Comparison of Posttransplant Outcomes in Living Donor Liver Transplantation for Obese and Nonobese Recipients

Background

Although living donor liver transplantation for obese recipients has increased, it has not been determined that posttransplant outcomes in obese recipients are inferior compared with nonobese recipients.

Analysis of Risk Factors for Allograft Outcome Comparing 2 Kidneys From the Same Donor in Separate Recipients

Background

An analysis of 2 kidney transplants from the same donor at the same center enables us to analyze the influence of risk factors on the outcome of the grafts in different recipients.

Conversion to Sirolimus Allows Preservation of Renal Function in Kidney and Kidney-Pancreas Allograft Recipients

The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr_baseline 51.4 vs CCr_6m 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 ± 37 vs. 186.6 ± 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.     

Approach to the Management of Allograft Recipients Following the Detection of Hepatitis B Virus in the Prospective Organ Donor

Hepatitis B virus (HBV) is a highly infectious blood-borne pathogen that can be transmitted by a solid organ allograft and result in substantial morbidity and mortality. Recent advances in the management of HBV infection prompt a reappraisal of the approach to the management of allograft recipients from cadaver donors previously exposed to HBV, because of the on-going shortage of organ donors. This report reviews current knowledge regarding the risk of HBV transmission by an organ from cadaver donors testing positive for markers of HBV infection and makes recommendations for the evaluation, treatment, and surveillance of the allograft recipients.     

活体肝移植术后受体肝脏储备功能和体积变化研究

目的探讨活体肝移植受体围手术期常规肝功能指标、肝脏储备功能和肝脏体积增长动态变化及其与患者近期临床结局的关系。方法收集30例受体术前基本资料,对围手术期常规肝功能指标、吲哚氰绿(ICG)血浆清除率(K)、CT肝体积以及术后近期(3个月内)的并发症情况进行分析。结果供肝重和受体体重比(GRBW)为0.63%～1.43%。受体术中移植肝脏体积为(638±103)ml,术后7、30及90d移植肝脏体积分别增长至(1096±152)ml、(1163±138)ml及(1158±140)ml,均大于术中的体积(P0.001),但术后各时间点肝脏体积间差异均无统计学意义(P0.05)。受体术后3、7、30和90d的KICG值逐渐升高〔(0.177±0.056)/min、(0.183±0.061)/min、(0.200±0.049)/min及(0.209±0.050)/min〕,均高于术前值〔(0.123±0.067)/min〕,差异均有统计学意义(P=0.006,P=0.002,P0.001,P0.001)。以供体术前KICG值(0.228±0.036)/min为基线,受体术后3d和7d的KICG值低于基线值(P=0.004,P=0.015),而术后30d和90d的KICG值已接近基线值(P=0.355,P=0.915)。根据术后14d总胆红素值将受体分为肝功能良好组(n=23)和肝功能不全组(n=7),与肝功能良好组相比,肝功能不全组术后3d的KICG值明显降低(P=0.001)。结论术后7d是活体肝移植受体肝脏体积增长的活跃期;受体肝脏储备功能的恢复要早于体积的恢复。ICG排泄试验可作为活体肝移植术后受体移植肝功能及预后的早期预测指标。     

Inflammatory Cytokines,Endothelial Function,and Chronic Allograft Vasculopathy in Children: An Investigation of the Donor and Recipient Vasculature After Heart Transplantation

Chronic allograft vasculopathy (CAV) limits the lifespan of pediatric heart transplant recipients. We investigated blood markers of inflammation, endothelial dysfunction, and damage to both the native and transplanted vasculature in children after heart transplantation. Serum samples were taken from pediatric heart transplant recipients for markers of inflammation and endothelial activation. The systemic vasculature was investigated using brachial artery flow‐mediated dilatation and carotid artery intima‐medial hyperplasia. CAV was investigated using intravascular ultrasound. Mean intima‐media thickness (mIMT) > 0.5 mm was used to define significant CAV. Forty‐eight children (25 male) aged 8–18 years were enrolled in the study. Patients were a median (interquartile range) 4.1 (2.2–8.7) years after transplant. Patients had increased levels of circulating IL6 (3.86 [2.84–4.95] vs. 1.66 [1.22–2.63] p < 0.0001), vascular cell adhesion molecule 1 (539 [451–621] vs. 402 [342–487] p < 0.001), intracellular adhesion molecule 1 305 (247–346) vs. 256 (224–294) p = 0.002 and thrombomodulin (7.1 [5.5–8.1] vs. 3.57 [3.03–4.71] p < 0.0001) and decreased levels of tumor necrosis factor‐α, E selectin, and P selectin, compared with controls. The systemic vasculature was unaffected. Patients with severe CAV had raised serum von Willebrand factor and decreased serum thrombomodulin. Posttransplant thrombomodulin levels are elevated after transplant but significantly lower in those with mIMT > 0.5 mm. This suggests that subclinical inflammation is present and that natural anticoagulant/thrombomodulin activity is important after transplant.     

Strain-Encoded Cardiac Magnetic Resonance for the Evaluation of Chronic Allograft Vasculopathy in Transplant Recipients

The aim of our study was to investigate the ability of Strain-Encoded magnetic resonance imaging (MRI) to detect cardiac allograft vasculopathy (CAV) in heart transplantation (HTx)-recipients. In consecutive subjects (n = 69), who underwent cardiac catheterization, MRI was performed for quantification of myocardial strain and perfusion reserve. Based on angiographic findings subjects were classified: group A including patients with normal vessels; group B, patients with stenosis <50%; and group C, patients with severe CAV (stenosis ≥ 50%). Significant correlations were observed between myocardial perfusion reserve with peak systolic strain (r =−0.53, p < 0.001) and with mean diastolic strain rate (r = 0.82, p < 0.001). Peak systolic strain and strain rate were significantly reduced only in group C, while mean diastolic strain rate and myocardial perfusion reserve were already reduced in group B and A. Myocardial perfusion reserve and mean diastolic strain rate had higher accuracy for the detection of CAV (AUC = 0.95, 95% CI = 0.87–0.99 and AUC = 0.93, 95% CI = 0.84–0.98, respectively) and followed peak systolic strain and strain rate (AUC = 0.80, 95% CI = 0.69–0.89 and AUC = 0.78, 95% CI = 0.67–0.87, respectively). Besides the quantification of myocardial perfusion, the estimation of the diastolic strain rate is a useful parameter for CAV assessment. In combination with the clinical evaluation, these parameters may be effective tools for the routine surveillance of HTx-recipients.     

Comprehensive Analysis of Donor Factors for Allograft Survival in Living Kidney Transplantation: A Single-Center Study in Japan

BackgroundVarious donor characteristics have been reported as predictive factors for graft survival in kidney transplantations. The living kidney donor profile index (LKDPI) was established in 2016 to evaluate the quality of living donor kidneys. Herein, we verified whether the index score was associated with graft survival and analyzed various donor factors to identify predictors of graft survival in living donor kidney transplantations.MethodsThis retrospective study included 130 patients who received a living donor kidney between 2006 and 2019 at our hospital. Clinical and laboratory data were obtained from the medical records. Living donor kidneys were categorized into 3 groups by LKDPI score, and the death-censored graft survival and predictors of graft survival were evaluated.ResultsThe median LKDPI score was 35 (IQR: 17-53). The index scores of the living donor kidneys in this study were higher than in previous studies. The groups with the highest scores (LKDPI >40) had significantly shorter death-censored graft survival compared with the group with the lowest scores (LKDPI <20; hazard ratio = 4.0, P = .005). There were no significant differences between the group with the middle scores (LKDPI, 20-40) and the other 2 groups. Donor/recipient weight ratio <0.9, ABO incompatibility, and 2 HLA-DR mismatches were identified as independent predictive factors for shorter graft survival.ConclusionThe LKDPI was correlated with death-censored graft survival in this study. However, more studies are required to establish a modified index that is more accurate for Japanese patients.     

Living Donor Liver Transplantation: Usefulness of Hemostatic and Prothrombotic Screening in Potential Donors

Bleeding and thrombosis are serious complications of living donor liver transplantation (LDLT). The aim of this paper was to describe the results of a screening for coagulation disorders, including for thrombophilic factors, in potential living liver graft donors and to evaluate thrombotic and bleeding events in donors and recipients, during and after the procedure. From January 2001 to January 2007, 41 LDLTs were performed at our institution. We performed systematic screening for bleeding or prothrombotic states among 188 potential donors, 38 (20.2%) of whom showed at least one abnormality. We rejected potential donors with factor V Leiden, prothrombin mutation G20210A, and deficiencies in anticoagulant proteins (protein C, protein S, and antithrombin) or coagulation factors. Bleeding and thrombotic events in donors and recipients of the 41 LDLTs were evaluated during 7 days to 70 months follow-up. No major bleeding events were detected in the donors. Neither donor nor recipient experienced venous thrombosis or pulmonary embolism. Among all recipients, six suffered hepatic artery thrombosis including five in the first month probably related to surgery. Deep venous thrombosis and pulmonary embolism are well-known complications of hepatic surgery; Prothrombotic abnormalities in the donor can be transmitted to the recipient, leading to increased risk of serious postoperative events. Although the cost-effectiveness is not definitely established, we recommend systematic screening for hemostatic and prothrombotic disorders to prevent more morbidity of a procedure that already has high risks of bleeding and thrombosis.     

Donor Hemosiderosis Does Not Affect Liver Function and Regeneration in the Setting of Living Donor Liver Transplantation

Living donor liver transplantation (LDLT) demands a careful assessment of abnormal findings discovered during the evaluation process to determine if there will be any potential risks to the donor or recipient. Varying degrees of elevated hepatic iron levels are not uncommonly seen in otherwise healthy individuals. We questioned whether mild expression of hemosiderin deposition presents a safety concern when considering outcomes of living donation for both the donor and the recipient. We report on three LDLT patients who were found to have low‐ to moderate‐grade hemosiderin deposition on liver biopsy. All other aspects of their evaluation proved satisfactory, and the decision was made to proceed with donation. There were no significant complications in the donors, and all demonstrated complete normalization of liver function postoperatively, with appropriate parenchymal regeneration. The recipients also had unremarkable postoperative recovery. We conclude that these individuals can be considered as potential donors after careful evaluation.     

Outcome of Transplantation in Renal Allograft Recipients From Cadaveric Donors With Standard and Expanded Criteria: A Single-Center Experience

IntroductionThe increasing number of patients requiring kidney transplantation and the lack of available organs has led to the utilization of kidneys from expanded criteria donors (ECD).AimThe comparison of the clinical outcome of renal transplantation, performed in a single center, between allograft recipients from standard (SCD) and expanded criteria donors (ECD).Patients and MethodsData from 215 cadaveric renal transplantations performed during a 16 year period at the University Hospital of Patras were retrospectively studied. Donors' and recipients' characteristics (gender, age, history of hypertension and diabetes mellitus, cold ischemia time, post-transplant and long term graft function) were analyzed.ResultsGrafts from donors with expanded criteria (ECD, n = 53) were allocated to older recipients whereas grafts from donors with standard criteria (SCD, n = 162) were allocated to younger recipients. The mean cold ischemia time was 1,146 min and was similar between the two groups of patients. Patients' survival rates were similar between allograft recipients from SCD and ECD up to the 5^th post-transplant year of follow-up. Graft survival was significantly better in allograft recipients from SCD during a 5-year follow-up period. A significantly lower eGFR was noted in allograft recipients from ECD in comparison to those from SCD throughout the observation period. Cold ischemia time was positively correlated to the development of DGF, while patients with DGF had significantly worse graft function throughout the observation period.ConclusionPatient survival from ECD is comparable to that from SCD but graft survival is significantly lower. However, since renal function of recipients from ECD is adequate for long term period, grafts from ECD should be used in older patients.     

Brain Death and Its Influence on the Lungs of the Donor: How Is It Prevented?

The need for lung grafts is currently greater than ever. Unfortunately, the availability of grafts is insufficient for this demand. So we are forced to request organs for transplantation in the “waste bin.” One possible solution to this problem may be the use of grafts from brain-dead patients. Sadly brain death is followed by devastating hemodynamic, inflammatory, and neurohumoral reactions in the potential donor which not only inflict direct damage, but also induce activation of the immune system which can cause rejection or even graft failure. Therefore, various groups have examined measures to prevent this outcome. In this review, we attempt to reconstruct the events that follow brain death, suggesting an algorithm to prevent a brain-dead patient's lungs from further damage. Finally, we are proposing potential measures of graft's protection of further investigation.     

Preoperative Donor Scores and Postoperative Early Measures of Graft Function: Relevance to the Outcome of Liver Transplantation

Background

Several donor and recipient parameters play a role in the determination of post-liver transplant allograft function. The identification of prognostic indices presents great implications for correct allocation of donors and more targeted recipient management. The aim of our review was to detect the role of preoperative scoring systems and early postoperative measures of graft function as predictive factors for the development of graft failure and recipient death.

Methods

We stratified a cohort of 97 patients in two groups according to a 1-year functional (Group A; n = 72) versus non-functional (Group B; n = 25) status of the allograft.

Results

Patients in group B showed higher preoperative Model for End-stage Liver Disease (MELD) values, longer warm ischemia times, reduced bile outputs and increased peak values of transaminases and INR content within the first 3 days after transplantation. Group B showed 48% of patients with initial poor graft function. The parameters which resulted in a significant prediction of graft loss by multivariate analysis were MELD (P = .012); postoperative day 1 serum alanine aminotransferase (ALT) (P < .0001) and day 3 ALT (P = .003). The predictive factors for patient death were postoperative day 1 serum ALT (P < .0001) and day 3 ALT (P = .001).

Conclusions

MELD score was a useful preoperative parameter for the prediction of post-transplant graft survival. Early ALT values predicted both graft and recipient survivals. Minimization of parameters related to their peaks (warm ischemia time) may improve graft and patients survival rates.     

Simultaneous Pancreas and Kidney Transplantation With Concurrent Allograft Nephrectomy for Recipients With Prior Renal Transplants Lost to BK Virus Nephropathy: Two Case Reports

Candidacy for retransplantation after allograft loss due to BK virus-associated nephropathy (BKVN) with or without allograft nephrectomy is controversial. This report describes 2 renal transplant recipients who lost their grafts to BKVN and subsequently underwent simultaneous kidney and pancreas transplantation with allograft nephrectomy.     

Living-Related Versus Deceased Donor Pediatric Liver Transplantation: A Multivariate Analysis of Technical and Immunological Complications in 235 Recipients

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.     

Evaluation of the Efficacy and Safety of Conversion to Sirolimus in 85 Renal Transplant Recipients

Objective

Treatment with sirolimus (SRL) is a potential therapeutic option for renal transplant recipients, especially those who have developed chronic graft nephropathy (CGN) or a neoplasm. Our aim was to analyze the efficacy and safety of conversion to SRL in renal transplant recipients.

Materials and Methods

We undertook a retrospective study of 85 patients converted to SRL, 47% for tumors, 39% for CGN, and 14% for other causes. The follow-up period was 34 months (range, 1-93 months).

Results

Baseline creatinine was 1.8 ± 0.69 mg/dL (1.6 ± 0.59 for tumors and 2.3 ± 0.6 for CGN). At 1 year, the creatinine was the same in both groups: 1.8 mg/dL (P = NS). Graft survival at 12 months was 89% (81% for tumors, 81% for CGN, and 100% for other causes). SRL was withdrawn in 34% of patients: 18% for severe side effects, 7% for patient death, and 9% for graft loss. The serum creatinine and proteinuria were significantly increased among those subjects who returned to dialysis because of CGN compared with those with conserved renal function. Patients who developed pneumonitis showed a lower baseline aMDRD, but no difference in SRL levels. Side effects occurred in 40% of patients, with no difference in renal function, proteinuria, or SRL levels. Renal function showed a significant improvement in the patients who continued SRL (aMDRD 45.7 vs 50.7 mL/min/1.73 m² at 12 months; P = .08), more marked among those who converted due to CGN. Increases were seen in levels of serum lipids, as well as in the percentage of patients treated with statins. Proteinuria increased significantly, as did the percentage of patients treated with ACE inhibitors/ARA2.

Conclusions

Conversion to SRL in patients with CGN was safe when renal function had not undergone marked worsening and there was no proteinuria. Patients who were converted experienced an improvement in renal function.     

The Impact of Meeting Donor Management Goals on the Development of Delayed Graft Function in Kidney Transplant Recipients

Many organ procurement organizations (OPOs) utilize preset critical care endpoints as donor management goals (DMGs) in order to standardize care and improve outcomes. The objective of this study was to determine the impact of meeting DMGs on delayed graft function (DGF) in renal transplant recipients. All eight OPOs of the United Network for Organ Sharing Region 5 prospectively implemented nine DMGs in every donor after neurologic determination of death (DNDD). “DMGs met” was defined a priori as achieving any seven of the nine DMGs and this was recorded at the time of consent for donation to reflect donor hospital ICU management, 12–18 h later, and prior to organ recovery. Multivariable analyses were performed to identify independent predictors of DGF (dialysis in the first week after transplantation) with a p < 0.05. A total of 722 transplanted kidneys from 492 DNDDs were included. A total of 28% developed DGF. DMGs were met at consent in 14%, 12–18 h in 32% and prior to recovery in 38%. DGF was less common when DMGs were met at consent (17% vs. 30%, p = 0.007). Independent predictors of DGF were age, Cr and cold ischemia time, while meeting DMGs at consent was significantly protective. The management of potential organ donors prior to consent affects outcomes and should remain a priority in the intensive care unit.