Outcomes of Delayed Graft Function in Kidney Transplant Recipients Stratified by Histologic Biopsy Findings.

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.

Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.

BACKGROUND: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. METHODS: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. RESULTS: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted ß coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. CONCLUSIONS: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.

Pre-transplant HLA Antibodies and Delayed Graft Function in the Current Era of Kidney Transplantation.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.

Comparison Between Kidney Transplantation After Circulatory Death and After Brain Death: A Monocentric Retrospective Study After 1 Year of Follow-up.

BACKGROUND: Donation after circulatory death (DCD) is a solid resource to widen the kidney donor pool. Italian activity has grown in the last years with encouraging results. Our center has been active in DCD kidney transplantation (KTX) since November 2017, providing 22.5% of Italian DCD donations in 2018. We present a single-center retrospective analysis after a 1-year follow-up comparing DCD and donation after brain death (DBD) KTX outcomes. METHODS: DCD (controlled only) and DBD KTX performed in our center from November 2017 to December 2018 were considered. All DCDs underwent in situ normothermic perfusion with extracorporeal membrane oxygenation, ex situ hypothermic oxygenated perfusion, and renal biopsy prior to allocation. We considered features of donors and recipients, immunosuppressive regimen, delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival (Kaplan-Meier), creatinine, and estimated glomerular filtration rate at 1 year. Mean comparison with a Student t test and with χ2 test for frequencies were elaborated. RESULTS: Twenty-eight DBD, 18 double (64.3%) and 10 single (35.7%), were performed; 7 DCD, 3 double (42.8%) and 4 single (57.2%), were performed. By comparing single and double KTX, no statistically significant difference was found. We recorded 7 DGFs (25%) in DBD and 1 (14.3%) in the DCD group (P > .99) and no PNF. No graft was lost during the first year. One-year estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was, respectively, 62.7 ± 25.3 and 54.71 ± 14.66 mL/min (P = .25). DBD patient survival rate was 92.8%, DCD was 100%, and Kaplan-Meier was not statistically significant (P = .72). CONCLUSIONS: Controlled DCD is a valid resource for KTX, with similar outcomes to DBD. A multidisciplinary donor evaluation, combining clinical, perfusion, and histologic data in the allocation process, allows excellent results.

Outcome of Kidney Transplantation Using Organs From Brain-dead Donors Older Than 75 Years.

PURPOSE: We investigated whether older donor kidneys aged >75 years have acceptable long-term function and if recipients can benefit sufficiently from the transplantation. METHODS: This single-center study retrospectively analyzed patient data from 217 deceased donor kidney transplants performed between 1998 and 2014 as part of the Eurotransplant Senior Program, where the organ donors were ≥65 years old. Depending on donor age, the groups "older donors" (OD; n = 161) and "very old donors" (VOD; n = 56) received transplants from donors aged 65 to 75 years and >75 years, respectively. Donor and recipient clinical characteristics, delayed graft function, estimated glomerular filtration rate, 1-year rejection rate, patient and graft survival, and postoperative complications were investigated. RESULTS: Comparing VOD group vs OD group, the 1-year, 3-year, and 5-year graft survival rates were 80.4% vs 76.4%, 62.5% vs 65.8%, and 42.6% vs 57.3%, respectively. Patient survival rates after 1, 3, and 5 years were 89.3% vs 88.2%, 71.4% vs 78.2%, and 57.5% vs 71.8%, respectively. There were no significant differences between the 2 groups (graft survival P = .107; patient survival P = .126). Kidney graft function after 1, 2, and 3 years was significantly better in the OD group than in the VOD group. No differences were found regarding postoperative complications, rejection rate, and delayed graft function. CONCLUSION: The utilization of selected kidney-grafts from donors >75 years resulted in acceptable outcomes after kidney transplantation and could expand the donor pool. In contrast to the high mortality rate during dialysis, recipients in both groups benefited from transplantation.

The Neglectable Impact of Delayed Graft Function on Long-term Graft Survival in Kidneys Donated After Circulatory Death Associates With Superior Organ Resilience.

OBJECTIVE: To explore putative different impacts of delayed graft function (DGF) on long-term graft survival in kidneys donated after brain death (DBD) and circulatory death (DCD). BACKGROUND: Despite a 3-fold higher incidence of DGF in DCD grafts, large studies show equivalent long-term graft survival for DBD and DCD grafts. This observation implies a differential impact of DGF on DBD and DCD graft survival. The contrasting impact is remarkable and yet unexplained. METHODS: The impact of DGF on DBD and DCD graft survival was evaluated in 6635 kidney transplants performed in The Netherlands. DGF severity and functional recovery dynamics were assessed for 599 kidney transplants performed at the Leiden Transplant Center. Immunohistochemical staining, gene expression profiling, and Ingenuity Pathway Analysis were used to identify differentially activated pathways in DBD and DCD grafts. RESULTS: While DGF severely impacted 10-year graft survival in DBD grafts (HR 1.67; P < 0.001), DGF did not impact graft survival in DCD grafts (HR 1.08; P = 0.63). Shorter dialysis periods and superior posttransplant eGFRs in DBD grafts show that the differential impact was not caused by a more severe DGF phenotype in DBD grafts. Immunohistochemical evaluation indicates that pathways associated with tissue resilience are present in kidney grafts. Molecular evaluation showed selective activation of resilience-associated pathways in DCD grafts. CONCLUSIONS: This study shows an absent impact of DGF on long-term graft survival in DCD kidneys. Molecular evaluation suggests that the differential impact of DGF between DBD and DCD grafts relates to donor-type specific activation of resilience pathways in DCD grafts.

Increased soluble fms-like tyrosine kinase 1 after ischemia reperfusion contributes to adverse clinical outcomes following kidney transplantation.

Renal ischemia reperfusion injury (IRI) adversely affects clinical outcomes following kidney transplantation. Understanding the cellular mechanisms and the changes in gene/protein expression following IRI may help to improve these outcomes. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), a circulating antiangiogenic protein, is increased in the first week following kidney transplantation. We evaluated the casual relationship of elevated sFlt-1 levels with renal microvascular dysfunction following IRI in a longitudinal study of 93 kidney transplant recipients and in several animal models. Transplant recipients with higher sFlt-1 levels had higher odds of delayed graft function, graft rejection, impaired graft function, and death. In a subgroup of 25 participants who underwent kidney biopsy within 4 months of kidney transplantation, peritubular capillary area was lower in those with elevated serum sFtl-1 levels. The administration of recombinant sFlt-1 into rodents resulted in significant structural and functional changes of the renal microvasculature, including reduced peritubular capillary density and intracapillary blood volume, and lead to increased expression of inflammatory genes and increased fibrosis. In a murine model of IRI, the kidney was a site of sFlt-1 production, and systemic neutralization of sFlt-1 preserved peritubular capillary density and alleviated renal fibrosis. Our data indicate that high sFlt-1 levels after IRI play an important role in the pathogenesis of microvascular dysfunction, thereby contributing to adverse clinical outcomes following kidney transplantation.

Outcome after extracorporeal membrane oxygenation-bridged lung retransplants: a single-centre experience.

OBJECTIVES: A lung retransplant has been shown to be a valid option in selected patients with chronic lung allograft dysfunction (CLAD). However, a subgroup of patients may require, in addition to invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) as a bridge to a retransplant. Overall and CLAD-free survival after ECMO-bridged retransplants are compared to first transplants with and without bridging ECMO and to retransplants without bridging ECMO. METHODS: We reported a retrospective, single-institution experience based on a prospective data set of all patients undergoing lung transplants between January 2004 and December 2016 with a mean follow-up of 51 ± 41 months. RESULTS: A total of 230 patients (96 men, 134 women, mean age 47.3 years) had lung transplants: 200 had first transplants without bridging ECMO; 13 had first transplants with bridging ECMO; 11 had retransplants without bridging ECMO; and 6 had retransplants with bridging ECMO. The 3- and 5-year survival rates were 81%/76%, 68%/68%, 69%/46% and 50%/25%, respectively. There was no significant difference in overall survival between those who had first transplants with and without bridging ECMO or retransplants without bridging ECMO. In contrast, patients undergoing ECMO-bridged retransplants had a significantly lower overall survival rate than those with a first transplant without bridging ECMO (P = 0.007). In addition, the post-transplant CLAD-free survival curves varied significantly among the 4 treatment groups (P = 0.041), paralleling overall survival. CONCLUSIONS: Patients requiring ECMO as a bridge to a retransplant had lower overall and CLAD-free survival rates compared to those who had a first transplant with and without bridging ECMO and a retransplant without bridging ECMO.

Kidney Transplantation in Elderly Recipients: A Single-Center Experience.

In this retrospective single-center study we evaluated the outcome after kidney transplant in recipients older than 65 years in terms of patient and graft survival and causes of death. PATIENTS AND METHODS: From 1993 to 2016, 109 consecutive first single kidney transplants in recipients older than 65 years were included. Furthermore, 2 age groups have also been identified (group A, 65-70 years old vs group B, 71-76 years old). Donor and recipient characteristics were analyzed. Other parameters were cold and warm ischemia times, delayed graft function, biopsy-proven acute rejection, and causes of death. Induction immunosuppressive therapy was performed with basiliximab or thymoglobulin. Baseline triple immunosuppression included calcineurin inhibitor, antimetabolite, and steroids. The results of preimplantation biopsies, which were performed in all expanded criteria donors were analyzed and graded according to Karpinski 2009 classification. RESULTS: Overall mortality was 39.4%: 23.2% women and 76.8% men. Causes of death were infections in 42%, tumors in 23%, cardiovascular disease in 14%, cerebrovascular disease in 7%, and unknown in 14%. The most common cause of death in men was infections (52%), and the most common cause in women was tumors (55%). At 1, 3, 5, and 10 years, overall patient survival was 89%, 84%, 72%, and 45%, and overall graft survival was 100%, 97%, 89%, and 84%, respectively. Patient and graft survival were statistically different between group A vs group B (P = .006 and P = .02, respectively). At univariate analysis significant risk factors for increased mortality were age, delayed graft function, and cold ischemia time. At multivariate analysis, delayed graft function maintained statistical significance. CONCLUSIONS: Kidney transplantation in patients older than 65 years is safe, feasible, and has good graft survival. Mortality is statistically significant in patients older than 71 years, despite a persistent low graft loss.

Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD.

Slow immune reconstitution is a major obstacle to the successful use of allogeneic hematopoietic cell transplantation (allo-HCT). As matched sibling donor (MSD) allo-HCT is regarded as the gold standard, we evaluated the pace of immune reconstitution in 157 adult recipients of reduced-intensity conditioning followed by MSD peripheral blood HCT (n = 68) and compared these to recipients of umbilical cord blood (UCB; n = 89). At day 28, UCB recipients had fewer natural killer (NK) cells than MSD recipients, but thereafter, NK cell numbers (and their subsets) were higher in UCB recipients. During the first 6 months to 1 year after transplant, UCB recipients had slower T-cell subset recovery, with lower numbers of CD3+, CD8+, CD8+ naive, CD4+ naive, CD4+ effector memory T, regulatory T, and CD3+CD56+ T cells than MSD recipients. Notably, B-cell numbers were higher in UCB recipients from day 60 to 1 year. Bacterial and viral infections were more frequent in UCB recipients, yet donor type had no influence on treatment-related mortality or survival. Considering all patients at day 28, lower numbers of total CD4+ T cells and naive CD4+ T cells were significantly associated with increased infection risk, treatment-related mortality, and chronic graft-versus-host disease (GVHD). Patients with these characteristics may benefit from enhanced or prolonged infection surveillance and prophylaxis as well as immune reconstitution-accelerating strategies.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

BACKGROUND: We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. METHODS: Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. RESULTS: We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. CONCLUSIONS: Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Association Between Overweight and Renal Transplant Outcomes: A Meta-Analysis.

OBJECTIVES: As the demand for kidney transplant allografts has increased, many centers are expanding the upper limit of acceptable body mass index for kidney donors. However, obesity is a risk factor for developing renal disease. Our goal was to quantify body mass index trends in donor nephrectomy patients and to institute nutrition counseling to promote sustainable weight loss to reduce the risk of metabolic syndrome-derived renal dysfunction. MATERIALS AND METHODS: Ninety patients who underwent donor nephrectomy between 2007 and 2012 consented to having height and weight data collected at multiple time points. After data collection, each patient underwent a standardized nutrition counseling session. One year later, body mass index was reassessed. RESULTS: Preoperatively, 52% of the patients were overweight or obese. The percentage of overweight and obese patients remained stable for 2 years after surgery. However, at 3, 4, and 5 years after surgery, these rates increased to 59%, 69%, and 91%. Each patient was counseled about obesity-related comorbidities and provided information about lifestyle modification. One year later, 94% of previously overweight patients and 82% of previously obese patients had a decrease in mean body mass index from 27.2 ± 4.0 kg/m2 to 25.1 ± 3.6 kg/m2. CONCLUSIONS: Living-donor nephrectomy patients are at risk of developing obesity, similar to the adult population. Nutrition counseling may be beneficial to help normalize body mass index in patients who have become overweight or obese to potentially prevent obesity-related comorbidities. All patients were evaluated by a nutrition specialist after surgery to review our donor nephrectomy nutrition brochure. Body mass index monitoring and primary care follow-up appear to be appropriate surveillance methods.

Management of the obese kidney transplant candidate.

Obesity is an increasingly common condition that can exclude end stage renal disease patients from consideration of kidney transplantation. The optimal management of obese transplant candidates is uncertain, especially the use of pharmacologic therapies or bariatric surgery. We review the rationale to consider transplantation in obese patients, the impact of obesity on access to kidney transplantation, the evidence for obese patients to lose weight loss prior to kidney transplantation, peri-operative management considerations and specific weight loss strategies prior to transplantation. We also propose an algorithm for pre-transplant management of obese transplant candidates that takes into consideration the patient's peri-operative risk, the anticipated time to transplantation and the risk of delayed graft function. Finally, we suggest a number of areas in need of further research as well as health policy considerations to improve the care of obese kidney transplant candidates.

Graft Survival in Patients Who Received Second Allograft, Comparing Those With or Without Previous Failed Allograft Nephrectomy.

INTRODUCTION: Nowadays, the number of patients receiving a second graft is growing, and the management of failed grafts is still controversial. OBJECTIVE: Our objective was to analyze the influence of graft nephrectomy on graft and patient survival. MATERIALS AND METHODS: We retrospectively evaluated the demographic features and graft outcomes of 63 recipients who received second allografts between August 1985 and April 2013. They were divided into two groups: group A, those who underwent nephrectomy of failed graft (n = 21, 33.3%), and group B, those whose failed graft was retained (n = 42, 66.6%). χ2 and Mann-Whitney U tests were used to compare demographic characteristics and graft features in both groups. Kaplan-Meier test was used to analyze graft and patient survival. Finally, univariate and multivariate analysis was done using Cox regression. RESULTS: Demographic characteristics of donor and receptors were similar in both groups. Overall panel-reactive antibody (P = .040) showed statistically significant differences between groups (72.0 ± 25.3 in group A and 54.8 ± 30.0 in group B). Hemodialysis duration was longer in group A (P = .023, 112.2 ± 72.8 vs 70.9 ± 66.9 months). The percentage of patients who had delayed graft function was higher in group A (58.8% vs 27.3%, P = .029). Kaplan-Meier test found no differences between groups (P = .344); group A, 107.4 months (95% confidence interval [CI] 74.0 to 140.8) and group B, 82.7 months (95% CI 62.5 to 102.8). We found no differences in terms of patient survival (P = .798) with the Kaplan-Meier test. In group A, patient survival was 164.5 months (CI 137.7 to 191.31) and in group B, 152.0 months (95% CI 125.5 to 178.5). CONCLUSIONS: Failed graft nephrectomy did not show a negative impact on graft and patient survival.

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

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

Waiting Time Between Failure of First Graft and Second Kidney Transplant and Graft and Patient Survival.

BACKGROUND: The number of patients with end-stage renal disease being relisted for a second kidney transplant is increasing worldwide. The aim of this study was to determine the relationship between waiting time for a second transplant and outcomes after that second transplant. METHODS: Using Australia and New Zealand Dialysis and Transplant registry, patients who have received second kidney transplants between 1997 and 2009 were included. The associations between waiting time, defined as duration of dialysis between first allograft failure and second transplantation, and clinical outcomes including acute rejection, graft and patient survival were examined using adjusted logistic and Cox regression models. RESULTS: Of the 911 recipients, the median follow-up time was 4.7 years resulting in 4825 person-years of follow-up. Increasing waiting time before second transplants was associated with an increased risk of early acute rejection occurring within the first 6 months after transplant (adjusted odds ratio, 1.11; 95% confidence interval [95% CI], 1.06-1.16; P < 0.001), severe vascular and/or humoral rejection (adjusted odds ratio, 1.06; 95% CI, 1.01-1.11; P = 0.011), overall graft failure (adjusted hazard ratio [HR], 1.06; 95% CI, 1.02-1.10; P = 0.001), all-cause mortality (adjusted HR, 1.13; 95% CI, 1.07-1.19; P < 0.001), and death with a functioning graft (adjusted HR, 1.12; 95% CI, 1.06-1.18; P < 0.001), independent of donor, recipient, and immunological factors. CONCLUSIONS: Prolonged waiting time for a second transplant was associated with inferior patient and graft outcomes.

Influence of Factors Associated With the Deceased-Donor on Kidney Transplant Outcomes.

OBJECTIVES: We analyzed different donor characteristics to determine those that significantly affect patient and graft outcomes after kidney transplant. MATERIALS AND METHODS: We conducted a retrospective analysis of patients who had received kidney transplants at our institution between 1990 and 2011 from deceased-donors. We tracked these patients until the end of 2014. Using univariate and multivariate analyses, we analyzed the following outcomes: patient status, graft status, chronic allograft nephropathy, and delayed graft function. RESULTS: In 342 recipients, univariate analysis revealed donor-associated predictors of transplant outcomes. Recipients of kidneys from older donors showed longer time to creatinine normalization (P = .047). We found a partial correlation between donor diagnosis and the number of dialyses after surgery (excluding the effect of donor age), with patients receiving kidneys from donors who had cerebrovascular events having higher risk of delayed graft function (P = .03). Donors with shorter stays in intensive care units resulted in longer graft survival (P = .02), and vasopressor use by donors was associated with delayed graft function in recipients (P = .018). Low serum sodium levels in donors predicted worse survival of recipients and transplants (P = .015 and P = .048). The number of hemodialysis procedures after transplant was correlated with the donors ' creatinine level (P = .027). Insufficient daily dieresis of donor predicted worse graft survival (P = .04). Correlation analysis showed that a higher PCO2 level in donors was significantly associated with longer creatinine normalization time after kidney transplant (P = .001). Cox regression analysis detected 2 significant independent predictors of graft outcomes: duration of perfusion of donor kidney (P = .016) and length of intensive care unit stay of donor (P = .032), with improved prognosis associated with longer perfusion time and shorter time in intensive care unit. CONCLUSIONS: The kidney donor has a direct effect on patient life expectancy.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction / Ampliando o pool de doadores de rim: utilização de órgãos com disfunção renal aguda

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction.

RESUMO Diante da escassez de órgãos para transplante, algumas estratégias têm sido adotadas pela comunidade transplantadora, no sentido de ampliar a oferta de órgãos. Uma delas é a utilização de rins de doadores com critérios expandidos, ou seja, doadores com idade >60 anos ou entre 50 e 59 anos, e que atendem a dois ou mais dos seguintes critérios: história de hipertensão, creatinina sérica terminal >1,5mg/dL e acidente vascular cerebral como causa de morte do doador. Nesta revisão, foi dada ênfase à utilização de doadores com disfunção renal aguda, condição considerada por muitos uma contraindicação para a aceitação de órgãos e, portanto, uma das principais causas de descarte de órgãos. Desde que sejam doadores bem selecionados e que não tenham doença renal crônica, como hipertensão ou diabetes, muitos trabalhos mostraram que o uso de doadores com disfunção renal aguda deve ser encorajado, pois, em geral, a disfunção renal aguda é de caráter reversível. Embora, a maioria dos estudos tenha demonstrado que há uma maior taxa de função retardada do enxerto com a utilização desses órgãos, os resultados de sobrevida do enxerto e do paciente após o transplante são muito semelhantes aos resultados obtidos da utilização de doadores padrão. Os achados clínicos e morfológicos do doador, a utilização da máquina de perfusão e a análise de seus parâmetros, principalmente a resistência intrarrenal, são importantes ferramentas de apoio para tomada de decisão no momento da oferta de órgãos com disfunção renal.

Effects of different trends on the development and outcome of early kidney allograft dysfunction.

OBJECTIVES: To show the effects of different factors on development and outcome of early kidney allograft dysfunction. MATERIALS AND METHODS: Two hundred thirty-one kidney transplant recipients were divided into 2 groups: group 1 (125 patients transplanted from 1999-2004) and group 2 (106 patients transplanted from 2008-2013). Age range was 12 to 62 years (group 1) and 7 to 71 years (group 2). Deceaseddonor transplant was more frequent in group 1 (76.8%), and living-donor transplant in group 2 (68.8%). In group 1, transplant was performed for glomerulonephritis or pyelonephritis; in group 2, additional risk factors (18 patients) included diabetes (11 patients), systemic lupus erythematosus (5 patients), amyloidosis (1 patient), and aortic and mitral valve replacement because of bacterial endocarditis (1 patient). In groups 1 and 2, immunosuppression after transplant included cyclosporine, mycophenolate mofetil, and steroids; patients in group 2 also had induction with anti-CD25 monoclonal antibodies. RESULTS: Primary graft function occurred in 89 patients in group 1 (71.2%) and 83 patients in group 2 (78.3%). Immediately after transplant, delayed graft function included anuria, oliguria, adequate amount of urine, and secondary delayed function (several days of polyuria followed by decreased urine output). Ischemia was a leading cause of delayed renal graft function. Anuria after living-donor transplant was a sign of vascular thrombosis. Rejection was the main cause of secondary delayed graft function, which occurred in only group 1. Survival at 1 year in patients with delayed graft function was 80% in group 1 and 100% in group 2 because of the absence of septic complications. CONCLUSIONS: Despite extension of indications, primary functioning of kidney transplants and patient survival increased. Improved care enables long-term rehabilitation of recipients and expanding criteria for kidney transplant.

Effect of N-acetylcysteine pretreatment of deceased organ donors on renal allograft function: a randomized controlled trial.

BACKGROUND: Antioxidant donor pretreatment is one of the pharmacologic strategy proposed to prevent renal ischemia-reperfusion injuries and delayed graft function (DGF). The aim of the study was to investigate whether a donor pretreatment with N-acetylcysteine (NAC) reduces the incidence of DGF in adult human kidney transplant recipients. METHODS: In this randomized, open-label, monocenter trial, 160 deceased heart-beating donors were allowed to perform 236 renal transplantations from September 2005 to December 2010. Donors were randomized to receive, in a single-blind controlled fashion, 600 mg of intravenous NAC 1 hr before and 2 hr after cerebral angiography performed to confirm brain death. Primary endpoint was DGF defined by the need for at least one dialysis session within the first week or a serum creatinine level greater than 200 µmol/L at day 7 after kidney transplantation. RESULTS: The incidence of DGF was similar between donors pretreated with or without NAC (39/118; 33% vs. 30/118; 25.4%; P = 0.19). Requirement for at least one dialysis session was not different between the NAC and No NAC groups (17/118; 14.4% vs. 14/118; 11.8%, P = 0.56). The two groups had comparable serum creatinine levels, estimated glomerular filtration rates, and daily urine output at days 1, 7, 15, and 30 after kidney transplantation as well as at hospital discharge. No difference in recipient mortality nor in 1-year kidney graft survival was observed. CONCLUSION: Donor pretreatment with NAC does not improve delayed graft function after kidney transplantation.