Effect of donor warm ischemia time during graft extraction in right lobe robotic donor hepatectomy on recipient outcomes-A propensity score matched analysis.

One of the concerns specific to minimally invasive donor hepatectomy (MIDH) is the prolonged time required for graft extraction after completion of the donor hepatectomy (donor warm ischemia time [DWIT]). There has never been an objective evaluation of minimally invasive donor hepatectomy-DWIT on allograft function in living donor liver transplantation. We evaluated the effect of DWIT following robotic donor hepatectomy (RDH) on recipient outcomes and compared them with a matched cohort of open donor hepatectomy (ODH). Demographic, perioperative, and recipient's postoperative outcome data for all right lobe (RL)-RDH performed between September 2019 and July 2023 were analyzed and compared with a propensity score matched cohort (1:1) of RL-ODH from the same time period. Of a total of 103 RL-RDH and 446 RL-ODH, unmatched and propensity score matched analysis (1:1) revealed a significantly longer DWIT in the RDH group as compared to the ODH group (9.33 ± 3.95 vs 2.87 ± 2.13, P < .0001). This did not translate into any difference in the rates of early allograft dysfunction (EAD), biliary complications, major morbidity, or overall 1-and 3-month survival. The receiver operating characteristic curve analysis threshold for DWIT-early allograft dysfunction was 9 minutes (area under receiver operating characteristic: 0.67, sensitivity = 80%, specificity = 53.8%). We show that prolonged DWIT within an acceptable range in RDH does not have deleterious effects on short-term recipient outcomes. Further long-term studies are required to confirm our findings, especially with regard to nonanastomotic biliary complications.

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.

Systematic review of techniques and devices used to avoid warm ischemia time injury during kidney transplantation.

PURPOSE: The lack of a reliable and reproducible technique to ensure a constantly low temperature of the graft during kidney transplantation (KT) may be a cause of renal nonfunction. The aim of this review was to assess all the methods and devices available to ensure hypothermia during vascular anastomosis in KT. METHODS: A literature search was conducted through May 2022 using PubMed/Medline, Cochrane Library, Embase and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The review protocol was registered on PROSPERO (CRD42022326550). RESULTS: A total of 20 studies reporting on four hypothermia techniques met our inclusion criteria. Simple instillation of cold serum is not sufficient, the graft reaching up to 33 ℃ at the end of warm ischemia time (WIT). Plastic bags filled with ice slush have questionable efficiency. The use of a gauze jacket filled with ice-slush was reported in 12/20 studies. It ensures a graft temperature up to 20.3 ℃ at the end of WIT. Some concerns have been linked to potentially inhomogeneous parenchymal cooling and secondary ileus. Novel devices with continuous flow of ice-cold solution around the graft might overcome these limitations, showing a renal temperature below 20 ℃ at all times during KT. CONCLUSION: The gauze filled with ice slush is the most common technique, but several aspects can be improved. Novel devices in the form of cold-ischemia jackets can ensure a lower and more stable temperature of the graft during KT, leading to higher efficiency and reproducibility.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

Laparoscopic donor nephrectomy-Technique and peri-operative outcomes in an Australian transplant center.

INTRODUCTION: Demand for donor kidneys far exceeds the availability of organs from deceased donors. Living donor kidneys are an important part of addressing this shortfall, and laparoscopic nephrectomy is an important strategy to reduce donor morbidity and increase the acceptability of living donation. AIM: To retrospectively review the intraoperative and postoperative safety, technique, and outcomes of patients undergoing donor nephrectomy at a single tertiary hospital in Sydney, Australia. METHOD: Retrospective capture and analysis of clinical, demographic, and operative data for all living donor nephrectomies performed between 2007 and 2022 at a single University Hospital in Sydney, Australia. RESULTS: Four hundred and seventy-two donor nephrectomies were performed: 471 were laparoscopic, two of which were converted from laparoscopic to open and hand-assisted nephrectomy, respectively, and one (.2%) underwent primary open nephrectomy. The mean warm ischemia time was 2.8 min (±1.3 SD, median 3 min, range 2-8 min) and the mean length of stay (LOS) was 4.1 days (±1.0 SD). The mean renal function on discharge was 103 µmol/L (±23.0 SD). Seventy-seven (16%) patients had a complication with no Clavien Dindo IV or V complications seen. Outcomes demonstrated no impact of donor age, gender, kidney side, relationship to the recipient, vascular complexity; or surgeon experience, on complication rate or LOS. CONCLUSION: Laparoscopic donor nephrectomy is a safe and effective procedure with minimal morbidity and no mortality in this series.

Fluorescein clearance kinetics in blood and bile indicates hepatic ischemia-reperfusion injury in rats.

Quantitative measurement of the degree of hepatic ischemia-reperfusion injury (IRI) is crucial for developing therapeutic strategies for its treatment. We hypothesized that clearance of fluorescent dye through bile metabolism may reflect the degree of hepatic IRI. In this study, we investigated sodium fluorescein clearance kinetics in blood and bile for quantifying the degree of hepatic IRI. Warm ischemia times (WITs) of 0, 30, or 60 min followed by 1 h or 4 h of reperfusion, were applied to the median and lateral lobes of the liver in Sprague-Dawley rats. Subsequently, 2 mg/kg of sodium fluorescein was injected intravenously, and blood and bile samples were collected over 60 min to measure fluorescence intensities. The bile-to-plasma fluorescence ratios demonstrated an inverse correlation with WIT and were distinctly lower in the 60-min WIT group than in the control or 30-min WIT groups. Bile-to-plasma fluorescence ratios displayed superior discriminability for short versus long WITs when measured 1 h after reperfusion versus 4 h. We conclude that the bile-to-blood ratio of fluorescence after sodium fluorescein injection has the potential to enable the quantification of hepatic IRI severity.NEW & NOTEWORTHY Previous attempts to use fluorophore clearance to test liver function have relied on a single source of data. However, the kinetics of substrate processing via bile metabolism include decreasing levels in blood and increasing levels in bile. Thus, we analyzed data from blood and bile to better reflect fluorescein clearance kinetics.

Normothermic Regional Perfusion and Hypothermic Oxygenated Machine Perfusion for Livers Donated After Controlled Circulatory Death With Prolonged Warm Ischemia Time: A Matched Comparison With Livers From Brain-Dead Donors.

Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD). To assess the value of abdominal normothermic regional perfusion (A-NRP) associated with dual hypothermic oxygenated machine perfusion (D-HOPE) in controlled DCD LT, prospectively collected data on LTs performed between January 2016 and July 2021 were analyzed. Outcome of controlled DCD LTs performed using A-NRP + D-HOPE (n = 20) were compared to those performed with grafts procured after brain death (DBD) (n = 40), selected using propensity-score matching. DCD utilization rate was 59.5%. In the DCD group, median functional WIT, A-NRP and D-HOPE time was 43, 246, and 205 min, respectively. Early outcomes of DCD grafts recipients were comparable to those of matched DBD LTs. In DCD and DBD group, incidence of anastomotic biliary complications and ischemic cholangiopathy was 15% versus 22% (p = 0.73) and 5% versus 2% (p = 1), respectively. One-year patient and graft survival was 100% versus 95% (p = 0.18) and 90% versus 95% (p = 0.82). In conclusion, the association of A-NRP + D-HOPE in DCD LT with prolonged WIT allows achieving comparable outcomes to DBD LT.

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.

Comparison of clamping strategies in minimally invasive partial nephrectomy for cT1 tumors.

OBJECTIVES: To determine whether artery only (AO) clamping promises any advantage over artery and vein (AV) clamping in patients undergoing partial nephrectomy with minimally invasive surgical techniques. MATERIAL AND METHODS: We retrospectively analyzed the data of 68 partial nephrectomy patients who were treated with minimally invasive techniques (robot-assisted laparoscopic or pure laparoscopic) for solitary, unilateral, cT1 renal masses during the period of 2008-2019 in a single institution. Patients were divided into two groups according to clamping strategy (AO and AV). The two groups were compared to each other in terms of perioperative outcomes and long-term functional results. RESULTS: The mean patient age and median follow-up period were 56.8 ± 10.8 years and 13.5 (9-44.5) months, respectively. Warm ischemia time, estimated blood loss, transfusion rate and length of hospital stay were similar between the two groups, while operative time was significantly higher in the AO clamping group (p = .726, p = .604, p = .675, p = .103, and p = .038, respectively). Patients who underwent AV clamping had a significantly lower estimated glomerular filtration rate (eGFR) and higher chronic kidney disease rates six months postoperatively (p = .001 and p = .044, respectively) and at the last follow-up (p = .020 and p = .048, respectively). The percentage of eGFR change at six months and the last follow-up was higher in the AV clamp group but the difference was not statistically significant (p = .056 and p = .082, respectively). CONCLUSIONS: Our findings suggest AO clamping is safe and comparable to AV clamping. In our study, AO clamping was found to be superior to AV in terms of long-term eGFR preservation.

Robotic-assisted laparoscopic tumor enucleation is a feasible technique for renal hilar tumors: A retrospective study.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the safety and efficacy of robot-assisted laparoscopic tumor enucleation (RAE) for the treatment of renal hilar tumors and to describe our experience with renorrhaphy-related surgical techniques. METHODS: Retrospective data were collected from 173 consecutive patients who underwent RAE for localized renal tumors (cT1-cT2N0M0) at our hospital between September 2014 and November 2019. RESULTS: Seventy-five patients had renal hilar tumors and 98 patients had nonhilar tumors. There were no statistical differences between the hilar and nonhilar groups in operation time (190 [115-390] vs. 190 [110-390] min, p = 0.889), warm ischemia time (26 [12-60] vs. 27 [17-41] min, p = 0.257), hospital stay duration (8 [3-16] vs. 7.5 [4-18] days, p = 0.386), renal function (estimated glomerular filtration rate, 102.5 [29.4-144] vs. 101.3 [64.2-134.7] ml/min/1.73 m2 , p = 0.631); creatinine level, (76 [43-169] vs. 78.5 [50-281.3] µmol/L, p = 0.673), perioperative complications rate, or surgical margin status. However, patients with hilar tumors lost significantly more blood than did those with nonhilar tumors (250 [50-1500] vs. 200 [20-1200] ml, p = 0.007). During the follow-up period (median, 30 months), three patients in each group experienced recurrence. The 5-year recurrence-free rates were 93.0% and 95.4% in the hilar and nonhilar tumor groups, respectively (p = 0.640). CONCLUSIONS: For experienced robot laparoscopists, RAE is a safe, effective, and feasible procedure for renal hilar tumors, without increased risk of positive surgical margins or worse midterm oncologic outcomes compared with nonhilar tumors.

Laparoscopic Live Donor Nephrectomy: Experience of High-Volume Center with 2,477 Cases.

OBJECTIVE: Donors' health and safety are mandatory in the living-donor kidney transplantation procedure. Laparoscopic live donor nephrectomy (LLDN) provides an increase in donor numbers with its benefits and becomes a standard of care. We aimed to explain the results, complication rates, tips, and tricks of the largest number of LLDN case series ever performed in the literature. MATERIALS AND METHODS: Between August 2012 and December 2019, 2,477 live donor case files were analyzed retrospectively. Age, gender, hospitalization times, body mass index, warm ischemia times, operation times, numbers of arteries, side of the kidneys, and complications were noted. RESULTS: 1,421 (57.4%) of 2,477 donors were female (p = 0.007). Operation times and warm ischemia times were found longer in right-sided LLDN and donors with multiple renal arteries (p = 0.046, <0.001, and <0.001, respectively). Obesity (BMI >30 kg/m2) did not affect warm ischemia times while prolonging the operation times (p = 0.013). Hospitalization times and numbers of complications were higher in obese donors. CONCLUSIONS: LLDN seems to be a reliable solution with fewer complications and higher satisfaction rates. We hope to illuminate the way with tips and trick points for beginner transplant surgeons based on the experience obtained from 2,477 LLDN cases.

Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience.

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. STUDY DESIGN: Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada between 1995 and 2016. RESULTS: Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P = .02). Adolescents aged 11-17 years (OR, 0.53; P = .03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90 days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). CONCLUSIONS: These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

The Self-Retaining Barbed Suture for Parenchymal Repair in Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-Analysis.

Objectives. The warm ischemia time (WIT) is key to successful laparoscopic partial nephrectomy (LPN). The aim of this study was to perform a meta-analysis comparing the self-retaining barbed suture (SRBS) with a non-SRBS for parenchymal repair during LPN. Methods. A systematic search of PubMed, Scopus, and the Cochrane Library was performed up to March 2018. Inclusion criteria for this study were randomized controlled trials (RCTs) and observational comparative studies assessing the SRBS and non-SRBS for parenchymal repair during LPN. Outcomes of interest included WIT, complications, overall operative time, estimated blood loss, length of hospital stay, and change of renal function. Results. One RCT and 7 retrospective studies were identified, which included a total of 461 cases. Compared with the non-SRBS, use of the SRBS for parenchymal repair during LPN was associated with shorter WIT (P < .00001), shorter overall operative time (P < .00001), lower estimated blood loss (P = .02), and better renal function preservation (P = .001). There was no significant difference between the SRBS and non-SRBS with regard to complications (P = .08) and length of hospital stay (P = .25). Conclusions. The SRBS for parenchymal repair during LPN can significantly shorten the WIT and overall operative time, decrease blood loss, and preserve renal function.

Prospective study of robotic partial nephrectomy for renal cancer in Japan: Comparison with a historical control undergoing laparoscopic partial nephrectomy.

OBJECTIVES: To evaluate the outcomes of robotic partial nephrectomy compared with those of laparoscopic partial nephrectomy for T1 renal tumors in Japanese centers. METHODS: Patients with a T1 renal tumor who underwent robotic partial nephrectomy were eligible for inclusion in the present study. The primary end-point consisted of three components: a negative surgical margin, no conversion to open or laparoscopic surgery and a warm ischemia time ≤25 min. We compared data from these patients with the data from a retrospective study of laparoscopic partial nephrectomy carried out in Japan. RESULTS: A total of 108 patients were registered in the present study; 105 underwent robotic partial nephrectomy. The proportion of patients who met the primary end-point was 91.3% (95% confidence interval 84.1-95.9%), which was significantly higher than 23.3% in the historical data. Major complications were seen in 19 patients (18.1%). The mean change in the estimated glomerular filtration rate in the operated kidney, 180 days postoperatively, was -10.8 mL/min/1.73 m2 (95% confidence interval -12.3-9.4%). CONCLUSIONS: Robotic partial nephrectomy for patients with a T1 renal tumor is a safe, feasible and more effective operative method compared with laparoscopic partial nephrectomy. It can be anticipated that robotic partial nephrectomy will become more widely used in Japan in the future.

Self-retaining barbed suture reduces warm ischemia time during laparoscopic partial nephrectomy.

OBJECTIVE: To evaluate the efficacy and safety of self-retaining barbed suture in renorrhaphy during laparoscopic partial nephrectomy by comparing surgical outcomes in a prospective randomized manner. MATERIAL AND METHODS: From July 2014 to July 2015, a total of 60 patients with T1 renal tumor were randomized into two equal groups: self-retaining barbed suture (SRBS) and conventional absorbable polyglactin suture (non-SRBS group). All patients were treated by retroperitoneal laparoscopic partial nephrectomy. One surgeon with high volume experience performed all procedures. The patient demographics and perioperative outcomes were compared. RESULTS: The patient demographics and tumor characteristics were comparable. The mean tumor size and R.E.N.A.L. scores were comparable between the two groups. LPN was successfully accomplished in all patients without open conversion. The warm ischemia and renorrhaphy times were significantly shorter in the SRBS group (18.8 ± 8.2 vs. 22.9 ± 7.3 min, P = .04; 10.4 ± 3.7 vs. 13.8 ± 5.6 min, P = .01). The minor complication rate was 13.3% vs. 10.0%, which was comparable. No major complication occurred. CONCLUSIONS: The randomized controlled trial demonstrates that SRBS for renorrhaphy during retroperitoneal laparoscopic partial nephrectomy is safe and efficient. Application of barbed suture simplifies the parenchymal repair procedure and reduces warm ischemia time in comparison with conventional suture.

Kidney temperature course during living organ procurement and transplantation.

Little is known about the actual kidney graft temperature during the 2nd warm ischemia time (WIT2). We aimed to determine the actual temperature course of the WIT2, with emphasis on the 15 °C metabolic threshold. Data of 152 consecutive adult living donor kidney transplantations were collected. The mean WIT2 was 41.3 ± 10.1 (SD) minutes with a temperature of 5.4 °C at baseline which gradually increased to 13.7, 17.4, and 20.2 °C after 10, 20, and 30 min, respectively. The percentage of kidneys with a temperature of 15 °C or higher was 81.2% after 20 min and 97.5% after 30 min. Duration of surgery (95% CI: -0.017 to -0.002, P = 0.02), multiple veins (95% CI: 0.0003-2.720, P = 0.05) and WIT2 (95% CI: 0.016-0.099, P = 0.006) were associated with a rapid temperature increase. No correlation could be determined between a rapid temperature rise and diminished graft function. This study showed a rapid increase in kidney temperature during WIT2, wherein the 15 °C threshold was reached within 20 min in more than 80% of the patients.

Super-Selective Artery Embolization before Laparoscopic Partial Nephrectomy in Treating Renal Angiomyolipoma.

INTRODUCTION: To investigate the feasibility and efficiency of super-selective artery embolization (SAE) before laparoscopic partial nephrectomy (LPN) in treating renal angiomyolipoma (RAML). MATERIALS AND METHODS: A retrospective analysis was conducted on 36 consecutive patients who underwent SAE before LPN (group A, n = 16) or LPN directly (group B, n = 20) from June 2010 to March 2016. Intraoperative blood loss, blood transfusion, operation time, warm ischemia time (WIT), and prognosis were compared between groups. RESULTS: SAE before LPN decreased operating time, intraoperative blood loss and WIT (p < 0.05), and improved postoperative renal function (p < 0.001). Complications in group B included intraoperative blood loss of 4 patients and postoperative hematuria of 2 patients who recovered a few days later. No complications were observed in group A. In the follow-up of 3 months, a patient in group B formatted retroperitoneal hematoma without any symptoms and received expectant treatment. CONCLUSIONS: The application of SAE before LPN can decrease the difficulty of the surgery, the complications, and the risk of rebleeding and RAMLs recurrence.

[The activity of proapoptotic genes increases after renal ischemia/reperfusion].

According to the World Health Organization, pathologies associated with ischemia/reperfusion occupy the leading position in the structure of mortality. The efficiency of localized kidney cancer surgery is limited by the damaging effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage to renal tissue may be related to changes in the expression profiles of pro- and antiapoptotic genes. Here, we have presented the longitudinal expression profiles of apoptosis-related genes in tissues of left and right (intact) kidneys of male rats exposed to unilateral ischemia followed by reperfusion. The profiles have been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX, p53, AIFM1, APAF1, CASP8, CASP3, CASP9,CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD, after normalization with respect to a reference gene ACTB. The study revealed a shift in the expression of pro- and antiapoptotic genes toward the predominance of proapoptotic processes, as was evinced by the increase in expression detected for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion, activation of mitochondrial, or intrinsic apoptosis was detected, while р53-dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA have only been detected 48 h after the restoration of blood flow. Changes have been observed in the transcription of pro- and antiapoptotic genes in tissues of both kidneys, which suggests the involvement of the contralateral kidney in systemic pathological process that develops during unilateral ischemia/reperfusion.

Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation.

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.