Donor-Recipient Matching to Optimize the Utility of High Kidney Donor Profile Index Kidneys.

BACKGROUND: In December 2014, the Kidney Donor Profile Index (KDPI) was developed to give more precise information on donor kidney quality. Kidneys with KDPI scores ≥ 85 (K ≥ 85) have been reported to have inferior outcomes to kidneys with KDPI scores < 85. METHODS: After the implementation of the new Kidney Allocation System, we developed a protocol to evaluate K ≥ 85 use. We analyzed the safety and efficacy of our institutional criteria and evaluated post-transplant outcomes. K ≥ 85 recipients were stratified based on their 1-year creatinine and estimated glomerular filtration rates to elucidate characteristics associated with serum creatinine < 1.7 mg/dL or estimated glomerular filtration rates ≤ 45 mL/min/1.73 m2. RESULTS: From December 2014 to December 2019, 304 deceased donor kidney transplants were performed at Hartford Hospital; 58 (19%) were K ≥ 85 with an average KDPI of 91%. There were 4 graft losses; 2 were death censored. Prolonged cold ischemia time and black recipient race were associated with inferior recipient graft function at 1 year. CONCLUSIONS: High KDPI kidney use requires a multifaceted evaluation that takes into account donor and recipient characteristics for an ideal match. We have identified several characteristics that may predict optimal post-transplant kidney function.

The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial.

BACKGROUND: N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. OBJECTIVE: To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. METHODS: Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644). RESULTS: The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively). CONCLUSIONS: N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.

Impact of allograft ischemic time on long-term survival in lung transplantation: a Swedish monocentric study.

Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end-point used was death/Re-LTx assessed by Cox regression and Kaplan-Meier survival. Results: Kaplan-Meier survival for mean IT (min) between subgroups ≤120, 121-240, 241-360 and 361+ showed significant difference for pairwise-comparisons with superior outcome for IT between ≤120 and 240 min. Cox regression analyses for each hour of IT in patients with a limited survival up to 1- and 5-year had a hazard ratio (HR) of 1.119 and 1.063 respectively (p < .05). Conclusions: In LTx, every 2-hour increase of IT is equivalent to an increased mortality of up to 24% within 5 years. LTx with an IT of ≤120 min had a superior survival in both 1- and 5 years in comparison to an IT of up to 360 min. Better application of IT provides a key role in improving LTx outcome.

Prolonged Cold Ischemia Time Offsets the Benefit of Human Leukocyte Antigen Matching in Deceased Donor Kidney Transplant.

BACKGROUND: The consequences of prolonging cold ischemia time (CIT) to facilitate HLA matching in kidney transplantation are not known. METHODS: Patients with a history of kidney transplant in the United States (2000-2016) with 0 HLA mismatch (MM) were categorized based on CIT (< 10; 10 to < 15; 15 to < 20; 20 to < 25; 25 to < 30; and ≥ 30 hours). Time to graft loss was compared for each CIT category to a reference group of individuals with > 0 HLA MM and short CIT (< 10 hours) using a multivariable Cox proportional hazards model. RESULTS: The adjusted risk of graft failure was significantly lower for 0 HLA MM with the shortest CIT compared to the reference group (hazard ratio, 0.82; 95% confidence interval, 0.72-0.94), and this survival advantage persisted to a threshold of < 20 hours of CIT. No survival advantage was observed for the 0 HLA MM group once CIT was > 20 hours. This trend persisted after excluding highly sensitized recipients (panel reactive antibody > 98%) where shipping of organs occurs to achieve more equitable access to organs rather than optimize HLA match. CONCLUSIONS: CIT > 20 hours offsets the benefit of 0 HLA MM in kidney transplantation. This may have implications in organ shipping to facilitate immunologic match.

Interaction Between Ischemic Time and Donor Age on Adult Heart Transplant Outcomes in the Modern Era.

BACKGROUND: We examined the effect of cold ischemic interval on modern outcomes to determine whether advances in patient management have made an impact. METHODS: Using the United Network of Organ Sharing database, we reviewed adult heart transplants between January 2000 and March 2016. We divided donor age into terciles: younger than 18 years, 18 to 33 years, and 34 years and older. Within each tercile, transplants were divided by cold ischemic interval of less than 4 hours, 4 to 6 hours, and more than 6 hours. Survival curves were compared between cold ischemic interval categories within each tercile. Covariate-adjusted and donor age-stratified Cox proportional hazards regression models were used to estimate overall mortality and graft failure hazards ratios. RESULTS: Of 29,192 transplants, no significant differences between cold ischemic interval groups in survival or graft failure were apparent in the group aged younger than 18. For donors older than 18, significant differences were found for survival and graft failure with cold ischemic interval exceeding 4 hours in both univariate and multivariate analysis, and survival functions at different ischemic intervals continued to diverge beyond 1 year. The interaction effect between donor age and cold ischemic interval on overall mortality was not significant when analyzed as continuous variables, however younger donor age appeared to attenuate increase in overall mortality with longer cold ischemic intervals. CONCLUSIONS: Despite advances in perioperative management during the past 30 years, for donors older than 18 years, cold ischemic interval exceeding 4 hours is associated with gradual but significantly diminished survival that persists well beyond the perioperative period. Comparison to historical data suggests that advances in management have somewhat attenuated the hazard associated with longer ischemic times.

Controlled Oxygenated Rewarming of Cold Stored Livers Prior to Transplantation: First Clinical Application of a New Concept.

BACKGROUND: Abrupt temperature shift from hypothermia to normothermia incurred on reperfusion of organ grafts has been delineated as a genuine factor contributing to reperfusion injury and graft dysfunction after transplantation. METHODS: In a first clinical series of 6 patients, cold-stored livers, all allocated by the rescue offer mechanism by Eurotransplant, were subjected to machine-assisted slow controlled oxygenated rewarming (COR) for 90 minutes before engrafting. A historical cohort of 106 patients basically similar in graft (all rescue offer organs) and recipient factors was used for comparison. RESULTS: The clinical benefit of COR was documented by a significant reduction by approximately 50% in peak serum transaminases after transplantation compared to untreated controls (AST 563.5 vs. 1204 U/L, P = 0.023). After 6 months graft survival was 100% in the COR group and 80.9% in the controls (P = 0.24). Respective patient survival was 100% and 84.7% (P = 0.28). Real-time assessment of glucose concentration in the perfusion solution correlated well with postoperative synthetic graft function (r = 0.78; P < 0.02). All treated recipients had normal liver function after a 6-month follow-up and are well and alive. CONCLUSIONS: This first clinical application suggests that controlled graft rewarming after cold storage is a feasible and safe method in clinical praxis and might become an adjunct in organ preservation.

Cardiac Donor Risk Factors Predictive of Short-Term Heart Transplant Recipient Mortality: An Analysis of the United Network for Organ Sharing Database.

INTRODUCTION: To address the shortage of donor hearts for transplantation, there is significant interest in liberalizing donor acceptance criteria. Therefore, the aim of this study was to evaluate cardiac donor characteristics from the United Network for Organ Sharing (UNOS) database to determine their impact on posttransplantation recipient outcomes. METHODS: Adult (≥18 years) patients undergoing heart transplantation from July 1, 2004, to December 31, 2012, in the UNOS Standard Transplant Analysis and Research (STAR) database were reviewed. Patients were stratified by 1-year posttransplantation status; survivors (group S, n = 13,643) and patients who died or underwent cardiac retransplantation at 1-year follow-up (group NS/R = 1785). Thirty-three specific donor variables were collected for each recipient, and independent donor predictors of recipient death or retransplantation at 1 year were determined using multivariable logistic regression analysis. RESULTS: Overall 1-year survival for the entire cohort was 88.4%. Mean donor age was 31.5 ± 11.9 years, and 72% were male. On multivariable logistic regression analysis, donor age >40 years (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.27 to 1.64), graft ischemic time >3 hours (OR 1.32, 1.16 to 1.51), and the use of cardioplegia (OR 1.17, 1.01 to 1.35) or Celsior (OR 1.21, 1.06 to 1.38) preservative solution were significant predictors of recipient death or retransplantation at 1 year posttransplantation. Male donor sex (OR 0.83, 0.74 to 0.93) and the use of antihypertensive agents (OR 0.88, 0.77 to 1.00) or insulin (OR 0.84, 0.76 to 0.94) were protective from adverse outcomes at 1 year. CONCLUSIONS: These data suggest that donors who are older, female, or have a long projected ischemic time pose greater risk to heart transplant recipients in the short term. Additionally, certain components of donor management protocols, including antihypertensive and insulin administration, may be protective to recipients.

Normothermic ex vivo allograft blood perfusion in clinical heart transplantation.

BACKGROUND: Cold ischemia associated with cold static storage is an independent risk factor for primary allograft failure and survival of patients after orthotopic heart transplantation. The effects of normothermic ex vivo allograft blood perfusion on outcomes after orthotopic heart transplantation compared to cold static storage have been studied. METHODS: In this prospective, nonrandomized, single-institutional clinical study, normothermic ex vivo allograft blood perfusion has been performed using an organ care system (OCS) (TransMedics, Andover, MA, USA). Included were consecutive adult transplantation patients who received an orthotopic heart transplantation (oHTx) without a history of any organ transplantation, in the absence of a congenital heart disorder as an underlying disease and not being in need of a combined heart-lung transplantation. Furthermore, patients with fixed pulmonary hypertension, ventilator dependency, chronic renal failure, or panel reactive antibodies >20% and positive T-cell cross-matching were excluded. Inclusion criteria for donor hearts was age of <55 years, systolic blood pressure >85 mmHg at the time of final heart assessment under moderate inotropic support, heart rate of <120 bpm at the time of explantation, and left ventricular ejection fraction >40% assessed by an transcutaneous echo/Doppler study with the absence of gross wall motion abnormalities, absence of left ventricular hypertrophy, and absence of valve abnormalities. Donor hearts which were conventionally cold stored with histidine-tryptophan-ketoglutarate solution (Custodiol; Koehler Chemie, Ansbach, Germany) constituted the control group. The primary end point was the recipients' survival at 30 days and 1 and 2 years after their heart transplantation. Secondary end points were primary and chronic allograft failure, noncardiac complications, and length of hospital stay. RESULTS: Over a 2-year period (January 2006 to July 2008), 159 adult cardiac allografts were transplanted. Twenty-nine were assigned for normothermic ex vivo allograft blood perfusion and 130 for cold static storage with HTK solution. Cumulative survival rates at 30 days and 1 and 2 years were 96%, 89%, and 89%, respectively, whereas in the cold static storage group survival after oHTx was 95%, 81%, and 79%. Primary graft failure was less frequent in the recipients of an oHTx who received a donor heart which had been preserved with normothermic ex vivo allograft blood perfusion using an OCS (6.89% versus 15.3%; P = .20). Episodes of severe acute rejection (23% versus 17.2%; P = .73), as well as, cases of acute renal failure requiring haemodialysis (25.3% versus 10%; P = .05) were more frequent diagnosed among recipients of a donor heart which had been preserved using the cold static storage. The length of hospital stay did not differ (26 days versus 28 days; P = .80) in both groups. CONCLUSIONS: Normothermic ex vivo allograft blood perfusion in adult clinical orthotopic heart transplantation contributes to better outcomes after transplantation in regard to recipient survival, incidence of primary graft dysfunction, and incidence of acute rejection.

Outcomes of adult orthotopic heart transplantation with extended allograft ischemic time.

BACKGROUND: Heart procurement for orthotopic heart transplant (OHT) is limited by the conventional 4 hours of ischemic time (IT). Based on a recent report from our center showing that extended IT from a young donor group is safe, we widened our geographical reach, resulting in almost 40% of our transplants having an IT > 4 hours. METHODS: We retrospectively reviewed records of adult patients who underwent OHT from January 2006 to December 2011. The primary outcome was survival, and secondary outcomes included resource utilization, end-organ dysfunction, and acute cellular rejection. Overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Secondary outcomes were compared with a combination of parametric and nonparametric statistics. RESULTS: A total of 323 patients underwent OHT. There was a significant difference in overall survival between the standard and extended IT groups (85.7% vs 76.4%, P = .03). There were no significant differences between the groups for secondary outcomes except a higher incidence of liver dysfunction in the extended IT group (84.9% vs 73%, P = .01). Further analysis revealed that mortality remains similar if IT is below 4 hours and between 4 and 5 hours, but begins to climb after 5 hours, driving the difference between our standard and extended IT. CONCLUSIONS: Limited donor availability for OHT dictates alternative strategies to enlarge the donor pool. Although there is an overall increasing risk with extended IT beyond 4 hours, it may be possible to safely increase the threshold to at least 5 hours without compromising the outcomes.

Post-reperfusion syndrome during isolated intestinal transplantation: outcome and predictors.

BACKGROUND: Post-reperfusion syndrome (PRS) during isolated intestinal transplantation (ITx) is characterized by decreased systemic blood pressure, systemic vascular resistance, and cardiac output and by a moderate increased pulmonary arterial pressure. We hypothesize that the more severe PRS causes a poorer long-term outcome. The primary aim of this study was to determine the independent clinical predictors of intra-operative PRS, as well as to investigate the link between the severity of PRS and the intra-operative profiles and to examine the post-operative complications and their relationship with transplant outcome. METHODS: This observational study was conducted on 27 patients undergoing isolated ITx in a single adult liver and multivisceral transplantation center. PRS was considered when the mean arterial blood pressure was 30% lower than the pre-unclamping value and lasted for at least one min within 10 min after unclamping. RESULTS AND CONCLUSIONS: The main results of this study can be summarized in two findings: in patients undergoing ITx, the duration of cold ischemia and the pre-operative glomerular filtration rate were independent predictors of PRS and the occurrence of intra-operative PRS was associated with significantly more frequent post-operative renal failure and early post-operative death.

The occurrence of postreperfusion syndrome in orthotopic liver transplantation and its significance in terms of complications and short-term survival.

BACKGROUND: Postreperfusion syndrome (PRS) is a state of significant hemodynamic instability following graft reperfusion during orthotopic liver transplantation (OLTx). We aimed to investigate its risk factors and influence on patient outcome based on a single centre's experience. MATERIAL/METHODS: A retrospective study on a group of 340 patients undergoing OLTx during the period 2005-2008 was conducted. Piggy-back technique was employed in 266 cases and classical technique in 64. PRS was defined as a decrease in mean arterial pressure greater than 30% below the baseline for a minimum of 1 minute during first 5 minutes of the reperfusion. Logistic regression analysis, Mann-Whitney test and 2-sample proportion test were used. P<0.05 was considered statistically significant. RESULTS: PRS occurred in 12.1% of patients. We observed correlations between PRS and the following: longer cold ischemia time, operation with classical technique, longer duration of the operation, higher intraoperative erythrocytal mass (EM) and fresh frozen plasma (FFP) requirements, more frequent early post-operative complications, and lower 1-year survival. Retransplantation was needed nearly twice as often in the PRS-group, but the correlation was not statistically significant (the group was very small, as only 8 patients requested re-OLTx). The study did not demonstrate any statistically significant relationship between PRS and donors' age, recipients' age or sex, duration of the hospitalization, and occurrence of complications after discharge. CONCLUSIONS: PRS occurrence seems to be associated with higher mortality rate and worse patient outcome. The study revealed a few risk factors that could be relevant in the prevention of PRS.

Reducing the ischemic time of donor hearts will decrease morbidity and costs of cardiac transplantations.

With liberalization of donor eligibility criteria, donor hearts are being harvested from remote locations, increasing ischemic times. The aim of this study was to examine the effect of total ischemic time (TIT) on length of stay in the intensive care unit (LOS in ICU) and its economic consequences. The study population included recipients without prior mechanical support undergoing heart transplantation between 1998 and 2008 at a single institution. The mean age of the 72 recipients (56 men, 16 women) was 50.6 years (range 15-68 years) and the mean donor age was 41.5 years (range 11-61 years). The median TIT was 181.2 min (range 107-243) and median LOS in ICU was 11.5 days (range 3-107 days). There was a statistically significant linear relationship between TIT and LOS in ICU r(72)=0.317, P=0.004. Each 5 min and 38 s of TIT equated to one more day in ICU. An ischemic time >180 min was associated with higher LOS in ICU, renal failure, and a more frequent use of nitric oxide in our cohort. For longer distance harvesting, the reduction of TIT by the fastest possible transport (learjet, helicopter) would have economic advantages with regards to the high cost of treatment in ICU.

[Risk factors for orthotopic liver transplantation failure in Rio Grande do Sul, Brazil]. / Fatores de risco para a falência do transplante ortotópico de fígado no Rio Grande do Sul, Brasil.

Risk factors for failure of liver transplantation from cadaveric donors were investigated in this retrospective study using data from medical records of patients in Rio Grande do Sul, Brazil, who were submitted to liver transplantation for the first time from January 1999 to July 2003 and were over 15 years of age at the time of surgery. Some 13% of failures occurred in the first month, 11% from 2 to 12 months, and 5% after 12 months; 88% of failures resulted in death and 12% in retransplantation. In the multivariate models, rate ratios for failure were higher for total family income less than 10 times the minimum wage, recipient's age > 45 years, non-whites, high clinical risk, and donor's age > or = 56 years. Female gender showed an effect in the unadjusted model only. Special attention to patients at increased risk, with income support for those with low family income, and early diagnosis of the need for transplantation may improve the success of liver transplantation.