renal function are less tolerant to ischemia damage. The use of a single cut-off interval of IT in the setting of PN is flawed.

Functional recovery after partial nephrectomy: next generation analysis.

OBJECTIVES: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. RESULTS: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25-42) and 22 (18-28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63-92) and 69 (54-81) mL/min/1.73 m2 , respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33-47) and 31 (24-38) mL/min/1.73 m2 , respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5-12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%-102%), 95% (89%-101%), and 97% (91%-102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin-dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. CONCLUSIONS: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia-related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.

Long-Term Renal Function Following Renal Cancer Surgery: Historical Perspectives, Current Status, and Future Considerations.

Knowledge of functional recovery after partial (PN) and radical nephrectomy for renal cancer has advanced considerably, with PN now established as the reference standard for most localized renal masses. However, it is still unclear whether PN provides an overall survival benefit in patients with a normal contralateral kidney. While early studies seemingly demonstrated the importance of minimizing warm-ischemia time during PN, multiple new investigations over the last 10 years have proven that parenchymal mass lost is the most important predictor of new baseline renal function. Minimizing loss of parenchymal mass during resection and reconstruction is the most important controllable aspect of long-term post-operative renal function preservation.

Safe heart flush technique during recovery from donors after circulatory death.

BACKGROUND: Donation after circulatory death is the donation after cardiac arrest. This technique has been employed and adopted by clinicians to overcome the shortage of available hearts for transplant. Warm ischemia time plays a pivotal role in the survival outcome of the heart recipients. AIM OF THE STUDY: To assess the efficacy of using the Foley catheter to flush the heart during procurement from donation after circulatory death donors. METHODS: We utilized a 2-WAY Foley catheter to flush the heart during procurement. The catheter was prepared and modified on the back table. RESULTS: We were successfully able to flush the heart within 3 minutes from skin incision with a good recipient outcome. CONCLUSIONS: Using the Foley catheter to flush the heart during recovery from donation after circulatory death donors was both efficient and fast.

[Evaluation of the results of sodium fumarate, furosemide, and mannitol on the initiation and outcome of renal warm ischemia in an experimental study].

While performing surgical treatment of the localized form of renal cell cancer by means of open or laparoscopic partial nephrectomy, renal warm ischemia is an important issue. Using renal warm ischemia allows to prevent parenchymal bleeding, to optimize conditions for resection of the tumor and to increase significantly the efficiency of hemostasis. However, an important problem is the probability of ischemic hypoxic damage of the remaining part of the kidney tissue during renal warm ischemia and renal functional impairment in the postoperative period. AIM: To compare nephroprotective activity of sodium fumarate, mannitol and furosemide using experimental model of 30- and 60-minute renal warm ischemia in rabbits. MATERIALS AND METHODS: The experiments were carried out on 360 conventional male-rabbits of the "Chinchilla" breed weighed 2,6+/-0,3 kg which were allocated into 10 groups. The control group No1 included intact animals, the control group No2 included the rabbits in which renal artery was not clamped. For the animals from the trial groups (No3-No10) the experimental model of 30- and 60-minute renal warm ischemia was used. In groups No3 and No4 no drugs were provided. Other rabbits undergone renal warm ischemia with a protection by sodium fumarate (groups No5 and No6 - 1,5 ml/kg IV), lasix (groups No7 and No8 - 3,0 mg/kg IV) and mannitol (No9 and No10 - 1,0 g/kg IV). The influence of renal warm ischemia on the renal tissue ultrastructure and the levels of NGAL, Cystatin-C and creatinine in blood and urine were studied. RESULTS: During experimental pharmacologically uncorrected 30-minute renal warm ischemia in animals, edema of the terminal part of microvilli of the proximal tubules epithelium, an increase of lysosome number in the hyaloplasm of epithelial cells, appearance of flaky content of medium electronic density in the lumens of distal tubules and collecting tubules, as well as sharp peak-like increase of NGAL and cystatin-C in blood and urine were observed. Increasing the time of ischemia up to 60 minutes was accompanied by more severe disturbances. In groups where sodium fumarate, lasix and mannitol were used the observed ultrastructural disturbances were expressed to lesser extent, whereas sodium fumarate demonstrated the best nephroprotective activity. After using mannitol the severity of disturbances was less than in the groups where mannitol, lasix or sodium fumarate were not given. Lasix and sodium salt of fumaric acid showed a higher nephroprotective activity. The best results were received in the animals received sodium fumarate. CONCLUSIONS: The studied drugs provided a nephroprotective effect regarding ischemia of rabbit kidney. The effect of sodium fumarate was the most pronounced, followed by furosemide and, to a lesser extent, mannitol. Use of sodium fumarate allows to protect and stimulate the kidney tissue effectively during oxygen deprivation under ischemic state.

Tolerable Duration of Warm Ischaemia After Circulatory Death Is Safe For At Least One Hour in Porcine Lungs: Functional Assessment with Ex Vivo Lung Perfusion.

BACKGROUND: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP). METHODS: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score. RESULTS: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed. CONCLUSION: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.

Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.

OBJECTIVE: Organ donation after circulatory death (DCD) is a potential solution for the shortage of suitable organs for transplant. Heart transplantation using DCD donors is not frequently performed due to the potential myocardial damage following warm ischemia. Heat shock protein (HSP) 90 has recently been investigated as a novel target to reduce ischemia/reperfusion injury. The objective of this study is to evaluate an innovative HSP90 inhibitor (HSP90i) as a cardioprotective agent in a model of DCD heart. METHODS: A DCD protocol was initiated in anesthetized Lewis rats by discontinuation of ventilation and confirmation of circulatory death by invasive monitoring. Following 15 minutes of warm ischemia, cardioplegia was perfused for 5 minutes at physiological pressure. DCD hearts were mounted on a Langendorff ex vivo heart perfusion system for reconditioning and functional assessment (60 minutes). HSP90i (0.01 µmol/L) or vehicle was perfused in the cardioplegia and during the first 10 minutes of ex vivo heart perfusion reperfusion. Following assessment, pro-survival pathway signaling was evaluated by western blot or polymerase chain reaction. RESULTS: Treatment with HSP90i preserved left ventricular contractility (maximum + dP/dt, 2385 ± 249 vs 1745 ± 150 mm Hg/s), relaxation (minimum -dP/dt, -1437 ± 97 vs 1125 ± 85 mm Hg/s), and developed pressure (60.7 ± 5.6 vs 43.9 ± 4.0 mm Hg), when compared with control DCD hearts (All P = .001). Treatment abrogates ischemic injury as demonstrated by a significant reduction of infarct size (2,3,5-triphenyl-tetrazolium chloride staining) of 7 ± 3% versus 19 ± 4% (P = .03), troponin T release, and mRNA expression of Bax/Bcl-2 (P < .05). CONCLUSIONS: The cardioprotective effects of HSP90i when used following circulatory death might improve transplant organ availability by expanding the use of DCD hearts.

Ex Vivo Lung Perfusion with K(ATP) Channel Modulators Antagonize Ischemia Reperfusion Injury.

Ex vivo lung perfusion (EVLP) has been implemented to increase the number of donor lungs available for transplantation. The use of K(ATP) channel modulators during EVLP experiments may protect against lung ischemia-reperfusion injury and may inhibit the formation of reactive oxygen species. In a rat model of donation after circulatory death with 2 h warm ischemic time, we evaluated rat lungs for a 4-hour time in EVLP containing either mitochondrial-specific or plasma membrane and/or sarcolemmal-specific forms of K(ATP) channel modulators. Lung physiological data were recorded, and metabolic parameters were assessed. When compared to the control group, in the EVLP performed with diazoxide or 5-hydroxydecanoic acid (5-HD) we recorded significantly lower pulmonary vascular resistance and only in the diazoxide group recorded significant lung weight loss. In the perfusate of the 5-HD group, interleukin-1ß and interleukin-1α were significantly lower when compared to the control group. Perfusate levels of calcium ions were significantly higher in both 5-HD and cromakalim groups, whereas the levels of calcium, potassium, chlorine and lactate were reduced in the diazoxide group, although not significantly when compared to the control. The use of a diazoxide mitochondrial-specific K(ATP) channel opener during EVLP improved lung physiological and metabolic parameters and reduced edema.

Reconditioning of circulatory death hearts by ex-vivo machine perfusion with a novel HTK-N preservation solution.

BACKGROUND: Warm ischemia followed by blood reperfusion is associated with reduced myocardial contractility. Circulatory death (CD) hearts are maintained by machine perfusion (MP) with blood. However, the impact of MP with histidine-tryptophane-ketoglutarate (HTK) or novel HTK-N solution on reconditioning of CD-heart contractility is unknown. METHODS: In a porcine model, native hearts were directly harvested (control), or CD was induced before harvesting, followed by left ventricular (LV) contractile assessment. In MP-groups, CD-hearts were maintained for 4 h by MP with blood (CD-B), cold oxygenated HTK (CD-HTK) or HTK-N (CD-HTK-N) before contractile evaluation (all groups n = 8). We performed immunohistochemistry of LV myocardial samples. We profiled myocardial expression of 84 oxidative stress-related genes and correlated the findings with myocardial contractility via a machine learning algorithm. RESULTS: HTK-N improved end-systolic pressure (ESP=172±10 vs 132±5 mmHg, p = 0.02) and maximal slope of pressure increment (dp/dtmax=2161±214 vs 1240±167 mmHg/s, p = 0.005) compared to CD, whereas CD-B failed to improve contractility. Dp/dtmax (2161±214 vs 1177±156, p = 0.08) and maximal rate of pressure decrement (dp/dtmin=-1501±228 vs -637±79, p = 0.005) were also superior in CD-HTK-N compared to CD-B. In CD-HTK-N, myocardial 4-hydroxynonenal (marker for oxidative stress; p<0.001), nitrotyrosine (marker for nitrosative stress; p = 0.004), poly(adenosine diphosphate-ribose)polymerase (marker for necrosis; p = 0.028) immunoreactivity and cell swelling (p = 0.008) were decreased compared to CD-B. Strong correlation of gene expression with ESP was identified for oxidative stress defense genes in CD-HTK-N. CONCLUSION: During harvesting procedure, MP with HTK-N reconditions CD-heart systolic and diastolic function by reducing oxidative and nitrosative stress and preventing cardiomyocytes from cell swelling and necrosis.

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study.

BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study.

BACKGROUND: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions. METHODS: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed. RESULTS: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047). CONCLUSION: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution.

Organs from donors after controlled circulatory death (DCD III) exhibit a higher risk for graft dysfunction due to an initial period of warm ischemia. This procurement condition can also affect the yield of beta cells in islet isolates from donor pancreases, and hence their use for transplantation. The present study uses data collected and generated by our Beta Cell Bank to compare the number of beta cells in isolates from DCD III (n = 141) with that from donors after brain death (DBD, n = 609), before and after culture, and examines the influence of donor and procurement variables. Beta cell number per DCD III-organ was significantly lower (58 x 106 versus 84 x 106 beta cells per DBD-organ; p < 0.001) but their purity (24% insulin positive cells) and insulin content (17 µg / 106 beta cells in DCD III-organs versus 19 µg / 106 beta cells in DBD-organs) were similar. Beta cell number correlated negatively with duration of acirculatory warm ischemia time above 10 min; for shorter acirculatory warm ischemia time, DCD III-organs did not exhibit a lower beta cell yield (74 x 106 beta cells). Use of Institut Georges Lopez-1 cold preservation solution instead of University of Wisconsin solution or histidine-tryptophan-ketoglutarate also protected against the loss in beta cell yield from DCD III-organs (86 x 106 for IGL-1 versus 54 x 106 and 65 x 106 beta cells respectively, p = 0.042). Multivariate analysis indicates that both limitation of acirculatory warm ischemia time and use of IGL-1 prevent the reduced beta cell yield in islet cell isolates from DCD III-organs.

Retroperitoneal or transperitoneal approach in robot-assisted partial nephrectomy, which one is better?

PURPOSE: To systematically assess the perioperative outcomes of retroperitoneal (RP) and transperitoneal (TP) approaches in robot-assisted partial nephrectomy (RAPN), we conducted an updated meta-analysis. METHODS: A literature retrieval of multi-database including PubMed, Web of Science, Embase, Cochrane Library, and CNKI was performed to identify eligible comparative studies from the inception dates to January 2021. Perioperative outcomes included operative time (OT), estimated blood loss (EBL), warm ischemia time (WIT), postoperative length of stay (PLOS), positive surgical margin (PSM), and complications (major complications and overall complications). Outcomes of data were pooled and analyzed with Review Manager 5.4.1. RESULTS: Twenty-one studies involving a total of 2482 RP and 3423 TP approach RAPN patients met the inclusion criteria. Operating time (OT) (weighted mean difference [WMD] -16.60; 95% confidence interval [CI] -23.08, -10.12; p < 0.01) and PLOS (WMD -0.46 days; 95% CI -0.69, -0.23; p < 0.01) were shorter in RP-RAPN. Besides, lower EBL (WMD -21.67; 95% CI -29.74, -13.60; p < 0.05) was also found in RP-RAPN. Meanwhile, no significant differences were found in other outcomes. CONCLUSIONS: RP-RARN was superior to TP-RAPN in patients undergoing RAPN in terms of OT, PLOS, and estimated blood loss. Besides these two approaches have no significant differences in PSMs or perioperative complications.

Safe Lung Flush Technique During Recovery From Donors After Circulatory Death.

Donation after circulatory death is defined as donation after cardiac arrest and circulatory cessation. The number of circulatory death donors is growing and significantly increases the organ donor pool. Shortening the warm ischemia time is pivotal in the outcomes and survival after transplant. We describe simplified and safe technique for lung flush during lung recovery from donors after circulatory death.

Impact of short warm ischemic time on longitudinal kidney function and survival rate after partial nephrectomy for renal cell carcinoma in patients with pre-existing chronic kidney disease stage III: A multi-institutional propensity score-matched study.

PURPOSE: It remains unclear whether a short warm ischemic time (WIT) improves long-term renal function after partial nephrectomy (PN) for patients with pre-existing chronic kidney disease (CKD). We evaluated renal function after PN according to WIT duration in patients with stage III CKD. MATERIALS AND METHODS: We identified 277 patients with stage III CKD who underwent PN during 2004-2017. Propensity score matching was used to created two matched groups of patients: Group A (WIT of <25 min) and Group B (WIT of ≥25 min). The outcomes of interest were longitudinal kidney function change, new-onset stage IV CKD (eGFR <30 mL/min/1.73 m2) and overall survival. RESULTS: The two matched groups contained 85 patients each. The median follow-up durations were 49 months in Group A and 42 months in Group B. The median pre-treatment eGFRs were 52.4 mL/min/1.73 m2 in Group A and 52.6 mL/min/1.73 m2 in Group B. There were no differences in kidney function between the two groups throughout the follow-up period (P > 0.05). The 5-year rates of new-onset stage IV CKD were not significantly different between Group A and Group B (8.2% vs. 7.1%), with no significant difference in the risk of developing stage IV CKD in Group A (vs. group B, hazard ratio: 0.527, 95% confidence interval: 0.183-1.521; P = 0.236). The 5-year overall survival rates were 90.3% for Group A and 96.2% for Group B (P = 0.549). CONCLUSIONS: A short WIT was not associated with better postoperative kidney function or survival after PN in patients with stage III CKD.

Pre-arrest doxycycline protects donation after circulatory death kidneys.

Kidney injury during donation after circulatory determination of death (DCDD) includes warm ischemic (WI) injury from around the time of asystole, and cold ischemic (CI) injury during cold preservation. We have previously shown that Matrix Metalloproteinases (MMPs) are involved in CI injury and that Doxycycline (Doxy), an antibiotic and known MMP inhibitor, protects the transplant kidney during CI. The purpose of our study was to determine if Doxy given before asystole can also prevent injury during WI. A rat model of DCDD was used, including Control, Preemptive Doxy (45 mg/kg iv), and Preemptive and Perfusion (100 microM) Doxy groups. Thirty minutes after asystole, both kidneys were removed. The left kidney was perfused at 4 °C for 22 h, whereas the right was used to establish the degree of warm ischemic injury prior to cold preservation. MMP-2 in the perfusate was significantly reduced in both treatment groups [Control 43.7 ± 7.2 arbitrary units, versus Preemptive Doxy group 23.2 ± 5.5 (p = 0.03), and 'Preemptive and Perfusion' group 18.0 ± 5.6 (p = 0.02)]. Reductions in NGAL, LDH, and MMP-9 were also seen. Electron microscopy showed a marked reduction in mitochondrial injury scores in the treatment groups. Pre-arrest Doxy was associated with a reduction in injury markers and morphologic changes. Doxy may be a simple and safe means of protecting transplant kidneys from both WI and CI.

Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation.

Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10; 20-25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ± 5% vs. 38% ± 4% compared to baseline; p < 0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ± 18% vs. 40% ± 30% after 3 h), increased PKA activity ratio (56% ± 3% vs. 32% ± 3%; p < 0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%; p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.

Making Every Liver Count: Increased Transplant Yield of Donor Livers Through Normothermic Machine Perfusion.

OBJECTIVE: Normothermic machine perfusion (NMP) enables optimized ex-vivo preservation of a donor liver in a normal physiologic state. The impact of this emerging technology on donor liver utilization has yet to be assessed. SUMMARY BACKGROUND DATA: NMP of the donor liver and ex-vivo enhancement of its function has been envisioned for decades, however only with recent technological advances have devices been suitable for transition to clinical practice. The present study examines the effect NMP on liver utilization in the United States. METHODS: The United Network for Organ Sharing database was queried to identify deceased donor livers procured from 2016 to 2019 (n = 30596). Donor livers were divided by preservation method: standard cold-static preservation (COLD, n = 30,368) versus NMP (n = 228). Donor and recipient risk factors, liver disposition, and discard reasons were analyzed. The primary outcome was liver discard rate between 2 groups. RESULTS: A total of 4037 livers were discarded. The NMP group had a 3.5% discard rate versus 13.3% in the COLD group (P < 0.001), and this was despite NMP donors being older (47.7 vs 39.5 years, P < 0.0001), more frequently donation after cardiac death (DCD) (18% vs 7%, P < 0.001), and having a greater donor risk index (1.6 vs 1.5, P < 0.05). The most common reasons for liver discard in the COLD group were biopsy findings (38%), DCD warm ischemic time (11%), and prolonged preservation time (10%). Survival analysis, following propensity score matching, found no significant difference in 1-year overall survival between recipients of NMP versus COLD livers. CONCLUSIONS: NMP reduces the discard rate of procured livers despite its use in donors traditionally considered of more marginal quality. NMP maintains excellent graft and patient survival. Broader application of NMP technology holds the potential to generate a significant number of additional liver grafts for transplantation every year, thus greatly reducing the nationwide disparity between supply and demand.

Histomorphometric evaluation of the rat kidney submitted to warm ischemia and the protective effect of resveratrol.

BACKGROUND: The objective of this study is to quantitatively evaluate the protective effects of resveratrol for using during renal warm ischemia. METHODS: Rats were allocated into 4 groups: Sham, Sham Resveratrol, Ischemia, Ischemia Resveratrol. Sham Resveratrol and Ischemia Resveratrol received resveratrol before surgery. Ischemia and Ischemia Resveratrol had renal vessels clamped. Animals were euthanized four weeks after. Serum urea and creatinine were measured. Renal weight and volume, cortex-non-cortex areas ratio, cortical volume, glomerular volumetric density, volume-weighted mean glomerular volume and number of glomeruli per kidney were evaluated. RESULTS: Serum urea in Ischemia increased by 10.4% compared to Sham and no differences were observed among Ischemia Resveratrol and sham groups. The glomerular volumetric density and number of glomeruli of Ischemia were lower than Sham but Ischemia Resveratrol had no difference compared to sham groups. CONCLUSIONS: Preoperative administration of resveratrol has renoprotective effects, preventing the glomerular number reduction observed in warm ischemia.

No ischemia technique, parenchymal preservation and age are the most important determinants of renal function after partial nephrectomy.

OBJECTIVE: The aim of the present study was to compare the outcomes of Off-Clamp to On -Clamp approach during robot-assisted partial nephrectomy (RAPN). MATERIEL AND METHODS: Retrospective study of 940 patients who underwent a RAPN between 2007 and 2015 for cT1a tumors using On-Clamp or Off-Clamp approaches. Patient with solitary kidney or multifocal were excluded. Overall, 103 patients underwent Off-Clamp approach and 37 patients On-Clamp approach. We matched the patients in terms of tumor size, Charlson comorbidity index and R.E.N.A.L. score. At all, 309 patients from the On-Clamp were matched to the Off-Clamp group. We compared the clinic-pathological characteristics, perioperative morbidity and late functional outcomes between the 2 propensity score matched groups. Limitation included retrospective analysis. RESULTS: After matching, there were no difference in clinic-pathological characteristics in terms of gender, age, race, body mass index, Charlson comorbidity index, American Society of Anesthesiologists score, baseline estimated glomerular filtration rate (e-GFR), tumor size, R.E.N.A.L. score complexity, hilar (H) location between the 2 groups. Regarding perioperative outcomes; while operative time (P=0,4), estimated blood loss (P=0,28), Clavien grade III-IV complications (P=0,8) surgical reoperation (P=1), 30-day readmission (P=1), positive surgical margin (5,5% vs. 5,8%, P=0,9) were comparable between the 2 groups, there were significant difference in excisional volume loss (median, 7,08 vs. 3,51cm3, P<0,01), e-GFR decline (median, -9,7 vs. -2,2ml/min/1,73 m2, P<0,01), percent of e-GFR preservation (median, 87% vs. 97%, P<0,01), and CKD upstaging (36,5% vs. 23,3%, P=0,01), Off-Clamp approach (P=0,01), and age (P=0,02) were predictors of renal function preservation, whereas excisional volume loss (OR=1,035, CI 95% (1,015-1,06), P<0,01) predicted upstaging. CONCLUSION: RAPN for selected renal mass using Off-Clamp approach offered renal functional advantage over On-Clamp, without adding morbidities. While no ischemia technique was associated with less excisional volume loss, Off-Clamp approach, and age were independent predictors of renal function preservation. Clinical significance of these findings in various clinical settings will require further investigation.