Randomized, Open-Label, Phase IV, Korean Study of Kidney Transplant Patients Converting From Cyclosporine to Prolonged-Release Tacrolimus Plus Standard- or Reduced-Dose Corticosteroids.

BACKGROUND: This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS: At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS: Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION: Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

Distribution of Anti-ABO Immunoglobulin G Subclass and C1q Antibody in ABO-incompatible Kidney Transplantation.

INTRODUCTION: To investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subclasses, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABOi) kidney transplant recipients. We also evaluated baseline anti-ABO C1q antibody. METHOD: Baseline anti-ABO IgG titers were measured by both FCM and column agglutination technique methods in 18 ABOi kidney transplant recipients. The mean florescence intensity (MFI) ratios of baseline anti-ABO IgG subclasses and anti-ABO C1q antibody were obtained by FCM and followed-up after rituximab treatment, each plasmapheresis (PP) session, and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer was analyzed. RESULTS: The baseline MFI ratios of total IgG, IgG1, IgG2, IgG3, and IgG4 were 202.46, 62.41, 30.01, 1.04, and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer was measured using the column agglutination technique. The numbers of PP sessions to reach the target titer were correlated with the baseline IgG and IgG1 levels. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. Anti-ABO C1q antibody was neither detected nor correlated with total IgG and any IgG subclasses. CONCLUSIONS: Our findings suggest that IgG1 and IgG2 are the dominant IgG subclass in ABOi kidney transplant recipients. Baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study.

Metabolomics Study for Identification of Potential Biomarkers of Long-term Survival in Kidney Transplantation Recipients.

BACKGROUND: The recent progress and appropriate use of immunosuppressive drugs have considerably improved the short-term survival in kidney transplantation recipients (KTRs). The development of new strategies to improve long-term survival outcome after kidney transplantation is also becoming important. Although current diagnosis of allograft dysfunction relies on serum creatinine concentration and biopsy, they are nonspecific indicators of allograft function. Therefore, noninvasive, sensitive, and specific biomarkers for the prediction of long-term survival are needed. The aim of this study was to discover potential biomarkers for long-term survival in KTRs through the use of liquid chromatography-tandem mass spectrometry. METHODS: We used the metabolic approach to explore the change of metabolites in the serum of KTRs. Twenty-four KTRs with long-term good survival (LGS) and 10 KTRs with chronic antibody-mediated rejection (CAMR) were included in this study. After quantile normalization with chromatographic data, multivariate statistical analysis was performed. We attempted to analyze metabolic profiling with LGS and CAMR groups. RESULTS: The orthogonal partial least-squares discriminant analysis score plot showed a separation between 2 groups in the principal component. In the corresponding loading plot, 344 metabolites responsible for the separation observed in the score plot were identified (variable influence on projection ≥1.0). We then selected 54 metabolites to compare mass with charge by searching a web database, and 11 compounds were identified. CONCLUSIONS: We found metabolites in serum that differ in LGS and CAMR groups. Further studies are needed to figure out potential metabolomic biomarkers to predict long-term survival in KTRs.

Cystatin C-Based Equation for Predicting the Glomerular Filtration Rate in Kidney Transplant Recipients.

BACKGROUND: Precise monitoring of the glomerular filtration rate (GFR) is needed to estimate the allograft function in kidney transplant recipients (KTRs). The GFR is widely estimated with the use of formulas based on serum cystatin C (SCys) and serum creatinine (SCr) levels. We compared the efficacy of SCys-based equations with that of SCr-based equations to predict the allograft function. METHODS: We calculated the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Cr), CKD-EPI creatinine-cystatin C (CKD-EPI Cr/Cys), and CKD-EPI cystatin C (CKD-EP ICys) equations in 70 KTRs. The measured GFR (mGFR) was defined as the GFR estimated by technetium-99m-diethylene triamine pentaacetic acid (99mTc-DTPA) clearance. The accuracy and precision of the equations were compared with the mGFR. The performance characteristics of SCr and SCys were analyzed with the use of receiver operating characteristic (ROC) curves to ascertain the sensitivity and specificity at the cutoff value of <45 mL/min/1.73 m2 DTPA. RESULTS: Overall, MDRD and CKD-EPICys did not show significant differences from mGFR (P = .05 and P = .077, respectively), whereas CKD-EPI Cr and CKD-EPI Cr/Cys significantly underestimated mGFR (P < .001 and P = .005, respectively). In the subgroup of patients with mGFR <45 mL/min/1.73 m2, CKD-EPI Cys showed little bias (P = .122), whereas MDRD significantly underestimated mGFR (P = .037). The area under the ROC curve for predicting mGFR <45 mL/min/1.73 m2 was 0.80 for SCys, which was better than that for SCr at 0.763. CONCLUSIONS: Cystatin C-based equations showed better predictive performance of the allograft function than creatinine-based equations for the KTRs, including patients with lower GFR. Cystatin C level might be a good alternate measurement to monitor the allograft function.

Effect of Changes in Body Mass Index on Cardiovascular Outcomes in Kidney Transplant Recipients.

BACKGROUND: A higher body mass index (BMI) before kidney transplantation (KT) is associated with increased mortality and allograft loss in kidney transplant recipients (KTRs). However, the effect of changes in BMI after KT on these outcomes remains uncertain. The aim of this study was to investigate the effect of baseline BMI and changes in BMI on clinical outcomes in KTRs. METHODS: A total of 869 KTRs were enrolled from a multicenter observational cohort study from 2012 to 2015. Patients were divided into low and high BMI groups before KT based on a BMI cutoff point of 23 kg/m2. Differences in acute rejection and cardiovascular disease (CVD) between the 2 groups were analyzed. In addition, clinical outcomes across the 4 BMI groups divided by BMI change 1 year after KT were compared. Associations between BMI change and laboratory findings were also evaluated. RESULTS: Patients with a higher BMI before KT showed significantly increased CVD after KT (P = .027) compared with patients with a lower BMI. However, among the KTRs with a higher baseline BMI, only persistently higher BMI was associated with increased CVD during the follow-up period (P = .003). Patients with persistently higher BMI had significantly decreased high-density lipoprotein cholesterol and increased hemoglobin, triglyceride, and hemoglobin A1c levels. Baseline BMI and post-transplantation change in BMI were not related to acute rejection in KTRs. CONCLUSIONS: BMI in the 1st year after KT as well as baseline BMI were associated with CVD in KTRs. More careful monitoring of obese KTRs who do not undergo a reduction in BMI after KT is required.

Malva verticillata seed extracts upregulate the Wnt pathway in human dermal papilla cells.

OBJECTIVE: Mesenchymal-epithelial interactions are important in controlling hair growth and the hair cycle. The ß-catenin pathway of dermal papilla cells (DPCs) plays a pivotal role in morphogenesis and normal regeneration of hair follicles. Deletion of ß-catenin in the dermal papilla reduces proliferation of the hair follicle progenitor cells that generate the hair shaft and induces an early onset of the catagen phase. In this study, a modulator of the Wnt/ß-catenin activity was studied in oriental herb extracts on cultured human DPCs. METHODS: The effect of Malva verticillata (M. verticillata) seeds on human DPCs was investigated by a Wnt/ß-catenin reporter activity assay system (ß-catenin-TCF/LEF reporter gene) and cell proliferation analysis. The synthesis of the factors related to hair growth and cycling was measured at both the mRNA and the protein level by semi-quantitative PCR and Western blot analysis, respectively. RESULTS: An extract from M. verticillata seeds increased Wnt reporter activity in a concentration-dependent manner and also led to increased ß-catenin levels in cultured human DPCs. Myristoleic acid, identified as an effective compound of M. verticillata seeds, stimulated the proliferation of DPCs in a dose-dependent manner and increased transcription levels of the downstream targets: IGF-1, KGF, VEGF and HGF. Myristoleic acid also enhanced the phosphorylation of MAPKs (Akt and p38). CONCLUSION: Overall, the data suggest that this extract of M. verticillata seeds could be a good candidate for treating hair loss by modulating the Wnt/ß-catenin pathway in DPCs.

Application of flow cytometry to measure anti-A/B antibody in ABO-incompatible kidney transplantation.

BACKGROUND: The aim of this study was to compare anti-ABO antibody levels as measured by means of flow cytometry (FCM) with the levels measured with the use of the column agglutination test (CAT), and to evaluate the clinical outcome as it relates to the baseline mean fluorescence intensity (MFI) ratio obtained by FCM. METHODS: We reviewed 21 cases of ABO-incompatible kidney transplantation (ABO-i KT). In these patients, baseline IgG titers were measured with the use of both FCM and CAT methods. We investigated the correlation between levels measured by FCM and those by CAT with the use of correlation coefficients. Patients were classified into a high MFI ratio group (≥200; n = 7) or low MFI ratio group (<200; n = 14). RESULTS: The MFI ratio for the FCM-based method was highly correlated with the titer measured by CAT (r = 0.890; P = .01). The relationship between MFI ratio and CAT titer can be expressed as follows: log (MFI ratio) = 0.879 × log (CAT titer) + 0.298. The number of pre-transplantation rounds of plasmapheresis significantly increased as the baseline MFI ratio increased. The allograft function was immediately recovered and stable. A single case of acute cellular rejection was observed in the low MFI ratio group. CONCLUSIONS: Anti-ABO antibody levels measured by means of the FCM-based method were highly correlated with the levels measured with the use of CAT in cases of ABO-i KT. The decreased level of anti-ABO antibody measured by means of FCM after plasmapheresis suggests its potential as an effective and objective method for assessment of anti-ABO antibody levels.

Clinical outcomes in Asian elderly kidney transplant recipients: a multicenter cohort study.

BACKGROUND: The kidney transplantation rate in elderly patients is increasing rapidly. However, the clinical outcomes of kidney transplantation in elderly patients have not yet been thoroughly evaluated. METHODS: This multicenter cohort study included adult kidney transplant recipients (KTRs) admitted to five major tertiary hospitals in Korea between 1997 and 2012. A total of 3,565 adult participants were enrolled. Patient survival, allograft survival, and biopsy-proven acute rejection (BPAR) of 242 elderly recipients (≥ 60 years) were assessed and compared with those of a younger population. RESULTS: Patients were divided into five groups according to age at time of transplantation. The proportion of elderly patients was 6.7 % (mean age, 63.1 ± 2.7 years; n = 242). The numbers of male patients (69.4%), those with diabetes mellitus history (36.3%), and those with pretransplantation ischemic heart disease history (17.7%) were significantly higher in the elderly group than in the younger age groups. Elderly patients were more likely to receive a cadaveric kidney, and overall mortality rates were significantly higher in the elderly patients (1-year survival 93.3%, 5-year survival 91.3%). However, death-censored allograft survival rate and BPAR were not affected by patient age (P = .104 and .501, respectively). Among the elderly, BPAR and female donors were independent risk factors for allograft loss. CONCLUSION: The overall survival rate of the elderly KTRs was significantly lower than that of younger KTRs. However, the death-censored allograft survival rate did not differ between groups. Kidney transplantation should not be stagnated especially in elderly patients with end-stage renal disease.

HLA gene dosage effect on renal allograft survival.

BACKGROUND: Human leukocyte antigen (HLA)-A, HLA-B, and HLA-DR matching has beneficial long-term effects on renal allograft survival. However, the gene dosage effect of mismatched HLA on transplant outcomes is not known. We investigated the HLA gene dosage effects on allograft survival in kidney transplant recipients (KTRs). METHODS: We analyzed HLA typing of KTRs and kidney donors at Kyungpook National University Hospital from January 1982 to December 2012. KTRs were divided into 2 groups: recipients from homozygous HLA donors and recipients from heterozygous HLA donors. Death-censored graft survival of KTRs was compared according to allele state of kidney donors. RESULTS: In this study, 697 KTRs were enrolled. According to Kaplan-Meier analysis, graft survival in KTRs of HLA-DR and HLA-B heterozygous donors was longer than that in KTRs of HLA-DR and HLA-B homozygous donors (P = .007 and P < .0001, respectively). Multivariate Cox proportional hazards model analysis showed that HLA-DR and HLA-B donor homozygosity was an independent risk factor for death-censored graft survival (P = .019 and P = .022, respectively). Death-censored graft survival was not associated with HLA-A and HLA-A, B, DR allele states. CONCLUSIONS: Compared with HLA donor mismatch caused by HLA-DR and HLA-B heterozygosity, HLA donor mismatch caused by HLA-DR and HLA-B homozygosity was associated with significantly increased risk of graft failure. In addition to the number of HLA mismatch between KTRs and donors, the donor allele state should be considered to predict transplant outcomes.

Clinical impact of BK virus surveillance on outcomes in kidney transplant recipients.

BACKGROUND: The objective of this study was to investigate the clinical impact of BK virus surveillance on graft injury in kidney transplantation. METHODS: BK viremia in kidney transplant recipients was evaluated by use of plasma quantitative polymerase chain reaction. The prevalence of BK viremia and BK virus-associated nephropathy (BKVAN) and the clinical impact of BK viremia on graft outcomes were assessed. RESULTS: This study took place between January 2008 and June 2013. A total of 213 kidney transplant recipients were included. The prevalence of BK viremia and high BK viremia (≥1 × 10(4) copies/mL) was 66.7% (142/213) and 17.4% (37/213), respectively. A diagnosis of BKVAN was confirmed by means of allograft biopsy in 9 patients (4.2%). The estimated glomerular filtration rate after transplantation was similar in both the low BK viremia (<1 × 10(4) copies/mL) and non-BK viremia groups but was significantly lower in the high BK viremia group after 18 months. In receiver operating characteristic curve analysis, the area under the curve value of plasma polymerase chain reaction was 0.980. We found that a viral load >92,850 copies/mL was able to predict BKVAN with 89% sensitivity and 94.6% specificity. The risk factors for viral loads ≥1 × 10(4) copies/mL were cytomegalovirus infection, steroid pulse therapy, and acute rejection. CONCLUSIONS: High BK viremia was associated with poor graft function after kidney transplantation. The serial monitoring of BK viremia in kidney transplant recipients was helpful in predicting BKVAN and might prevent further progression.

Effect of transient post-transplantation hyperglycemia on the development of diabetes mellitus and transplantation outcomes in kidney transplant recipients.

BACKGROUND: Hyperglycemia occurs frequently after kidney transplantation and may be reversed when the dosage of the immunosuppressive agents is tapered. However, the effect of transient post-transplantation hyperglycemia (PTH) on transplantation outcomes is not well described. METHODS: Kidney transplant recipients without diabetes who underwent kidney transplantation between 2001 and 2012 were enrolled in the study. Transient PTH was defined as recovery from PTH without further antidiabetic therapy and the maintenance of glycated hemoglobin levels <6.5% at 1 year after transplantation. Persistent PTH until 1 year after transplantation was considered to be new-onset diabetes after transplantation (NODAT). The factors associated with increased risk of PTH were analyzed. We compared the development of diabetes mellitus, cardiovascular disease, and other transplantation outcomes among patients with no PTH, transient PTH, and NODAT. RESULTS: Among 176 kidney transplant recipients, 106 (60.2%) developed PTH and 58 (54.7%) of 106 patients with PTH had transient PTH. Older age, high body mass index (BMI), and female gender were independent risk factors for transient PTH. The incidence of diabetes was not significantly different between patients with no PTH and those with transient PTH. The incidence of cardiovascular disease was significantly increased in NODAT group compared with that in no PTH and transient PTH groups. However, the incidences of acute rejection, allograft loss, and patient death were comparable among the three groups. CONCLUSIONS: Transient hyperglycemia after kidney transplantation was found to be associated with older age, high body mass index, and female gender. Transient elevation of blood glucose level did not affect post-transplantation outcomes, including diabetes mellitus and cardiovascular disease. However, patients with NODAT should be carefully monitored for the occurrence of cardiovascular disease.

Growth performance, carcass yield, and quality and chemical traits of meat from commercial korean native ducks with 2-way crossbreeding.

This work was conducted to investigate the performance and meat characteristics of commercial Korean native duck (KND). A total of 180 1-d-old ducklings of 2-way crossbreds from A and B lines (from National Institute of Animal Science) were used in this work and divided into 4 groups (3 replicates/group, 15 birds/replicate). The four groups were 4 crossbreds as AA (A line [♀]×A line [♂]), AB (A line [♀]×B line [♂]), BB (Pure line B strains) and BA (B strains [♀]×A strain [♂]). Ducks were fed diets based on corn-soybean meal for 0 to 3 wk (22.4% crude protein [CP], 2,945 kcal/kg metabolizable energy [ME]) and 3 to 8 wk (18.4% CP, 3,047 kcal/kg ME). As a result of this study, average body weight of 4 crossbreds were 625, 1,617, 2,466, and 2,836 g at 2, 4, 6, and 8 weeks, respectively, and significantly increased over the period of time (p<0.05). Body weight of BB group was greater than other crossbreds at the age of 6 weeks (p<0.05). There was a significant difference in weekly body weight gains (p<0.05), which were 573, 991, 850, and 371 g at 2, 4, 6, and 8 weeks old, respectively. Uniformity of 4 crossbreds was 84.9%, 80.5%, and 72.5% at 6, 7, and 8 weeks, respectively, and there was no difference among crossbreds. Body weight gain of BB crossbred was highest among crossbreds (p<0.05). Weekly feed intake significantly increased with weeks as 669, 1,839, 2,812, and 3,381 g at 2, 4, 6, and 8 weeks respectively (p<0.05). Feed intakes of AA and BB crossbreds were higher at 2 to 4 weeks old than others and that of BB crossbred was highest at 4 to 6 weeks old (p<0.05). Weekly feed conversion ratios were 1.17, 1.86, 3.32, and 9.37 at 0 to 2, 2 to 4, 4 to 6, and 6 to 8 weeks old, respectively, and it increased with age (p<0.05). There was no significant difference in feed conversion ratio among crossbreds. Carcass yields of 4 crossbreds were 73.6%, 71.6%, 73.5%, and 71.7%, respectively, so there was no significant difference among crossbreds. There was no difference in wing, neck, breast and leg ratios among crossbreds. However, back ratios of 4 crossbreds were 17.6%, 18.0%, 15.8%, and 17.6%, respectively, and back ratio of BB was the highest among crossbreds. Finally, these results may provide the basic data on the production, carcass quality, fatty acid and amino acid composition of commercial KND with 2-way crossbreeding.

Rhabdomyolysis associated with cytomegalovirus infection in kidney transplant recipients.

Rhabdomyolysis is a pathological syndrome caused by skeletal muscle cell damage that affects the integrity of the cellular membrane and leads to the release of toxic intracellular constituents into the bloodstream. Although cytomegalovirus (CMV) has rarely been reported as a cause of rhabdomyolysis, CMV infection could be considered as a possible cause because of its clinical significance in kidney transplant recipients (KTRs). We report 2 cases of rhabdomyolysis associated with CMV infection in KTRs. A 64-year-old woman (Case 1) and a 65-year-old man (Case 2), who had each received a kidney from a living unrelated donor, were admitted with complaints of weakness in both legs and myalgia. Laboratory findings revealed highly increased creatine phosphokinase and myoglobinuria. In both cases, no recent alterations of medications had occurred, and other causes of rhabdomyolysis--such as trauma, alcohol, drugs, and electrolyte abnormalities - were excluded. CMV pp65 antigen was positive, and patients were diagnosed with rhabdomyolysis associated with CMV infection. Both patients recovered without complications after ganciclovir treatment. In conclusion, CMV infection should be considered as a possible cause of rhabdomyolysis in KTRs.

Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study.

BACKGROUND: Isotretinoin has been frequently used for acne therapy. However, it has limitation in acceptance because of its adverse effects. Although antihistamine recently revealed to decrease the lipogenesis, evidence is lacking regarding the clinical relevance of antihistamine in the treatment of acne. OBJECTIVES: To evaluate the clinical efficacy and tolerability of antihistamine as an adjuvant treatment of isotretinoin. METHODS: Forty patients with moderate acne were included in this randomized, controlled comparative study. Twenty patients were treated with isotretinoin and 20 patients were treated with additional antihistamine, desloratadine. Assessment was made at baseline, after 2, 4, 8 and 12 weeks of treatment. RESULTS: At week 12, compared with isotretinoin only group, isotretinoin with additional antihistamine group showed more statistically significant decrease in acne lesion counts (non-inflammatory lesions: 44.8% vs. 17.8%; inflammatory lesions: 55.8% vs. 22.9%; total lesions: 45.6% vs. 18.7%; all P < 0.05). Significant decrease was also observed in the score of global acne grading system and the measured value of sebum and erythema. Moreover, acne flare during the treatment occurred less frequently and adverse events of isotretinoin were more tolerable in additional antihistamine group. CONCLUSIONS: This results provide early evidence that antihistamine has a synergic effect with minimizing the side-effect of isotretinoin, and may be used as an adjuvant treatment of moderate acne.

Successful withdrawal of antiviral treatment in kidney transplant recipients with chronic hepatitis B viral infection.

BACKGROUND: The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long-term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection. METHODS: We retrospectively investigated the hepatitis B surface antigen (HBsAg)-positive KTR with antiviral agents between January 2002 and January 2012. Antiviral treatments were withdrawn in patients who met all of the following 7 criteria: (i) no clinical and histologic evidence of cirrhosis, (ii) normal liver biochemistry, (iii) negative for both HBV DNA and hepatitis B envelope antigen (HBeAg), (iv) no resistance to antiviral agent, (v) antiviral therapy > 9 months, (vi) maintenance dosage of immunosuppressant for > 3 months, and (vii) no history of acute rejection during recent 6 months. All patients were followed regularly at approximately 3-6 months for liver enzyme, viral markers, and HBV DNA level after antiviral withdrawal. RESULTS: Among a total of 445 KTR, 14 HBsAg-positive patients were included in this study. Antiviral agents were used, with lamivudine in 11 patients, and with adefovir, entecavir, and telbivudine in 3 patients, respectively. Discontinuation of antiviral agent was attempted in 6 (42.9%) of 14 patients who satisfied the criteria. The median duration of antiviral therapy before withdrawal was 14.3 months (range, 9-24 months). Four (66.7%) of 6 patients were successfully withdrawn and remained negative for HBV DNA for a median 60.5 months (range, 47-82 months). The baseline HBV DNA level was not related to maintenance of remission after withdrawal. Two reactivated patients resumed antiviral treatment immediately, with subsequent normalization of HBV DNA. During the follow-up, 1 patient developed hepatocellular carcinoma; however, no patient death or graft failure was reported for all HBsAg-positive KTR. CONCLUSIONS: Antiviral therapy can be discontinued successfully and safely in selected KTR with chronic HBV infection, after complete suppression of HBV and sufficient duration of antiviral therapy.

Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study.

BACKGROUND: Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. OBJECTIVE: We investigated the effect of PPIs on melanogenesis in vivo and in vitro. METHODS: We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. RESULTS: In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose-dependent manner. CONCLUSION: These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients.

Influence of monochromatic light on quality traits, nutritional, fatty acid, and amino acid profiles of broiler chicken meat.

The role of monochromatic lights was investigated on meat quality in 1-d-old straight-run broiler chicks (n = 360), divided into 6 light sources with 6 replicates having 10 chicks in each replicate. Six light sources were described as incandescent bulbs (IBL, as a control) and light-emitting diode (LED) light colors as white light (WL), blue light, red light (RL), green light, and yellow light. Among LED groups, the RL increased the concentration of monounsaturated fatty acids (P < 0.001), saturated fatty acids (P < 0.001), and the saturated:polyunsaturated fatty acid ratio (P < 0.001), but reduced the concentration of polyunsaturated fatty acid, n-3 fatty acid, and n-6 fatty acid. The IBL increased the n-3 and sulfur-containing amino acids but reduced the n-6:n-3 nonessential amino acids. The WL improved the concentration of most of the essential amino acids (P < 0.01) and nonessential amino acids (P < 0.01) of breast meat. It can be extracted that the light produced by LED responded similar to the IBL light in influencing nutrient contents of meat. Moreover, LED is not decisive in improving fatty acid composition of meat. However, the role of IBL in reducing n-6:n-3 ratio and enhancing n-3 cannot be neglected. Among LED, WL is helpful in improving essential and nonessential amino acid contents of broiler meat.

Comparison of QuantiFERON-TB Gold with tuberculin skin test for detection of latent tuberculosis infection before kidney transplantation.

INTRODUCTION: Screening for latent tuberculosis infection (LTBI) before kidney transplantation (KT) is an indispensable process, purposes of this study were to compare the QuantiFERON-TB Gold In-Tube test (QFT-GIT) with the tuberculin skin test (TST) for screening of LTBI in kidney transplant recipients (KTRs). METHODS: We compared prospectively the results of QFT-GIT with TST in 97 KTRs screened for LTBI between July 2008 and July 2012. Isoniazid (INH) prophylaxis was applied to KTRs with a positive TST or positive QFT-GIT or clinical risk factors for LTBI. Post-transplant tuberculosis (TB) was diagnosed by clinical evidence. RESULTS: The mean patients follow-up was 24.6 ± 14.4 months. Positive results on QFT-GIT and TST was obtained among 19 (20.4%) and 12 (12.9%) subjects, respectively, an overall agreement of 79.3% (κ = 0.27, 95% confidence interval [CI] -0.03-0.50; P < .014). The incidence of TB was 0.52 per 100 person-years (95% CI 0.02-3.68). None of the patients in the INH prophylaxis group developed TB, whereas 1 in the no prophylaxis group developed disease at 14 months after KT. Sensitivity of the 2 tests could not be compared because patients who showed positive results on QFT-GIT or TST did not develop TB. The difference of specificity between QFT-GIT (79.3%) and TST (86.9%) was not significant (P = .l67). Abnormal chest radiographs (odds ratio [OR] 27.94, 95% CI 1.22-636.61, P = .037) and positive TST (OR 7.65, 95% CI 1.75-33.30, P = .007) showed significant associations with positive QFT-GIT results. Only positive QFT-GIT (OR 6.03, 95% CI 1.51-24.01, P = .011) showed an association with positive TST results. CONCLUSIONS: QFT-GIT and TST for diagnosis of LTBI in KTRs showed reasonable concordance but no superiority of either test.

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.