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Background: Adequate kidney donor management after donation is increasingly emphasized due to concerns of renal function impairment after nephrectomy with increasing life expectancy. In this study, the clinical impact of a protocolized kidney donor follow-up system by nephrologists was evaluated., Methods: A total of 427 living kidney donors underwent nephrectomy from January 2010 to December 2014 and were followed for at least 2 years at the Samsung Medical Center. Donors were followed-up by nephrologists after the establishment of a donor clinic with systemized protocols in January 2013. The primary outcomes were incidence of post-donation low estimated glomerular filtration rate (eGFR) and renal function adaptability. Secondary outcomes were changes in compliance and incidence of hyperuricemia and microalbuminuria., Results: The patients were divided into 2 groups according to the time of nephrectomy: the pre-donor clinic period (n = 182) and the donor clinic period (n = 172). Preoperative eGFR in patients in the pre-donor clinic period was higher than that in patients in the donor clinic period. After donation, poor renal adaptation was less frequent in the donor clinic period compared to the pre-donor clinic period. Low eGFR tended to be less common during the donor clinic period. Shorter mean outpatient clinic visit intervals with more visits within 6 months after donation and earlier detection of de novo hyperuricemia were found during the donor clinic period., Conclusion: A protocolized donor clinic run by nephrologists may improve post-nephrectomy renal outcomes and compliance and facilitate better management of potential risk factors of chronic kidney disease in donors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite compensatory hyperfiltration in remaining nephrons following donor nephrectomy, some donors show impaired renal adaptation and low estimated glomerular filtration rate (eGFR). We investigated the factors predicting early renal adaptation after nephrectomy and identified kidney donors at risk of inadequate renal adaptation., Methods: A total of 265 living kidney donors from 2010 to 2013 were retrospectively analyzed. Renal function was serially followed for 6 months after the operation. Regression analyses were performed to identify the independent predictors of low eGFR (eGFR <60 mL/min/1.73 m 2 ) and impaired renal adaptation (%Modification of Diet in Renal Disease [MDRD] <66% of baseline eGFR)., Results: A total of 148 donors belonged to the low eGFR group, and changes in eGFR (ΔeGFR) at postoperative (PO) 1 day and 1 month were identified as independent predictors of low eGFR. Impaired renal adaptation was related to age, ΔeGFR PO 2-3 days, and ΔeGFR PO 1 month. Early renal adaptation was associated with age, male gender, and residual kidney computerized tomography angiography (CTA) volume. The best sensitivity and specificity were obtained with a cutoff value of ΔeGFR 31 at PO 1 day and 1 month for predicting low eGFR and with a value of ΔeGFR 27 at PO 2-3 days and 1 month for predicting impaired renal adaptation., Conclusions: Our study showed that the degree of early renal adaptation determines subsequent renal function in kidney donors. Closer monitoring and management may be required in old or male donors with small residual CTA kidney volume as well as donors with persistent ΔeGFR >27 within 1 month of nephrectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF., Methods: From April 1999 to April 2011, 60 patients underwent LT for acute liver failure, including 42 patients for FHF at Samsung Medical Center, Seoul, Korea. Among 42 patients, 30 patients underwent LDLT for FHF, and the database of these patients was analyzed retrospectively to investigate the prognostic factors after LDLT for FHF., Results: Among 30 patients, 7 patients (23%) died during the in-hospital period within 6 months, and 23 patients (77%) survived until recently. In univariate analyses, donor age (>35 years), graft volume (GV)/standard liver volume (SLV) (<50%), cold ischemic time (>120 minutes), hepatic encephalopathy (grade IV), hepato-renal syndrome (HRS), and history of ventilator care were associated with fatal outcome after LDLT for FHF. In multivariate analyses, HRS, GV/SLV (<50%), and donor age (>35 years) were significantly associated with fatal outcome. Although the statistical significance was not shown in this analysis (P = .059), hepatic encephalopathy grade IV also appears to be a risk factor predicting fatal outcome., Conclusions: The survival of patients with FHF undergoing LDLT was comparable to that in published data. In this study, HRS, GV/SLV <50%, and donor age >35 years are the independent poor prognostic factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM., Methods: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement. In this study, we performed a subtotal pancreatectomy combined with reduced STZ injection to induce IDDM and procure islets in a nonhuman primate model., Results: Twelve cynomolgus monkeys received low-dose STZ injections (60 mg/kg) simultaneously with subtotal pancreatectomy. All monkeys recovered from the procedure without complications. IDDM was induced in the animals. 57,691 ± 16,050 islets were isolated from the resected pancreas and transplanted into other monkeys., Conclusions: Simultaneous subtotal pancreatectomy and low-dose STZ injection represent an effective and safe method to create an animal model of insulin dependence diabetes, while at the same time providing sufficient amounts of fresh islet cells for allotransplantation without requiring killing of additional animals., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation., Methods: We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points., Results: We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice., Conclusions: Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Organ donation after brain death is a major source for obtaining transplantable organs for patients with end-stage organ disease. However, the time from declaring brain death to organ procurement is often longer than expected. Analyzing factors that delay organ procurement may help to prevent damage to organs from marginal and unstable donors and aid in preparation for recipient operation. The aim of this study was to examine factors associated with the interval between the time of declaring brain death and organ procurement., Methods: Medical records of patients who underwent organ procurement after brain death from February 2009 to April 2015 were retrospectively reviewed., Results: Of the 77 patients which were scheduled to undergo organ procurement, 68 eventually underwent procurement of ≥1 organ. The average time interval from 1st exam for brain death to organ procurement decreased from 1,248 minutes in 2009 to 910 minutes in 2015. Although not statistically significant, during the 6-year period, the time interval decreased from 1,105 minutes to 1,075 minutes in the latter half of the period (P = .623). Organ procurement was extensively delayed most commonly owing to false negative electroencephalogram (EEG; 62.5%)., Conclusions: With increasing experience in dealing with brain death donors, the time interval from declaring brain death to organ procurement decreased. We suggest that an EEG be performed during the initial stages of examination for brain death to prevent unnecessary preparation of recipient operation owing to a false EEG test., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: Agitated delirium has frequently occurred after liver transplantation in the intensive care unit (ICU) and sedative agents are used to treat patients. Recently, dexmedetomidine has been considered to be a promising agent for agitated delirium., Methods: This study took place between January 2010 and October 2012 and 42 recipients were retrospectively enrolled. Sixteen recipients were enrolled in the dexmedetomidine group and 26 recipients were placed in the haloperidol group. To compare dexmedetomidine and haloperidol, the total ICU length of stay (ICU LOS), the ICU LOS after drug administration, and the supplemental doses of sedative agents used were assessed. The endpoint was discharge from the ICU., Results: There were no significant drug-related complications in either group. Dexmedetomidine significantly decreased the ICU LOS and ICU LOS after the occurrence of delirium compared to haloperidol (13.7 days vs. 8.3 days, P = .039, 10.1 days vs. 3.1 days, P = .009). In the dexmedetomidine group, the dose of supplemental midazolam needed was lower than in the haloperidol group (1.5 mg vs. 6.85 mg, P < .001)., Conclusion: Dexmedetomidine is a promising agent for the treatment of ICU-associated agitated delirium in liver transplantation recipients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The influence of human leukocyte antigen (HLA) mismatch on liver transplantation has been widely studied, but is still controversial. The aim of this large single-center study was to analyze the role of HLA compatibility between donor and recipient in the graft outcomes of living donor liver transplantation (LDLT)., Materials and Methods: A total of 925 recipients who had undergone LDLT between March 2001 and April 2012 were retrospectively analyzed. HLA typing was performed using a standard complement-dependent cytotoxicity technique. The degree and type of HLA-A, HLA-B, and HLA-DR mismatch were assessed. We also investigated the posttransplantation laboratory data, incidence of rejection, recurrence of hepatitis B virus (HBV), and graft survival as outcome parameters., Results: The type of HLA-A, HLA-B, and HLA-DR mismatch had no effect on rejection episodes, whereas the beneficial effect of a much lower degree (0-2) of HLA mismatch was notable. Recipients with 2 HLA-B mismatches or recipients with a higher degree of mismatch were associated with elevated bilirubin level, a higher recurrence rate of HBV, and inferior graft survival. A complete mismatch of 2 at the DR locus also decreased graft survival in LDLT recipients., Conclusions: This study confirmed that the degree of HLA mismatch, as well as the locus-specific type of HLA mismatch, namely B and DR, play a major role in graft outcomes after LDLT. To obtain an improved graft outcome, HLA compatibility should be considered in the setting of LDLT, which provides sufficient time to select a more favorable donor-recipient combination., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: As patient and graft survival rates have been improving after kidney transplantation, health-related quality of life (HR-QOL) has become an important indicator of effective treatment. This study aimed to evaluate changes in HR-QOL after kidney transplantation., Materials and Methods: The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) is a multicenter, observational, 9-year, cohort study. The HR-QOL of patients in the KNOW-KT study was assessed before transplantation and 2 years after transplantation using the Kidney Disease Quality of Life Short Form (KDQOL-SF) including chronic kidney disease targeted area and the Medical Outcome Study 36-item Short Form Health Survey (SF-36). Multivariate linear regression was used to identify significant factors associated with follow-up QOL scores., Results: A total of 175 patients from 8 centers were analyzed. All QOL scores including the total QOL score, chronic kidney disease targeted score, and SF-36 at the 2-year follow-up were significantly increased compared to baseline values. Both physical and mental scale scores were improved after transplantation., Conclusion: The QOL scores for both the mental and physical scales were improved at 2 years after kidney transplantation. High glomerular filtration rate at 2 years, high baseline QOL score, and low body mass index were associated with good follow-up QOL scores. Kidney transplantation for an Asian population with end-stage renal disease can result in better QOL as well as better patient and graft survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Compliance with immunosuppressive regimens may affect clinical outcomes in renal transplant recipients. The aim of this study was to assess the safety and efficacy of standard-dose tacrolimus modified-release (TAC-MR) once daily versus tacrolimus (TAC) twice daily in stable renal transplant recipients., Methods: Ninety-nine stable renal transplant recipients were randomized to receive standard-dose tacrolimus twice daily or standard-dose modified-release tacrolimus once daily on a 1:1 (mg:mg) basis. The primary end point was the incidence of adverse events (AEs) in both groups. Secondary end points included biopsy-proven acute rejection, graft survival, patient survival, clinical indicators, and change in score of questionnaire., Results: The incidence of AEs was not different between the TAC and TAC-MR groups (56.0% vs 53.1%, P > .05). There were no significant differences in mean calculated glomerular filtration rate, blood pressure, glycosylated hemoglobulin (HbA1c), blood concentration of tacrolimus, and drug compliance. The scores of all items in the 36-item short form health survey (SF-36) were not different between groups, except for vitality. With respect to the subject questionnaire, there was no difference in question scores between the two treatment groups., Conclusion: A regimen of TAC-MR once daily can be considered as an effective and safe alternative formulation of tacrolimus in stable renal transplant patients., (Copyright © 2015. Published by Elsevier Inc.)

Background: Given the fragility of adult porcine islets, reduction of shearing stress in islet purification using histidine-tryptophan-ketoglutarate (HTK) solution and iodixanol could be an effective strategy. We examined the effect of ductal preservation with HTK solution and an islet purification protocol that utilizes HTK solution and iodixanol in adult porcine islet isolation., Methods: Islets were isolated with a modified Ricordi method using adult Prestige World Genetics (PWG) and Yucatan pigs. The discontinuous density gradient was composed of either HTK solution/iodixanol (n = 23, iodixanol group) or Hank's balanced salt solution (HBSS)/Ficoll (n = 17, Ficoll group). In the iodixanol group, ductal injection of HTK solution was performed before purification., Results: In PWG pigs, significantly higher islet yield after purification (3480 ± 214.2 islet equivalent [IEQ]/g, P = .003) and higher recovery rate (85.45% ± 3.49%, P = .0043) were obtained from the HTK/iodixanol group as compared to the HBSS/Ficoll group (1905 ± 323.2 IEQ/g, and 67.22% ± 4.77%, respectively). Similar results were obtained in Yucatan pigs with greater body weight., Conclusion: Ductal preservation and iodixanol-based islet purification using HTK solution improved the yield of adult porcine islet isolation compared to the conventional method using HBSS and Ficoll. The results of this study support the feasibility of an adult porcine islet isolation protocol using HTK solution and iodixanol, which have the favorable physical properties., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Some research groups have produced immunodeficient mice with human liver tissue as a model system for the analysis of drug metabolism and liver regeneration. Mouse models are important for research and development of drugs and vaccines for viral infections. Recent progress in developing humanized mouse models permits studies of adaptive immune responses, innate host responses, and therapeutic approaches for several liver diseases of viral etiology. In this study, we generated a humanized liver mouse model by transplant with fresh patient-derived hepatocytes (1 × 10(6) cells/mouse, intrasplenic injection) into preconditioned (50 mg/kg ganciclovir, intraperitoneal injection) mice (herpes simplex virus type 1 thymidine kinase [TK] transgene expressed within the liver of a highly immunodeficient mouse strain [NOG]). Successful reconstitution of human hepatocytes in TK-NOG mouse liver tissues was observed with a strong proliferation of human cells in a time-dependent manner, using cytokeratin 8/18 stain. Similarly, we detected significantly increased human albumin levels in TK-NOG mouse liver tissue and blood sera on immune staining and enzyme-linked immunosorbent assay. Therefore, this humanized liver mouse model provides a biomedical tool for studying human liver physiology, drug metabolism, and liver pathogenesis of viral etiology or liver regeneration., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size ≤6 cm, ≤7 tumors, and/or AFP levels ≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size ≤6 cm, tumor number ≤7, and/or AFP levels ≤1000 ng/mL., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Recurrence of hepatitis B virus (HBV) occurs despite prophylaxis, and covalently closed circular DNA (cccDNA) is thought to play a role owing to its resistance to prophylactic agents used. The aim of this study was to evaluate the changes of HBV DNA and cccDNA within the liver graft during liver transplantation (LT). Polymerase chain reaction (PCR) primers and probes were designed to measure total HBV DNA (tDNA) and cccDNA by real-time PCR. One hundred fifty samples from 70 patients who underwent LT for HBV were used for analysis. A 1st biopsy was taken from the donor before donor hepatectomy (Bx1), a 2nd from the recipient after reperfusion (Bx2), and a 3rd (Bx3) during follow-up after LT in 18 patients. Both tDNA and cccDNA after reperfusion were detected more frequently in pre-LT HBeAg(+) and high-HBV DNA titer recipients. However, the type and duration of antiviral agents and presence of mutation before LT did not influence the presence of tDNA or cccDNA in Bx2. tDNA positivity within the graft decreased from 41.4% to 22.2% during follow-up, but cccDNA did not (4.3% in Bx2 and 5.6% in Bx3). Although HBV recurrence was not related to pre-LT recipient HBeAg or HBV DNA titer, the presence of tDNA after reperfusion had strong correlation. The presence of tDNA within the graft is influenced by pre-LT viral replicative status, and although its presence decreases with prophylaxis, it is strongly correlated with recurrence. cccDNA does not have a role in predicting recurrence but is preserved within the graft despite prophylaxis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Biliary tract complications are the main concern associated with living-donor liver transplantation (LDLT). Many laboratory parameters have been studied for the early detection of post-LDLT complications, including various cytokines. To explore immunologic activation status and its clinical significance, the cytokine secretion patterns of LDLT patients who developed biliary complications were analyzed. Serum samples from LDLT recipients were collected 1 day before and 3, 7, 14, and 30 days after transplantation. Each sample was tested for interleukin (IL) 2, IL-4, IL-6, IL-8, IL-10, IL-12, interferon-α, and tumor necrosis factor α with the use of multiplex bead flow cytometry. Fifteen patients without any complications and 6 patients with biliary complications showed differential serum cytokine profiles. The biliary complication group (4 biliary stricture and 2 biliary obstruction patients) displayed significantly increased concentrations of IL-2 and IL-12 on post-transplantation days 3 and 7 and of IL-4 on post-transplantation day 7. Profiling cytokine secretion in the serum of patients in the first month of LDLT may be helpful for the prediction and diagnosis of biliary complications within 1 year., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Donor and recipient age in kidney transplantation are known to affect graft and patient survival. To address the question of whether the age difference between donor and recipient impacts on graft survival and death-censored graft survival after transplantation, we examined the impact of age matching (less than 10-year age difference) on the survivals after living donor kidney transplantation., Methods: Two hundred one cases of the primary living donor kidney transplantation were performed and were divided into two groups, age-matched (n = 123) versus age-discrepant (n = 78). Variables included in this study were age, gender, body weight, height, kidney disease, type and duration of dialysis before transplantation, degree of human leukocyte antigen mismatch, ischemic time, graft weight, episode of rejection, type of immunosuppression, recipient serum creatinine after transplantation, and causes of patient death and graft loss., Results: We observed the disparities of graft survival (P = .008) and death-censored graft survival (P = .003) between the groups. One-, 3-, and 5-year death-censored graft survival was 100%, 100%, and 97% in the age-matched group, respectively; and 97%, 90%, and 88% in the age-discrepant group, respectively. By Cox regression multivariate analysis, the variable of age-matching was an independent predictor for both graft survival (ß = 1.325, P = .017) and death-censored graft survival (ß = 2.217, P = .021)., Conclusion: During living donor and recipient matching, age difference between donor and recipient should be minimized., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: A national organ transplant registry is an indispensable organizational requirement for patient care, research, and planning. Even though the Korean Network for Organ Sharing (KONOS) has established a database for a waiting list, organ allocation, and incidence of organ transplantation since 2000, an integrated registry including post-transplantation data is needed for better understanding of organ transplantation. Recently, the Korean Society for Transplantation (KST) and the Korean Center for Disease Control (KCDC) designed a web-based organ transplant registry, named the Korean Organ Transplant Registry (KOTRY). As an initial project of KOTRY, we retrospectively analyzed kidney transplantations (KTs) performed in 2009 and 2010., Methods: A total of 2292 KTs (91.9%) from 46 hospitals (80.7%) were collected and analyzed. Ninety-five elements related to KT were selected and analyzed., Results: Proportions of male recipients and retransplantations were 58.4% and 7.1%, respectively. Even though glomerulonephritis was the most common cause of end-stage renal disease (ESRD) (28.4%), the number of diabetic nephropathy cases was increasing. The living donor (LD) to deceased donor (DD) ratio was 1.69:1. Because of a serious organ shortage in Korea, DD kidneys with a low initial estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m(2) (21.2%) and expanded criteria donors (ECDs; 18.3%) are frequently used. Other noticeable findings are the increasing number of wife donors and ABO-incompatible (ABOi) transplants for O(+) recipients., Conclusions: The epidemiological profile of transplantation is different from country to country. The number of organ transplantations in East Asian countries is rapidly growing, however, there are few epidemiological data about this region in the literature. With the establishment of KOTRY, it was possible to present the first nationwide epidemiological data of Korean KTs., (Copyright © 2014. Published by Elsevier Inc.)

Purpose: An increased incidence of de novo malignancy (dM) is an established complication among solid organ transplant (SOT) recipients compared with the general population. The aims of this study were to describe the incidence and cumulative risk for development of dM among our transplanted population, depending on various clinical and pathologic variables., Methods: We retrospectively reviewed the medical records and pathologic data of SOT recipients performed from February 1995 to December 2010., Results: Among 2673 consecutive SOT recipients, the dM that developed in 66 (2.5%) patients included, 16 (0.6%; 24.2% of overall dM) lymphoid dM and 50 (1.9%; 75.8% of overall dM) nonlymphoid dM. Cumulative incidence of dM in liver was significantly higher than that in kidney transplant recipients. A significantly higher cumulative incidence of dM was observed among living donor versus deceased donor SOT. Although the more frequent development of lymphoid dM was observed during the first year posttransplantation, the cumulative risk of nonlymphoid dM increased year by year, reaching a substantially higher incidence than that of lymphoid dM beyond 5 years after SOT. Comparing the various immunosuppressive regimens, the cumulative incidence was greater among the group with basiliximab induction. However, the hazard of occurrence was unaffected by whether tacrolimus or cyclosporine was used for maintenance immunosuppression. The increased risk of dM was not dependent on recipient age or gender., Conclusion: This study demonstrated distinctive cumulative incidences of dM in different clinical and pathologic settings., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Advanced donor age is a well-known risk factor for poor graft function after living donor liver transplantation (LDLT). In addition, advanced recipient age has a significant impact because of the high prevalence of comorbidities. We investigated the relationship between donor-recipient age gradient (DRAG) and the posttransplant outcomes in LDLT., Methods: We included 821 consecutive adult recipients who underwent LDLT from June 1997 to May 2011. According to the value of DRAG, they were divided into 2 groups: Negative years (the donor was younger than the recipient) and positive years (the donor was older than the recipient). These groups were further divided into subgroups (≤-21, -20 to -1, 0 to 20, and ≥21 years). We collected retrospectively patient characteristics, laboratory results, medical and surgical complications, and graft loss., Results: The positive DRAG group had higher level of posttransplant alkaline phosphatase, but a lower incidence of biliary complications. The negative DRAG group, particularly DRAG ≤ -21 years was associated with the superior 1-, 3-, 5-, and 10-year graft survivals. Recipients with DRAG ≥ 21 showed persistently inferior graft survival during the observation period. In cases of young donors, transplants utilizing lower DRAG seen between young donors and older recipients showed more favorable graft survival than that of young-to-young transplants., Conclusion: This study demonstrated that DRAG and a fixed donor age limit could be significant factors to predict graft survival after LDLT. Patients should carefully consider the worse graft survival if the donor is older than the recipient by ≥20., (Copyright © 2013. Published by Elsevier Inc.)

Background: Chronic immunosuppression is associated with unwanted adverse effects and increased morbidities. Long-term acceptance of transplanted organs without the requirement for immunosuppression, or operational tolerance, remains an important goal in clinical transplantation., Methods: We reviewed the characteristics of recipients who achieved spontaneous operational tolerance after liver transplantation (OLT) among a consecutive series of 1014 adult recipients in a single center., Results: We observed 5 cases (0.5%) of operational tolerance. All cases were men who underwent transplantations for hepatitis B virus-related liver cirrhosis. The mean time from OLT to achievement of spontaneous operational tolerance was 83.1 ± 62.9 months (range, 21.3-156.2). Characteristics common to all tolerant recipients were superior graft quality and good pretransplant recipient condition: specifically, high graft-recipient weight ratio (median, 1.18; range, 1.15-2.69), low hepatic macrosteatosis (median, 3; range, 0-15), low score of model for end-stage liver disease (median, 13; range, 7-21), and no history of preoperative intensive care., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC., Patients and Methods: From 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively., Results: The poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (>5 cm), small safety margin (<2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (n = 68) and the liver transplant group (n = 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, P = .333; 5-year OS: 42.1% vs 50%, P = .591). In the small tumor subgroup (tumor size <5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin >2 cm), survival was comparable., Conclusions: In well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Introduction: We investigated the optimal method for transportation of isolated porcine islets from an isolation facility to a transplant hospital or research center in terms of temperature, oxygen supply, and shaking effect., Methods: Commercially available insulator boxes with thermoregulators exposed for 5 hours under two external temperatures (4°C and 37°C) were monitored using HOBO temperature loggers. To find the optimal transport device, we compared islet counts, viability, quality, and function in conical tubes, gas-permeable bags (GPB) and gas-permeable flasks (GPF) after 1, 3 and 5 hours. To evaluate the effects of shaking on islets, we also analyzed the difference between a control and a shaking group in each device with time., Results: Commercially available Styrofoam insulators with thermoregulators maintained the internal temperature near the target. Islet recovery rate for GPF, which was higher than other devices, was maintained, while those decreased with time for conical tube and GPB containers adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio for GPF was lower than other devices, albeit not significantly fluoroscein acrimide/propidium iodide (AO/PI) ratio for GPF was higher than other devices after 5 hours. Glucose stimulated index was not different among the devices. In comparison with the control group, shaking yielded comparable islet survival, viability and function., Conclusion: Our study demonstrated that the use of commercially available insulator boxes with thermoregulators maintained internal temperature close to the target value and that GPF was more favorable for islet oxygenation during transportation. This study also suggested negligible impact of shaking on isolated porcine islets during transportation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We investigated the effect of the donor kidney weight (Kw) to recipient body weight (Rw) ratio (Kw/Rw) on long-term graft function. To investigate the impact of the Kw/Rw ratio on the graft function, we retrospectively collected data from 213 kidney transplant recipients at least 5 years Post-transplantations. Renal function showed a positive correlation with the Kw/Rw ratio until 5 years after transplantation (at 60 months after transplantation, R = 0.158, P = .023); however, this ratio does not affect graft survival (P = .794). We used the mixed-effect model to identify the factors that affect the estimated glomerular filtration rate (eGFR) over time. In univariate analysis, donor age, BSA, kidney weight, and Kw/Rw ratio were associated with eGFR. To identify independent factors that affect to the eGFR, multivariate analysis using a mixed model was applied. Donor age (P < .001) and Kw/Rw ratio (P < .001) were independent factors that affected the eGFR. To identify the cutoff values of the Kw/Rw ratio and donor age that affect long-term graft function, multiple testing using a mixed model was applied. The cutoff value for the Kw/Rw ratio was 3.16 (P = .0104) and the cutoff value of donor age was 44 years (P = .0001). Based on our results, we conclude that the Kw/Rw ratio and donor age are important factors for the long-term function of graft., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Successful kidney transplantation leads to greater survival and improved quality of life for patients with end-stage renal disease. Among the most important influences on graft outcomes is donor age. We evaluated the relationships between the donor-recipient age gradient (DRAG) and the graft outcomes after deceased-donor kidney transplantation (DDKT)., Methods: From February 1995 to March 2011, a consecutive series of 526 adult DDKT recipients were analyzed. DRAG values were divided into two groups (negative versus positive years) and then four groups (≤-21, -20 to -1, 0 to 20, and ≥21 years)., Results: Median age of donors and recipients were 39 (range, 1-75) and 41 (range, 18-74) years, respectively. The degree of DRAG was not associated with episodes of allograft rejection. High or low DRAG had no effect on posttransplant serum creatinine levels or estimated glomerular filtration rates. However, negative levels of DRAG, particularly less than -20 years, were significantly correlated with superior 10-year death-censored graft survival (86.4% and 83.1% vs 72.2% vs 53.9%; overall P = .031), but not increased overall graft or patient survival., Conclusion: This study demonstrated that DRAG is a prognostic indicator of long-term graft outcomes after DDKT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Donor age is a well-known factor influencing graft function after deceased donor liver transplantation (DDLT). However, the effect of donors older than recipients on graft outcomes remains unclear. This study investigated the relationship between the donor-recipient age gradient (DRAG) and posttransplant outcomes after DDLT., Methods: We included 164 adult recipients who underwent DDLT between May 1996 and April 2011. Patients were divided into 2 groups according to the value of DRAG: Negative (DRAG -20 to -1; n = 99) versus positive (DRAG 0-20; n = 65). Medical records were reviewed and laboratory data were retrospectively collected., Results: The median age of donors and recipients was 43 (range, 10-80) and 46 (range, 19-67) years, respectively. The mean follow-up time was 57.4 months. A positive DRAG had a negative effect on levels of alkaline phosphatase until 2 weeks after transplantation. However, the positive group showed a lower incidence of hepatitis B viral disease recurrence. The 1-, 3-, and 5-year graft survival rates were 80.4%, 76.8%, and 71.4% in the negative group, and 65.8%, 58.4%, and 56.3% in the positive group, respectively. The positive DRAG group showed significantly inferior graft survival compared with the negative DRAG group (P = .036)., Conclusion: This study demonstrated that donors older than recipients had a deleterious effect on graft outcomes. DRAG could be a meaningful determinant of graft survival among DDLT recipients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Acute-on-chronic liver failure (AoCLF) occurs in lymphoma patients because of hepatitis B virus (HBV) reactivation. We aimed to identify characteristics of patients who underwent liver transplantation (OLT) because of AoCLF that occurred due to HBV reactivation in the setting of lymphoma and to compare these patients with AoCLF patients who did not have lymphoma., Methods: Twenty patients underwent OLT due to AoCLF between February 2009 and June 2011. Among these patients, five were diagnosed with lymphoma before OLT and assigned to group 1. The remaining patients (n = 15) were assigned to group 2., Results: Hospitalization after transplantation in group 2 was longer than in group 1 (P = .014). However, there were no differences in other variables between the two groups. The overall survival rate of group 1 was lower than that of group 2, but there was no difference between the two groups (P = .134). With the exception of one patient, the median time from complete remission to liver transplantation in group 1 was 4.5 months (range, 1-15) in group 1. Lymphoma recurrence occurred in one patient 8 months after transplantation., Conclusion: Our study revealed that OLT is a feasible and effective approach in AoCLF due to HBV reactivation in select lymphoma patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Successful arterial reconstruction is essential for liver transplantation. In the case of inadequate arterial inflow, an arterial conduit from the aorta using artery graft or re-establishment of arterial flow through other arteries such as the splenic artery, gastroepiploic, or sigmoid artery is considered. Herein we report our experience of 27 cases of hepatic artery reconstruction using alternative methods. The most common cause of hepatic artery reconstruction requiring alternative methods was intimal dissection for which we usually used the gastroepiploic artery. Many patients had a previous operation or transarterial chemoembolization history. Among these cases, hepatic artery reconstruction using the jejunal artery was performed for 2 cases of living donor liver transplantation due to the absence of suitable alternatives. These patients have been followed up with patent hepatic arterial flow until now. Thus, the jejunal artery can be a useful option for arterial reconstruction in living donor liver transplantation when suitable arterial inflow is absent., (Copyright © 2013. Published by Elsevier Inc.)

Background: This single-center study sought to examine the clinical outcomes of kidney transplant recipients from donors displaying acute kidney injury (AKI)., Methods: We analyzed retrospectively the medical records of the donors and recipients of 54 deceased-donor kidney transplantations performed in our center between March 2009 and March 2012., Results: Among the 54 deceased donors, 36 (66.7%) experienced AKI as determined by the final mean serum creatinine levels measured before graft harvest of 2.66 ± 1.62 mg/dL versus 0.82 ± 0.28 mg/dL among non-AKI donors. The risks of delayed graft function and slow graft function were increased among the AKI versus non-AKI groups in the early post-transplantation period. However, the renal function status of recipients at 3, 6, and 12 months after transplantation was not significantly different between the two groups. Moreover, rejection-free survival rates during the study period were similar. Multivariate analysis revealed an acute rejection episodes (P = .047) and a lower body mass index in the donor relative to the recipient (P = .011) to be independent risk factors predicting poor graft function defined as a 1-year estimated glomerular filtration rate less than 50 mL/min/l.73 m(2). Donor AKI with either a high level (>4.0 mg/dL), an increasing trend of creatinine, or greater severity by the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) classification was not a significant risk factor., Conclusion: Transplantation of kidneys from the AKI donors, namely, patients with severely decreased renal function, displayed excellent short-term outcomes. Accordingly, kidney transplantations from deceased donors with AKI should be considered more actively to expand the donor pool in Korea., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The BK nephropathy (BKN) shows a 10% prevalence among cases of kidney transplantation (KT). We assessed the incidence of BK replication in KT recipients as well as our updated screening strategy and the impact of interventions on BK virus infections., Methods: Since September 2007, our screening protocol for BK virus included examination of urine cytology or BK virus DNA real-time polymerase chain reaction (PCR) detection on postoperative days 1, 5, 9, 16, 24, 36, 48 weeks up to 1 year. IR present, we tested urine BK virus DNA PCR quantitation. We applied the updated screening protocol from August 2010. It urine BK DNA PCR quantification was above 10(7) copies/mL, we checked regularly blood the BK virus DNA PCR quantification. In addition, if the blood BK virus DNA load was above 10(4) copies/mL and the serum creatinine elevated, we was performed an allograft biopsy. Between September 2007 and December 2011, the 58 recipients who showed BK viremia were enrolled in the present study in 2 groups according to the period of screening protocol (era I, era II)., Results: The time between kidney transplantation and BK viremia detection of era II was shorter than that of era I (16 vs 29 weeks; P = .001). Viremia clearance rate at 6 months in era II was significant higher than that of era I (82% vs 36.8%; P = .001) as well as at 12 months (100% vs 61.1%, P < .001) after intervention. Interestingly, viremia clearance at 12 months after intervention was 100% in era II., Conclusion: An updated screening protocol for BK virus allowed early detection and accurate diagnosis of BKN. Early detection of BK virus infection enabled early intervention and improved viral clearance rate., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: We studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function., Methods: We performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function., Results: Thirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I (n = 6), grade II (n = 30), or grade III (n = 14) reflux. Patients followed for a median 61 months (range 44-74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR (P = .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation., Conclusions: VUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Background: Aging plays a profound role in the ability of the kidney to function. Aging which varies among individuals, has been associated with the matrix metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients., Methods: Transplant outcomes were evaluated according to the sum of the A alleles in the recipients and the donors. The group with a high number of A alleles (≥3) was compared with the group with a low number (<3)., Results: The group with a high number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion than the group with a low number (P = .009). The group with a high number of MMP20 A alleles had showed better long-term kidney function at 10 years after transplantation than the group with a low number (P = .026). Furthermore, the group with a high number of MMP20 A alleles showed a trend toward better graft survival compared with the group with a low number, especially among recipients followed for >1 year (P = .022)., Conclusions: Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Physiologic regulation of glucose metabolism is different between donor and recipient of xenogeneic pancreatic islet transplantation. We sought to assess whether the capacity of donor islets to adapt to recipient metabolic requirements should be considered in determining the success of pancreatic islet xenotransplantation., Methods: Rhesus macaque hosts rendered diabetic by streptozotocin were transplanted with porcine islets into the liver. Porcine c-peptide and insulin levels as well as intravenous glucose tolerance test (IVGTT) were measured at intervals., Results: At 2 months after islet transplantation, glucose responses on IVGTT showed a normoglycemic pattern. There was a 2.48 fold increase in C-peptide level during the initial 15 minutes of IVGTT in normal monkeys: from 3.122 ng/mL at baseline to 7.728 ng/mL at 15 minutes. Monkeys transplanted with porcine islets showed 2.38- and 2.45-folds the initial increases in C-peptide on IVGTT at 2 and 4 months after transplantation, respectively. Histopathologic evaluation identified the host endothelial cells having well lined the vessels of the porcine islets in the monkey liver., Conclusions: The glucose response on IVGTT of porcine islets engrafted in the monkey liver resembled the normal monkey pattern rather than that of pigs. The presence of monkey endothelial cells suggested that porcine islets were well adapted to the local environment of the recipient., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Apoptosis is a central mechanism of ischemic-reperfusion injury (IRI) to the liver. Among the methods to reduce IRI, ischemic preconditioning (IP) has been shown to confer protection. Therefore, the aim of this study was to determine if IP conferred protection against hepatic IRI under isoflurane anesthesia in rats and to investigate underlying protective mechanisms., Materials and Methods: Twenty-three rats weighing 270 to 300 grams were randomly divided into three groups: (1) the sham operated group (n = 5); (2) the non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion); and (3) the IP group (n = 9); IP induced by 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of prolonged hepatic ischemia). Anesthesia was maintained with isoflurane (1.5%). We compared the degrees of hepatic injury and expressions of B cell lymphoma 2 (Bcl-2) and caspase 3 and 8 mRNAs., Results: The IP group showed significantly lower levels of aspartate transaminase and alanine transaminase as well as reduced histological grades of hepatocyte injury compared with the non-IP group at 2 hours after reperfusion. At the corresponding time, the Bcl-2 mRNA level was 2-fold higher in the IP group. Caspase 3 mRNA levels were highest in the non-IP group significantly compared with the sham cohort. Similarly, caspase 8 mRNA levels were highest in the Non&#95;IP group albeit not significancely., Conclusion: IP protected against hepatic IRI under isoflurane anesthesia in rats. The mechanism of protection appeared to involve upregulation of Bcl-2 expression resulting in inhibited apoptosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The use of new selective immunosuppressants as well as the emergence of new antimicrobial resistances raise the use of prophylactic antibiotics as a matter of controversy. The purpose of this study was to retrospectively analyze the clinical significance of prophylactic antibiotics in kidney transplantation., Methods: This retrospective study included 174 renal allograft recipients who were divided into two groups: group A including patients who received perioperative prophylactic antibiotics and group B, who did not receive them. We analyzed who the incidence of infectious complications as well as the causative micro-organisms and their antimicrobial resistance within 1 month after kidney transplantation., Results: Overall bacterial infections were observed during the first postoperative month in 13 cases (7.4%): 6 (3.4%) surgical site 4 (2.3%) urinary tract, 2 (1.1%) bacteremic, and 1 (0.6%) central catheter infections. There was no respiratory infection. The incidence of bacterial infection was not significantly different between the two groups. The major micro-organisms isolated after kidney transplantation, were Staphylococcus aureus and Escherichia coli; both of which had already shown multidrug resistance at the initial time of infection., Conclusion: Not only did use of prophylactic antibiotics have little impact to prevent bacterial infections after kidney transplantation, but also it may induce antimicrobial resistance against the antibiotics used for prophylaxis. Moreover, the increased antibiotic resistance prior to kidney transplantation hampers the effectiveness of prophylactic antimicrobial agents. Guidelines for perioperative antibiotic prophylaxis should be therefore revised., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The present study compared the efficacy and safety of mizoribine (MZR) with mycophenolate mofetil (MMF) in kidney transplantation. This multicenter, randomized clinical trial. Employed doses of study drug tailored to the immunosuppressive need. The primary efficacy outcome was the incidence of biopsy-proven acute rejection episodes (BPAR). The safety of the study drug was assessed using the incidences of adverse events, drug discontinuations, and abnormal laboratory results. The 7 (6.4%) BPARs above grade II were observed in the MZR group noninferior to the 2 (1.8%) in the MMF group (95% confidence interval, -0.007-0.097 > noninferiority limit [-0.2]). BPAR was significantly decreased in the MZR group after the dose change (17/41 [41.4%] vs 8/69 [11.6%]; P < .0001) and the incidence of BPAR was similar between the MZR and MMF groups after the dose change (P = .592). The uric acid level was significantly elevated in the MZR group (P = .002). In conclusion, the efficacy and safety of MZR were similar and statistically noninferior to MMF in combination therapy with tacrolimus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Recently, the ImmuKnow assay (Cylex Inc., Columbia, Md) has been reported to be a global immune monitoring tool for organ transplants recipients. We assessed whether immunKnow ATP values predicted infectious syndromes., Methods: We prospectively enrolled 71 kidney transplant patients between September 2008 and May 2011. lmmuKnow assay monitoring was performed at one dav before as well as 4, 8, 12, 16, 20, 24, 36, and 52 weeks after the operation. ImmuKnow assay values were compared as well as BK viral infection pre-infection(PI), at first detection of infectious syndrome (DI), 4 weeks there after (4W), 8 weeks there after (8W) and 12 weeks there after (12W) and pre-recovery (PR), recovery (R) times., Results: Serial ImmuKnow assays showed significant differences over time and BK viral infectious state (P = .026). Interestingly, PI was significantly lower than DI and PR but PR significant greater than PI, 8W and 12W. However, we did not observe an adequate or absolute cutoff value of ImmuKnow by ROC curve: 377 ng/mL ImmuKnow showed 0.471 of AUC and 57.1% and 56.2%, of sensitivity and specificity., Conclusion: Longitudinal evaluation and adjustment of the value of ImmuKnow assay seemed to be a favorable modality to monitor infectious syndromes especially those involving BK virus., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Proteinuria in the nontransplant population is a progressive renal disease. We analyzed the prevalence and clinical significance of proteinuria as well as factors related to its degree at posttransplant year 1 among kidney transplant recipients., Methods: We measured protein in a 24-hour urine among 644 recipients from January 1996 to December 2010., Results: Among 372 male and 272 female recipients, the mean amount of urinary protein was 424.4 ± 1010 mg/d (range, 13.88-8691) including 388 (60.2%) subjects with microproteinuria and the other 256 (39.8%) with overt proteinuria. Nephrotic range proteinuria was observed in 17 (2.6%) and nonnephritic range proteinuria, in 239 (37.1%) recipients. The latter cohort was categorized into low-grade proteinuria (n = 224; 34.8%) and high-grade proteinuria (n = 15; 2.3%). Proteinuria at posttransplant 1 year highly correlated with serum creatinine values at posttransplant years 1 and 2 as well as estimated glomerular filtration rate but not creatinine clearance at postoperative year 2. A greater incidence of graft loss was observed among recipients with more severe proteinuria. Males, recipients with anti-hepatitis C virus antibody, unrelated donors, anti-thymocyte immunoglobulin at the time of reperfusion, maintenance immunosuppression with cyclosporine or without mycophenolate mofetil were strongly associated with the amount of proteinuria., Conclusion: This study demonstrated the prevalence of proteinuria in kidney transplant recipient to be high. The presence as well as level of proteinuria were predictive markers for inferior allograft function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although human leukocyte antigen (HLA)-identical renal transplantation achieves superior graft outcomes, it does not uniformly allow indefinite graft survival. Recurrence of the original disease and effects of acute rejection episodes (ARE) may preclude indefinite survival. Herein, we have analyzed the factors that affect the graft outcomes among HLA zero-mismatch cases., Methods: We performed a retrospective, single-center study to evaluate the effect of recurrent glomerulonephritis (GN) and ARE on outcomes of grafts with zero HLA-mismatches (n = 122) versus three to four mismatches (n = 317), and five to six mismatches (n = 102). Forty-one percent of patients had GN as underlying disease., Results: Overall graft survival was 92.4% at 5 years and 79.6% at 10 years. HLA incompatibility did not affect graft survival: zero versus three to four versus five to six mismatches = 92.8% versus 90.8% versus 95.8% at 5 years and 82.5% versus 74.3% versus 85.1% at 10 years, respectively (P = .399). Subgroup analysis for subjects with GN revealed that ARE (P = .001) and recurrent GN (P = .003) were the risk factors for graft loss, whereas living donation was protective (P = .029). ARE was more prevalent with greater HLA incompatibility [0 (reference) < three to four < five to six mismatches; P = .047 and P = .014]. However, recurrent GN showed the opposite trend [0 (reference) > three to four > five to six mismatches; P = .106 and P = .022]. Furthermore, graft loss due to recurrent GN was significant among the HLA zero versus the three- to four-mismatch group (P = .047)., Conclusions: Graft survival was not affected by the degree of HLA incompatibility, which was mainly due to the recurrence of underlying disease. Therefore, a main focus should be the management of recurrence, especially among HLA-identical kidney transplantations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: End-stage renal disease is associated with severe abnormalities in reproductive function. However, the abnormalities are reversed by successful kidney transplantation. The aim of the present study was to compare hormonal levels between recipients with successful kidney transplantations and healthy women with the same gynecologic conditions., Methods: The study group consisted of 31 women of reproductive age with end-stage renal disease who underwent successful kidney transplantation. The ratio of the control group, composed of healthy woman, to the study group was 3:1 matched for age and symptoms., Results: Abnormal bleeding (n = 14) and infertility were the most common gynecologic conditions in kidney transplant recipients. The levels of estrogen (E2) and follicle-stimulating hormone (FSH) in the study group were higher than in the control group, but the levels of progesterone (P4) and luteinizing hormone (LH) were lower in the study group than in the control group. There were no significant differences in prolactin and thyroid-stimulating hormone between the two groups. The incidence of infertility in patients who receive steroid was higher than those with no steroid use (P = .007)., Conclusions: Compared with healthy age- and symptom-matched women, female kidney transplant recipients have increased levels of E2 and FSH and decreased levels of P4 and LH. These differences in hormone profiles may predispose kidney transplant recipients to increased risk of gynecologic pathologies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Salvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT., Methods: Between September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT., Results: Intrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion., Conclusions: Five-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor for survival., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence., Methods: We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008., Results: We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT., Conclusion: Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible., (Copyright © 2012. Published by Elsevier Inc.)

Introduction: Anatomic variants of the hepatic vasculature are common, so precise preoperative donor evaluation, including variations in the vasculature, is essential. We analyzed the anatomic similarity according to the donor-recipient relationship., Methods: Among the cases who underwent living donor liver transplantations from September 2008 to January 2011 we selected 104 cases with clearly defined hepatic artery and portal vein on preoperative computed tomography. They were classified according to Hiatt et al for the hepatic artery and Cheng for the portal vein. We categorized the 104 cases into three groups: parents-child (n=40), sibling (n=24) and no-relation (n=40), for analysis of the concordance of the hepatic artery and portal vein., Result: Anatomic variations were observed in 25% of donors and 23.1% of recipients in the hepatic artery and 6.7% of donors and 10.6% of recipients in the portal vein. There was no significant difference in the distribution of the type of hepatic vasculature. Identical anatomic variations between donors and recipients were observed in 62.5% of the parent-child; 66.7% of the sibling and 52.5% of no-related group (P=.493) in the hepatic artery and 92.5%, 100%, and 77.5% (P=.014) in the portal vein respectively., Conclusion: There was no similarity in the anatomic variations of the hepatic artery according to the donor-recipient relationship, but a similarity in portal venous anatomy according to the donor-recipient relationship., (Copyright © 2012. Published by Elsevier Inc.)

Purpose: Prostaglandin E1 (PGE1) has been used to improve hepatic blood flow and to reduce ischemia reperfusion injuries of allografts in liver transplantation. However, PGE1 undergoes extensive metabolic clearance in the pulmonary and splanchnic circulation during intravenous administration. We analyzed the effect of intraportally administered PGE1., Methods: Sixty living-donor liver transplant recipients received continuous infusions of PGE1 for 10 days immediately after the reperfusion of the allografts. Of them, 40 recipients received PGE1 intravenously (IV group) via the internal jugular vein, and 20 recipients received PGE1 intraportally (IP group) through a catheter in the inferior mesenteric vein. Data were collected for 3 weeks postoperatively., Results: The IP group exhibited lower initial aspartate aminotransferase and alanine aminotransferase levels compared with the IV group. However, no apparent differences were recognized in the serum albumin, total bilirubin, alkaline phosphatase, r-glutamyl transpeptidase, or prothrombin time levels between the 2 groups. Chylorous ascites were observed more frequently in the IP group. There was no difference in portal venous flow measured by Doppler sonogram between the 2 groups during the first postoperative week., Conclusion: This study demonstrated that intraportal administration of PGE1 had a better cytoprotective effect against hepatocellular damage than intravenous administration, although it did not have additional benefits for perihepatic hemodynamics., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Recently, the impact of human leukocyte antigen (HLA) mismatch (MM) on graft outcome has diminished since the introduction of potent immunosuppressive agents, whereas previous reports support the notion that greater numbers of HLA matches are beneficial. This study was undertaken to evaluate outcomes after five or six HLA-mismatched living donor kidney transplantations (LDKT)., Methods: The authors retrospectively reviewed graft function after 2687 LDKTs performed between June 1984 and February 2010. A database of 1364 living related and 1063 living-unrelated donor (LURD) kidney transplantations was used for this study. LURD kidney transplantations were classified into three groups; (1) zero to one HLA MM (n = 158); (2) two to four HLA MM (n = 851); and (3) five to six MM (n = 54). An acute rejection episode was diagnosed based on clinical deterioration of graft function or biopsy findings. Graft survival was calculated using the Kaplan-Meier method., Results: Graft survivals in the zero to one HLA MM, two to four HLA MM, five to six HLA MM, and one-haplo MM LDKT were not significantly different. The rates of acute rejection episodes within 1 year after transplantation were similar irrespective of the HLA MM; (1) zero to one HLA MM (37.3%), (2) two to four HLA MM (35.3%), (3) five to six HLA MM (33.3%; P = .832)., Conclusions: Survival of five or six HLA-mismatched LDKTs was comparable to that of one-haplo MM and relatively well-matched LDKT. The study showed that the presence of five or six HLA MM was not a risk factor for graft survival after LDKT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received thymoglobulin or ATGAM as an induction agent., Methods: We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation., Results: One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008)., Conclusion: The efficacy of thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure., (Copyright © 2012. Published by Elsevier Inc.)

Many studies have explored the participation of cytokines and their genes in renal allograft rejection by using biopsy tissues. To screen for rejection, a biopsy is too invasive to perform without a clinical clue. Therefore, we studied the expression of cytokines that contribute to the early phase of allograft rejection by analyzing mRNA transcripts in sequential blood samples of peripheral blood mononuclear cells (PBMCs) 120 of 6 among patients transplanted before diagnosis of rejection. for comparison with 6 control recipients. The relative expression amount of cytokine genes encoding interleukin (IL) 2, IL-4, IL-10, IL-15, and interferon-γ were assessed using real-time reverse-transcription polymerase chain reactions. IL-2, IL-4, and IL-15 mRNA expressions in clinically stable prerejection phase of the rejection group were significantly higher than those of the control group. In the prerejection samples, the expression of mRNA encoding IL-10 negatively correlated with the expressions of IL-2, IL-4, and IL-15 mRNAs, which were not different from the positive correlations in the postoperative samples from the control group. The expression patterns of IL-2, IL-4, IL-10, and IL-15 genes in PBMCs after transplantation may help to identify acute rejection episodes before clinical deterioration to monitor the efficacy of immunosuppressive treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Enteric-coated mycophenolate sodium (myfortic, Novartis Pharma AG, Basel, Switzerland) is designed to improve the gastrointestinal tolerability of micophenolic acid. This study was designed to evaluate the efficacy and safety of myfortic in Korean de novo renal transplantation. A total of 65 patients from four transplantation centers received the study drug at least once and were included in the intention-to-treat analysis. This study was an open-label, single-arm, multicenter trial with 6-month patient follow-up. Patients received 360 mg (body weight < 50 kg) or 720 mg (body weight > 50 kg) of myfortic per day with tacrolimus and steroids. Induction therapy included basiliximab. The incidence of biopsy-confirmed acute rejection (primary endpoint) within 6 months after transplantation was 7/65 (10.8%). There were 2 (3.1%) graft losses due to severe acute rejection and 1 (1.5%) patient-death due to cardiac arrest. Twenty-two (38.8%) patients experienced gastrointestinal discomfort; however, only 3 (4.5%) cases were associated with an apparent drug reaction. Seventeen (25.4%) patients underwent dose adjustment or myfortic discontinuation during the study period. Patient and graft survival rates at 6 months posttransplantation were 98.1% and 97.0%. Myfortic with tacrolimus-based immunosuppression was efficient and safe after de novo renal transplantation in Korean patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients., Methods: We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids., Results: There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups., Conclusions: ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: We initially performed a study to evaluate the safety and efficacy of modified-release tacrolimus (FK506E) in a phase 3, 2-arm, 6-month, randomized, open-label, multicenter trial in Korean living donor de novo kidney transplant recipients. We then performed an extended study to evaluate the long-term safety and efficacy of a FK506E-based regimen up to 45 months posttransplantation in recipients already treated with FK506E., Methods: Initial study was designed as a randomized, open-label, comparative, multicenter study in de novo living donor kidney transplant recipients. The patients were randomized to an FK506E versus a control (FK506) group (1:1). Recipients who completed a 6-month FK506E treatment study were enrolled in the 39-month follow-up study. Primary end-points were patient and graft survivals at posttransplantation 45 months. Secondary end-point was the incidence of a clinical or biopsy-proven acute rejection episode between 6 and 45 months posttransplantation., Results: In the initial 6-month de novo study 124 enrolled patients were randomized into either the FK506E (n = 62) or the control group (n = 62). The incidence of an acute rejection episode was 19.4% (n = 12) in the FK506E versus 16.1% (n = 10) in the control group (P = .638). There was no mortality or graft failure among the 44 recipients enrolled in this additional 39-month follow-up study. There was 1 patient with biopsy-proven acute cellular rejection episode (2.3%) who underwent steroid pulse therapy with renal function recovery. At the time of study completion 40/44 recipients (90.9%) maintained FK506E treatment., Conclusion: This 39-month study following the initial 6-month FK506E study period showed an FK506E-based immunosuppressive regimen in living donor kidney transplantation recipients to be safe and effective., (Copyright © 2012 Elsevier Inc. All rights reserved.)