Joo Hee Jung

Isoniazid treatment to prevent TB in kidney and pancreas transplant recipients based on an interferon-γ-releasing assay: an exploratory randomized controlled trial

BACKGROUND We performed a randomized trial of isoniazid treatment based on interferon-γ-releasing assay (IGRA) in kidney transplant (KT) recipients in an intermediate-TB-burden country. METHODS All adult patients admitted to a KT institute between June 2010 and May 2013 were enrolled. The IGRA (T-SPOT.TB assay) was performed on all patients, and isoniazid treatment was given to those with clinical risk factors for latent TB infection (LTBI). Patients with positive IGRA who had no clinical risk factors for LTBI were randomly assigned to isoniazid treatment or a control group. The development of TB after KT was monitored between June 2010 and November 2013. The primary endpoint was the development of TB. RESULTS Of the 784 patients who had no clinical risk factors for LTBI, 445 (57%) gave negative results in the IGRA, 76 (10%) indeterminate results and 263 (33%) positive results. Of the latter, 131 were allocated to isoniazid treatment and 132 to the control group. Three (2%) of the control group developed TB, whereas none of the isoniazid treatment group developed TB (rate difference 1.22 per 100 person-years, P = 0.09). Of the 521 patients with negative or indeterminate IGRA results, 4 [0.8%, 0.43 per 100 person-years (95% CI 0.12-1.09)] developed TB after KT. CONCLUSIONS IGRA-based isoniazid treatment has a trend towards reducing TB development in KT recipients without clinical risk factors, but careful monitoring of TB development is needed in negative-IGRA KT recipients.

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

Background/Aims: Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. Methods: We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. Results: The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). Conclusions: The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.

Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study

Background Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation. Materials and Methods All adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves. Results A total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04). Conclusion Negative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

Pancreas Transplantation From Living Donors: A Single Center Experience of 20 Cases.

Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage–related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK.

Long‐term impact of human leukocyte antigen mismatches combined with expanded criteria donor on allograft outcomes in deceased donor kidney transplantation

The long‐term impact of human leukocyte antigen (HLA) mismatches combined with expanded criteria donors (ECD) on clinical outcomes has not been fully evaluated in recipients of deceased donor (DD) kidney transplantations. Of 595 DD renal transplant recipients in our center between 1991 and 2011, 210 recipients (36%) had 0–3 HLA mismatches/standard criteria donor (SCD), 353 (59%) had 4–6 HLA mismatches/SCD or 0–3 HLA mismatches/ECD, and 32 (5%) had 4–6 HLA mismatches/ECD. The mortality rate was significantly highest in the patients with 4–6 HLA mismatches/ECD (p = 0.040). The most common cause of death in this group was infection (50%). There were no significant differences in overall graft survival and death‐censored graft survival. The biopsy‐proven acute rejection rate was significantly higher in the 4–6 HLA mismatches/ECD group (p = 0.011). Cox‐regression multivariate analyses showed that 4–6 HLA mismatches plus ECD (adjusted hazard ratio [AHR], 3.2; 95% confidence interval [CI], 1.17–10.56) and diabetes (AHR, 4.3; 95% CI, 1.50–12.28) were significant predictors of recipient mortality. In conclusion, ≥4 HLA mismatches plus ECD were associated with significantly higher rates of biopsy‐proven acute rejection and mortality compared with other groups undergoing DD kidney transplantation.

Long-term Effects of Delayed Graft Function on Pancreas Graft Survival After Pancreas Transplantation.

Background Compared with the impact of delayed graft function (DGF) after renal transplantation, DGF after pancreas transplantation has not been fully evaluated. Methods We retrospectively verified the impact of DGF on long-term pancreas graft survival in surgically successful cases. Pancreas graft failure was defined by the recipient’s return to exogenous insulin administration. Results Between May 2004 and April 2013, we performed 135 technically successful primary pancreas transplantations. Delayed graft function was defined as a total cumulative insulin requirement of 19 UI or greater within postoperative 7 days. Of the 135 recipients in our study cohort, 47 (34.8%) developed DGF after the pancreas transplantation. By multivariate analysis, DGF was found to be associated with a donor age of 30 years or older (odds ratio, 3.4; 95% confidence interval, 1.50–7.69; P=0.003) and the increased ratio of body mass index in a recipient to a donor (odds ratio, 26.1; 95% confidence interval, 2.53–270.0; P=0.006). There was a trend toward higher acute rejection (P=0.622) and mortality (P=0.49) rates in recipients with versus without DGF, although this did not reach statistical significance. Delayed graft function was found to be associated with a greater risk of overall pancreas graft failure (P=0.016) and death-censored graft failure (P=0.037). Conclusion Delayed graft function after pancreas transplantation was found to be associated with a greater risk of overall pancreas graft failure and death-censored graft failure.

Analysis of 4000 kidney transplantations in a single center: Across immunological barriers.

AbstractKidney transplant (KT) is the optimal renal replacement therapy for patients with end-stage renal disease (ESRD). The demand for kidneys, however, continues to exceed the supply. To overcome this problem, efforts to extend the donor pool by including human leukocyte antigen (HLA)- and ABO-incompatible (ABOi) KTs are increasing. The aim of this article was to retrospectively review data on recipients, donor profiles, and clinical outcomes in 4000 cases of KT. In addition, we analyzed clinical outcomes in ABOi and flow-cytometric crossmatch (FCXM) positive KT in a subgroup analysis.This was a retrospective, observational study using data extracted from medical records. A total of 4000 consecutive patients who underwent KT at our institution from January 1990 to February 2015 were included in this study. KTs across immunological barriers such as ABO incompatible (276 cases, 6.9%), FCXM positive (97 cases, 2.4%), and positive complement-dependent cytotoxicity (CDC) XM KT (16 cases, 0.4%) were included.From a Kaplan–Meier analysis, overall patient survival (PS) rates after KT at 1, 5, 10, and 20 years were 96.9%, 95.1%, 92.0%, and 88.9%, respectively. The overall graft survival (GS) rates after KT at 1, 5, 10, and 20 years were 96.3%, 88.9%, 81.2%, and 67.4%, respectively. Our subgroup analysis suggested that overall PS, GS, death-censored GS, and rejection-free GS in ABOi KT showed no significant differences in comparison with ABO-compatible KT if adequate immunosuppressive treatment was performed. The overall PS rate in patients who underwent FCXM positive KT did not differ significantly from that of the control group during the 3-year follow-up (P = 0.34). The overall GS, death-censored GS, and rejection-free GS also did not differ significantly between the FCXM KT and control groups (P = 0.99, 0.42, and 88).The outcomes of KTs continually improved during the study period, while the annual number of KTs increased. ABO or FCXM positive KTs can be performed safely with successful graft outcomes.

Long-term Metabolic Outcomes of Functioning Pancreas Transplants in Type 2 Diabetic Recipients.

Background Limited data are available regarding the long-term metabolic outcomes of functioning pancreas transplants in patients with type 2 diabetes mellitus (T2DM). Methods To compare the long-term effects of pancreas transplantation in terms of insulin resistance and &bgr; cell function, comparison of metabolic variables was performed between type 1 diabetes mellitus (T1DM) and T2DM patients from 1-month posttransplant to 5 years using generalized, linear-mixed models for repeated measures. Results Among 217 consecutive patients who underwent pancreas transplantation at our center between August 2004 and January 2015, 193 patients (151 T1DM and 42 T2DM) were included in this study. Throughout the follow-up period, postoperative hemoglobin A1c did not differ significantly between T1DM and T2DM patients, and the levels were constantly below 6% (42 mmol/mol) until 5 years posttransplant, whereas C-peptide was significantly higher in T2DM (P = 0.014). There was no difference in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, HOMA &bgr; cell, or the insulinogenic index between the groups. Furthermore, fasting insulin and HOMA-insulin resistance steadily decreased in both groups during the follow-up period. Conclusions There was no significant difference in the insulin resistance or &bgr;-cell function after pancreas transplantation between T1DM and T2DM patients. We demonstrated that pancreas transplantation is capable of sustaining favorable endocrine functions for more than 5 years in T2DM recipients.

Analysis of 400 ABO Incompatible Kidney Transplantations : a Single Center Experience

Objectives This study describes the single center experience and long-term results of ABO incompatible kidney transplantation (ABO i KT). Methods 400 patients who received an ABO i KT in the period from February 2009 to December 2016 in Asan Medical Center were retrospectively reviewed. After we experienced lethal infectious complications in the first 89 patients (Era1), a pre-transplantation protocol was modified using lower dose of rituximab, selective use of calcineurin inhibitors and anti-metabolite reduction, and prophylactic strategy(Era2). Results The overall patient survival rates after ABO i KT at 1, 3,and 5 years were 97.9%, 97.4%, and 95.9%.The death censored graft survival rates at 1, 3,and 5 years were 98.9%, 98.1%, and 97.7%. The rejection free graft survival rates at 1, 3,and 5 years were 91.4%, 85.0%, and 82.6%. The overall patient survival rates stratified by era showed a significant difference between era1 and era2 during 5-year follow-up(88.7% vs. 96.7%, P = 0.014) due to infectious complications. Neither was there a significant difference in the 5-year death censored graft survival rates (era1 vs. era2; 98.9% vs. 97.8%, P = 0.85) and the 5-year rejection free graft survival (era1 vs. era2; 85.6% vs. 82.2%, P = 0.34). Infectious complications decreased significantly in era2, including cytomegaloviremia (64.1% vs 30.1%, P < 0.001) and BK viremia ≥ 4logs (15.6% vs 11.3%, P=0.08). Conclusion ABO-incompatible kidney transplantation can be performed safely with a successful graft outcome. Modification of immunosuppression according to host conditions is recommended for the prevention of infectious complications. Figure. No caption available. Figure. No caption available. Figure. No caption available.

Clinical Outcome after Simultaneous Heart and Kidney Transplantation

Background Simultaneous heart kidney transplantation (SHKT) is an acceptable treatment for patients with end stage heart disease associated with severely impaired kidney function. Methods We reviewed medical record of our registered patients from September 1990 and July 2017. 5 patients underwent SHKT in our center. All the patients were treated with basiliximab induction and maintained with tacrolimus, steroid and mycophenolate. Results 4 patients were male (80.0%). Mean age at transplant was 49.6 ± 12.4 years (range, 33~66). All patients were on dialysis at transplant. The indications for heart transplantation included dilated cardiomyopathy (n=4), ischemic cardiomyopathy (n=1). Surgical procedures were uneventful in all patients. Median follow-up after transplantation was 53 months (range, 5~152). 2 patients had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant). 1 patient had coronary artery disease, but no cardiac allograft rejection was noted. Acute cellular kidney rejection occurred in 2 patients. There was no cardiac or kidney graft failure during follow-up. Conclusion SHKT is a good choice for long-term survival in patients with end stage heart and kidney failure.