Donation After Cardiac Death Kidney Transplantation Research Articles

404.7: Study on the Regulatory Effect of iPS-Derived Exosomes on the Local Immune Microenvironment in DCD Kidney Transplanted Rats

Introduction: Ischemia reperfusion injury (IRI) of donation After Cardiac death (DCD) transplanted kidney is the key factor of acute renal injury, acute and chronic rejection of renal transplantation and transplanted kidney disease.The latest researches show that mesenchymal stem cells (MSCs) have the function of protecting damaged tissues and organs and strong immune regulation. Induced pluripotent stem (iPS) cells have higher proliferative capacity and exosome secretion potential than MSCs. In addition to the functions of stem cells, exosomes have the unique ability to cross the blood-brain barrier and deliver remotely, which means that exosomes have better advantages in clinical disease treatment compared with the therapeutic potential of stem cells. Therefore, the main purpose of this study is to clarify the role of IPS derived exosomes in protecting the IRI of DCD transplanted kidney and regulating its local immune microenvironment. Methods: The iPS cells were passaged to the third passage and massively expanded. After 48 hours of culture, 100 mL of cell culture supernatant was collected and exosomes were extracted from the supernatant by the kit method, and the morphology and surface membrane marker proteins of the exosomes were identified. The SD rats were established with DCD renal transplantation model and 10, 50, and 100 μg of exosomes were infused into that SD rats respectively, and a PBS control group was set at the same time. On the 3rd, 5th, 7th, 14th and 28th days after transplantation, the content of cytokines in the serum of the recipient rats, the proportion of lymphocyte subsets CD4+CD25+Foxp3+Tregs in the spleen and the relative expression of Foxp3 mRNA were detected. The proliferation of renal tubular cells was detected by PCNA immunofluorescence. The pathological changes of renal tissue were determined by HE staining, and the apoptosis of renal tubular epithelial cells was detected by Tunel staining. The infiltration of inflammatory cells was detected by immunohistochemistry. The expression changes of regulatory T cells in renal tissue and macrophage phenotypic characteristics were analyzed by flow cytometry. Results: The experimental amount of exosomes was successfully obtained, and the morphology was observed by transmission electron microscope. The exosomes were round or oval membranous vesicles with uniform size, and the edges were clearly visible. The TSG101, CD63, and CD9 proteins were highly expressed on the exosome membrane surface by western-blot. A DCD rat kidney transplantation model was successfully established. The expression levels of IL-12, IL-2, IFN-γ, and TNF-α in the serum of each group were increased to varying degrees from the 3rd day after operation. On the 3rd and 7th days, the levels of IL-12, IL-2, IFN-γ, and TNF-α in the 100 μg exosome infusion group were significantly lower than those in the 10 μg, 50 μg and PBS groups (P<0.05), and the expression level of IL-10 in the 100 μg exosome infusion group was significantly higher than 10μg, 50μg and PBS groups (P<0.05). On the 28th day, the expression level of IL-10 in the 100 μg exosome infusion group was significantly higher than other groups (P<0.01). Compared with other groups, the CD4+CD25+Tregs and CD4+CD25+Foxp3+Tregs accounted for the highest proportion of CD4+T cells in the spleen of the 100μg infusion group (P<0.05). On the 28th day, the expression level of Foxp3 mRNA in the 100 μg infusion group was significantly higher than that in the 50 μg group (P<0.05). The stainings of PCNA, HE and Tunel showed that SD rats infused with 100μg exosomes could significantly reduce the pathological damage, inflammatory response and apoptosis of renal tubular epithelial cells in the transplanted kidney, promote the proliferation of renal tubular epithelial cells, and have a protective effect on IRI kidney. On the 28th day, the expression of CD4+CD25+Foxp3+Tregs cells in the transplanted kidney tissue was significantly increased, which further promoted the differentiation of macrophages into the immunomodulatory M2 subset. Conclusions: The infusion of iPS-derived high-dose exosomes is involved in the protection of the DCD kidney transplant during IRI process, and alleviates the acute and chronic injury of the DCD kidney transplant, and promotes the formation of the local immunosuppressive microenvironment in the DCD kidney transplantation. The National Natural Science Foundation of China (No.81900686).

Outcome of Kidney Transplantation From Donor After Cardiac Death: Reanalysis of the US Mycophenolic Renal Transplant Registry

BackgroundKidney transplantation is limited by the shortage of donor kidneys. Donation after cardiac death (DCD) has been explored to alleviate this problem. To better understand the outcome of DCD kidney transplantation, we reanalyzed the Mycophenolic Renal Transplant (MORE) Registry. MethodsWe compared delayed graft function (DGF), biopsy-proved acute rejection (BPAR), graft loss, and patient death between DCD and donation after brain death (DBD) kidney transplantations. Recipients were further stratified into depleting and nondepleting induction groups for exploratory analysis. ResultsThere were 548 patients who received kidney transplants from deceased donor in the MORE Registry. Among them, 133 received grafts from DCD donors and 415 received from DBD donors. The incidence of DGF was 29.4% and 23.5% in the DCD group and the DBD group, respectively (P = .1812), and the incidence of BPAR at 12 months was 9.0% and 9.9% respectively (P = .7713). The 1-year graft loss rate in the DCD group was higher than that in the DBD group (7.5% vs 3.1%, P = .0283), and the 4-year graft loss rate and patient death rate were not significantly different between the 2 groups. ConclusionsThe DCD kidney transplant group had acceptable short-term outcomes and good long-term outcomes as compared with the DBD kidney transplant group.

Association Between Delayed Graft Function and Graft Loss in Donation After Cardiac Death Kidney Transplants-A Paired Kidney Registry Analysis.

Delayed graft function (DGF) is an established complication after donation after cardiac death (DCD) kidney transplants, but the impact of DGF on graft outcomes is uncertain. To minimize donor variability and bias, a paired donor kidney analysis was undertaken where 1 kidney developed DGF and the other did not develop DGF using data from the Australia and New Zealand Dialysis and Transplant Registry. Using paired DCD kidney data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between DGF, graft and patient outcomes between 1994 and 2012 using adjusted Cox regression models. Of the 74 pairs of DCD kidneys followed for a median of 1.9 years (408 person-years), a greater proportion of recipients with DGF had experienced overall graft loss and death-censored graft loss at 3 years compared with those without DGF (14% vs 4%, P = 0.04 and 11% vs 0%, P < 0.01, respectively). Compared with recipients without DGF, the adjusted hazard ratio for overall graft loss at 3 years for recipients with DGF was 4.31 (95% confidence interval [95% CI], 1.13-16.44). The adjusted hazard ratio for acute rejection and all-cause mortality at 3 years in recipients who have experienced DGF were 0.98 (95% CI, 0.96-1.01) and 1.70 (95% CI, 0.36-7.93), respectively, compared with recipients without DGF. Recipients of DCD kidneys with DGF experienced a higher incidence of overall and death-censored graft loss compared with those without DGF. Strategies aim to reduce the risk of DGF could potentially improve graft survival in DCD kidney transplants.

Experiences of rescuing infective arterial hemorrhage and pseudoaneurysm in DCD kidney transplantation

Objective: To summarize experiences of rescuing arterial hemorrhage and pseudoaneurysm caused by infection in donation after cardiac death (DCD) kidney transplantation. Methods: A total of 198 consecutive DCD kidney transplantations between 1 June 2013 and 30 July 2016 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The means of rescuing infective arterial hemorrhage and pseudoaneurysm after operation and their therapeutic effects were summarized. Results: A total of 5 infective arterial hemorrhage, 2 infective pseudoaneurysm with hemorrhage, and 1 infective pseudoaneurysm developed in 198 DCD kidney transplantation recipients with total morbidity of 4.0%, and the morbidity of fungal infection accounted for 2.5%. One case received open surgical therapy. Two cases were treated with endovascular interventional therapy. Five cases received combined treatments of open surgery and endovascular intervention. Selective antibiotics were used based on drug sensitivity test postoperation. The wound was drained, and the drainage was repeatedly cultured to monitor the pathogen till the results turned to negative. Five patients received graft nephrectomy and were restored to hemodialysis. Two patients were successfully rescued with stable graft function. One case died. The mortality of patient was 1/8. Graft loss rate was 5/8. Both patients with stable graft function were mainly treated by intervention. Conclusions: Infective arterial hemorrhage and pseudoaneurysm were primary risk factors causing patient/graft death postoperation in DCD kidney transplantation. Endovascular therapy can be used as an effective rescuing method under the circumstance of infection. The measure allows opportunity of successfully rescuing kidney graft and deserves recommendation.

Clinical analysis of 42 cases of pediatric renal transplantation for donor kidney of children cardiac death organ donation

Objective To explore the pediatric kidney transplantation renal recovery and survival status of the donation after cardiac death (DCD) donor. Methods A retrospective analysis of 42 cases of DCD kidney transplantation for pediatric renal receptors was done by collecting clinical data. 24 cases of donor had an average age (7.2±8.4) years (25days-16years), body weight (25.8±16.7) kg (2.5-41.6)kg. 42 cases of receptors had a mean age (10.8±3.5)years (4-18)years, body weight (31.2±12.6) kg (10.7-48)kg. Data including serum creatinine, uric acid and renal changes in the size, the occurrence of adverse events were recorded. Results At one year post-operation, The preoperative serum creatinine from (784.7±231.5) μmol/L was down to surgery (63.2±22.1) μmol/L (P<0.05); the graft length was increased from preoperative (52.5±20.7) mm postoperatively (105.8±19.5) mm (P<0.05). Acute rejection was occurred in 4 (9.5%). By daily administered sequentially administered methylprednisolone 0.25g, 0.12g, 0.08g shock treatment for 3 days, three case of shock were reversal and one patient with renal allograft ruptured and removed. Two cases got renal dysfunction at 4 and 6 months after operation, then died of severe hepatitis and multiple organ failure. Pulmonary infection in 4 cases (9.5%), after given the sensitive antibiotics, two cases were cured and two cases got respiratory failure and death. Follow-up one year, four cases were death for severe hepatitis and multiple organ failure, five cases had renal dysfunction. The human/kidney survival rates were 90.5%/88.1%. Conclusion DCD donor child for pediatric renal transplantation offers a good donor kidney. Key words: Child; Donation after cardiac death; Donors; Kidney transplantation

The effect of donor/recipient body surface area ratio on the selection of potential recipient after DCD renal transplantation

Objective To evaluate the effect of donor/recipient(D/R)body surface area(BSA)ratio on the recovery of renal transplantation from donation after cardiac death(DCD) and guidance of potential recipients. Methods The clinical data of 127 recipients with the functioned graft and 69 donors of DCD kidney transplantation performed in our hospital from July 2012 to March 2015 were retrospectively analyzed.69 donors contained 58 males and 11 females, with the mean age of (41.9±13.5) years(ranged from 18 to 66 years) and the mean BSA of (1.77±0.15) m2(ranged from 1.25 to 2.05 m2); 127 recipients contained 100 males and 27 females, with the mean age of (37.7±9.3) years(ranged from 18 to 58 years) and the mean BSA of (1.70±0.16) m2(ranged from 1.34 to 2.21 m2). According to D/R BSA ratio, recipients were divided into D/R BSA ratio≤1.0 group(39 recipients)and D/R BSA ratio>1.0 group(88 recipients). According to donor eGFR, recipients were divided into four subgroups further: Group A [D/R BSA ratio≤1.0 group, eGFR≤40 ml/(min·1.73 m2)]with 5 recipients, group B [D/R BSA ratio ≤1.0, eGFR >40 ml/(min·1.73 m2)]with 34 recipients, group C[D/R BSA ratio> 1.0 group, eGFR≤40 ml/(min·1.73 m2)]with 16 recipients, Group D[D/R BSA ratio> 1.0 group, eGFR> 40 ml/(min·1.73 m2)]with 72 recipients; In addition, two recipients who received the kidneys from the same donor and whose D/R BSA ratio difference was more than 10% were divided into high BSA ratio group (27 recipients)and low BSA ratio group(27 recipients). The serum creatinine(SCr) and graft eGFR of the recipients were recorded at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 12 months post-operation respectively. Results Recipients in D/R BSA ratio>1.0 group showed lower SCr and higher graft eGFR at each time point post-transplantation as compared to D/R BSA ratio≤1.0 group, and the difference was statistically significant (P 0.05); Recipients in high BSA ratio group showed slightly lower SCr as compared to low BSA ratio group within 3 months post-operation, but the difference was not statistically significant (P>0.05); 3 months later, Scr in high BSA ratio group was lower than low BSA ratio group, and the difference was statistically significant (P 0.05); 1 month later, eGFR in high BSA ratio group was higher than low BSA ratio group, and the difference was statistically significant (P<0.05). Conclusions D/R BSA ratio should be used as an important reference index to choose potential recipients. To potential marginal donors with older age or inferior renal function, the recovery of renal function after operation is relatively better when the D/R BSA ratio is higher than 1.0. When kidneys of the same donor are accepted, recipients with higher D/R BSA ratio show a more ideal long-term recovery of renal function and achieve a better postoperative effect. Key words: Donation after citizen death; Body surface area; Renal transplantation

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.

Massive hemorrhage caused by fungal infections after donation-after-cardiac-death kidney transplantation: clinical features, prevention and treatment experience

To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac-death (DCD) kidney transplantation. A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized. Ninety-one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group. Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation.

Basiliximab induction in kidney transplantation with donation after cardiac death donors.

Basiliximab is a monoclonal antibody that binds to the α-chain of the interleukin (IL)-2 receptor. It is used as induction therapy in kidney transplantation. The objective of the present study was to evaluate induction therapy with single-dose basiliximab (Simulect®) in kidney transplantation with donation after cardiac death (DCD) donors. A total of 33 DCD kidney transplants were performed between December 2010 and July 2013 in patients who received single-dose basiliximab (20 mg) as induction therapy. The maintenance immunosuppression included calcineurin inhibitor (cyclosporine A or tacrolimus), mycophenolate mofetil and corticosteroids. The follow-up time was 1 year. The mean ages of the DCD donors and recipients were 29.3 and 41.1 years, respectively. Within the 1-year follow-up, the overall incidence of acute rejection was 9.1%. There were 10 cases of delayed graft function among the recipients. Mean serum creatinine values at 1 week and at 1, 3, 6, 9 and 12 months post-transplantation were 257.6, 238.2, 194.5, 159.3, 137.9 and 110.8 µmol/l, respectively, with a favorable trend to allograft function recovery over time. The 1-year patient and graft survival rates were 96.9 and 90.9%, respectively, with an infection rate of 24.2%. Increased alanine aminotransferase/aspartate transaminase levels in only 2 patients were considered to be associated with basiliximab. This experience with single-dose basiliximab for induction therapy in DCD kidney transplantation showed that favorable clinical outcomes were achieved in terms of graft survival and function within 1 year.

Hypothermic Machine Perfusion in DCD Kidney Transplantation: A Single Center Experience

Introduction: Donation after cardiac death (DCD) began in 2011 after the program hosted by the First Affiliated Hospital of Sun Yat-sen University in China. The aim of this study is to report on our experience regarding the method of preserving donated kidneys for DCD kidney transplantation. Material and Methods: A total of 37 donors and 73 primary kidney transplant recipients during the period 2011-2014 in the Urology Center of the First Hospital of Jilin University were enrolled in the study. Recipients were assigned to traditional static cold storage (SCS) group and hypothermic machine perfusion (HMP) group based on the preservation environment of donated kidneys after organ harvest. Clinical data were collected for each group. Result: The HMP group had a lower rate of delayed graft function (DGF), better postoperative recovery and kidney function compared with that of SCS group. There is no significant difference in postoperative rejection incidence between the 2 groups. Conclusions: DCD kidneys stored by hypothermic machine contribute to a lower rate of DGF and promoted the rehabilitation progress.

Preliminary results of transplantation with kidneys donated after cardiac death: a path of hope for organ transplantation in China.

This article aims to explore the feasibility and effect of kidney transplantation (KT) from donation after cardiac death (DCD) donors in China. From July 2011 to April 2013, 94 DCD kidneys retrieved and transplanted by our centre were reviewed in this largest single-centre cohort study. Patients with and without delayed graft function (DGF) were compared between DCD KT cohorts. Estimated glomerular filtration rate (eGFR), post-operative complications and graft loss at different time points were recorded. Factors related to DGF were examined and analysed. There was no primary non-function (PNF) graft observed from patients. DGF rate was 27.7%; and 1-year overall graft and patient survival rates were 95.7 and 98.9%, respectively. In the first 6 months post-transplantation, eGFR was significantly lower in the DGF group compared with the non-DGF group (46 versus 52 mL/min; P = 0.04); but the difference disappeared thereafter (50 versus 47 mL/min, after 1 year). Despite early DGF and short-term observations, we are pleased to have this opportunity of sharing our initial experience and results, and justifying the continued DCD KT programmes in China.

Outcomes Following Transplantation of ECD and SCD Kidneys After Circulatory Death With or Without Acute Kidney Injury.

Aim: Expanded criteria donors (ECDs) and acute kidney injury (AKI) result in high discard rates for kidneys from deceased donors. In contrast, we have consistently used kidneys from such marginal donors, especially in donation after cardiac death (DCD) donors. The aim of this study is to compare the outcomes in recipients of ECD vs. standard criteria donors (SCD) DCD kidney transplants (KTx) with/without AKI. Methods: One hundred and twenty adult recipients from DCD donors were enrolled in this study. The recipients were divided into four groups according to the type of donor and AKI status as follows: ECD with AKI (Group 1), ECD without AKI (Group 2), SCD with AKI (Group 3), and SCD without AKI (Group 4). The recipients were followed up for an average of 6.3 ± 3.4 years after KTx. Results: Of the 120 DCD grafts, primary non-function was noted in 10 (8%), and 13 (11%) functioned immediately after KTx. The incidence of delayed graft function was 97 (81%). The overall graft survival rates at 1, 5, and 10 years were 88%, 83% and 75%, respectively. The graft survival rate in Group 1 was significantly poorer than that of Groups 3 and 4 (Log-rank test, p < 0.05). The graft survival rate in Group 2 tended to be poorer than that of Groups 3 and 4, but was not significantly different.Figure: No Caption available.In Group 1, the graft survival rates at 1, 5, and 10 years were 77%, 69% and 69%, respectively. A multivariate Cox regression analysis showed that donor age was independently associated with graft outcome. Conclusion: Although the graft survival rate in recipients of ECD kidneys with AKI was inferior to SCD grafts, ECD DCD donors with AKI could be a valuable source of kidneys for KTx with promising long-term outcomes.

Kidneys From DCD Donors Are Underutilized in Pediatric Patients.

Background. In pediatric patients, donation after cardiac death (DCD) organs account for just over 2% of all kidney transplants. It is difficult to definitively ascertain survival of DCD grafts through single center studies when the frequency of DCD transplantation is so low. A comprehensive study of national data is necessary to better define outcomes and utilization of DCD compared to donation after brain death (DBD) kidneys. Methods. SRTR data (April 1994 to September 2013) of 7,318 pediatric kidney-only deceased donor transplant recipients (age<18) were analyzed. Death censored graft survival was defined as the time from transplantation to graft loss or last date of follow-up with a functional graft. Kaplan Meier survival analysis was used to compare graft loss between DCD and DBD kidneys. Lorenz curves and Gini coefficient were used to compare center-level clustering in use of DCD versus DBD kidneys in pediatric recipients across US centers. Results. Graft survival was not statistically significantly different between DCD and DBD organs in pediatric kidney recipients (p=0.88).Figure: No Caption available.There was a slight but not statistically significant difference in the occurrence of delayed graft function (2.9% and 0.7%, p=0.06), however the mean creatinine at discharge following transplantation was higher among those receiving DCD kidneys compared to DBD (2.1 mg/dL and 1.5 mg/dL, p < 0.05). Lorenz curves demonstrate that around 25% of centers in the US performed 100% of DCD kidney transplants in pediatric recipients, in a pattern far more center-clustered than DBD transplants.Figure: No Caption available.Conclusions. DCD kidneys offer comparable outcomes in pediatric kidney transplantation, but only a small number of pediatric transplant centers currently utilize these organs.

Comparison of Kidney Function Between Donation After Cardiac Death and Donation After Brain Death Kidney Transplantation

Kidney graft survival is comparable between donation after cardiac death (DCD) and donation after brain death (DBD) kidney transplantation. However, data concerning kidney function after DCD kidney transplantation are lacking. We retrospectively compared kidney function between 64 DCD and 248 DBD kidney transplant recipients. Graft function was assessed using iothalamate glomerular filtration rate at 1, 4, and 12 months, then annually. The primary endpoint was the composite of death-censored graft loss or two consecutive iothalamate glomerular filtration rates less than 50 mL/min/1.73 m² occurring within 5 years from transplantation. Secondary endpoints included death and graft loss or death. Of the 312 patients, 102 (33%) experienced the primary endpoint, 78 (25%) experienced graft loss or death, and 44 (14%) died. In multivariable Cox regression analysis, there was no difference between DCD and DBD recipients regarding the primary endpoint (relative risk [RR], 1.16; P=0.59), death (RR, 0.97; P=0.94), or graft loss or death (RR, 1.09; P=0.79). In the subgroup of 64 DCD recipients, each 10-year increase in donor age was associated with increased risk of the primary endpoint (RR, 1.51; P=0.027) with the highest risk observed for donors older than 45 years (RR, 4.81; P=0.001). Delayed graft function affected 45% of the DCD recipients but had no impact on kidney function, graft survival, or patient survival. Posttransplantation kidney function is comparable between DCD and DBD kidney transplantations. In the subgroup of DCD recipients, kidneys from donors older than 45 years may be associated with a higher risk of poor kidney function; however, this finding requires validation in a larger patient group.

Kidney Transplantation From Donors After Cardiac Death: An Initial Report of 71 Cases From China

Shortage of deceased donors is a severe problem in recent years in China especially in a culture in which brain death criteria is not widely accepted. Donation after cardiac death (DCD) has been reported to expand the donor pool despite higher rates of primary nonfunction (PNF) and delayed graft function (DGF) after transplantation. We collected 71 DCD kidney transplants performed at our hospital between February, 2007 and June, 2012 with aims to demonstrate the feasibility of DCD donation in China. All patients were followed up, and postoperative complications and graft loss were recorded. The PNF rate was 2.8%, and DGF rate was 28.2%. The 1- and 3-year graft survival was 95.7% and 92.4%. In conclusion, graft survival of DCD kidney transplantation in China is excellent despite of higher rates of PNF and DGF after transplantation.

The Value of Machine Perfusion Biomarker Concentration in DCD Kidney Transplantations

Donation after cardiac death (DCD) increases the number of donor kidneys but is associated with more primary nonfunction (PNF) and delayed graft function (DGF). It has been suggested that biomarkers in the preservation solution of machine perfused kidneys may predict PNF, although evidence is lacking. We analyzed the diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, lactate dehydrogenase (LDH), heart-type fatty acid binding protein, redox-active iron, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin to predict PNF and DGF in 335 DCD kidneys preserved by hypothermic machine perfusion at our center between 1 January 1997 and 1 January 2008. The diagnostic accuracy of these biomarkers to predict PNF was evaluated with the area under the receiver operating characteristics curves. Additionally, the risk of DGF and graft failure was assessed. LDH and IL-18 concentrations were associated with PNF (odds ratio [95% confidence interval], 1.001 [1.000-1.002]; P=0.005 and 1.001 [1.000-1.002]; P=0.003, respectively) in a multivariate analysis; the diagnostic accuracy for PNF was "poor" for all biomarkers but increased to "fair" for redox-active iron and IL-18 in a multivariate analysis (area under the receiver operating characteristics curves, 0.701 and 0.700, respectively). LDH and IL-18 concentrations were associated with DGF; biomarker concentration was not associated with 1-year graft survival. The diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, LDH, heart-type fatty acid binding protein, redox-active iron, IL-18, and neutrophil gelatinase-associated lipocalin to predict viability of DCD kidneys varies from "poor" to "fair". Therefore, DCD kidneys should not be discarded because of high biomarker perfusate concentration.

Does Expanded Criteria Donor Status Modify the Outcomes of Kidney Transplantation From Donors After Cardiac Death?

The outcomes of kidney transplants that simultaneously exhibit donation after cardiac death (DCD) and expanded criteria donor (ECD) characteristics have not been well studied. We examined the outcomes of DCD versus non-DCD kidney transplants as a function of ECD status and the kidney donor risk index (KDRI). A cohort study of 67816 deceased donor kidney transplant recipients (KTR), including 562 ECD/DCD KTR, from January 1, 2000 to December31, 2009 was conducted using the Scientific Registry of Transplant Recipients. In a multivariable Cox proportional hazards model, the modestly increased risk of total graft failure in DCD versus non-DCD KTR was not significantly modified by ECD status (hazard ratio1.07 [95% CI: 1.01, 1.15] for non-ECD vs. 1.21 [95% CI: 1.04, 1.40] for ECD, p for interaction = 0.14).Moreover, the hazard ratios did not significantly vary by KDRI quintiles (p = 0.40). Similar trends were seen for death-censored graft failure and death with graft function. In conclusion, ECD status or higher KDRI score did not appreciably increase the relative hazard of adverse graft and patient outcomes in DCD KTR. These findings suggest that the judicious use of ECD/DCD donor kidneys may be an appropriate strategy to expand the donor pool.

Influence of Delayed Graft Function and Acute Rejection on Outcomes After Kidney Transplantation From Donors After Cardiac Death

Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.

Five-year experience with donation after cardiac death kidney transplantation in a Canadian transplant program: Factors affecting outcomes.

: Donation after cardiac death (DCD) has led to an increase of up to 40% in the number of kidney transplants in some programs. Unfortunately, the increase in warm ischemic time results in higher rates of delayed graft function (DGF). The purpose of our study was to examine our initial 5-year experience with DCD kidney transplantation and to determine the factors involved in early postoperative function and function at 1 year. : This retrospective study included a review of the recipient and donor charts of 63 DCD kidneys retrieved and transplanted by the London Multi-Organ Transplant Program between July 2006 and October 2011. Comparisons were carried out between our early (n=31, July 2006 to January 2009) and our recent experience (n=32, March 2009 to October 2011). DGF and creatinine clearance at 3, 7 and 365 days were examined with regression analyses. : DGF was seen in 65% of transplanted kidneys. Mean creatinine clearance (CrCl) at 1 year was 66.7 mL/min. Low pre-transplant recipient daily urine output was the most statistically significant predictor of DGF in multivariate analysis (p < 0.001). In comparisons between our early and more recent results, improvements were noted in time from asystole to flush (16.0 vs. 12.0 minutes, p = 0.003), while cold ischemic time increased (464 vs. 725 minutes, p = 0.006). Experience contributed to a significant reduction in hospital length of stay (16 vs. 13 days, p = 0.035) and improved early renal function (CrCl at 3 days 7.8 vs. 11.9 mL/min, p = 0.027). The use of machine cold perfusion and higher recipient preoperative daily urine output predicted improved early renal function, while increasing donor age predicted poorer function at 1 year. : Despite early DGF, our results justify the continued transplantation of kidneys from DCD donors.

Five-year experience with donation after cardiac death kidney transplantation in a Canadian transplant program: Factors affecting outcomes

Background: Donation after cardiac death (DCD) has led to an increase of up to 40% in the number of kidney transplants in some programs. Unfortunately, the increase in warm ischemic time results in higher rates of delayed graft function (DGF). The purpose of our study was to examine our initial 5-year experience with DCD kidney transplantation and to determine the factors involved in early postoperative function and function at 1 year.Methods: This retrospective study included a review of the recipient and donor charts of 63 DCD kidneys retrieved and transplanted by the London Multi-Organ Transplant Program between July 2006 and October 2011. Comparisons were carried out between our early (n=31, July 2006 to January 2009) and our recent experience (n=32, March 2009 to October 2011). DGF and creatinine clearance at 3, 7 and 365 days were examined with regression analyses.Results: DGF was seen in 65% of transplanted kidneys. Mean creatinine clearance (CrCl) at 1 year was 66.7 mL/min. Low pre-transplant recipient daily urine output was the most statistically significant predictor of DGF in multivariate analysis (p &lt; 0.001). In comparisons between our early and more recent results, improvements were noted in time from asystole to flush (16.0 vs. 12.0 minutes, p = 0.003), while cold ischemic time increased (464 vs.725 minutes, p = 0.006). Experience contributed to a significant reduction in hospital length of stay (16 vs. 13 days, p = 0.035) and improved early renal function (CrCl at 3 days 7.8 vs. 11.9 mL/min, p = 0.027). The use of machine cold perfusion and higher recipient preoperative daily urine output predicted improved early renal function, while increasing donor age predicted poorer funcion at 1 year.Discussion: Despite early DGF, our results justify the continued transplantation of kidneys from DCD donors.