Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation

Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single‐center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney‐alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient (P < 0.0001), longer CS time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post‐transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation.     

Graft protection in organ transplantation

Preserving donor organs in optimal condition is a prerequisite for successful transplantation. The donor organ is subjected to a multitude of stresses. In this review, we will discuss the consequences of brain death on donor organs. The effects of an extended ischaemic period followed by the reperfusion necessary for the harvest, storage and implantation of transplant organs will be evaluated. As progressively more is known about the underlying pathophysiological mechanisms, focused and efficient therapeutic interventions can be developed. We will review current organ protection techniques and look at possible future strategies to further improve the final donor organ quality.     

The organ preservation and enhancement of donation success ratio effect of extracorporeal membrane oxygenation in circulatory unstable brain death donor

Between 2010 and 2013, we recorded 66 cases of failed organ donation after brain death (DBD) due to the excessive use of the vasoactive drugs resulting in impaired hepatic and/or renal function. To investigate the effect of extracorporeal membrane oxygenation (ECMO) in donor management, ECMO was used to provide support for DBD donors with circulatory and/or respiratory failure from 2013 to 2015. A retrospective cohort study between circulatory non‐stable DBD with vasoactive drugs (DBD‐drug) and circulatory non‐stable DBD with ECMO (DBD‐ECMO) was designed to compare the transplant outcomes. A total of 19 brain death donors were supported by ECMO. The incidence rate of post‐transplant liver primary non‐function (PNF) was 10% (two of 20) in DBD‐drug group and zero in DBD‐ECMO group. Kidney function indicators, including creatinine clearance and urine production, were significantly better in DBD‐ECMO group, as well as the kidney delayed graft function (DGF) rate was found to be decreased by the use of ECMO in our study. Donation success rate increased steadily from 47.8% in 2011 to 84.6% in 2014 after the ECMO intervention. The use of ECMO in assisting circulatory and respiratory function of DBD can reduce liver and kidney injury from vasoactive drugs, thereby improving organ quality and reducing the organ discard rates.     

Organ donation and management of the potential organ donor

Solid organ transplant offers the potential of disease-free survival for hundreds of thousands of patients worldwide. Transplantation not only increases life expectancy and improves quality of life, but offers long-term financial savings to health care systems. The clinician’s role in early identification and management of potential donors ensures that the maximum benefit can be gained from the gift of donation. A chronic shortfall in transplantable organs has led to broadened inclusion criteria for donors, and a move towards presumed consent models for donation. Protocolized and goal-directed donor management with early involvement of the transplant multidisciplinary team increases both the quality and quantity of grafts successfully donated.     

Organ donation and management of the potential organ donor

Solid organ transplant offers the potential of disease-free survival for hundreds of thousands of patients worldwide. Transplantation not only increases life expectancy and improves quality of life, but offers long-term financial savings to health care systems. The clinician's role in early identification and management of potential donors ensures that the maximum benefit can be gained from the gift of donation. A chronic shortfall in transplantable organs has led to broadened inclusion criteria for donors, and a move towards presumed consent models for donation. Protocolized and goal-directed donor management with early involvement of the transplant multidisciplinary team increases both the quality and quantity of grafts successfully donated.     

Donor pre‐treatment in clinical kidney transplantation: a critical appraisal

Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly more initial graft injury and limited organ and patient survival. This has led to an increased need for interventions aiming to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre‐treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre‐treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre‐treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor interventions, and pre‐treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre‐treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.     

A simple bedside approach to therapeutic goals achievement during the management of deceased organ donors – An adapted version of the “VIP” approach

The disproportion between the supply and demand of transplant organs could be alleviated by improving the quality of clinical management of deceased potential donors. As a large number of donor losses by cardiac arrest occur due to hemodynamic instability, without instituting all essential maintenance measures, it is likely that the application of simplified potential donor maintenance protocols will help to decrease potential donor losses and increase the supply of organs for transplantation. The Ventilation, Infusion and Pumping (VIP) strategy is a mnemonic method that brings together key aspects of the restoration of oxygen delivery to tissues during hemodynamic instability: adequate mechanical Ventilation, volume Infusion and evaluation of heart Pump effectiveness. The inclusion of the additional initials, “P” and “S,” refers to Pharmacological treatment and Specificities involved in the etiology of shock. The use of simplified care standards can assist in adhering to essential potential donor management measures. Therefore, using a simplified method as the adapted VIP approach can contribute to improving management standards of potential organ donors and increasing the supply of organs for transplantation.     

Living donor transplantation of a pelvic kidney

Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living-donor transplantation using a pelvic kidney in a 17-month-old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment.     

胰肾联合移植的供体切取与修整7例

目的　总结胰肾一期联合移植手术的供体切取和修整方法。方法　采用原位灌注联合切取和体外修整的方法完成7例尸 体供胰、十二指肠和肾的联合切取与修整。结果　7例获取器官的热缺血时间平均3分30秒,联合切取器官时间14分20秒,灌 注液平均用量1050mL。用切取、修整的胰、肾完成了3例胰肾联合移植和9例肾移植,均迅速恢复功能,未出现严重外科并发 症。3例胰肾联合移植术后均完全停用胰岛素,正常饮食,胰肾功能正常存活已分别达34个月、25个月和21个月。结论　供体 切取和修整的质量是胰肾联合移植成功的关键之一,此原位灌注联合切取和体外修整的方法可提供保证。     

Unrelated living donor kidney transplantation

Since 1966, we have performed 41 renal transplants from unrelated living donors (ULD), 39 of which were emotionally related. All donor-recipient pairs included in the present series were AB0-compatible. Recipients included 37 with primary and 4 with secondary transplants; 2 of the latter were diabetics. We compared these results to those of 41 recipients of cadaver donor kidneys matched for age, sex, immunosuppressive regimen, rank, and year of transplant, focusing our attention of the subgroups of patients under cyclosporin A (CyA) therapy (n=24). We found that ULD transplantation was as successful as cadaver transplantation with good HLA matching: at 3 years, graft survival rates were 81% in ULD versus 86% in the control group under CyA. Moreover, grafts from ULD functioned more rapidly (no post-transplant dialysis and 70% of the patients with serum creatinine below 2 mg/dl within 3 days post-transplant). Graft tolerance was equivalent in both groups (50% of the patients experienced no rejection). We conclude that despite poor HLA matching, ULD transplantation with CyA as the basic immunosuppressive agent offers good results: benefiting from the quality of living donor kidney grafts, it helps to alleviate the persistent shortage of cadaver donors.     

胰肾联合移植术的供体切取与修剪

目的: 总结胰肾一期联合移植手术有关供体切取与修剪的方法.方法: 结合我院临床开展胰肾联合移植的经验及在美国匹兹堡大学Starzl器官移植研究所进修学习的体会,对供体切取及修剪方法进行分析讨论.结果: 如此修剪后的供肾和供胰植入受体后立即恢复良好的血液循环,无出血及漏血现象,并且迅速恢复功能.结论: 掌握正确的供体切取与修剪方法是保证移植成功的关键因素之一,其中包括供体切取的速度与质量以及修剪过程中注意的要点等.     

Living-donor kidney transplantation: risks of the donor – benefits of the recipient

Abstract:  For patients with end-stage renal disease, kidney transplantation is the optimal therapy. Due to organ shortage, however, most patients have to wait on dialysis for a considerable period of time prior to transplantation. Living-donor kidney transplantation is a valid option to expand the organ pool and to reduce waiting time. The risk–benefit ratio of living-donor kidney transplantation needs to be evaluated critically, as healthy persons voluntarily donate an organ for transplantation. The available data from the literature seem to prove that the donor operation can be performed with a minimal perioperative risk. Regarding the long-term course after kidney donation, the published data suggest that the risk is minimal for well-selected healthy donors who are closely followed postoperatively. The potential donor, however, needs to be completely informed regarding the potential short- and long-term risks of kidney donation prior to the planned procedure. From the recipient point of view, transplantation of a kidney from a living donor is a very good if not the optimal option, as the short- and long-term outcomes seem to be favorable compared with cadaveric kidney transplantation. With donor safety being constantly monitored, it seems to be justified to further pursue living-donor kidney transplantation programs.     

Deceased organ donor factors influencing pancreatic graft transplantation and survival

Criteria for organ acceptance in brain‐dead organ donors remain inconsistent, especially when concerning pancreatic transplants. We sought to examine donor‐specific predictors of pancreatic graft use and survival to better guide the selection and management of potential donors. A prospective observational study of all donors from ten organ procurement organizations was conducted from March 2012 to January 2015. Critical care endpoints were collected at 4 standardized time points. Data associated with pancreatic transplantation and graft survival rates were first determined using univariate analyses, and then logistic regression was used to identify independent predictors of these two outcomes. From 1819 donors, 238 (13.1%) pancreata were transplanted, and at a mean follow‐up of 192 days, 218 (91.6%) grafts had survived. After regression analysis, donor age (OR = 0.89), HgbA1C (OR = 0.07), and achieving the donor management goal (DMG) for ejection fraction at allocation of ≥50% (OR = 3.29) remained as independent predictors of pancreatic utilization. On regression analysis, graft survival was independently predicted by lower donor age (OR = 0.93) and achieving the DMGs for mean arterial pressure (60‐110 mm Hg) and glucose (≤180 mg/dL) at separate time points. These results may help guide the management and selection of potential pancreatic donors after brain death.     

Successful transplantation of organs from a donor who died from acute cocaine intoxication

One to two percent of the general population of western countries are regular consumers of cocaine, 10% being sporadic consumers. This proportion increases considerably in the population age groups which are most frequently organ donors. Cocaine may directly cause brain death, or be present in those with brain death who died from other causes, especially head trauma. We present a 30-yr-old female donor, a regular consumer of inhaled cocaine, who died of brain anoxia after cocaine inhalation. Twenty-five hours after cocaine inhalation, the liver and kidneys were removed for transplantation. The liver was transplanted to a patient with acute hepatocellular failure caused by isoniazids, and the kidneys to two recipients with renal polycystosis. Toxicity attributable to the cocaine was not observed in any of the three recipients. All three grafts presented immediate function, and the clinical evolution of all three recipients and the function of all three grafts were excellent during the 5 yr of follow-up. The serum creatinines of the two kidney recipients 5 yr from transplantation were 76 and 72 micro mol/L, respectively.     

Optimisation of the organ donor and effects on transplanted organs: a narrative review on current practice and future directions

Mortality remains high for patients on the waiting list for organ transplantation. A marked imbalance between the number of available organs and recipients that need to be transplanted persists. Organs from deceased donors are often declined due to perceived and actual suboptimal quality. Adequate donor management offers an opportunity to reduce organ injury and maximise the number of organs than can be offered in order to respect the donor's altruistic gift. The cornerstones of management include: correction of hypovolaemia; maintenance of organ perfusion; prompt treatment of diabetes insipidus; corticosteroid therapy; and lung protective ventilation. The interventions used to deliver these goals are largely based on pathophysiological rationale or extrapolations from general critical care patients. There is currently insufficient high-quality evidence that has assessed whether any interventions in the donor after brain death may actually improve immediate post-transplant function and long-term graft survival or recipient survival after transplantation. Improvements in our understanding of the underlying mechanisms following brain death, in particular the role of immunological and metabolic changes in donors, offer promising future therapeutic opportunities to increase organ utilisation. Establishing a UK donor management research programme involves consideration of ethical, logistical and legal issues that will benefit transplanted patients while respecting the wishes of donors and their families.     

生理盐水替代HTK保存液保存活体供肾的临床研究

目的 探讨生理盐水替代组氨酸-色氨酸-酮戊二酸(histidine-tryptophan-ketoglurate,HTK)保存液对活体移植肾功能恢复的作用及可行性.方法 亲属活体供肾肾移植的患者82例,按患者意愿分为生理盐水组(29例)和HTK组(53例).生理盐水组用生理盐水作为移植肾灌注液,HTK组用HTK保存液作...     

Growth of a nation part I: impact of organ donor obesity on whole-organ pancreas transplantation

Obesity has reached epidemic proportions in the USA. Consequently, there are an increasing number of potential organ donors that are obese, but would otherwise be appropriate donors for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing donors with body mass index (BMI) <25, 25-29.9, and ≥30 kg/m(2) . Data included recipient and donor demographics, seven and 90-d graft loss, one-yr pancreas, kidney (for simultaneous pancreas and kidney transplant only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c-peptide. Of the 308 donors, 84 (27%) were overweight and 43 (14%) were obese. The overweight donors were significantly older, and the obese donors had hypertension significantly more frequently than the other two groups. There were no significant differences in recipient transplant demographics. There was no significant difference in length of stay or 90-d readmissions, seven or 90-d pancreas graft loss, one-yr graft or patient survival, peak serum amylase or lipase, HbA1C, or c-peptide. The incidence of post-transplant technical, immunological, and infectious complications were similar. Although technically challenging, PTx of allografts from obese donors can be accomplished with similar results compared to normal BMI donors.