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 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.

Risk factors for acute kidney injury and 30-day mortality after liver transplantation.

INTRODUCTION: The aim of this study is to evaluate the risk factors for acute kidney injury (AKI) and 30-day mortality after liver transplantation. MATERIAL AND METHODS: This is a retrospective cohort of consecutive adults undergoing orthotopic liver transplantation (OLT) at a referral hospital in Brazil, from January 2013 to January 2014. Risk factors for AKI and death were investigated. RESULTS: A total 134 patients were included, with median age of 56 years. AKI was found in 46.7% of patients in the first 72 h after OLT. Risk factors for AKI were: viral hepatitis (OR 2.9, 95% CI = 1.2-7), warm ischemia time (OR 1.1, 95% CI = 1.01-1.2) and serum lactate (OR 1.3, 95%CI = 1.02-1.89). The length of intensive care unit (ICU) stay was longer in AKI group: 4 (3-7) days vs. 3 (2-4) days (p = 0.001), as well as overall hospitalization stay: 16 (9-26) days vs. 10 (8- 14) days (p = 0.001). The 30-day mortality was 15%. AKI was an independent risk factor for mortality (OR 4.3, 95% CI = 1.3-14.6). MELD-Na ≥ 22 was a predictor for hemodialysis need (OR 8.4, 95%CI = 1.5-46.5). Chronic kidney disease (CKD) was found in 36 patients (56.2% of AKI patients). CONCLUSIONS: Viral hepatitis, longer warm ischemia time and high levels of serum lactate are risk factors for AKI after OLT. AKI is a risk factor for death and can lead to CKD in a high percentage of patients after OLT. A high MELD-Na score is a predictor for hemodialysis need.

The evolving use of higher risk grafts is associated with an increased incidence of acute kidney injury after liver transplantation.

BACKGROUND & AIMS: The growing discrepancy between supply and demand for liver transplantation has necessitated a greater use of higher risk grafts. Donation after Circulatory Death (DCD) liver transplant recipients have an increased frequency of acute kidney injury (AKI). We hypothesised that other higher risk grafts might also impact negatively on renal function. Our aim was to examine the effect of the evolving use of higher risk grafts on the incidence of post liver transplant AKI. METHODS: Single-centre study of 1152 patients undergoing first-single-organ liver transplantation for chronic liver disease 01/2000-12/2011. To assess the impact of the evolution of graft quality over time; donor/graft/recipient variables were compared over three 4-year periods. RESULTS: Pretransplant recipient renal function improved during follow-up (p<0.001), and the median postoperative day-1 (p<0.001), -2 (p<0.001), and -3 (p<0.001) tacrolimus trough levels fell. The proportion of patients receiving a higher risk graft was 31.8% in 2000-2003, 40.9% in 2004-2007, and 59.1% in 2008-2011 (p<0.001). There was a progressive increase in AKI (2000-2003, OR 1.00; 2004-2007, OR 1.43; 2008-2011, OR 2.40, p<0.001). After adjusting for recipient variables increasing recipient warm ischaemic time (p=0.019), DCD transplantation (p<0.001), donor age ≥60 years (p=0.020), and donor body mass index ≥30 kg/m(2) (p<0.001) were independent predictors of AKI. CONCLUSIONS: The increasing use of higher risk liver grafts is associated with an increased incidence of AKI. These findings support the need for therapies that minimise the hepatic ischaemia-reperfusion injury.

In Situ Normothermic Regional Perfusion for Liver Donation From China Category III (Organ Donation After Brain Death Followed by Circulatory Death): A Single-Center Cohort Study.

OBJECTIVES: Organ donation after brain death followed by circulatory death is practiced in China. This study evaluated the application of normothermic regional perfusion to protect the liver grafts from these donors from warm ischemia in a large transplant center in China. MATERIALS AND METHODS: This prospective study involved 19 liver transplants from brain death followed by circulatory death donors that were conducted between December 2014 and June 2017. We evaluated the baseline characteristics of the donors and recipients and compared outcomes of both groups. Graft and recipient survival and postoperative complications were also analyzed. RESULTS: Although the normothermic regional perfusion group consisted of marginal donors with prolonged warm ischemia and recipients with higher Model for End-Stage Liver Disease scores (P < .05), postoperative tests indicated no differences in liverfunction recovery in both groups. Furthermore, total bilirubin decreased significantly faster in the normothermic regional perfusion group than in the control group (P < .05). Both groups showed similar 1-year recipient survival rates. No recipients in the normothermic regional perfusion group had any biliary complications, whereas 2 recipients in the control group developed ischemic cholangiopathy and received invasive treatment during follow-up. CONCLUSIONS: In situ normothermic regional perfusion demonstrated a significant benefit in grafts from brain death followed by circulatory death donors and could potentially increase both the number and quality of donated organs.

Regulated hepatic reperfusion mitigates ischemia-reperfusion injury and improves survival after prolonged liver warm ischemia: a pilot study on a novel concept of organ resuscitation in a large animal model.

BACKGROUND: Ischemia-reperfusion injury (IRI) can occur during hepatic surgery and transplantation. IRI causes hepatic mitochondrial and microcirculatory impairment, resulting in acute liver dysfunction and failure. We proposed a novel strategy of regulated hepatic reperfusion (RHR) to reverse the cellular metabolic deficit that incurred during organ ischemia by using a substrate-enriched, oxygen-saturated, and leukocyte-depleted perfusate delivered under regulated reperfusion pressure, temperature, and pH. We investigate the use of RHR in mitigating IRI after a prolonged period of warm ischemia. METHODS: Using a 2-hour liver warm ischemia swine model, 2 methods of liver reperfusion were compared. The control group (n = 6) received conventional reperfusion with unmodified portal venous blood under unregulated reperfusion pressure, temperature, and pH. The experimental group (n = 6) received RHR. We analyzed the effects of RHR on post-reperfusion hemodynamic changes, liver function, and 7-day animal survival. RESULTS: RHR resulted in 100% survival compared with 50% in the control group (p = 0.05). Post-reperfusion syndrome was not observed in the RHR group, but it occurred in 83% of the control group. RHR resulted in a lesser degree of change from baseline serum alanine aminotransferase levels, aspartate aminotransferase, and lactate dehydrogenase after reperfusion compared with the control group. Histopathologic evaluation showed minimal ischemic changes in the RHR group, whereas a considerable degree of coagulative hepatocellular necrosis was observed in the control group. CONCLUSIONS: Regulated hepatic reperfusion mitigates IRI, facilitates liver function recovery, and improves survival after a prolonged period of hepatic warm ischemia. This novel strategy has potential applicability to clinical hepatic surgery and liver transplantation when marginal grafts are used.

Impact of warm ischemia time on survival after heart transplantation.

BACKGROUND: There is little data available on the specific effects of warm ischemia time (WIT) as opposed to cold ischemia or storage time. With current research endeavors focusing on warm continuous perfusion, storage of donor hearts, and utilization of hearts from non-heart-beating donors, the impact of WIT on outcomes is increasingly relevant. The aim of this study was to analyze our results in cardiac transplantation with specific focus on the impact of WIT. METHODS: A retrospective review of 206 patients who underwent orthotopic heart transplantation at our institution between June 2001 and November 2010 was performed. Donor, recipient, and operative factors were analyzed. The main outcome variables were all cause mortality, survival, and primary graft failure. RESULTS: WIT of >80 minutes was associated with reduced survival compared with a shorter WIT of <60 minutes. Multivariate analysis showed increasing donor age to be the most significant variable associated with increased risk of mortality (hazard ratio 1.04; P = .004) per year of increasing donor age. CONCLUSIONS: This study has demonstrated a reduced survival in heart transplant recipients with increased WIT. This finding may be of particular relevance to potential future heart transplantation using organs procured from non-heart-beating donors.

Deleterious influence of prolonged warm ischemia in living donor kidney transplantation.

BACKGROUND: Recent studies investigating early graft function (EGF) after living donor kidney transplantation (LDKT) identified prolonged warm ischemia time (WIT) as a risk factor for the occurrence of poor EGF. The latter is associated with long-term graft loss; therefore the question arises whether prolonged WIT affects long-term outcomes in LDKT. METHODS: Data were collected on 472 consecutive adult LDKTs. Patients were divided according to the total WIT into 3 groups with short (<30 minutes), intermediate (30-45 minutes), or prolonged (>45 minutes) WIT. RESULTS: Of all patients, 193 (40.9%) experienced short, 249 (52.8%) intermediate, and 30 (6.4%) prolonged WIT. Prolonged WIT was a significant risk factor for the occurrence of poor EGF with an adjusted odds ratio of 4.252 (95% confidence interval [CI), 1.914 -9.447). Long-term graft survival was impaired in patients with prolonged WIT, with an adjusted hazard ratio of 3.163 (95% CI, 1.202-8.321). Multivariate analysis revealed determinants of prolonged WIT, including laparoscopic procurement, recipient overweight, right donor kidney, and multiple renal arteries. CONCLUSION: Prolonged WIT impairs long-term graft survival in LDKT. This finding underlines the need to develop strategies to avoid the occurrence of prolonged WIT in LDKT.

Life-years gained by reducing donor heart ischemic times.

BACKGROUND: Transplantation is limited by the number of available donor organs. Donor organ maintenance systems are a recent technological advance. These systems may increase the number of donor organs that can be used and improve outcomes by decreasing donor organ ischemic time (IT). The purpose of this study was to determine the potential life-years gained if IT in the United Kingdom were decreased for cardiac transplantation. METHODS: Proportional hazards regression and extrapolation of survival rates beyond 20 years posttransplantation were used to estimate the effect of decreasing total IT on survival and the life-years gained over the lifetime of UK heart transplantation patients. RESULTS: Median survival posttransplantation was 10.4 years (95% CI 9.9 to 10.9). For each additional hour of donor organ IT, patients had a 25% increased risk of death after heart transplantation in the first year after transplant, with a 5% increase thereafter (P<0.001). On average, a recipient surviving 10 years posttransplantation could potentially gain 0.4 (95% CI 0.1 to 0.7) life-years if IT was reduced to 1 hr. The longer the IT, the greater the potential life-years to gain; for example, a recipient of an organ that would have had an IT of 6 hr without the use of an organ maintenance system might expect to gain 2.9 life-years (95% CI -0.6 to 6.4) if IT was reduced to 1 hr. CONCLUSIONS: Use of cardiac donor organ maintenance systems has the potential to increase posttransplantation survival.

Heart transplantation for adults with congenital heart disease: analysis of the United network for organ sharing database.

BACKGROUND: Congenital heart disease (CHD) in the adult is an uncommon indication for heart transplantation but has been increasing. We assessed survival and predictors of death after heart transplantation for adults with CHD. METHODS: Adult primary heart transplant recipients (aged > 17 years) reported to the United Network for Organ Sharing (1987 to 2006) were reviewed and categorized by diagnosis of CHD vs other diagnoses. Kaplan-Meier survival analysis and Cox regression modeling were performed. RESULTS: During the study period, 35,334 adults underwent primary heart transplantation, and 689 (2%) had CHD. Adult CHD recipients had longer mean waiting list time (218 vs 195 days; p = 0.004), longer ischemic time (3.5 vs 2.9 hours, p < 0.0001), and were more likely to have pretransplant pulmonary vascular resistance exceeding 4 Woods Units (62% vs 51%, p < 0.0001) vs other recipients. Thirty-day mortality was 16% vs 6% (p < 0.0001), although Kaplan-Meier survival did not differ between groups (p = 0.92) out to 10 years. Ischemic time (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.02 to 1.35; p = 0.02), African American race (HR, 1.9; 95% CI, 1.04 to 3.58; p = 0.03), and pulmonary vascular resistance exceeding 4 Woods Units (HR, 1.5; 95% CI, 1.01 to 2.19; p = 0.04) were predictors of death for adult CHD recipients. CONCLUSIONS: Heart transplantation for adults with CHD is effective and has good long-term prognosis. The 30-day mortality rate is high, but 5- and 10-year survival is not statistically different from patients without CHD.