Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39.

We previously reported that normothermic ex vivo kidney  perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation.

Comparison of single-port versus multi-port robotic assisted partial nephrectomy: a systematic review and meta-analysis of perioperative and oncological outcomes.

The safety and efficacy of single-port and multi-port robot-assisted partial nephrectomy (SP-RAPN and MP-RAPN, respectively) were assessed for treating partial nephrectomy in this study. A systematic review of PubMed, Cochrane Library, and Web of Science databases was conducted up to June 2024 to compare studies on SP-RAPN and MP-RAPN. Primary outcomes included perioperative results, complications, and oncological outcomes. Eight studies involving 1014 patients were analyzed. For binary outcomes, comparisons were performed using odds ratios (OR), and for continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CI). The search failed to discover significant meaningful variations in operating times (p = 0.54), off-clamp procedure (P = 0.36), blood loss (p = 0.31), positive surgical margins (PSMs) (p = 0.78), or major complications (Clavien-Dindo grade ≥ 3) (p = 0.68) between SP-RAPN and MP-RAPN. However, shorter hospital stays (WMD - 0.26 days, 95% CI - 0.36 to - 0.15; p < 0.00001) and longer warm ischemia times (WIT) (WMD 3.13 min, 95% CI 0.81-5.46; p = 0.008) were related to SP-RAPN, and higher transfusion rate (OR 2.99, 95% CI 1.31-6.80; p = 0.009) compared to MP-RAPN. SP-RAPN performed better in terms of hospital stay but had slightly higher rates of transfusion, off-clamp procedures, and warm ischemia time (WIT) compared to MP-RAPN. As an emerging technology, preliminary research suggests that SP-RAPN is a feasible and safe method for carrying out a nephrectomy partial. However, compared to MP-RAPN, it shows inferior outcomes regarding (WIT) and transfusion rates.

Impact of Warm Ischemia Time on Donation After Circulatory Death Kidney Transplant Outcomes.

BACKGROUND: Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable. METHODS: We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60 min), low fWIT (≤60 min), and kidneys transplanted from donors after brain death (DBD). RESULTS: Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI = 2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI = 1.4-3.1) have higher hazard ratios for 1-year graft failure. CONCLUSIONS: Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.

Use of perfusion device for free flap salvage after ischemia in swine.

INTRODUCTION: In free flap reconstruction, improving flap tolerance to warm ischemia (WI) is fundamental. WI is the result of a venous or arterial thrombosis, which can only be addressed through surgical revision. No additional treatments have shown superior efficacy at salvaging free flaps after or during WI. Custom perfusion machines (PM), used to reduce the intensity of lesions of the flap stored in cold ischemia, have not been evaluated for WI flap salvage. This proof-of-concept study assessed whether the Lifeport® perfusion machine could improve the salvage procedure's success rates after one hour of venous WI. METHODS: Five different groups were evaluated with four porcine latissimus dorsi free flaps included in each group. Depending on the group, the flaps were subjected to one hour of WI followed by revascularization, static hypothermic submersion, or dynamic Lifeport® perfusion. Additionally, two flap perfusion liquids were evaluated: KPS-1® and IGL-1®. Biopsies were performed before in vivo warm ischemia of the flap, after in vivo warm ischemia of the flap, and after one and two hours of preservation. Interstitial edema, muscular cell size and muscular diffuse necrosis were quantified by histological assessment. RESULTS: Static submersion did not demonstrate any efficacy for venous flap salvage. Dynamic perfusion on Lifeport® machine showed a significant improvement in tissue parameters. Thrombi and fibrine, present during the WI period, were no longer visible inside vessels and the perfusion machine flow evacuated the inflammatory cells and their substrates from the flap. The flap weights did not increase during perfusion time, confirming the benefits of the Lifeport® perfusion machine. CONCLUSION: Evaluating Lifeport® advantages on human free flap salvage is necessary to confirm the benefits for the tissue and to increase post-operative results after congestive free flap revision surgery.

Achieving trifecta outcomes in robotic-assisted partial nephrectomy within a fellowship training centre.

To assess the robotic-assisted partial nephrectomy (RAPN) trifecta rate within a fellowship program. Patients undergoing RAPN 01/01/2010-01/07/2023 were enrolled from a prospectively maintained database. All cases were performed jointly with surgical fellows, except when privately insured. Patients were excluded if they were converted to open or radical nephrectomy. The primary outcome was achieving the 'trifecta' of negative surgical margins, no complications < 30 days post-operatively and warm ischaemia time (WIT) < 25 min. The secondary outcomes were factors associated with trifecta success. Ethics approval was obtained. In the enrolment period, 355 patients underwent intended RAPN, of whom seven were excluded due to conversion to conversion to radical nephrectomy (6 patients) or conversion to open (one). Amongst the 348 eligible patients, median age was 60 years, 115 (33%) were female and 19 were private patients. WIT was < 25 min for 324/337 patients (96%), surgical margins were negative in 325 (93%), 294 (84%) were complication-free at 30 days and 301/320 (94%) had a < 30% decline in estimated glomerular filtration rate at 3-6 months postoperatively. Subsequently, trifecta outcomes were achieved in 253/337 (75%) patients. Comparing with patients without those with trifecta success were similar in all thirteen measured patients and tumour factors. In a teaching hospital, with a fellowship training programme, trifecta outcome is achievable for most RAPN patients, and at a rate comparable to international standards. Fellowship centres should monitor their outcomes to ensure high patient outcomes are maintained alongside training requirements.

En Bloc Simultaneous Liver-Kidney Transplantation Compared to the Traditional Technique: Results From a Single Center.

BACKGROUND: Simultaneous liver-kidney transplantation is indicated for patients with concomitant end-stage liver disease and end-stage renal disease. The traditional technique involves separate implantations of the liver and the kidney. In the en bloc approach, the liver is recovered en bloc with the right kidney and the donor renal artery is anastomosed to the donor splenic artery. We aimed to compare the outcomes of the traditional and en bloc techniques for simultaneous liver-kidney transplantation in a single center. METHODS: This single-center retrospective study involved all adult patients who underwent simultaneous liver-kidney transplantation from brain-dead donors from January 2017 to December 2022. RESULTS: A total of 15 patients were included: 10 transplanted with the traditional technique and 5 with the en bloc approach. Patients in the en bloc group presented higher body mass index, shorter kidney cold and total ischemia times, shorter overall surgical time and longer kidney warm ischemia time (29.07 kg/m2vs 23.20 kg/m2 [P = .048]; 560 minutes vs 880 minutes [P = .026]; 615 minutes vs 908 minutes [P = 0.025]; 405 minutes vs 485 minutes [P = .046]; 46 minutes vs 33.5 minutes [P = 0.027], respectively). Ureteroneocystostomy was performed in 2 patients of the en bloc group and ureteroureterostomy in the remaining 3 patients. One patient in the en bloc group presented stenosis of renal artery anastomosis and underwent percutaneous angioplasty. This same patient eventually developed late urinary fistula. In the traditional technique group, there were 2 cases of renal vein thrombosis and 1 of ureteral stenosis. CONCLUSIONS: Compared with the traditional technique, the en bloc approach is feasible and safe, reducing kidney total ischemia time and overall surgical time.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

A Novel Cooling Device for Kidney Transplant Surgery.

Background: Prolonged warm ischemia time (WIT) in kidney transplantation is associated with numerous adverse outcomes including delayed graft function and decreased patient and graft survival. Circumventing WIT lies in maintaining renal hypothermia and efficiently performing the vascular anastomosis during this portion of the procedure. Although numerous methods of intra-operative renal cooling have been proposed, most suffer from practical limitations, and none have been widely adopted. Herein we describe a novel device specifically designed to maintain renal hypothermia during kidney transplant surgery.Methods: Aluminum tubing was organized in a serpentine pattern to create a malleable, form-fitting cooling jacket to manipulate renal allografts during transplant surgery. Adult porcine kidneys were used to test the device with 4°C saline as coolant. Kidneys were placed at 24°C; surface and core temperatures were monitored using implanted thermocouples. Anastomosis of porcine kidney vessels to GORE-TEX® vascular grafts in an ex-vivo operative field was performed to assess the functionality of the device.Results: The device maintained surface and core graft temperatures of ≤5°C after 60 minutes of WIT. Furthermore, the device provided hands-free retraction and support for the allograft. We found that ex-vivo anastomosis testing was enhanced by the presence of the cooling jacket.Conclusions: This proof-of-concept study demonstrated that our novel device is a practical tool for renal transplantation and can maintain sufficiently cool graft temperatures to mitigate WIT in an ex-vivo setting. This device is the first of its kind and has the potential to improve kidney transplant outcomes by eliminating WIT during graft implantation.

Minimising warm ischaemia time during robot-assisted partial nephrectomy. A video-based assessment of tumour excision, kidney reconstruction and intermediate time.

INTRODUCTION: Surgical video review is an emerging tool for assessing patient outcomes, especially in complex surgeries such as robot-assisted partial nephrectomy (RAPN). Assessing and measuring warm ischaemia time (WIT) during RAPN by dividing it into the time used for tumour excision time (ExcT), time used for kidney reconstruction time (RecT) and intermediate time (IntT) has not been performed before. This study aimed to analyse the factors that can influence all surgical times and assess their impact on positive surgical margins (PSMs) and complication rates. METHODS: We evaluated 32 surgical video recordings from patients undergoing RAPN and measured WIT, ExcT, RecT and IntT with a stopwatch. Factors such as tumour characteristics and surgeon experience were also recorded. SPSS software was used to identify the predictors for all surgical times and to correlate ExcT with PSM and RecT with complication rate. RESULTS: We recorded a median WIT of 1,048 s (17 min and 28 s). The median of ExcT, RecT and IntT was 398 s (37.1% of WIT), 518 s (46.7% of WIT) and 180 s (16.2% of WIT), respectively. We found a significant correlation (P < 0.001) between R.E.N.A.L. score and all surgical times. No correlation was found between ExcT and PSM (P = 0.488) and between RecT and the probability of developing complications (P = 0.544). CONCLUSION: Tumour morphology influences all surgical times, and surgeon experience influences only ExcT. We observed a short RecT during RAPN though at the cost of increased ExcT, and we believe that improving surgical experience, especially for the excision of more complex tumours, can reduce WIT during RAPN.

Successful Recovery of Cardiac Function Following 20 min of a No-touch Period in a Donation After Circulatory Death: A Case Report.

BACKGROUND: Withdrawal of life-sustaining therapy (WLST) performed in the circulatory determination of death (DCD) donors leads to cardiac arrest, challenging the utilization of the myocardium for transplantation. The rapid initiation of normothermic regional perfusion or extracorporeal membrane oxygenation after death helps to optimize organs before implantation. However, additional strategies to mitigate the effects of stress response during WLST, hypoxic/ischemic injury, and reperfusion injury are required to allow myocardium recovery. METHODS: To this aim, our team routinely used a preconditioning protocol for each DCD donation before and during the WLST and after normothermic regional perfusion/extracorporeal membrane oxygenation. The protocol includes pharmacological treatments combined to reduce oxidative stress (melatonin, N -acetylcysteine, and ascorbic acid), improve microcirculation (statins), and mitigate organ's ischemic injury (steroids) and organ ischemia/reperfusion injury (remifentanil and sevoflurane when the heart is available for transplantation). RESULTS: This report presents the first case of recovery of cardiac function, with the only support of normothermic regional reperfusion, following 20 min of a no-touch period and 41 min of functional warm ischemic time in a DCD donor after the preconditioning protocol. CONCLUSIONS: Our protocol seems to be effective in abolishing the stress response during WLST and, on the other hand, particularly organ protective (and heart protective), giving a chance to donate organs less impaired from ischemia/reperfusion injury.

Asystolic donor warm ischemia time is associated with development of postreperfusion syndrome in donation after circulatory death liver transplant.

BACKGROUND: Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor warm ischemia time (dWIT), and may have differing effects on the outcome of the liver graft. This study aimed to identify risk factors for postreperfusion syndrome (PRS), a state of severe hemodynamic derangement following graft reperfusion, and its impact on DCD liver transplantation (LT) outcomes. METHODS: This was a retrospective analysis using 106 DCD LT. Detailed information for events during procurement (withdrawal of life support; systolic blood pressure < 80 mmHg; oxygen saturation < 80%; circulatory arrest; aortic cold perfusion) and their association with the development of PRS were examined using logistic regression. RESULTS: The overall incidence of PRS was 26.4%, occurring in 28 patients. Independent risk factors for PRS were asystolic dWIT (odds ratio (OR) 3.65, 95% confidence interval (CI) 1.38-9.66) and MELD score (OR 1.06, 95% CI 1.01-1.10). Total bilirubin was significantly higher in the PRS group at postoperative day (POD) 1 (p = .02; 5.2 mg/dL vs. 3.4 mg/dL), POD 3 (p = .049; 4.5 mg/dL vs. 2.8 mg/dL), and POD 7 (p = .04; 3.1 mg/dL vs. 1.9 mg/dL). Renal replacement therapy after LT was more likely to be required in the PRS group (p = .01; 48.2% vs. 23.1%). CONCLUSION: Asystolic dWIT is a risk factor for the development of PRS in DCD LT. Our results suggest that asystolic dWIT should be considered when selecting DCD liver donors.

Amputated Digit Replantations: Critical Digit Ischemia Timing, Temperature, and Other Predictors of Survival.

INTRODUCTION: A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates. METHODS: The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval. RESULTS: Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0-12 hours of warm ischemia time ( P ≤ 0.05). The odds of survival in the early (0-6 hours) replantation group were around 40% greater than the later (6-12 hours) replantation group ( P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers ( P ≤ 0.05). DISCUSSION: Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.

Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion.

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide-releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.

Robotic versus laparoscopic versus open nephrectomy for live kidney donors.

BACKGROUND: Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major disincentives to potential kidney donors are the pain and morbidity associated with surgery. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), hand-assisted LDN (HALDN) and robotic donor nephrectomy (RDN) as appropriate surgical techniques for live kidney donors. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 31 March 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing LDN with ODN, HALDN, or RDN were included. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Thirteen studies randomising 1280 live kidney donors to ODN, LDN, HALDN, or RDN were included. All studies were assessed as having a low or unclear risk of bias for selection bias. Five studies had a high risk of bias for blinding. Seven studies randomised 815 live kidney donors to LDN or ODN. LDN was associated with reduced analgesia use (high certainty evidence) and shorter hospital stay, a longer procedure and longer warm ischaemia time (moderate certainty evidence). There were no overall differences in blood loss, perioperative complications, or need for operations (low or very low certainty evidence). Three studies randomised 270 live kidney donors to LDN or HALDN. There were no differences between HALDN and LDN for analgesia requirement, hospital stay (high certainty evidence), duration of procedure (moderate certainty evidence), blood loss, perioperative complications, or reoperations (low certainty evidence). The evidence for warm ischaemia time was very uncertain due to high heterogeneity. One study randomised 50 live kidney donors to retroperitoneal ODN or HALDN and reported less pain and analgesia requirements with ODN. It found decreased blood loss and duration of the procedure with HALDN. No differences were found in perioperative complications, reoperations, hospital stay, or primary warm ischaemia time. One study randomised 45 live kidney donors to LDN or RDN and reported a longer warm ischaemia time with RDN but no differences in analgesia requirement, duration of procedure, blood loss, perioperative complications, reoperations, or hospital stay. One study randomised 100 live kidney donors to two variations of LDN and reported no differences in hospital stay, duration of procedure, conversion rates, primary warm ischaemia times, or complications (not meta-analysed). The conversion rates to ODN were 6/587 (1.02%) in LDN, 1/160 (0.63%) in HALDN, and 0/15 in RDN. Graft outcomes were rarely or selectively reported across the studies. There were no differences between LDN and ODN for early graft loss, delayed graft function, acute rejection, ureteric complications, kidney function or one-year graft loss. In a meta-regression analysis between LDN and ODN, moderate certainty evidence on procedure duration changed significantly in favour of LDN over time (yearly reduction = 7.12 min, 95% CI 2.56 to 11.67; P = 0.0022). Differences in very low certainty evidence on perioperative complications also changed significantly in favour of LDN over time (yearly change in LnRR = 0.107, 95% CI 0.022 to 0.192; P = 0.014). Various different combinations of techniques were used in each study, resulting in heterogeneity among the results. AUTHORS' CONCLUSIONS: LDN is associated with less pain compared to ODN and has comparable pain to HALDN and RDN. HALDN is comparable to LDN in all outcomes except warm ischaemia time, which may be associated with a reduction. One study reported kidneys obtained during RDN had greater warm ischaemia times. Complications and occurrences of perioperative events needing further intervention were equivalent between all methods.

Major determinants of primary non function from kidney donation after Maastricht II circulatory death: A single center experience.

PURPOSE: Organ shortage greatly limits treatment of patients with end-stage chronic kidney. Maastricht type 2 donation after circulatory death (DCD) has been shown to have similar results in long term outcomes in kidney transplantation, when compared with brain dead donation. Our main goal was to assess Maastricht type 2 DCD and evaluate factors that impact on early graft function. METHODS: A retrospective study was conducted in an ECMO Referral Centre. All patients who received a kidney transplant from Maastricht type 2 DCD were included in study. Early graft function and short term outcomes were assessed. RESULTS: From October 2017 to December 2022, 47 renal grafts were collected from 24 uDCD donors. Median warm ischemia time was 106 min (94-115), cannulation time was 10 min (8; 20) and duration of extracorporeal reperfusion (ANOR) was 180 min (126-214). Regarding early graft function, 25% had immediate graft function, 63.6% had delayed graft function and 11.4% had primary non-function (PNF). There was a correlation between cannulation time (p = 0.006) and ANOR with PNF (p = 0.016). CONCLUSIONS: Cannulation time and ANOR were the main factors that correlated with PNF. Better understanding of underlying mechanisms should be sought in future studies to reduce the incidence of PNF.

Liver machine perfusion technology: Expanding the donor pool to improve access to liver transplantation.

The imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended-criteria donors. Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network and the Standard Transplant Analysis and Research dataset, we reviewed the effect of MP implementation on the behavior of transplant centers. We identified 15 high-utilizing MP centers that were matched to suitable controls based on volume and geographical proximity. We conducted a differences-in-differences analysis using linear regression to estimate the impact of MP adoption on the transplant centers' donor utilization. We found a significant increase in cold ischemia time and organs with donor warm ischemia time over 30 minutes (P < .05). After removing one outlier center, the analysis showed that these centers through MP accepted overall more donation after circulatory death donors, donation after circulatory death donors over 50 years old, donors with macrovesicular steatosis greater than 30% on liver biopsy, and donor warm ischemia time over 30 minutes (P < .05). MP has allowed centers to expand their use of extended-criteria donors beyond traditional cutoffs and to increase patient access to liver transplantation.

Sequential Normothermic Regional Perfusion and End-ischemic Ex Situ Machine Perfusion Allow the Safe Use of Very Old DCD Donors in Liver Transplantation.

BACKGROUND: In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach. METHODS: All cDCD older than 70 y were evaluated during normothermic regional perfusion and then randomly assigned to dual hypothermic or normothermic MP. RESULTS: In the period from April 2021 to December 2022, 17 cDCD older than 70 y were considered. In 6 cases (35%), the graft was not considered suitable for liver transplantation, whereas 11 (65%) were evaluated and eventually transplanted. The median donor age was 82 y, being 8 (73%) older than 80. Median functional warm ischemia and no-flow time were 36 and 28 min, respectively. Grafts were randomly assigned to ex situ dual hypothermic oxygenated MP in 6 cases (55%) and normothermic MP in 5 (45%). None was discarded during MP. There were no cases of primary nonfunction, 1 case of postreperfusion syndrome (9%) and 2 cases (18%) of early allograft dysfunction. At a median follow-up of 8 mo, no vascular complications or ischemic cholangiopathy were reported. No major differences were found in terms of postoperative hospitalization or complications based on the type of MP. CONCLUSIONS: The implementation of sequential normothermic regional and end-ischemic MP allows the safe use of very old donation after circulatory death donors.

Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury.

Liver failure secondary to metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause for liver transplantation in many parts of the world. Moreover, the prevalence of MASLD not only increases the demand for liver transplantation, but also limits the supply of suitable donor organs because steatosis predisposes grafts to ischemia-reperfusion injury (IRI). There are currently no pharmacological interventions to limit hepatic IRI because the mechanisms by which steatosis leads to increased injury are unclear. To identify potential novel mediators of IRI, we used liquid chromatography and mass spectrometry to assess temporal changes in the hepatic lipidome in steatotic and non-steatotic livers after warm IRI in mice. Our untargeted analyses revealed distinct differences between the steatotic and non-steatotic response to IRI and highlighted dynamic changes in lipid composition with marked changes in glycerophospholipids. These findings enhance our knowledge of the lipidomic changes that occur following IRI and provide a foundation for future mechanistic studies. A better understanding of the mechanisms underlying such changes will lead to novel therapeutic strategies to combat IRI.