Prospective assessment of the impact of intraoperative diuretics in kidney transplant recipient surgery.

BACKGROUND: The use of intraoperative diuretics, such as furosemide or mannitol, during kidney transplantation has been suggested to reduce the rate of delayed graft function (DGF). The evidence base for this is sparse, however, and there is substantial variation in practice. We sought to evaluate whether the use of intraoperative diuretics during kidney transplantation translated into a reduction in DGF. METHODS: We conducted a cohort study evaluating the use of furosemide or mannitol given intraoperatively before kidney reperfusion compared with control (no diuretic). Adult patients receiving a kidney transplant for end-stage renal disease were allocated to receive furosemide, mannitol, or no diuretic. The primary outcome was DGF; secondary outcomes were graft function at 30 days and perioperative changes in potassium levels. Descriptive and comparative statistics were used where appropriate. RESULTS: A total of 162 patients who received a kidney transplant from a deceased donor (either donation after neurologic determination of death or donation after circulatory death) were included over a 2-year period, with no significant between-group differences. There was no significant difference in DGF rates between the furosemide, mannitol, and control groups. When the furosemide and mannitol groups were pooled (any diuretic use) and compared with the control group, however, there was a significant improvement in the odds that patients would be free of DGF (odds ratio 2.10, 95% confidence interval 1.06-4.16, 26% v. 44%, p = 0.03). There were no significant differences noted in any secondary outcomes. CONCLUSION: This study suggests the use of an intraoperative diuretic (furosemide or mannitol) may result in a reduction in DGF in patients undergoing kidney transplantation. Further study in the form of a randomized controlled trial is warranted.

Heparin Thromboprophylaxis in Simultaneous Pancreas-Kidney Transplantation: A Systematic Review and Meta-Analysis of Observational Studies.

Thrombosis is a leading causes of pancreas graft loss after simultaneous pancreas kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). There remains no standardized thromboprophylaxis protocol. The aim of this systematic review and meta-analysis is to evaluate the impact of heparin thromboprophylaxis on the incidence of pancreas thrombosis, pancreas graft loss, bleeding, and secondary outcomes in SPK, PAK, and PTA. Following PRISMA guidelines, we systematically searched BIOSIS®, PubMed®, Cochrane Library®, EMBASE®, MEDLINE®, and Web of Science® on April 21, 2021. Primary peer-reviewed studies that met inclusion criteria were included. Two methods of quantitative synthesis were performed to account for comparative and non-comparative studies. We included 11 studies, comprising of 1,122 patients in the heparin group and 236 patients in the no-heparin group. When compared to the no-heparin control, prophylactic heparinization significantly decreased the risk of early pancreas thrombosis and pancreas loss for SPK, PAK and PTA without increasing the incidence of bleeding or acute return to the operating room. Heparin thromboprophylaxis yields an approximate two-fold reduction in both pancreas thrombosis and pancreas loss for SPK, PAK and PTA. We report the dosage, frequency, and duration of heparin administration to consolidate the available evidence.

A Prospective Study of the Effect of Gastroduodenal Artery Reconstruction on Duodenal Oxygenation and Enzyme Content After Pancreas Transplantation.

BACKGROUND: Whole pancreas transplantation provides durable glycemic control and can improve survival rate; however, it can carry an increased risk of surgical complications. One devastating complication is a duodenal leak at the site of enteroenteric anastomosis. The gastroduodenal artery (GDA) supplies blood to the donor duodenum and pancreas but is commonly ligated during procurement. Since we have not had expressive changes in pancreatic back table surgical techniques in the recent decades, we hypothesized whether back table GDA reconstruction, improving perfusion of the donor duodenum and head of the pancreas, could lead to fewer surgical complications in simultaneous pancreas-kidney (SPK) transplants. MATERIAL AND METHODS: Between 2017 and 2021, we evaluated demographic information, postoperative complications, intraoperative donor duodenum, recipient bowel O2 tissue saturation, and patient morbidity through the Comprehensive Complication Index (CCI®). RESULTS: A total of 26 patients were included: 13 underwent GDA reconstruction (GDA-R), and 13 had GDA ligation (GDA-L). There were no pancreatic leaks in the GR group compared to 38% (5/13) in the GDA-L group (p = 0.03913). Intraoperative tissue oxygen saturation was higher in the GDA-R group than in the GDA-L (95.18 vs.76.88%, p < 0,001). We observed an increase in transfusion rate in GDA-R (p < 0.05), which did not result in a higher rate of exploration (p = 0.38). CCI® patient morbidity was also significantly lower in the GDA-R group (s < 0.05). CONCLUSIONS: This study identified improved intraoperative duodenal tissue oxygen saturation in the GDA-R group with an associated reduction in pancreatic leaks and CCI® morbidity risk. A larger prospective multicenter study comparing the two methods is warranted.

Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation.

The global donor kidney shortage crisis has necessitated the use of suboptimal kidneys from donors-after-cardiac-death (DCD). Using an ex vivo porcine model of DCD kidney transplantation, the present study investigates whether the addition of hydrogen sulfide donor, AP39, to University of Wisconsin (UW) solution improves graft quality. Renal pedicles of male pigs were clamped in situ for 30 min and the ureters and arteries were cannulated to mimic DCD. Next, both donor kidneys were nephrectomized and preserved by static cold storage in UW solution with or without AP39 (200 nM) at 4 °C for 4 h followed by reperfusion with stressed autologous blood for 4 h at 37 °C using ex vivo pulsatile perfusion apparatus. Urine and arterial blood samples were collected hourly during reperfusion. After 4 h of reperfusion, kidneys were collected for histopathological analysis. Compared to the UW-only group, UW+AP39 group showed significantly higher pO2 (p < 0.01) and tissue oxygenation (p < 0.05). Also, there were significant increases in urine production and blood flow rate, and reduced levels of urine protein, serum creatinine, blood urea nitrogen, plasma Na+ and K+, as well as reduced intrarenal resistance in the UW+AP39 group compared to the UW-only group. Histologically, AP39 preserved renal structure by reducing the apoptosis of renal tubular cells and immune cell infiltration. Our finding could lay the foundation for improved graft preservation and reduce the increasingly poor outcomes associated with DCD kidney transplantation.

Application of carbon monoxide in kidney and heart transplantation: A novel pharmacological strategy for a broader use of suboptimal renal and cardiac grafts.

Carbon monoxide (CO) was historically regarded solely as a poisonous gas that binds to hemoglobin and reduces oxygen-carrying capacity of blood at high concentrations. However, recent findings show that it is endogenously produced in mammalian cells as a by-product of heme degradation by heme oxygenase, and has received a significant attention as a medical gas that influences a myriad of physiological and pathological processes. At low physiological concentrations, CO exhibits several therapeutic properties including antioxidant, anti-inflammatory, anti-apoptotic, anti-fibrotic, anti-thrombotic, anti-proliferative and vasodilatory properties, making it a candidate molecule that could protect organs in various pathological conditions including cold ischemia-reperfusion injury (IRI) in kidney and heart transplantation. Cold IRI is a well-recognized and complicated cascade of interconnected pathological pathways that poses a significant barrier to successful outcomes after kidney and heart transplantation. A substantial body of preclinical evidence demonstrates that CO gas and CO-releasing molecules (CO-RMs) prevent cold IRI in renal and cardiac grafts through several molecular and cellular mechanisms. In this review, we discuss recent advances in research involving the use of CO as a novel pharmacological strategy to attenuate cold IRI in preclinical models of kidney and heart transplantation through its administration to the organ donor prior to organ procurement or delivery into organ preservation solution during cold storage and to the organ recipient during reperfusion and after transplantation. We also discuss the underlying molecular mechanisms of cyto- and organ protection by CO during transplantation, and suggest its clinical use in the near future to improve long-term transplantation outcomes.

Late-onset allograft rejection, cytomegalovirus infection, and renal allograft loss: Is anti-CMV prophylaxis required following late-onset allograft rejection?

Renal transplant recipients remain at risk of delayed-onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early-vs late-onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long-term allograft outcome. Median (IQR) duration of follow-up was 1186.0 (904.7-1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R- CMV serostatus (OR: 5.5, 95% CI: 2.5-12.2) and LAR (OR: 7.9, 95% CI: 2.8-22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed-onset CMV infection (HR: 2.51, 95% CI: 1.08-5.86) and LAR (HR: 5.46, 95% CI: 2.26-13.14) significantly increased the risk of allograft loss. Patients with LAR are at risk of late-onset CMV infection. Post-LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR.

Canadian survey on the rates of use of intraoperative diuretics and justification for their use during renal allograft reperfusion.

BACKGROUND: Mannitol and furosemide have been used as diuretics intraoperatively to facilitate early renal allograft function and reduce delayed graft function. As the evidence of any efficacy of these agents is limited, we sought to characterize the use of diuretics among transplant surgeons. METHODS: An anonymous online survey was sent to all Canadian transplant programs where kidney transplants are routinely performed. Questions were related to the use and indications for mannitol and furosemide. Responses were collected and analyzed as counts and percentages of respondents. We used χ2 analysis to assess the relationship between demographic factors and survey responses. RESULTS: Thirty-five surgeons completed the survey (response rate 50%). Seventy per cent of respondents reported performing 26 or more transplants per year, 88% had formal transplant fellowship training and 67% indicated that they currently train fellows. Only 24% and 12% reported believing that delayed graft function is reduced by mannitol and furosemide use, respectively. However, 73% routinely gave mannitol to patients and 53% routinely gave furosemide. The most common justification given for mannitol use was to induce diuresis (54%); 37% of respondents reported using mannitol because of training dogma. Likewise, 57% used furosemide for diuresis, with 23% reporting that their use of this agent was based on dogma. No relationship emerged between fellowship training, case volume or training program status and the use of any agent. Interestingly, 71% of respondents indicated that a randomized controlled trial evaluating the utility of intraoperative diuretics is needed and that they were interested in participating in such a trial. CONCLUSION: Use of intraoperative diuretics and the rationale for their use vary among surgeons. A substantial proportion of surgeons use these medications on the basis of dogma alone. A randomized controlled trial is needed to clarify the role of intraoperative diuretics in kidney transplant surgery.

CONTEXTE: On a utilisé le mannitol et le furosémide comme diurétiques peropératoires pour stimuler le fonctionnement précoce de l'allogreffe rénale et réduire le retard de fonctionnement du greffon. Comme les données probantes quant à l'efficacité de ces agents sont limitées, nous avons voulu caractériser l'utilisation des diurétiques chez les chirurgiens qui effectuent ces transplantations. MÉTHODES: Un sondage anonyme en ligne a été envoyé à tous les programmes de greffe canadiens où des greffes rénales sont couramment effectuées. Les questions avaient trait à l'utilisation et aux indications du mannitol et du furosémide. Les réponses ont été recueillies et analysées sous forme de nombres et de pourcentages des répondants. Le test du χ2 a été utilisé pour évaluer le lien entre les facteurs démographiques et les réponses au sondage. RÉSULTATS: Trente-cinq chirurgiens ont répondu au sondage (taux de réponse 50 %). Soixante-dix pour cent des répondants ont indiqué effectuer annuellement 26 greffes ou plus, 88 % avaient suivi une spécialisation formelle pour l'exécution des greffes et 67 % ont dit être en cours de spécialisation. Seulement 24 % et 12 % respectivement ont dit croire que le mannitol et le furosémide permettent de réduire le retard de fonctionnement du greffon. Toutefois, 73 % et 53 % respectivement administraient de routine du mannitol et du furosémide aux patients. La justification la plus fréquente de l'utilisation du mannitol était d'induire la diurèse (54 %); 37 % des répondants ont dit utiliser le mannitol parce que c'est ce qu'on leur a enseigné durant leur formation. De même, 57 % utilisaient le furosémide pour la diurèse, dont 23 % disaient que c'est ce qu'on leur avait enseigné durant leur formation. Aucun lien n'est ressorti entre la spécialisation, le volume de cas ou le statut à l'égard du programme de formation et l'utilisation d'un agent quelconque. Fait à noter, 71 % des répondants ont indiqué qu'un essai randomisé et contrôlé sur l'utilité des diurétiques peropératoires serait nécessaire et qu'ils y participeraient volontiers. CONCLUSION: L'utilisation de diurétiques peropératoires et la justification de leur utilisation varient d'un chirurgien à l'autre. En majeure partie, les chirurgiens utilisent ces médicaments sur la base des notions théoriques seulement. Un essai randomisé et contrôlé s'impose pour clarifier le rôle des diurétiques peropératoires dans la greffe rénale.

Missed opportunities for DCD kidney donors: Evaluation of warm ischemic time and associated functional warm ischemic time.

INTRODUCTION: Many transplant centers utilize a hard cutoff of 2 hours of warm ischemic time (WIT), defined as the time from withdrawal of life-sustaining measures to cold organ flush, to exclude donation after circulatory determination of death (DCD) kidney donation. As a result, almost a quarter of withdrawals to retrieve DCD organs fail to produce kidney transplants in Ontario. In order to assess our ability to increase organ yield, we wanted to characterize WIT and functional WIT (fWIT, time from systolic blood pressure <50 mm Hg to cold organ flush), as well as determine the time at which potential donors eventually die in those that did not become organ donors. METHODS: A retrospective review of all DCD kidney donors in Ontario was performed utilizing the Trillium Gift of Life Database from April 2013 to February 2018. RESULTS: Of 350 DCD kidney donors analyzed, 46.9% had < 0.5 hours, 51.7% between 0.5 and 2 hours, and 1.4% >2 hours of WIT. In each of these categories (WIT <0.5 hours, 0.5-2 hours and >2 hours), the percentage of patients with fWIT <30 minutes was 100%, 94.4%, and 100%, respectively (P = NS). There were 106 potential donors who did not end up donating due to WIT >2 hours. Of these, 20.8% died between 2 and 4 hours, 10.4% between 4 and 6 hours, and 68.8% beyond 6 hours. DISCUSSION: The percentage of donors with fWIT >30 minutes did not increase with increasing WIT in DCD donors that went on to donate organs. These data support assessment of waiting up to 4 hours for DCD kidney donation as long as fWIT remains low.

Significance of atypical urinary cytology in the evaluation of patients with end-stage renal disease for kidney transplantation - a retrospective study.

To determine what percentage of renal transplant candidates have atypical urinary cytology, what proportion have urothelial carcinoma and whether cystoscopy is necessary with atypical cytology. All end-stage renal disease (ESRD) patients (703) presenting for renal transplantation at our institution were retrospectively reviewed. Individuals producing sufficient urine were screened with urine cytology and those with atypical cytology or risk factors for bladder cancer underwent cystoscopy. Four hundred and thirty patients had available urinary cytology and, of these, 151 (35%) had atypical cytology. Of patients with atypical cytology, three were identified to have urothelial carcinoma. However, three additional patients with urothelial carcinoma did not present with atypical cytology. In total, 6 of 703 (0.85%) patients had bladder cancer. All were treated with transurethral resection and eventually underwent renal transplant. One patient has had disease progression post-transplant to distant metastases. This is the largest study to date evaluating the incidence of urothelial carcinoma in ESRD patients presenting for transplant workup. We found the incidence of bladder cancer to be higher than in the general Canadian population, however, most lesions were low grade. We found atypical cytology in transplant candidates to be a poor predictor for these low-grade lesions and do not recommend routine cystoscopy for atypical cytology.

Transplantation of pediatric renal allografts from donors less than 10 kg.

Few transplant programs use kidneys from donors with body weight (BW) < 10 kg. We hypothesized that pediatric en bloc transplants from donors with BW < 10 kg would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N = 28). Data were stratified by smaller (donor BW < 10 kg; n = 11) or larger donors (BW > 10 kg; n = 17). Renal volume was assessed during follow-up with ultrasound. Demographic characteristics were similar between the 2 groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 months (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1 day posttransplant, mean total renal volume in the smaller donors was 28 ± 9 mm3 vs 45 ± 12 mm3 (P < .01). By 3 weeks, it was 53 ± 19 mm3 (smaller donors) versus 73 ± 19 mm3 (larger donors) (P = NS). Complication rates were similar between both groups with 1 case of venous thrombosis in the smaller group. With experience, outcomes are equivalent to those from larger pediatric donors.

Randomized open-label crossover assessment of Prograf vs Advagraf on immunosuppressant pharmacokinetics and pharmacodynamics in simultaneous pancreas-kidney patients.

INTRODUCTION: We assessed the pharmacokinetic and pharmacodynamic impact of converting stable simultaneous pancreas-kidney (SPK) recipients from standard tacrolimus (Prograf) to long-acting tacrolimus (Advagraf). METHODS: In a randomized prospective crossover study, stable SPK recipients on Prograf were assigned to Prograf with 1:1 conversion to Advagraf or vice versa. Demographics, tacrolimus, mycophenolic acid levels, and Cylex CD4 + ATP levels were taken at specified intervals in addition to standard blood work. RESULTS: Twenty-one patients, who were a minimum of 1 year post-transplant, were entered into the study. No difference in tacrolimus or mycophenolic acid levels was noted between patients who were first assigned to Prograf or Advagraf. Additionally, Cylex levels as well as serum creatinine, lipase, and blood sugar levels were unchanged. There were no episodes of rejection during the 6-month study. CONCLUSIONS: It is safe to convert between Prograf and Advagraf 1:1, without major impact on pharmacokinetics or pharmacodynamics in SPK recipients.

Dual en bloc technique for adult renal transplantation.

INTRODUCTION: We describe and provide follow-up for a novel simplified technique permitting dual en bloc (DEB) transplantation of adult organs using single in situ arterial and venous anastomoses. METHODS: Twenty-two adult DEB transplants were performed at our center between 2001 and 2012, utilizing 44 kidneys en bloc. Results were compared with 20 solitary transplants from expanded criteria donors (ECD) associated with lower terminal serum creatinines and Remuzzi biopsy scores vs DEB group. Adult DEB implants had donor inferior vena cava connected to recipient external iliac vein and "Y" arterial interposition graft anastomosed to the recipient iliac artery. Ureters were conjoined prior to implantation as a single patch into the recipient bladder. RESULTS: Mean operative time was 206±57 minutes in DEB vs 180±30 minutes in single transplants (P<.05). Delayed graft function rate was 23% vs 25% in both groups. At 12-month follow-up, mean serum creatinine was 152±66 µmol/L vs in 154±52 µmol/L DEB and single kidney transplant recipients, respectively (P=NS). Three-year overall and graft specific survival were 86% and 84% in the DEB group, respectively (P=NS). Complication rates were similar between groups. CONCLUSIONS: This DEB renal transplantation technique is safe and effective in adults. By employing techniques used to conjoin organ vasculature ex vivo, the number of in situ anastomoses is reduced, thereby minimizing operative ischemic time and potential for complications associated with extensive vascular dissection.

First Canadian experience with donation after cardiac death simultaneous pancreas and kidney transplants.

BACKGROUND: Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death (DCD) donor organs have traditionally been considered of inferior quality owing to warm ischemia experienced during procurement. We present, to our knowledge, the first analysis of simultaneous pancreas and kidney (SPK) transplants using DCD donor organs in Canada. METHODS: We carried out a retrospective cohort study of SPK transplants from 13 DCD and 68 NDD donors performed between October 2008 and July 2016. In all patients immunosuppression was induced with thymoglobulin and continued with tacrolimus, mycophenolate mofetil and prednisone maintenance therapy. RESULTS: Donor and recipient characteristics of DCD and NDD groups were similar with respect to age, sex, body mass index, kidney and pancreas cold ischemia times, and donor terminal creatinine. Mean DCD graft warm ischemia time was 0.5 (range 0.4-0.7) hours. Median follow-up was 2.2 (range 0.1-6.7) years and 2.7 (range 0.3-6.3) years for the DCD and NDD groups, respectively. The DCD and NDD groups were similar with regards to recipient percent panel reactive antibody and presence of human leukocyte antigen antibodies. The groups also received similar total doses of thymoglobulin. In total 38% of patients in the DCD group experienced renal delayed graft function (DGF) compared with 10% in the NDD group (p = 0.027). There were 7 cases of pancreas graft thrombosis requiring relaparotomy in the NDD group compared with none in the DCD group. No patients from either group required insulin at any time after transplant. Although the estimated glomerular filtration rate (eGFR) was lower in the DCD than the NDD group on postoperative days 7 and 14 (p = 0.025), no difference was noted on day 30 or through 4 years after transplant. No differences were seen between the groups with respect to amylase, lipase, or glycosated hemoglobin (HbA1c) up to 4 years after transplant, or in kidney, pancreas, or patient survival at any time after transplant. CONCLUSION: Our results show that, apart from a higher renal DGF rate, SPK transplants with DCD donor organs have comparable outcomes to standard transplants with NDD donor organs.

CONTEXTE: Comparativement aux organes prélevés après détermination de la mort cérébrale (ou détermination du décès neurologique [DDN]), les organes prélevés après détermination du décès cardiocirculatoire (DDC) sont en général considérés de moindre qualité en raison du phénomène d'ischémie chaude inhérent à ce type de prélèvement. Nous présentons, à notre connaissance, la première analyse sur la double greffe rein-pancréas effectuée avec des organes prélevés après DDC au Canada. MÉTHODES: Nous avons procédé à une étude de cohorte rétrospective sur les doubles greffes rein-pancréas effectuées entre octobre 2008 et juillet 2016, soit 13 après DDC et 68 après DDN. Chez tous les patients, l'immunosuppression a été induite par la thymoglobuline et a été maintenue au moyen d'un traitement d'entretien par le tacrolimus, le mycophénolate mofétil et la prednisone. RÉSULTATS: Les caractéristiques des donneurs et des receveurs des 2 groupes (DDC et DDN) étaient semblables sur les plans de l'âge, du sexe, de l'indice de masse corporelle, de la durée de l'ischémie froide du rein et du pancréas, et de la créatinine terminale (donneur). La durée moyenne de l'ischémie chaude des greffons prélevés après DDC a été de 0,5 (étendue : 0,4-0,7) heure. Le suivi médian a été d'une durée de 2,2 (étendue : 0,1-6,7) ans et de 2,7 (étendue : 0,3-6,3) ans, respectivement, pour les groupes DDC et DDN. Les 2 groupes étaient similaires pour ce qui est des pourcentages d'anticorps réactifs et de la présence d'anticorps anti-HLA (human leukocyte antigen) chez les receveurs. Les 2 groupes avaient aussi reçu des doses totales semblables de thymoglobuline. En tout, 38 % des patients du groupe DDC ont manifesté un retard de fonctionnement du greffon rénal, contre 10 % dans le groupe DDN (p = 0,027). On a dénombré 7 cas de thrombose du greffon pancréatique ayant nécessité une réintervention dans le groupe DDN, contre aucun dans le groupe DDC. Aucun des patients n'a eu besoin d'insuline après la transplantation. Le débit de filtration glomérulaire estimé (DFGe) était moins élevé dans le groupe DDC que dans le groupe DDN aux jours 7 et 14 (p = 0,025), mais on n'a plus noté de différence à ce chapitre au jour 30 ni au cours des 4 années suivant la greffe. On n'a observé aucune différence entre les groupes pour ce qui est de l'amylase, de la lipase ou de l'HbA1c jusqu'à 4 ans suivant la greffe, ni pour ce qui est de la survie des greffons rénaux ou pancréatiques ou celle des patients, peu importe le temps écoulé depuis la greffe. CONCLUSION: Selon nos résultats, si ce n'est un taux plus élevé de retard de fonctionnement du greffon rénal, les receveurs d'une double greffe rein-pancréas après DDC obtiennent des résultats semblables à ceux qui subissent une greffe standard d'organes prélevés après DDN.

Heparin infusion in simultaneous pancreas and kidney transplantation reduces graft thrombosis and improves graft survival.

INTRODUCTION: Thrombosis of the pancreas after transplantation is the most common cause of relaparotomy and resultant graft loss. There is currently no standard protocol consistently proven to prevent thrombosis following transplantation. Our objective was to determine whether our protocol of post-operative low-dose intravenous (IV) heparin infusion would prevent graft thrombosis without additional complications in our patients. METHODS: A total of 66 simultaneous pancreas kidney (SPK) transplants were performed at our institution from 2004 to 2014. Patients were divided into 2 retrospective cohort groups. Group 1 patients received only acetylsalicylic acid (ASA) 81 mg/d started on post-operative day 1. Group 2 patients received IV heparin infusion beginning in the recovery room at a rate of 500 IU/h for the first 24 hours, reduced by 100 IU/h every day to stop on day 5, and then received ASA 81 mg/d afterward. Outcome and complication rates were compared between the two groups for 5 years post-transplant. RESULTS: We observed a significant reduction in graft thrombosis and graft loss with (0/29) patients in the heparin group vs (7/33) 25.7% from the non-heparin (P<.01) with no differences in complication rates. CONCLUSIONS: We present a heparin infusion protocol which may help prevent graft thrombosis and graft loss in SPK transplantation.

Optimal management of distal ureteric strictures following renal transplantation: a systematic review.

Our objective was to define optimal management of distal ureteric strictures following renal transplantation. A systematic review on PubMed identified 34 articles (385 patients). Primary endpoints were success rates and complications of specific primary and secondary treatments (following failure of primary treatment). Among primary treatments (n = 303), the open approach had 85.4% success (95% CI 72.5-93.1) and the endourological approach had 64.3% success (95% CI 58.3-69.9). Among secondary treatments (n = 82), the open approach had 93.1% success (95% CI 77.0-99.2) and the endourological approach had 75.5% success (95% CI 62.3-85.2). The most common primary open treatment was ureteric reimplantation (n = 33, 81.8% success, 95% CI 65.2-91.8). The most common primary endourological treatment was dilation (n = 133, 58.6% success, 95% CI 50.1-66.7). Fourteen complications, including death (4 weeks post-op) and graft loss (12 days post-op), followed endourological treatment. One complication followed open treatment. This is the first systematic review to examine the success rates and complications of specific treatments for distal ureteric strictures following renal transplantation. Our review indicates that open management has higher success rates and fewer complications than endourological management as a primary and secondary treatment for post-transplant distal ureteric strictures. We also outline a post-transplant ureteric stricture evaluation and treatment algorithm.

Donation after Circulatory Death Renal Allografts--Does Donor Age Greater than 50 Years Affect Recipient Outcomes?

PURPOSE: Donation after circulatory death renal allografts are associated with excellent outcomes. We performed a retrospective chart review to investigate the impact of donor age on postoperative and intermediate term outcomes. MATERIALS AND METHODS: We compared recipient outcomes of donation after circulatory death allografts from donors older vs younger than 50 years. A total of 118 single donations after circulatory death renal transplants were performed at our institution between July 2006 and September 2013. Outcome variables (creatinine clearance, readmission rate, length of hospital stay, delayed graft function, graft loss and rejection) were compared between the 2 age categories using the Student t-test and the Pearson chi-square test. Independent prognosticators of creatinine clearance at 12 months were assessed with multivariate linear regression modeling. RESULTS: Mean ± SD recipient age was 53.8 ± 14.7 years and 45.8% of donation after circulatory death donors were older than 50 years. Median followup was 21 months (range 1 to 87). Recipients of kidney transplants from donation after circulatory death donors older than 50 years demonstrated lower creatinine clearance at 1 month (mean 50.3 ± 25.3 vs 72.7 ± 31.7 ml per minute, p <0.001), 3 months (62.5 ± 22.9 vs 87.9 ± 36.4, p <0.001) and 1 year (66.2 ± 26.8 vs 87.8 ± 38.7, p = 0.013). However, the 2 groups did not differ with regard to delayed graft function, graft loss, hospital readmissions or length of hospital stay. Multivariate linear regression demonstrated that donor age, recipient age, recipient gender and cold ischemia time were independent predictors of creatinine clearance at 12 months. CONCLUSIONS: Recipients of allografts from donors older than 50 years showed inferior renal function at 1 year but the 2 groups had similar graft survival and short-term outcomes. Longer followup is required to determine long-term allograft survival.

Donation after cardiac death pediatric en bloc renal transplantation.

PURPOSE: Use of small pediatric kidneys obtained from extremely young donors after cardiac death has been limited. This potential organ source remains under used by transplant teams. MATERIALS AND METHODS: We reviewed all renal transplants at our institution from 2000 to 2013 to identify recipients of an en bloc pair of kidneys from deceased pediatric donors younger than 4 years. The outcomes of donation after cardiac death en bloc allografts were compared with neurological determination of death en bloc allografts. RESULTS: A total of 21 recipients of en bloc renal allografts were identified, of which 4 organ pairs were obtained through donation after cardiac death. Mean ± SD donor age was 20.6 ± 11.6 months and weight was 12.4 ± 3.7 kg. Delayed allograft function occurred in 2 of 4 recipients of allografts obtained from donation after cardiac death en bloc and 3 of 17 recipients of allografts from neurological determination of death en bloc. One year after transplantation mean ± SD glomerular filtration rates were similar, at 80.7 ± 15.3 and 85.7 ± 33.4 ml/minute/1.73 m(2) in the cardiac and neurological allograft groups, respectively (difference not significant). Surgical complications occurred in 3 patients, and no allograft was lost to thrombosis. CONCLUSIONS: We report successful transplantation of a small cohort of pediatric en bloc kidneys obtained through donation after cardiac death from donors younger than 4 years. Outcomes at 1 year are comparable to those in neurological determination of death en bloc allograft recipients.

Hypothermic machine perfusion improves Doppler ultrasonography resistive indices and long-term allograft function after renal transplantation: a single-centre analysis.

OBJECTIVES: To evaluate whether hypothermic machine perfusion (HMP) of transplanted kidneys can improve long-term renal allograft function compared with static cold storage (CS). METHODS: We evaluated whether graft Doppler ultrasonography resistive indices improved with the use of HMP compared with CS preservation, and examined whether these improvements were predictive of long-term graft function. A total of 30 kidney transplants (15 pairs) were examined. One of the kidney pairs was placed on CS and transplanted first (CS group, n = 15). The other kidney of each pair was placed on HMP and transplanted after the CS group (HMP group, n = 15). Doppler ultrasonography was performed on days 1 and 7 after transplantation and resistive indices were evaluated. The estimated glomerular filtration rate (eGFR) was monitored for 24 months after transplantation. RESULTS: Despite longer cold ischaemia times, kidneys maintained with HMP had lower resistive indices (P = 0.005) with correspondingly higher eGFR throughout the follow-up. Subgroup analysis showed that the HMP-induced improvement in postoperative eGFR was greatest in kidneys obtained from donation after cardiac death (DCD), even at 2 years after transplantation (P = 0.008). CONCLUSIONS: HMP of transplant kidneys appears to improve vascular resistance after transplantation and has a positive impact on long-term allograft function compared with CS in the population of recipients of DCD kidneys.

The prognostic value of time needed on dialysis in patients with delayed graft function.

INTRODUCTION: We hypothesize that in patients with delayed graft function (DGF), the need for a longer time needed on dialysis (TND) post-kidney transplant is associated with poorer long-term function and an increase in complications. METHODS: This was a retrospective chart review involving collaboration between Western University (WU) Renal Transplant Program of London, Ontario and the Saskatchewan renal transplant program (SRTP). A total of 774 patients (567 WU and 207 SRTP) received kidney transplants between 2004 and 2011, of which 83 patients with deceased donor transplants (59 WU and 24 SRTP) developed DGF, defined as the need for dialysis in the first week posttransplant. RESULTS: Patients with DGF were divided into three groups depending on TND [group 1: <7 days (n = 52), group 2: 7-14 days (n = 13) and group 3 (n = 18): >14 days]. The creatinine clearance (CrCl) at 30 days (42.5, 33.8, 20.0 cc/min; P < 0.001) and 1 year (56.7, 49.2, 37.3 cc/min, P = 0.031) were significantly different between the three groups. Multivariate regression analysis identified length of TND posttransplant (ß = -0.5, P < 0.001) and donation after cardiac death (DCD) donor (ß = 19.5, P < 0.001) as the most significant predictors of CrCl at 1 year in these patients with DGF. DCD kidneys with DGF had a higher CrCl at 1 year and fewer readmissions in the first year compared with non-DCD kidneys with DGF. DISCUSSION: Our study suggests that increased TND is associated with worse CrCl at 1 year. The data also support the hypothesis of a different mechanism for DGF in DCD and non-DCD kidneys.

Preoperative Cylex assay predicts rejection risk in patients with kidney transplant.

INTRODUCTION AND OBJECTIVES: The ImmuKnow assay measures cell-mediated immunity by quantifying ATP release from CD4+ T-cells in peripheral blood. Herein, we hypothesized that this assay could predict complications associated with over-/under-immunosuppression in patients with kidney transplant (KT). METHODS: Sixty-seven patients undergoing KT were recruited prospectively and had ATP levels measured preoperatively, and at specified intervals over two months. Clinicians were blinded to ATP levels. Clinical events including rejection and infection/cancer were documented with a median follow-up of 21 months. Parameters including absolute ATP levels and changes in ATP patterns (slopes, delta) were analyzed. Association between ATP parameters and clinical outcomes was compared using the likelihood-ratio test and Kaplan-Meier curves. RESULTS: Absolute ATP values postoperatively had poor predictive value with regard to rejection or infection/malignancy. As well, changes in ATP values were poorly associated with complications. Importantly, patients with pre-transplant ATP values <300 ng/mL had significantly less rejection episodes vs. those with ATP values >300 ng/mL (p < 0.0001). CONCLUSIONS: For the first time, we have evidence that a preoperative ImmuKnow level can stratify patients with KT into low/high risk groups for rejection. Future studies used to assess the utility of this assay to design individualized immunosuppressive regimens are required.