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Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own. Their attempts to do so may result in adverse consequences such as peritonitis. PD exchange is a complex procedure demanding knowledge and skill which requires close supervision and guidance by a renal nurse specialist. In this study, a non-immersive virtual reality (VR) training program using a Leap motion hand tracking device was developed to facilitate patients' understanding and learning of the PD exchange procedure before attempting real task practice. This study was a two-center single-blinded randomized controlled trial on 23 incident PD patients. Patients in the experimental group received 8 sessions of VR training, while patients in the control were provided with printed educational materials. The results showed that there were significant differences between the two groups in performance of the overall PD exchange sequence, especially on the crucial steps. VR had a patient satisfaction rate of 89%, and all patients preferred to have the VR aid incorporated in PD training. Our findings conclude VR can be a useful aid in the training and reinforcement of PD exchange procedures, with distinct merits of being free from restrictions of time, space, and manpower.

AIM Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. METHODS Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. RESULTS Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. CONCLUSION Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.

Background The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. Methods In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3–4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Results Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Conclusion Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.

Background Fluid overload (FO) in peritoneal dialysis (PD) patients is associated with mortality. We explore if low daily sodium removal is an independent risk factor for mortality. We examined severely FO PD patients established for >1yr in expectation that PD prescription would have been optimised for solute clearance and ultrafiltration. We also wish to determine the relationship between kt/v and sodium removal. Methods Retrospective analysis of 231 PD patients with FO ≥2.0L and compared with 218 PD patients who were euvolaemic throughout their PD treatment. Patients were followed up until death censored for transplantation. Results Mean daily sodium removal in overhydrated patients was only 75mmoles (=1.7g). CAPD usage was more common in patients with highest sodium removal. Achievement of UK guidelines for solute clearance and daily fluid removal were not independent predictors of mortality. Markers of sarcopenia (low serum albumin and high CRP) were associated with increased mortality, but these parameters were not independent predictors in a model that included functional assessment (Karnofsky Score). Daily sodium removal was not predictive of mortality but imprecision of clinically used sodium assay should be noted. Correlation between Na and kt/v is statistically significant but R2 was weak at 0.07. Conclusions Whilst diabetic males were more likely to become overhydrated, these factors did not increase mortality further. Traditional targets of "dialysis adequacy" did not predict survival. Kt/v is not a good indicator of sodium removal which can be surprisingly low. Measuring sodium clearance may help clinicians optimise PD modality (CAPD vs APD). This article is protected by copyright. All rights reserved.

Background This study aimed to determine the lifetime cost-effectiveness of first-line dialysis modalities for end-stage renal disease (ESRD) patients under the “Peritoneal Dialysis First” policy. Methods Lifetime cost-effectiveness analyses from both healthcare provider and societal perspectives were performed using Markov modelling by simulating at age 60. Empirical data on costs and health utility scores collected from our studies were combined with published data on health state transitions and survival data to estimate the lifetime cost, quality-adjusted life-years (QALYs) and cost-effectiveness of three competing dialysis modalities: peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD. Results For cost-effectiveness analysis over a lifetime horizon from the perspective of healthcare provider, hospital-based HD group (lifetime cost USD$142,389; 6.58 QALYs) was dominated by the PD group (USD$76,915; 7.13 QALYs). Home-based HD had the highest effectiveness (8.37 QALYs) but with higher cost (USD$97,917) than the PD group. The incremental cost-effectiveness ratio (ICER) was USD$16,934 per QALY gained for home-based HD over PD. From the societal perspective, the results were similar and the ICER was USD$1195 per QALY gained for home-based HD over PD. Both ICERs fell within the acceptable thresholds. Changes in model parameters via sensitivity analyses had a minimal impact on ICER values. Conclusions This study assessed the cost-effectiveness of dialysis modalities and service delivery models for ESRD patients under “Peritoneal Dialysis First” policy. For both healthcare provider and societal perspectives, PD as first-line dialysis modality was cost-saving relative to hospital-based HD, supporting the existing PD First or favoured policy. When compared with PD, Nocturnal home Home-based HD was considered a cost-effective first-line dialysis modality for ESRD patients.

Objective.To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients.Methods.We retrospectively reviewed 16 class III/IV/V patients with LN who have received prednisolone (PSL) and sirolimus either as initial or maintenance treatment.Results.Sixteen patients received sirolimus treatment (9 because of intolerance to standard immunosuppressants and 7 because of a history of malignancy) for 45.3 ± 36.5 months. In 5 patients, sirolimus and PSL were given as induction for active nephritis, and they showed improvements in proteinuria (2.8 ± 1.9 g/day at baseline, 0.1 ± 0.1 g/day after 36 mos, p = 0.011), anti-dsDNA (107.7 ± 91.9 IU/ml and 37.0 ± 55.4 IU/ml, respectively, p = 0.178), and C3 (54.8 ± 26.1 mg/dl and 86.3 ± 18.6 mg/dl, respectively, p = 0.081). Eleven patients received sirolimus and low-dose PSL as longterm maintenance, and they showed continued improvement in C3 (90.4 ± 18.1 mg/dl and 117.7 ± 25.1 mg/dl at commencement and after 36 mos, respectively, p = 0.025), stable renal function (estimated glomerular filtration rate 58.6 ± 25.8 ml/min and 63.0 ± 29.6 ml/min, respectively, p = 0.239), and proteinuria (0.8 ± 0.7 g/day and 0.7 ± 0.7 g/day respectively, p = 0.252). Renal flare occurred in 1 patient, and another patient who had stage 4 chronic kidney disease when sirolimus was started developed endstage renal failure after 27 months. Sirolimus was discontinued in 5 patients, in 4 cases related to drug side effects. Deterioration of dyslipidemia occurred in 4 patients, but was adequately controlled with statin therapy.Conclusion.The preliminary evidence suggests that sirolimus may serve as an alternative treatment for patients with LN who do not tolerate standard treatment or who had a history of malignancy, and it has an acceptable longterm safety profile.

Background Serological activity may precede clinical flares of lupus nephritis (LN) but the management of asymptomatic serological reactivation (ASR) remains undefined. Methods We conducted a retrospective analysis of 138 episodes of ASR, which included 53 episodes in which immunosuppression was increased preemptively and 85 episodes in which treatment was unaltered. Preemptive immunosuppressive treatment comprised increasing the dose of prednisolone to ∼0.5 mg/kg/day, and in patients already on mycophenolate mofetil (MMF) or azathioprine (AZA), increasing the dose to 1.5 g/day and 100 mg/day, respectively. Results Thirty-four episodes of renal flare occurred during follow-up (88.8 ± 77.3 and 82.8 ± 89.7 months in the preemptive group and controls, respectively), following 5 (9.4%) of preemptively treated ASR and 27 (31.8%) of untreated ASR [hazard ratio 0.3 (confidence interval 0.1-0.7), P = 0.012]. Preemptive treatment was associated with superior survival free of renal relapse (99, 92 and 90% at 6, 12 and 24 month, respectively, compared with 94, 69 and 64% in controls; P = 0.011), whereas survival rate free of extrarenal relapse was similar in the two groups. Preemptively treated patients who did not develop renal flares showed better renal function preservation (estimated glomerular filtration rate slope +0.54 ± 0.43 mL/min/1.73 m2/year, compared with -2.11 ± 0.50 and -1.00 ± 0.33 mL/min/1.73 m2/year, respectively, in controls who did and did not develop subsequent renal flares; P = 0.001 and 0.012, respectively). Preemptive treatment was associated with an increased incidence of gastrointestinal side effects attributed to MMF (P = 0.031), whereas infection rate did not differ between the two groups. Conclusion A preemptive moderate increase of immunosuppression for ASR in LN patients may reduce renal flares and confer benefit to long-term renal function.

Objective.To examine the disease flare rate in lupus nephritis (LN), focusing on renal flares, and the factors associated with relapse risk in recent years.Methods.We analyzed data on 139 Chinese patients with class III/IV ± V LN diagnosed from January 1983 to December 2013. We also compared data before and after 1998, when maintenance immunosuppression was changed from azathioprine (AZA) to mycophenolic acid (MPA).Results.Over 112.5 ± 88.4 months, 135 episodes of renal flare occurred, giving a flare rate of 0.108 episodes per patient-year. The renal relapse-free survival rate was 96%, 90%, 86%, 80%, 69%, and 57% after 1, 2, 3, 4, 5, and 10 years, respectively, calculated from the start of induction treatment. Reduced risk of flare was associated with MPA maintenance (OR 0.314, 95% CI 0.099–0.994, p = 0.049), complete remission after induction immunosuppression (OR 0.329, 95% CI 0.133–0.810, p = 0.016), and diagnosis after 1998 (OR 0.305, 95% CI 0.133–0.700, p = 0.005). Relapse-free survival was significantly better in patients treated with prednisolone and MPA as maintenance immunosuppression (91% after 5 yrs and 83% after 10 yrs, respectively) compared with prednisolone and AZA (70% and 52%, respectively, p = 0.044). LN diagnosed in 1998–2013 showed 5-year and 10-year relapse-free survival rates of 93% and 86%, respectively, compared with 81% and 66%, respectively (p = 0.017) for LN that presented in 1983–1997.Conclusion.Our data show a relatively low flare rate for LN in the more recent era, attributed to effective induction of immunosuppression and MPA as maintenance treatment.

BackgroundBurkholderia cepacia is a hardy bacterium with intrinsic resistance to multiple antibiotics and high transmissibility. Opportunistic healthcare-associated B. cepacia infections among immunocompromised or critically ill patients have been reported, but there is limited data on the clinical characteristics and treatment outcomes of exit-site infection (ESI) in peritoneal dialysis (PD) patients.Patients and methodsPatients who suffered from B. cepacia ESI from 1 January 2004 to 31 December 2014 were reviewed. The clinical characteristics and treatment outcomes of the patients and the antibiotic susceptibility patterns of the bacterial isolates were analyzed.ResultsTwenty-two patients were included for analysis. Eight patients (36.4%) had medical conditions which impaired host immunity, while 7 (31.8%) had pre-existing skin abnormalities. Three patients (13.6%) progressed to tunnel-tract infection and another 3 patients (13.6%) developed associated peritonitis. Fifteen patients (68.2%) responded to medical treatment while 7 (31.8%) required catheter removal. Eleven patients (50.0%) had recurrent B. cepacia ESI, which occurred at 7.8 months (95% confidence interval [CI] 0.1 – 19.4 months) after the first episode. Most B. cepacia strains were susceptible to ceftazidime (95.5%), piperacillin/tazobactam (95.5%), and piperacillin (90.9%). Besides aminoglycosides (80 – 100%), high rates of resistance were also observed for ticarcillin/clavulanate (90.9%).ConclusionBurkholderia cepacia ESI is associated with low rates of tunnel-tract infection or peritonitis, but the risk of recurrence is high. Most cases can be managed with medical treatment alone, although one third of patients might require catheter removal.

PurposeTo estimate the direct and indirect costs of end-stage renal disease (ESRD) patients in the first and second years of initiating peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD.MethodsA cost analysis was performed to estimate the annual costs of PD, hospital-based HD and nocturnal home HD for ESRD patients from both the health service provider’s and societal perspectives. Empirical data on healthcare resource use, patients’ out-of-pocket costs, time spent on transportation and dialysis by ESRD patients and time spent by caregivers were analysed. All costs were expressed in Hong Kong year 2017 dollars.ResultsAnalysis was based on 402 ESRD patients on maintenance dialysis (PD: 189; hospital-based HD: 170; and nocturnal home HD: 43). From the perspective of the healthcare provider, hospital-based HD had the highest total annual direct medical costs in the initial year (mean ± SD) (hospital-based HD = $400 057 ± 62 822; PD = $118 467 ± 15 559; nocturnal home HD = $223 358 ± 18 055; P ConclusionsThis study quantified the economic burden of ESRD patients, and assessed the annual healthcare and societal costs in the initial and second years of PD, hospital-based HD and nocturnal home HD in Hong Kong. From both perspectives, PD is cost-saving relative to hospital-based HD and nocturnal home HD, except that nocturnal home HD has the lowest cost in the second year of treatment from the societal perspective. Results from this cost analysis facilitate economic evaluation in Hong Kong for health services and management targeted at ESRD patients.

Background Starting dialysis is an important life event. The prevalence and evolution of psychological symptoms at commencement of long-term dialysis is unclear. We examined the prevalence of and risk factors for depression and anxiety, and the quality of life (QOL) of incident peritoneal dialysis (PD) patients, and also the change of these parameters in the first year of PD in relation to clinical outcomes under the PD-first policy. Methods All patients commencing long-term PD from March 2011 to April 2015 were asked to complete the Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF and the Kidney Disease Quality of Life Instrument Short Form questionnaire. Patient demographics and the incidence of hospitalization, peritonitis, exit-site infection, and all-cause mortality were studied. The HADS was repeated after 9 – 12 months. Results A high depression score was present in 39.6% of 191 patients at commencement of PD and was more common in diabetes patients (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.09 – 3.81). A high anxiety score was present in 23.6%, and the risk factors included younger age (OR 0.96 per year, 95% CI 0.94 – 0.99) and diabetes (OR 2.59, 95% CI 1.20 – 5.57). Both high depression and anxiety scores were associated with an inferior QOL, overall and across most QOL domains. Depression and anxiety symptoms did not change in the first year of PD and were not associated with short-term clinical outcomes. Conclusions High depression and anxiety scores were prevalent in incident PD patients where PD-first policy is adopted and were associated with inferior QOL. There was no improvement after 1 year of PD. The impact of strategic interventions targeting patient groups at risk such as those with diabetes or of younger age warrants further investigation.

Background Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. Results We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. Conclusions The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study.

H2 receptor antagonists are commonly employed to manage gastro-esophageal reflux and peptic ulcer diseases with a very low incidence of side effects. Herein, we report an extremely rare incidence of famotidine-induced acute confusion in a patient with end-stage renal failure. We also discuss the pharmacokinetic properties of famotidine and its interplay with compromised renal function to result in neuropsychiatric manifestations, highlighting the importance of dosage adjustment in individuals with renal insufficiency.

OBJECTIVE Calcineurin inhibitors are effective immunosuppressants. They also reduce proteinuria in glomerular diseases but are potentially nephrotoxic. Short-term data suggest that tacrolimus (TAC) combined with corticosteroids is effective in LN, but long-term data are lacking. This study examined the long-term outcomes and tolerability of TAC for the treatment of LN. METHODS We retrospectively reviewed 29 LN patients who received TAC treatment for 46.9 months (s.d. 37.9). RESULTS In 17 patients with class III/IV or V LN and persistent proteinuria >2 g/day despite induction immunosuppression, response rates after 12 and 24 months of add-on TAC treatment were 66.7% and 80.0%, respectively. In 10 patients with nephrotic syndrome due to class V LN who were given prednisolone and TAC as initial treatment, the response rate was 60.0% and 90.0% after 12 and 24 months, respectively. TAC facilitated steroid minimization in two patients with lupus podocytopathy. As a group, proteinuria decreased from 3.6 g/day (s.d. 2.6) to 1.0 (s.d. 1.1) (P < 0.05). Four patients developed end-stage renal failure, with 3-, 5- and 8-year renal survival rates of 93%, 83% and 83%, respectively. In the remaining patients, serum creatinine and estimated GFR remained stable after 36 months. One patient with pre-existing chronic renal failure developed TAC nephrotoxicity. Four renal flares occurred, all associated with low TAC blood levels. Six patients (20.1%) had deterioration of hypertension and one patient (3.4%) had new-onset diabetes mellitus. Six patients (20.1%) had infections that required hospitalization. Two deaths occurred: one due to pneumonia and one to breast cancer. CONCLUSION The results suggest efficacy of TAC in LN, especially in reducing proteinuria, and its role as a long-term maintenance agent warrants further investigation.

Patients with influenza infection most commonly present with upper and occasionally lower respiratory tract symptoms. However, extrapulmonary presentations such as hepatitis are infrequently observed. We report a case of a hemodialysis patient with influenza A infection who presented with severe hepatitis and liver failure, while his respiratory symptoms were mild. It is important to recognize influenza infection as an unexplained cause of hepatitis and liver failure. In our case, liver failure resolved with supportive treatment.

Aim Accumulating literature indicates that late acute rejection (LAR) after kidney transplantation portends an unfavorable prognosis. There is no data on the incidence of LAR in Asian subjects, nor its risk factors and associated clinical outcomes. Methods We conducted a retrospective single-centre case-control study to investigate the incidence, risk factors and prognosis of LAR in Chinese kidney transplant recipients. Subjects with or without LAR were matched for age, gender, era of transplantation, allograft type, and maintenance immunosuppression regimen. Results Thirty-two episodes of LAR occurred within an observation period of 12 years giving an incidence rate of 0.46 episodes per 1000 patient-years. Acute rejection within the first year after transplantation was associated with an increased risk of LAR (OR 3.59, p = 0.041). In patients receiving maintenance immunosuppression regimen with steroid, cyclosporin A (CsA) and mycophenolate or an m-TOR inhibitor, patients with LAR showed lower trough CsA levels prior to and at the time of rejection compared to Controls (86.0 ± 26.1 vs. 105.6 ± 13.3ug/l, p = 0.049; and 75.7 ± 35.7 vs. 106.0 ± 20.5ug/l, p = 0.032, respectively). Trough CsA level below 80ug/l was associated with the development of LAR (OR 10.82, p = 0.032). Patients with LAR showed an inferior allograft survival (p

Background Urine from kidney transplant recipient has proven to be a viable source for donor DNA. However, an optimized protocol would be required to determine mis-matched donor HLA specificities in view of the scarcity of DNA obtained in some cases. Methods In this study, fresh early morning urine specimens were obtained from 155 kidney transplant recipients with known donor HLA phenotype. DNA was extracted and typing of HLA-A, B and DRB1 loci by polymerase chain reaction-specific sequence primers was performed using tailor-made condition according to the concentration of extracted DNA. Results HLA typing of DNA extracted from urine revealed both recipient and donor HLA phenotypes, allowing the deduction of the unknown donor HLA and hence the degree of HLA mis-match. By adopting the modified procedures, mis-matched donor HLA phenotypes were successfully deduced in all of 35 tested urine samples at DNA quantities spanning the range of 620–24,000 ng. Conclusions This urine-based method offers a promising and reliable non-invasive means for the identification of mis-matched donor HLA antigens in kidney transplant recipients with unknown donor HLA phenotype or otherwise inadequate donor information.

We investigated the long-term outcome of patients with proliferative LN treated with CSs and MMF.This was a single-centre retrospective study on patients with biopsy-proven class III/IV ± V LN treated with prednisolone and MMF continuously as both early and maintenance immunosuppression.Sixty-five patients were included, and followed for 91.9 (47.7) months. All received prednisolone and MMF as induction immunosuppression. In 31 patients, maintenance immunosuppression comprised prednisolone and MMF only (MMF-MMF group). MMF was replaced with AZA in 23 patients (MMF-AZA), and with calcineurin inhibitors (CNIs) in 11 patients (MMF-CNI) at sometime during follow-up. Ten-year patient and renal survival rates were 91% and 86%, respectively, and were similar in the three groups. MMF-MMF group showed better relapse-free survival than MMF-AZA and MMF-CNI patients (76% vs 56% vs 43%, respectively at 5 years; 69% vs 32% vs 0%, respectively at 10 years; MMF-MMF vs MMF-AZA or MMF-CNI, P = 0.049 or 0.019, respectively; MMF-AZA vs MMF-CNI, P = 0.490). Patients treated with MMF for24 months had better relapse-free survival than those treated for shorter durations (88% vs 48% at 5 years; 81% vs 28% at 10 years; P0.001). Renal function at 10 years was better in the MMF-MMF group. Anaemia was associated with MMF treatment. Other adverse events were comparable and relatively minor with MMF, AZA or CNI as maintenance.Long-term treatment with CSs and MMF from induction to maintenance phase is associated with relatively favourable long-term outcome in Chinese LN patients. Discontinuation of MMF before 24 months may increase the risk of flares.

Vitamin D deficiency is common globally. There is evidence that vitamin D status may be related to immune function and cardiovascular disease. The vitamin D status of Chinese kidney transplant recipients has never been investigated. We performed a cross-sectional study and measured the level of 25-hydroxyvitamin D [25(OH)D] in 94 Chinese renal transplant recipients with stable allograft function. Vitamin D deficiency and insufficiency were detected in 43.6% and 54.2% of patients, respectively. About 53.2% of the patients also had elevated parathyroid hormone (PTH) levels. The level of 25(OH)D was lower in kidney transplant recipients compared with healthy controls matched for age and sex (52.5 ± 15.6 nmol/L vs. 57.5 ± 19.0 nmol/L, p = 0.05), but the level of serum creatinine was higher in kidney transplant recipients (120.3 ± 48.5 μmol/L and 78.3 ± 15.3 μmol/L, p 0.01). The level of 25(OH)D was negatively correlated with that of PTH (p = 0.001). The latter was associated with serum creatinine (p = 0.001) and duration of dialysis (p = 0.001). Patients with a history of acute rejection showed lower levels of 25(OH)D (45.3 ± 11.9 nmol/L vs. 54.2 ± 16.0 nmol/L, p = 0.003). We conclude that vitamin D deficiency is prevalent among Chinese renal transplant recipients. In view of the potential immunomodulatory effect of vitamin D, the relationship between vitamin D level and rejection and the effect of vitamin D supplementation in renal transplant recipients warrant further investigations.

Background: Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition that is notoriously difficult to manage; the relative risk of adverse cardiovascular events in these patients compared with euthyroid patients is largely unknown. Objective: We compared the clinical characteristics and major adverse cardiovascular events (MACE) in AIT and euthyroid patients. Method: Patients at a tertiary referral center who had been prescribed amiodarone for at least 3 months were retrospectively analyzed. Baseline clinical characteristics, laboratory parameters, and outcome events were evaluated. MACE was defined as cardiovascular mortality, myocardial infarction, stroke and heart failure, or ventricular arrhythmias that required hospitalization. Results: A total of 354 patients (61.8 ± 14.1 yr; 64.7% male) with a mean follow-up of 48.6 ± 26.7 months were studied. AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively. No differences in baseline clinical characteristics were observed between AIT and euthyroid patients. Nonetheless AIT patients demonstrated a higher MACE rate (31.6 vs. 10.7%, P < 0.01), mostly driven by a higher rate of ventricular arrhythmias that required admission (7.0 vs. 1.3%, P = 0.03). Cox-regression multivariate analysis revealed that AIT (hazard ratio 2.68; confidence interval 1.53–4.68; P < 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43–4.42; P < 0.01) were independent predictors of MACE. Conclusion: In patients prescribed long-term amiodarone therapy, occurrence of AIT is associated with a 2.7-fold increased risk of MACE. Regular and close biochemical surveillance is thus advisable to identify and treat this high-risk group of patients.

A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after conversion, including subjects receiving concomitant treatment with diltiazem. Eighteen stable renal allograft recipients were followed prospectively for 12 weeks after conversion from Prograf to Advagraf at the same daily dose. Tacrolimus blood trough level decreased significantly within 8 weeks after conversion (p 0.01). Twelve patients required escalation of the Advagraf dose by 1.10 ± 0.36 mg. For the whole group the daily tacrolimus dose was increased from 0.057 ± 0.032 mg/kg to 0.068 ± 0.033 mg/kg (p 0.0001). At week 12 the daily dose of Advagraf was 127 ± 32% of the original daily dose of Prograf. In the subgroup of patients receiving diltiazem, their tacrolimus trough level decreased significantly after conversion (p = 0.001), and the daily tacrolimus dose was increased from 0.060 ± 0.036 mg/kg to 0.073 ± 0.036 mg/kg (p 0.0001). At week 12, their daily dose of Advagraf was 131 ± 34% of the original daily dose before conversion. To conclude, conversion from Prograf to Advagraf in renal allograft recipients with or without diltiazem co-treatment necessitated an increase in the daily dose by approximately 30% to maintain the target blood trough level unchanged.

Lentiviral latency remains a principal obstacle to curative AIDS therapy. Transcriptional repression and latency permits lentiviruses to evade host immune responses and antiretroviral drugs. We have established a model of peripheral CD4+ T cell lentiviral latency in cats experimentally infected with feline immunodeficiency virus (FIV). Multiple mechanisms of lentiviral transcriptional repression have been proposed including epigenetic mechanisms resulting in promoter hypermethylation and/or chromatin condensation. Methylation of promoter-associated cytosines in the cytosine-guanine dinucleotide (CpG) has been associated with transcriptional repression in both eukaryotic promoters and integrated retroviral genomes. Using methylcytosine mapping, we examined the CpG methylation patterns in both the 5′ and 3′ long terminal repeats (LTR) of the FIV provirus in peripheral blood mononuclear cells, monocytes and CD4+ T cells isolated during the acute and asymptomatic phases of infection. Here we report no evidence that proviral promoter hypermethylation is associated with lentiviral latency in peripheral CD4+ T cells and monocytes obtained from experimentally FIV-infected cats.

To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE).A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events.Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS100 (all p0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS100 (40.0%) than those with CCS=0 (1.0%, p0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events.Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.

Editor: We report a case of exit-site infection due to Burkholderia cepacia in a peritoneal dialysis (PD) patient. A 31-year-old lady suffered from end-stage renal failure due to focal segmental glomerulosclerosis and was initiated on PD in 2011. She had a history of umbilical hernia and was put on low-volume exchanges. She presented with bloody discharge and pain at the exit site for 1 day. Physical examination revealed a partially protruding external cuff of the PD catheter but there was no tunnel tract involvement or associated peritonitis. Exit-site culture grew Burkholderia cepacia which was sensitive to ceftazidime. After trimming the external cuff, she was successfully treated with 2 weeks of intravenous ceftazidime with no recurrence. Burkholderia cepacia is a ubiquitous organism which is found most commonly on plant roots, soil, and in moist environments (1). B. cepacia infection usually occurs in cystic fibrosis patients and immunocompromised hosts (1). Nosocomial outbreaks of Burkholderia bacteremia have also been reported in intensive care and dialysis units due to contaminated medical devices (2-4). The immunocompromised state related to inadequate dialysis and the protruding external cuff are possible predisposing factors for Burkholderia exit-site infection in our patient. There is limited data regarding the treatment of PD-related peritonitis and exit-site infections due to B. cepacia. This organism is intrinsically resistant to drugs commonly used for exit-site infection such as first- and second-generation cephaolosporins, and aminoglycoside. The antimicrobials recommended against B. cepacia include ceftazidime, meropenem and cotrimoxazole (1). Our experience suggested that B. cepacia exit-site infection can be treated with appropriate antibiotics without the need for Tenckhoff catheter removal.

Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial.To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients.Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay.SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/μl, p0.001) as well as FMD% (4.8% vs. 7.8%, p0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/μl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter.Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.

A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.

OBJECTIVE: To investigate the oral health condition and saliva flow of southern Chinese patients with Sjogren's syndrome (SS). METHOD: 51 SS patients (26 primary and 25 secondary cases) and 29 controls took part in this cross-sectional study. Stimulated whole and parotid saliva flow rates, pH, and buffer capacity, and xerostomia, oral mucosal lesions, oral hygiene status, dental and periodontal conditions, prosthetic status were assessed and compared between groups. RESULTS: Stimulated whole saliva (SWS) flow was reduced in primary and secondary SS cases (p

summary The effect of oral symptoms of Sjogren's syndrome (SS) on health-related quality of life is presently uncertain. This study aimed to investigate oral health-related quality of life (OHRQOL) among southern Chinese people with SS. Twenty-six primary SS cases, 25 secondary cases and 29 matched controls took part in this cross-sectional study. Each participant completed a SF-36 questionnaire, the Oral Health Impact Profile and a dry mouth measure, assisted by a trained interviewer. Data on socio-demographic variables were also collected. The dry mouth measure revealed that people with primary and secondary SS had significant problems associated with subjective symptoms of dry mouth generally, and dry mouth when eating and speaking (P

To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors.Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE.At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients.The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.

To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance.45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters.ILD was present in 39/45 (86.7%) patients. Abnormal (80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function.Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Lymphoepithelioma-like carcinoma (LELC) is an Epstein-Barr virus (EBV) related malignancy. It is not a common condition and is usually found in the head and neck region. We describe the development of LELC involving the parotid gland in a patient with rheumatoid arthritis (RA) who had been receiving long-term azathioprine. A brief review is also made on the clinical presentation and histological features of LELC and the association of RA with EBV related diseases. The latter may be attributed to an increase in risk of malignancy associated with RA or as a result of the long-term immunosuppressive used.

Aim Previous studies demonstrated that mismatched donor HLA phenotype could be successfully deduced from either fresh or archival formalin-fixed paraffin-embedded renal allograft tissue by polymerase chain reaction-specific sequence primers (PCR-SSP) genotyping [1] , [2] . In this study, a modified non-invasive urine protocol was further validated. Methods Fresh early morning urine was centrifuged and the cell pellets were washed with phosphate buffered saline. DNA was extracted from the urinary cells by TBG EZmag Genomic DNA Whole Blood Kit. The HLA-A, B and DRB1 loci were typed by PCR-SSP. The performance of the PCR reaction was enhanced by using a hot-start Taq polymerase together with tailor-made extended PCR profiles according to the DNA yields. Results Urine samples were collected from recipients of renal transplant centers in Hong Kong during May to December 2012. 34.8%, 25.8%, 18.1% and 21.3% yielded DNA amount >5000, 2000–5000, 1000–2000 and [3] . The HLA phenotypes of the donor-recipient pairs could be completely determined in all tested samples. Conclusions In previous study, it was revealed that the presence of sufficient donor-derived substrate for HLA typing appeared critical [4] . By adopting the modified procedures, mismatched donor HLA phenotypes in urine samples containing various DNA quantities could be successfully deduced. This non-invasive approach is promising and reliable for the identification of mismatched donor HLA in kidney transplant recipients with unknown donor HLA phenotype.

To examine the safety of the use of disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with chronic viral hepatitis (CVH).Records of 600 Chinese patients satisfying the ARA criteria for RA in two rheumatology centers were reviewed. Patients with CVH were studied. Liver enzymes were checked before (baseline) and during DMARD use at 3-month intervals or more frequently if necessary. Drug-episodes (D-Ep), defined as the continuous use of DMARD, singly or in combination, for more than 6 months in a patient, were analysed. Changes in serum liver alanine transaminase (ALT) levels as multiples of the upper range of normal were taken to reflect the severity of hepatotoxicity. Changes of ALT toor = 1.5 times the upper range of normal if they were measured at baseline oror = 2 times the upper range of normal if they were measured during and after the use of DMARD were considered as abnormal. Control patients included those with CVH alone (n = 623) or RA without CVH (n = 62) matched for age, sex and D-Ep.30 RA patients were found to have concomitant CVH. One patient was excluded because of use of NSAID alone (n = 1). Among the 29 patients, 23 were HBsAg +ve and 6 were anti-HCV Ab +ve. A total of 47 D-Ep were analysed. 20/47 (42.6%) of D-Ep in 16/29 (55.2%) RA + CVH patients developed abnormal ALT levels after a mean 1.9-year duration of DMARD use. This was statistically significant when compared with 13/94 (13.8%) of D-Ep which ended with abnormal ALT levels in 13/62 (21%) patients with RA alone (p0.0001 for D-Ep which ended up with abnormal ALT, and p0.02 for the number of patients who developed abnormal ALT) and 128/623 (20.5%) patients with CVH alone (p0.005). 53% (9/17) of hydroxychloroquine (HCQ) D-Ep were associated with an abnormal outcome. Corresponding figures for sulphasalazine (SAZP) and oral or intramuscular gold preparations were 55.6% (5/9) and 0% (0/3) respectively. Two patients on methotrexate, used either singly or in combination, had normal ALT levels throughout the study period. One patient on azathioprine developed reactivation of hepatitis B infection. When D-Ep of the RA + CVH group were further analysed, 16/43 (37.2%) and 4/4 (100%) D-Ep which started with normal and abnormal baseline ALT respectively developed further liver enzyme derangement.The use of DMARD in RA + CVH patients is associated with a high incidence of hepatotoxicity. The effect is likely to be synergistic. This includes drugs such as HCQ, which is generally believed to be less hepatotoxic.

Aim We previously demonstrated that mismatched donor human leukocyte antigen (HLA) could be deduced from HLA typing of fresh or archived paraffin-embedded renal allograft tissue (Clin. Transplant 2010;24:E178-81; Histopathology, In press), thereby allowing the detection of donor-specific antibodies. In the present study, we investigated the detection of mismatched donor HLA using the kidney recipient’s urine sample. Methods Forty-three urine samples from kidney transplant recipients with known HLA in both donor and recipient were studied. Each 40 ml sample was centrifuged at 2500 rpm for 20 minutes. The supernatant was discarded, the sediment washed with 1X PBS, after which the mixture was centrifuged at 2500 rpm for 20 minutes. DNA extraction was performed on samples with sufficient cell sediment through visual inspection. Genomic DNA was extracted using EZmag Genomic DNA Whole Blood Kit (Texas BioGene Inc., Taiwan). HLA Class I and II antigens were typed by PCR-SSP. Results 62.8% (27/43) of urine samples showed sufficient sediment. Extracted DNA concentration was in the range of 1700-2600 η g with purity (A260/A280) of 1.66-1.98. 41.9% (18/43) had sufficient DNA for HLA testing. One case had zero mismatch between donor and recipient. Of 17 mismatched cases, the HLA typing of recipients was achieved in all subjects. Mismatched donor HLA phenotypes were detected completely in 3 of the 17 subjects (17.6%), with the samples collected on Day 5, 14, and 1268 after kidney transplantation. Mismatched donor HLA data was partially detected in another 6 subjects (35.3%). Conclusions Detection of mismatched donor HLA from the urine of kidney transplant recipients has an overall success rate of 7% (3/42). The presence of sufficient donor-derived substrate for HLA typing appears critical. Further investigations are warranted to explore ways to improve the performance of this non-invasive technique for the detection of mismatched donor HLA in kidney transplant recipients with unknown donor HLA phenotype.