Comparison of the tuberculin skin test and interferon-γ release assay for the diagnosis of latent tuberculosis infection before kidney transplantation.

PURPOSE: The evaluation of latent tuberculosis infection (LTBI) is recommended before kidney transplantation. The interferon-γ release assay has been reported to be more specific than the tuberculin skin test (TST) for detecting LTBI. We compared the TST and QuantiFERON-TB Gold In-Tube test (QFT-GIT) for the screening for LTBI and determined the agreement between the two tests in renal transplant recipients before transplantation. METHODS: Adult patients who were evaluated for renal transplantation between May 2010 and February 2012 at Severance Hospital in South Korea were prospectively enrolled. We performed TST and QFT-GIT. RESULTS: Of the 126 patients, 23 (19.3 %) had positive TST results and 53 (42.1 %) had positive QFT-GIT results. Agreement between the TST and QFT-GIT was fair (κ = 0.26, P < 0.001). The induration size of TST was significantly correlated with a positive rate of QFT-GIT (P = 0.015). Age (odds ratio [OR] 1.08, 95 % confidence interval [CI] 1.03-1.13, P = 0.003), male sex (OR 2.73, 95 % CI 1.17-6.38, P = 0.021), and risk for LTBI (OR 4.62, 95 % CI 1.15-18.64, P = 0.031) were significantly associated with positive QFT-GIT results. For positive TST results, only male sex was associated (OR 4.29, 95 % CI 1.40-13.20, P = 0.011). CONCLUSION: The positivity for QFT-GIT was higher than the positivity for TST, and QFT-GIT more accurately reflected the risk for LTBI. However, a further longitudinal study is needed in order to confirm that the QFT-GIT test can truly predict the development of TB after renal transplantation.

Invasive pulmonary aspergillosis after solid organ transplantation: diagnosis and treatment based on 28 years of transplantation experience.

Invasive pulmonary aspergillosis (IPA) is a serious and lethal complication among organ transplant recipients. This report described the clinical manifestations and treatment of IPA over a 28-year period. From January 1979 to December 2007, 3215 organ transplant patients (2954 kidney and 261 liver recipients) were enrolled in the study. Nine patients developed IPA (7 kidney and 2 liver recipients), yielding an incidence of 0.003% (9/3215). Five IPA patients (55.6%) were diagnosed by transbronchial lung biopsy or autopsy, and 3 (33.3%) by sputum culture study. One patient was diagnosed through clinical manifestations and observations of IPA characteristics on chest X ray. We used amphotericin B (n = 4; 44.4%), voriconazole (n = 2; 22.2%), or fluconazole (n = 1; 11.1%) as the primary antifungal agents, but 2 patients could not receive antifungal agents due to rapid disease progression and sequential mortality. This study showed a high mortality rate among IPA patients (55.6%; 5/9). Only patients who received early antifungal agent thereby after a prompt diagnosis recovered from IPA. This survival advantage warrants careful monitoring for invasive fungal infections after organ transplantation with immediate administration of antifungal agents or surgical intervention.

Coculture With Ischemia/Reperfusion-Preconditioned Hepatocytes Improves Islet Function and Survival.

In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-ß1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion.

Acquisition of Carbapenemase-Producing Enterobacteriaceae in Solid Organ Transplantation Recipients.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) can lead to life-threatening outcomes with rapid spread of the carbapenemase gene in solid organ transplantation (SOT) recipients because of limitations of available antibiotics. We examined the characteristics and importance of CPE acquisition in SOT recipients with large numbers of CPE isolates. METHODS: Between November 2015 and October 2016, 584 CPE isolates were found in 37 recipients and verified by carbapenemase gene multiplex polymerase chain reaction (PCR). One hundred recipients with at least 2 negative results in carbapenemase PCR for stool surveillance and no CPE isolates in clinical samples were retrospectively included. RESULTS: Most CPE isolates were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (546, 93.5%). The most frequent transplantation organ was lung (43.3%), and the most common sample with CPE isolates other than stool was respiratory tract (22.6%). The median time between SOT and first CPE acquisition was 7 days. All-cause mortality was significantly higher in recipients with CPE than in those without CPE (24.3% vs 10.0%; P = .03). In multivariate regression analysis, stool colonization of vancomycin-resistant Enterococci and/or Clostridium difficile during 30 days before SOT (odds ratio [OR], 3.28; 95% CI, 1.24-8.68; P = .02), lung transplantation (OR, 4.50; 95% CI, 1.19-17.03; P = .03), and intensive care unit stay ≥2 weeks (OR, 6.21; 95% CI, 1.72-22.45; P = .005) were associated with acquisition of CPE. CONCLUSIONS: Early posttransplantation CPE acquisition may affect the clinical outcome of SOT recipients. Careful screening for CPE during the early posttransplantation period would be meaningful in recipients with risk factors.

Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets.

BACKGROUND: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments. METHODS: Splenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4(+) T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies. RESULTS: Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg. CONCLUSION: Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells.

Comparative Proteomic Analysis of Rapamycin Versus Cyclosporine Combination Treatment in Mouse Podocytes.

BACKGROUND: The mechanism of podocyte injury observed with the use of rapamycin (RPM) remains unclear. The conversion from calcineurin inhibitors (CNIs) to RPM in kidney transplant recipients has been associated with a higher incidence of proteinuria and renal injury. In this study, we performed proteomic analyses to investigate the alteration of protein expression in mouse podocytes treated with RPM in comparison with CNI/RPM combination. METHODS: Immortalized mouse podocytes were treated with 20 nmol/L RPM or 20 nmol/L RPM + 1 µg/mL cyclosporine. Podocyte proteins were separated by 2-dimensional polyacrylamide gel electrophoresis (2DE) and identified by matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry and peptide fingerprinting. Selected proteins were analyzed by means of Western blot assay. RESULTS: We identified 36 differently expressed proteins after isolated RPM or CNI/RPM combination treatment in cultured mouse podocytes. There are 3 distinct patterns of protein expression: (1) potentiated down- or upregulation of proteins by CNI/RPM treatment compared with isolated RPM treatment (n = 4); (2) partial offset of down-regulation by CNI/RPM in comparison with RPM treatment (n = 25); (3) no difference in down-regulation between RPM and CNI/RPM treatment (n = 5). We found a significant interplay between RPM and CNI on the expression of the selected proteins in mouse podocytes. This might explain the higher incidence of proteinuria by CNI/RPM combination in clinical settings. CONCLUSIONS: Further study is required to elucidate the target protein associated with RPM-induced podocyte injury.

Significance of Time-Zero Biopsy for Graft Renal Function After Deceased Donor Kidney Transplantation.

BACKGROUND: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. METHODS: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. RESULTS: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. CONCLUSIONS: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.

Development and Applicability of the A-P 200 Criteria for Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: The Milan criteria are widely accepted for indicating liver transplantation in patients with hepatocellular carcinoma (HCC). However, a 7% to 20% possibility of HCC recurrence remains, even among patients who fulfill the Milan criteria. METHODS: We retrospectively reviewed 88 patients with HCC who underwent liver transplantation at Pusan National University Yangsan Hospital between May 2010 and December 2014. The risk factors for HCC recurrence were analyzed, and the overall survival and disease-free survival rates were calculated based on each risk factor. RESULTS: Seventeen patients (19.3%) experienced HCC recurrence. Multivariate analyses revealed that the independent risk factors for HCC recurrence were protein induced by vitamin K absence or antagonist II (PIVKA-II) levels of >200 mAU/mL, levels of >200 for alpha-fetoprotein (ng/mL) or PIVKA-II (mAU/mL), and microvascular invasion. Therefore, we defined the A-P 200 criteria as simultaneously exhibiting alpha-fetoprotein levels of ≤200 ng/mL and PIVKA-II levels of ≤200 mAU/mL. The 3-year overall survival rates among patients who fulfilled or exceeded the A-P 200 criteria were 89.2% and 80.0%, respectively (P = .79). The 3-year disease-free survival rates among patients who fulfilled or exceeded the A-P 200 criteria were 89.9% and 43.1%, respectively (P < .001). We also applied the A-P 200 criteria to patient data from another major center and observed similar results. CONCLUSION: These findings confirm that the A-P 200 criteria can be used to predict recurrence after liver transplantation among patients with HCC.

Results of ABO-incompatible liver transplantation using a simplified protocol at a single institution.

BACKGROUND: Because of the development of various desensitization strategies, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has become a feasible option for patients with end-stage liver disease. However, there has been no united desensitization protocol for ABOi LDLT. We analyzed the outcomes after establishment of simplified protocol without splenectomy, intravenous immunoglobulin, and local infusion therapy. METHODS: We analyzed 19 ABOi LDLT cases that had been performed between January 2012 and December 2013, without splenectomy and local infusion. We used a single dose of rituximab (375 mg/m(2)) 10 days before transplantation and several series of plasma exchange according to the recipients' iso-agglutinin titer-to-target titer ratio of 1:32. RESULTS: Nineteen recipients received ABOi LTs from living donors. The mean initial immunoglobulin (Ig) M and IgG anti-ABO titers were 76.63 ± 78.81 (range, 8∼256) and 162.53 ± 464.1 (0∼2048). We performed preoperative plasma exchange to 16 recipients (mean number of sessions, 3.58; range, 1-10). After surgery, 9 patients received plasma exchange (mean, 1.84; range 1∼14). One death occurred as the result of pneumonia (5.3%). There were 4 cases of acute rejections (21.1%), and all of them were treated successfully with steroid pulse or thymoglobulin. Antibody-mediated rejection and graft failure did not occur. Six cases of postoperative complications (31.6%) occurred, including 3 cases of infections. There were 2 cases of biliary anastomotic stricture (10.5%) and 1 case of portal vein stenosis (5.3%). CONCLUSIONS: ABOi LDLT with the use of simplified protocol can be safely performed without increased risk of antibody-mediated rejection and other complications.

Application of synthetic poly(DADM) flocculants for dye wastewater treatment.

Poly(DADM) flocculants were synthesized and applied for the removal of color, turbidity and organic materials from dye wastewater. The effect of poly(DADM) on color removal was investigated by comparing two treatments: (i) alum alone and (ii) alum/poly(DADM) in combination. The effects of poly(DADM) flocculant, poly(DADM) concentration, poly(DADM) types and pH on the removal efficiency of coloring materials were investigated. Poly(DADM) flocculants were highly efficient in the removal of color and turbidity from dye wastewater. Compared to treatment with alum alone, the addition of a small amount of poly(DADM) (25 mg l(-1)) reduced alum dosage by 50% while improving color removal efficiency. Highly efficient color removal was obtained in wide pH ranges by adding poly(DADM) as a flocculant. Our results indicate that the use of poly(DADM) flocculant is cost effective in dye wastewater treatment by reducing sludge production and the dosage of inorganic coagulant. Effects of zeta potential were also investigated.

PRMT3: new binding molecule to RhoGDI-α during mycophenolic acid-induced ß-cell death.

Mycophenolic acid (MPA)-induced beta cell toxicity limits islet graft survival. However, the signal transduction mechanisms underlying MPA-induced ß-cell toxicity have not been fully elucidated. Previously, we showed that MPA-induced pancreatic ß-cell apoptosis proceeds via RhoGDI-α down-regulation linked to Rac1 activation. In the present study, we investigated factors affecting RhoGDI-α during MPA-induced ß-cell apoptosis. The presence of RhoGDI-α-related protein was determined with the use of yeast 2-hybrid (Y2H) analysis. Y2H screening of RhoGDI-α was performed in yeast PBN204 strain containing 3 reporters (URA3, lacZ, and ADE2) under the control of different GAL promoters. INS-1E cells (an insulin-secreting pancreatic ß-cell line) were treated with MPA for 12, 24, and 36 hours. Eighty-three real positives were obtained by Y2H analysis, and of these, arginine N-methyltransferase 3 (PRMT3) protein interacted with RhoGDI-α in INS-1E cells. PRMT3 gene expressions and its protein levels were significantly decreased during MPA-induced apoptosis. In summary, PRMT3 and RhoGDI-α were found to interact in INS-1E cells. Furthermore, MPA was found to regulate this interaction in INS-1E cells by down-regulating the gene expression of PRMT3. These findings suggest that control of the interaction between PRMT3 and RhoGDI-α could be used to prevent MPA-induced ß-cell death.

Do the abnormal results of an implantation renal biopsy affect the donor renal function?

BACKGROUND: Living kidney donation has become an important source for renal transplantation. Thus, renal function after donation is an important issue. In this study, we examined histological abnormalities in implantation biopsy specimens from living kidney donors and analyzed the renal function of the remaining kidney. METHODS: Using the 2007 Banff classification system, we analyzed 121 kidneys from living donors who underwent implantation biopsies (IBs) between 2010 and 2011. Donor characteristics, intraoperative factors, and perioperative renal functions, such as serum creatinine and glomerular filtration rate (GFR), were evaluated. Univariate and multivariate regression analyses were performed to identify the factors related to each histological abnormality and postoperative 1-year donor renal function. RESULTS: Most histological abnormalities in healthy living donors were scored as 1 on the Banff scale. Univariate and multivariate analyses revealed that donor age was the only preoperative factor related to tubular atrophy (odds ratio [OR] = 1.104; P = .012) and glomerular sclerosis (OR = 1.050; P = .019). Intraoperative factors were not related to histological parameters. And histological abnormalities did not affect postoperative 1-year renal function. In contrast, donor age, preoperative GFR, and estimated blood loss were significantly related to 1-year postoperative GFR. CONCLUSION: Most histological abnormalities in healthy living donors were minor. The incidence of abnormalities correlated with donor age. However, postoperative renal functions in living donors were not affected by histological abnormalities. Larger-scale investigations with long-term follow-up analysis will be needed.

Preconditioning effects of the anesthetic administered to the donor on grafted kidney function in living donor kidney transplantation recipients.

BACKGROUND: In living donor kidney transplantation (LDKT), we evaluated if there was any difference in grafted kidney function according to the type of anesthetic used in the donor because some laboratory studies have demonstrated that volatile anesthetics at clinically relevant concentrations protect the kidneys against renal ischemia-reperfusion injury. METHODS: In part I of the study, we retrospectively compared grafted kidney function [serum creatinine levels (Cr) and estimated glomerular filtration rates (eGFR) in recipients of LDKT] according to the type of donors' volatile anesthetic (sevoflurane [group Sevo, 166 patients], isoflurane [group Iso, 55] or desflurane [group Des, 61]). In part II, we prospectively compared grafted kidney function and neutrophil gelatinase-associated lipocalin (NGAL) levels in the serum and urine of recipients according to the anesthetic used in the donor (desflurane [group Des, N.=50] vs. propofol [group Pro, N.=50]). RESULTS: In part I, the eGFR of the Des group was greater than that of the Sevo or Iso groups (P=0.017) until POD 7. However, in part II, there were no significant changes in Cr and eGFR by POD 7, no differences in the levels of NGAL in the serum and urine on POD 1 and 2, or in Cr and eGFR on the day of discharge between the Des and Pro groups. CONCLUSIONS: The inhalational anesthetic administered to donors does not improve grafted kidney function in recipients undergoing LDKT to a greater extent than propofol.

Laparoscopic fenestration versus percutaneous catheter drainage for lymphocele treatment after kidney transplantation.

BACKGROUND: Laparoscopic fenestration (LF) and percutaneous catheter drainage (PCD) are widely accepted treatments for symptomatic lymphoceles. The aim of this study was to review the results and compare the outcomes of LF with those of PCD. PATIENTS AND METHODS: Among 1363 patients who underwent kidney transplantation at our institute between 1999 and 2011, 35 (2.5%) developed symptomatic lymphoceles. Among them, 7 were treated by LF after PCD; 10, LF only, and 18 PCD only. The patients were divided into 2 groups based upon the treatment method: LF (n = 17) and PCD-only groups (n = 18). RESULTS: No intergroup differences in age, gender, diabetes prevalence, retransplant rate, delayed graft function, or serum creatinine was observed at 7 days after the treatment. However, acute rejection episodes and sirolimus use were more frequent among the LF group (P = .028). Furthermore, median drainage on the first day was significantly greater in the LF versus PCD group. After catheter insertion, the PCD group showed a significant decrease in drainage on the following day, but no decrease was observed in the LF group. CONCLUSIONS: LF is a safe treatment for symptomatic lymphocele. LF should be held in reserve for treatment failures after PCD. LF seems to be a more reasonable first-line treatment for symptomatic lymphoceles in patients at high risk for graft dysfunction.

The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells.

Mycophenolic acid (MPA) is one of many effective immunosuppressive drugs. However, MPA can induce cellular toxicity and impair cellular function in ß-cells. To explore the effects of MPA and the relation between MPA and Trx-1, we used various methods, including an Illumina microarray, to identify the genes regulated during pancreatic ß-cell death following MPA treatment. INS-1E cells (a pancreatic ß-cell line) and isolated rat islets were treated with MPA for 12, 24, or 36 h, and subsequent microarray analysis showed that (Trx1) gene expression was significantly reduced by MPA. Further, Trx1 overexpression increased the cell viability, decreased the activations of c-jun N-terminal kinase (JNK) and caspase-3 by MPA, and attenuated ROS upregulation by MPA. Furthermore, siRNA knockdown of Trx1 increased MPA-induced cell death and the activations of p-JNK and caspase-3, and MPA significantly provoked the apoptosis of insulin-secreting cells via Trx1 downregulation. Our findings suggest that the prevention of Trx1 downregulation in response to MPA is critical for successful islet transplantation.

The impact of time-zero biopsy on early graft outcomes after living donor kidney transplantation.

BACKGROUND: In contrast with deceased donor transplantation, the clinical significance of pathologic findings in time-zero biopsies after living donor kidney transplantation are rarely reported, due to the expectation that histologic findings and renal function are normal. The aim of this study was to identify subclinical pathologic findings in living donors and examine the effect on early graft renal function. METHODS: Between December 2006 and July 2011, 146 living-donor kidney transplant recipients were enrolled in this study. We retrospectively analyzed donor and recipient-related clinical parameters, and post-transplant 6 months and 1 year estimated glomerular filtration rate (eGFR) as early graft renal function. Time-zero biopsies were evaluated using the 2007 Banff criteria. RESULTS: Most abnormal histologic findings were of mild degree as determined by Banff scores. Global glomerulosclerosis (GS, 35.6%), tubular atrophy (CT, 36.3%), interstitial fibrosis (CI, 20.5%), vascular fibrous intimal thickening (CV, 4.1%), arteriolar hyaline thickening (AH, 14.4%), interstitial inflammation (I, 3.4%) were pathologic findings in time-zero biopsies. The univariate analysis revealed that donor age and gender were significantly associated with eGFR at post-transplant 6 months and at 1 year (P < .05). Furthermore, GS and CT were significantly associated with early graft renal function (P < .05). However, multivariate linear regression analysis showed only donor age was significantly associated with early graft renal function (P = .001). CONCLUSION: A mild degree of subclinical, pathologic findings on time-zero biopsy did not affect early graft renal function in living-donor kidney transplantation.

Prognostic value of model for end-stage liver disease scores in patients with fulminant hepatic failure.

BACKGROUND: This study was undertaken to investigate risk factors of mortality in patients with fulminant hepatic failure (FHF). METHODS: Fifty-three patients with FHF treated from January 2006 to April 2011 were allocated to a spontaneous survival group (group 1), a death without liver transplantation (LT) group (group 2), and an LT group (group 3). To analyze risk factors associated with mortality in FHF, we excluded group 3 patients. Clinical features, Model for End-Stage Liver Disease (MELD) scores, and King's College Hospital criteria at the time of hepatic encephalopathy in group 2 were compared with those of group 1. RESULTS: The causes of FHF were acute viral infection (n = 29, hepatitis A:B, 28:1), drugs (n = 18; including 4 acetaminophen and 14 herbal medication), autoimmune (n = 4), and miscellaneous (n = 2). Of the 53 patients, 19 were allocated to group 1, 18 to group 2, and 16 to group 3. According to univariate analysis, risk factors for mortality in group 2 were acute renal failure requiring renal replacement therapy and a MELD score ≥30 at the time of hepatic encephalopathy. However, by multivariate analysis, a MELD score ≥30 was the only independent risk factor for mortality in group 2 (P = .042; hazard ratio, 4.500). CONCLUSIONS: A MELD score ≥30 was found to be the only independent risk factor of mortality in FHF patients without LT. Therefore, the findings of this study suggest that these patients may need emergent LT for survival.

Graft function measured by transient elastography in living donor liver transplantation: preliminary.

INTRODUCTION: Liver stiffness measurements (LSMs) using transient elastography (TE) provide a noninvasive means to assess liver fibrosis that correlate with hepatic cholestasis. However, few studies have examined the correlation of TE to obtain LSMs with perioperative clinical and laboratory parameters in living donor liver transplantation (LDLT). PATIENTS AND METHODS: We retrospectively reviewed forty-eight subjects who underwent LDLT between November 2010 and October 2012. All donors and recipients underwent TE, abdominal computed tomography (CT), and biochemical tests within 1 month before and at 1 week after transplantation. Using a cut-off LSM of 7.5 kPa, which we arbitrarily assigned to be indicative of significant fibrosis, we divided our study population into ≤7.5 kPa (group L; n = 15, 31.3%) versus >7.5 kPa; (group H; n = 33, 68.8%). RESULTS: Pretransplantation serum total bilirubin, international normalized ratio, and Model for End-stage Liver Disease scores of recipients were significantly higher in group H than group L. Regarding the pretransplantation donor characteristics, the graft-recipient weight ratio was significantly smaller among those in group H (P = .039). In addition, the post-transplantation 1-week serum total bilirubin level was significantly higher in group H (2.3 mg/dL versus 1.2 mg/dL, P = .015), although neither biliary complications norhepatic congestion was identified by abdominal CT. Among the 1-week post-transplantation laboratory findings, only total bilirubin positively correlated with LSM (P = .044). CONCLUSIONS: This pilot study suggested that a high LSM after LDLT suggests intrahepatic cholestasis and portal hypercirculation in the graft, irrespective of liver fibrosis, outflow obstruction, or biliary obstruction.

Mizoribine versus mycophenolate mofetil in combination therapy with tacrolimus for de novo kidney transplantation: evaluation of efficacy and safety.

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.

Accompanying renal injuries did not impact graft survival in patients with transplant glomerulopathy.

Transplant glomerulopathy (TG) a morphological feature of chronic active antibody-mediated rejection, is associated with donor-specific antibody, peritubular capillary deposition of C4d, and multilayering of peritubular capillary basement membranes. To evaluate the significance of accompanying nonimmunologic injuries in TG, we retrospectively reviewed 2839 renal allograft cases at our institute among which TG was diagnosed in 81 patients (2.9%). Among TG cases, 48 samples showed accompanying diseases such as chronic calcineurin inhibitor toxicity, hepatitis viral infection, posttransplant diabetes, and glomerulonephritis. Comparing the pure form of TG with TG-mixed diseases, there was no difference in patient demography, serum creatinine values, and proteinuria. Among histological parameters, severe hyalinosis was more frequently observed among the TG plus other diseases group. The two groups did not show significant difference in graft survival (P = .216).