Youn Joo Jeon

Successful Renal Transplantation with Desensitization in Highly Sensitized Patients: A Single Center Experience

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients.

Clinical Impacts of CD38+ B Cells on Acute Cellular Rejection With CD20+ B Cells in Renal Allograft

Background. There is an increasing evidence that the presence of CD20+ B cells is associated with poor clinical outcomes in acute cellular rejection (ACR), but clinical significance of CD38+ B cells is undetermined. We attempted to examine the clinical significance of the CD38+ B cells alone or in combination with CD20+ B cells in renal transplant recipients with ACR. Methods. Fifty-four patients with ACR were included. Biopsy specimens were stained for CD20 and CD38. The clinical outcomes of CD20 or CD38+ B cells were evaluated with late-onset and repeated ACR, steroid resistance, incomplete recovery after rejection treatment, and allograft survival. Results. Twenty-three patients (42.6%) had CD20+ and 25 (46.3%) patients had CD38+ B cells. Of these, 15 patients (27.8%) were positive for both CD20 and CD38 (CD20+CD38+). CD38+ patients had higher rates of late-onset or repeated ACR and incomplete recovery compared with CD38− patients (P<0.05). The patients with CD20+CD38+ had a higher incomplete recovery rate than did patients with only CD20+ or CD38+ (P<0.05). The 5-year allograft survival was lower in CD20+ and CD38+ patients than in CD20− or CD38− patients (P<0.05 for each). CD20+CD38+ patients had lower graft survival than did patients with CD20+ or CD38+ alone (P<0.05). Conclusion. Infiltration of CD38+ B cells alone or in combination with CD20+ B cells is a predictor for poor clinical outcomes of ACR in renal allograft.

Clinical significance of slow recovery of graft function in living donor kidney transplantation.

Background. The clinical significance of slow recovery of graft function (SGF) in living donor kidney transplantation is unclear. We evaluated the incidence, risk factors, and clinical outcome of SGF in living donor transplantation. Methods. Three hundred ten living donor kidney recipients were included and categorized into immediate recovery of graft function (IGF; n=239) and SGF (n=71), according to estimated glomerular filtration rate (60 mL/min/1.73 m2) at posttransplant day 14. We compared the clinical parameters, protocol biopsy findings, acute rejection (AR), and 10-year graft survival between the two groups. Results. The SGF group had an older recipient age, lower ratio of donor to recipient body mass index, and higher incidence of AR than IGF group, as shown by protocol biopsies. The SGF group had significantly more AR episodes than IGF group within 12 months (21.1% vs. 13.4%, P<0.05) and during follow-up period (32.4% vs. 20.1%, P<0.05). The 10-year graft survival rate did not differ between groups, but AR presence was significantly associated with a lower graft survival in the SGF group than the IGF group (64.9% vs. 78.9%, P<0.05). Conclusions. SGF in the early posttransplant period is immunologically active and should be considered as one of the risk factors for determining long-term graft survival in living donor kidney transplantation.

Safety and Efficacy of a Quinolone-Based Regimen for Treatment of Tuberculosis in Renal Transplant Recipients

BACKGROUND Rifampin (RFP) is a first-line antituberculosis drug, but it increases the risk of acute rejection (AR) in transplant recipients. This study evaluated whether quinolone (QNL) can replace RFP in renal transplant recipients with tuberculosis. METHODS One hundred nine patients with active tuberculosis were included. Patients consisted of RFP (n = 91) and QNL (n = 18) groups based on the initial treatment regimen. Patients with RFP-associated adverse effects were subdivided into RFP-maintenance (RFP-M; n = 18) and QNL-conversion (QNL-C; n = 8) groups. Clinical outcomes were compared between groups. RESULTS The incidence of AR was higher in the RFP group than in the QNL group (24.2% vs 5.6%). The QNL group showed significantly higher 10-year graft survival rates than the RFP group (88.1% vs 66.5%; P = .022). The QNL-C group showed significantly higher 10-year graft survival rates than the RFP-M group (87.5% vs 27.8%; P = .011). The rate of complete functional recovery after AR was higher in the QNL-C group than in the RFP-M group (50% vs 22.2%). CONCLUSIONS A QNL-based regimen may be safe and effective for treatment of tuberculosis and may lower the risk of graft failure in renal transplant recipients.

The efficacy and safety of ezetimibe and low-dose simvastatin as a primary treatment for dyslipidemia in renal transplant recipients.

Background/Aims The efficacy and safety of a combination of ezetimibe and low-dose statin as primary treatment for dyslipidemia in renal transplant patients were evaluated prospectively. Methods The study enrolled 77 renal transplant recipients with dyslipidemia. They were given ezetimibe (10 mg) and simvastatin (10 mg) for 6 months as the initial treatment for dyslipidemia. Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects. The effects on proteinuria and high sensitivity C-reactive protein (hsCRP) levels were also evaluated. Results Ezetimibe and low-dose simvastatin significantly decreased the levels of total cholesterol (34.6%), triglyceride (16.0%), and low-density lipoprotein cholesterol (LDL-C) (47.6%), and 82.5% of the patients reached the target LDL-C level of <100 mg/dL. No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed. Fourteen patients (18.2%) discontinued treatment; eight patients (11.7%) developed muscle pain or weakness without an increase in creatinine kinase levels, and two patients (2.6%) developed elevated liver transaminase levels. The proteinuria and hsCRP levels did not change significantly. Conclusions Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients.

Comparison of Long-Term Outcomes between Spousal Transplants and Other Living Unrelated Donor Transplants: Single-Center Experience

Background/Aims: The greater use of living unrelated donors (LUDs) as kidney donors is a worldwide trend in the current era of organ shortage, and spouses are an important source of LUDs. This study was to compare the long-term outcomes of spousal donor grafts with other LUD grafts. Methods: Among 445 LUD grafts, 77 were spouses and 368 were other LUDs. The clinical characteristics and long-term survival rates for spousal transplants were compared with those for other LUD transplants, and risk factors affecting graft survival were assessed. Results: Spousal donors had a significantly higher average number of human leukocyte antigen (HLA) mismatches (4.2 vs. 3.4, p < 0.001) and were older (41 vs. 33 years, p < 0.001) than LUDs. The 10-year survival rates for spousal donor grafts were 60.6%, similar to those for LUD grafts (58.5%, p = 0.61). The 10-year biopsy-proven acute rejection-free survival rates (85.5 vs. 89.6%, p = 0.45) and patient survival rates were also similar (84.3 vs. 79.6%, p = 0.35). The degree of HLA mismatching, the spousal donor type or donor age did not affect the graft survival. Conclusion: Renal transplants from spousal donors show similar long-term outcomes to those from better HLA-matched and younger LUDs.

Comparison of antibody monitoring system with flow cytometric crossmatch test in renal transplant recipients with high panel-reactive antibody.

Background/Aims: The antibody monitoring system (AMS) is a recently developed enzyme-linked immunosorbent assay (ELISA) crossmatch assay to detect donor-specific anti-HLA immunoglobulin G antibodies (DS-HLA Abs). This study was conducted to compare the AMS with the flow cytometric crossmatch (FCXM) test in renal transplant recipients with high panel-reactive antibody (PRA). Methods: Thirty-two sera were obtained from 10 patients with panel reactivity above 50%. When anti-HLA Ab was detected by ELISA PRA and the matched donor had the corresponding HLA antigen, it was considered to indicate DS-HLA Ab. The results of the AMS assay and FCXM were compared with the DS-HLA Abs. Results: Twenty-three (71.9%) sera were positive for DS-HLA Abs by ELISA PRA. The AMS assay showed that the number of compatible sera with DS-HLA Abs was 27 (84.4%), and it was significantly concordant (κ = 0.649, p < 0.0001). For FCXM, the number of compatible sera with DS-HLA Abs was 26 (81.3%), and it was also significantly concordant (κ = 0.614, p < 0.0001). There was a significant degree of concordance between the AMS assay and FCXM in detection of DS-HLA Abs (κ = 0.452, p = 0.010). Conclusion: The AMS assay is comparable to FCXM in detecting DS-HLA Abs in high PRA recipients.

Cyclosporin a inhibits albumin synthesis in Huh7 cells.

Background/Aims Hypoalbuminemia occurs frequently in renal transplant recipients immediately after renal transplantation. We studied the regulation of hepatic albumin synthesis by cyclosporin A (CsA) in Huh7 cells. Methods Huh7 cells were incubated with various concentrations of CsA for 4, 8, 16, and 24 hours. Albumin was measured in Huh7 cell-conditioned medium by sandwich enzyme-linked immunosorbent assay and Western blot. Albumin mRNA expression was analyzed by Northern blotting in CsA-treated cells. Results CsA (10-7-10-4 M) inhibited albumin synthesis in Huh7 cells in a dose- dependent manner. A Western blot analysis for albumin in the conditioned medium released from CsA-treated (10-7-10-5 M) cells also showed significant inhibition of albumin synthesis in a dose-dependent manner. Vehicle (olive oil) did not affect albumin synthesis. In contrast, a Northern blot analysis revealed no inhibition of albumin mRNA expression by CsA at any time point from 1-24 hours, indicating that the inhibition of albumin synthesis occurred at the translational level. Conclusions Our results suggest that inhibition of hepatic albumin synthesis by high dose CsA contributes to the hypoalbuminemia in renal transplant recipients.

Clinical Outcomes of Colonizer With MRSA and VRE Among Living Donor Liver Transplant Recipients.: Abstract# C1951

C1951 Clinical Outcomes of Colonizer With MRSA and VRE Among Living Donor Liver Transplant Recipients. S. Kim,1 Y. Kim,1 Y. Jeon,1 J. Choi,1 S. Yoon,1 J. Kim,2 I. Moon,2 Y. Yoo,2 D. Kim.2 1Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, Republic of; 2Department of Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, Republic of. Introduction Liver transplant patients have high risk of colonization with multidrug resistant bacteria such as MRSA and VRE, because their multiple admission, prolonged hospitalization and recent use of broad spectrum antibiotics. We evaluated the prevalence of colonization at immediate postoperative care among liver transplant recipients by active surveillance culture (ASC) and clinical outcomes of MRSA and VRE colonizer. Methods We performed ASC for MRSA and VRE in 162 liver transplant recipients who admitted in transplant ICU within 24 hours of ICU admission. Results Among a total of 162 liver transplant recipients, 142 patients (87.7%) had both a nasal and rectal ASC. VRE colonization was detected from 37 patients (22.8%) on initial ASC. Five patients (13.5%) developed VRE infection among 37 VRE colonizer, including 3 cholangitis and 2 peritonitis. Among 105 patients who were not colonized VRE at initial ASC, 8 (7.6%) patients developed VRE infection; 4 cholangitis, 3 peritonitis and 1 urinary tract infection. Liver transplant recipients with VRE colonization at initial ASC developed more VRE infection than noncolonized patients, however this is not signifi cant (13.5% [5/37] vs. 7.6% [8/105], p= 0.28). VRE colonization was not associated with high mortality or increased duration of postoperative stay. MRSA nasal colonization was detected from 12 patients (7.4%) on initial ASC. MRSA infections were developed in 20 patients, including 7 pneumonia, 7 peritonitis, 4 catheter related infection and 2 wound infection. Patients who was colonized with nasal MRSA at initial ASC signifi cantly developed more MRSA infection than those who were not colonized with MRSA (58.4% [7/12] vs. 10% [13/130]), p<0.001). MRSA colonizer showed higher infection-related mortality than noncolonized patients, but this was not signifi cant (8.3% [1/12] vs. 6.9% [9/130], p=0.86) Conclusion In our study, MRSA colonized liver transplant recipients have higher risk of MRSA infections, and greater mortality, compared with noncolonized recipients, although failed to show a signifi cant difference. VRE colonization is associated with an increased risk of VRE infections and mortality. Abstract# C1952 Prospective Analysis of Predictors of New Onset Diabetes After Liver Transplantation. J. Reynolds, Y. Chang, H. Chakkera, B. Aqel, T. Byrne, D. Douglas, A. Moss, H. Vargas, E. Carey. Mayo Clinic, Phoenix, AZ. Background: New-onset diabetes mellitus after solid organ transplant (NODAT) is a poorly understood phenomenon associated with decreased allograft and patient survival. Most existing literature on NODAT is limited to retrospective studies. Aim: We sought to prospectively study the incidence and timing of NODAT in a cohort of non-diabetic liver transplant (LT) recipients. We also studied the role of oral glucose tolerance testing (OGTT), adiponectin, leptin, and C-reactive protein (CRP) to determine their prognostic signifi cance in the development of NODAT. Methods: We prospectively identifi ed a cohort of non-diabetic adult subjects undergoing initial LT between April 2010 and January 2013. Recipients of multiorgan transplant, and subjects on corticosteroids prior to LT were excluded. Demographics, clinical characteristics, and lab data including adiponectin, leptin, 2-hour OGTT, and CRP were collected at baseline and at regular intervals for one year post-LT. The primary outcome was the onset of NODAT within 1-, 4-, or 12-months post-LT. Onset of NODAT was defi ned by fasting glucose >126 mg/dL, random glucose >200 mg/dL, or 2-hour OGTT >200 mg/dL. Secondary outcomes included identifying predictors of NODAT. Continuous variables were assessed with descriptive statistics. A time-to-event analysis using Kaplan-Meier survival curve was used for the primary outcome. The Cox-proportional hazards model was used to identify predictors of NODAT. Results: Of 49 subjects, 8 (16.3%) developed NODAT with 7/8 cases identifi ed in the fi rst month post-LT. Baseline clinical characteristics were similar in both groups pre-LT. Baseline fasting glucose was higher in subjects who developed NODAT (96.9 vs 105.3 mg/dL, p=0.046), although 2-hour OGTT was not signifi cantly different (157.1 vs 155.4 mg/dL, p=0.843). On multivariate analysis, a 10-unit increase in fasting glucose at baseline had an 80% increase in the hazard of NODAT (HR 1.80, 0.91-3.57, p=0.094). A 10-unit increase in leptin at baseline had a 14% increase in hazard of NODAT (HR 1.14, 0.998-1.305, p=0.054). Although neither variable reached statistical signifi cance, both showed trends which may have been limited by sample size. Conclusions: We found a 16% incidence rate of NODAT in our LT recipients. Baseline fasting glucose and serum leptin levels may be predictive of the future development of NODAT. Further studies with larger sample sizes will be needed. Abstract# C1953 Combined Liver Kidney Transplant (CLKT) and Subsequent Kidney Transplant in Liver Transplant Recipients (KALT) in a Single Center. L. Requiao-Moura,1 A. Matos,1 E. Tonato,1 M. Silva,1 M. Dias,2 M. Durao,1 A. Pacheco-Silva.1 1Renal Transplant Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil; 2Liver Transplant Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. C1953 Combined Liver Kidney Transplant (CLKT) and Subsequent Kidney Transplant in Liver Transplant Recipients (KALT) in a Single Center. L. Requiao-Moura,1 A. Matos,1 E. Tonato,1 M. Silva,1 M. Dias,2 M. Durao,1 A. Pacheco-Silva.1 1Renal Transplant Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil; 2Liver Transplant Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. Background: The increasing survival in patients submitted to liver transplantation as well as the implementation of the MELD score has substantially increased the prevalence of chronic kidney disease (CKD) among these individuals. Aim: To evaluate the experience of a decade of CLKT and KALT in a Transplant Program with a large number of liver transplanted patients in São Paulo, Brazil. Methods: we performed a longitudinal and observational trial to evaluate the CLK and KAL transplants performed at the institution since the beginning of transplantation program at the institution, in 2002. The analyzed outcomes were: acute rejection (AR-k) and delayed graft function (DGF-k) in kidney graft, estimated glomerular fi ltration rate (GFR) and one year kidney graft survival. Results: In this period (2002 to May/2011), 56 transplants (CLKT and KALT) were performed: 39 were submitted to CLKT (69.6%) and 17 to KALT (30.4%). The main cause of liver failure in the study population was hepatitis C virus (HCV) infection, with no signifi cant differences between CLKT (41%) and KALT (26%). The cause of CKD was undetermined in most patients (32.1%) of both subgroups, being the toxicity of calcineurin inhibitors the most important cause among KALT patients (0 vs. 29.4%). As expected, waiting time to transplant was longer in KALT than in CLKT (18.2 vs. 25.1 months p= 0.003). CIT was lower among KALT patients (13.0 vs. 21.2, p<0.001), and patients submitted to CLKT were inducted with Thymoglobulin more frequently: 8.1% vs. 80%, p<0.001. The prevalence of DGF-k was similar among both groups (66.7 vs. 70.6%, p=NS), despite of similar cold ischemia time. The prevalence of AR-k was 24.3% among KALT and 12.5% among CLKT (p=NS). It has been observed a trend towards higher 1-year-GFR in the KALT group (65.5 vs. 61.0 ml/min p = 0.63). Death was more frequent in CLKT (35.9% vs. 23.5%, p=0.26). Conclusion: acute rejection was more frequent in patients submitted to KALT, probably because of Thymoglobulin use. Graft function and death were similar among both groups. Abstract# C1954 Smoking History Is Strongly Associated With Decreased Grip Strength in Cirrhotic Patients Undergoing Evaluation for Liver Transplantation. V. Vilchez, R. Galuppo, A. Zanni, K. Esser, T. Patel, S. Alagusundaramoorthy, A. Dela Cruz, R. Gedaly-Eidelman. Surgery, University of Kentucky, Lexington, KY. C1954 Smoking History Is Strongly Associated With Decreased Grip Strength in Cirrhotic Patients Undergoing Evaluation for Liver Transplantation. V. Vilchez, R. Galuppo, A. Zanni, K. Esser, T. Patel, S. Alagusundaramoorthy, A. Dela Cruz, R. Gedaly-Eidelman. Surgery, University of Kentucky, Lexington, KY.