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We report an unusual case of veno-caliceal fistula that developed because of high ureteric pressure caused by graft ureteric stricture after kidney transplantation in a 60-year-old patient. We further confirmed its presence with radiological images. Recirculation of creatinine and other uremic toxins resulted in a biochemical picture of renal failure in the presence of normal kidney function, confirmed by normal scintigraphy findings. Drainage of the pelvi-caliceal system could not be assessed accurately by means of diuretic renogram using technetium-99m diethylenetriaminepentaacetic acid with frusemide because of the rapid clearance of tracer activity from the system in the presence of a veno-caliceal fistula. The patient's renal function improved rapidly after interrupting urine recirculation by using percutaneous drainage, confirming 'pseudo renal failure' as the cause of his persistently increased serum creatinine concentration. The ureter was re-implanted later, and the veno-caliceal fistula was not seen in the nephrostogram after the operation. He remains well with stable renal function at 3 years' follow-up. Clinicians should exercise judgment when evaluating patients with allograft dysfunction, especially when the investigation and clinical findings show contradicting results.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Massive, coordinated cellular changes accompany the transition of central nervous system (CNS) progenitors from forebrain neurectodermal cells to specified neuroepithelial cells. We have previously found that MYC regulates the changing ribosomal and proteostatic landscapes in mouse forebrain precursors at embryonic days E8.5 and E10.5 (before and after neural tube closure; NTC) (Chau et al., 2018). Here, we demonstrate parallel coordinated transcriptional changes in metabolic machinery during this same stage of forebrain specification. Progenitors showed striking mitochondrial structural changes transitioning from glycolytic cristae at E8.5, to more traditional mitochondria at E10.5. Accordingly, glucose use shifted in progenitors such that E8.5 progenitors relied on glycolysis, and after NTC increasingly used oxidative phosphorylation. This metabolic shift was matched by changes in surrounding amniotic and cerebrospinal fluid proteomes. Importantly, these mitochondrial morphological shifts depend on MYC downregulation. Together, our findings demonstrate that metabolic shifting accompanies dynamic organelle and proteostatic remodeling of progenitor cells during the earliest stages of forebrain development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Introduction: While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed., Methods: A 1-year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin)., Findings: NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age-adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77-20.99, P = 0.04). They consumed less aluminum-based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol 2 /L 2 , P < 0.01), with similar hemoglobin levels., Discussion: NHHD appeared to offer higher employment rate, lower dosage of aluminum-based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong., (© 2017 International Society for Hemodialysis.)

Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous Myc proto-oncogene protein is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to the anterior choroid plexus and ciliary body. To uncover the consequences of persistent Myc expression, MYC expression was forced in multipotent neural precursors (nestin-Cre:Myc), which produced fully penetrant models of choroid plexus carcinoma and ciliary body medulloepithelioma. Nestin-mediated MYC expression in the epithelial cells of choroid plexus leads to the regionalized formation of choroid plexus carcinoma in the posterior domain of the lateral ventricle choroid plexus and the fourth ventricle choroid plexus that is accompanied by loss of multiple cilia, up-regulation of protein biosynthetic machinery, and hydrocephalus. Parallel MYC expression in the ciliary body leads also to up-regulation of protein biosynthetic machinery. Additionally, Myc expression in human choroid plexus tumors increases with aggressiveness of disease. Collectively, our findings expose a select vulnerability of the neuroepithelial lineage to postnatal tumorigenesis and provide a new mouse model for investigating the pathogenesis of these rare pediatric neoplasms., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated at E10.5. This was matched by decreases in ribosome biogenesis and protein synthesis, together with age-related changes in proteomic content of the adjacent fluids. Notably, c-MYC expression and mTOR pathway signaling were also decreased at E10.5, providing potential drivers for the effects on ribosome biogenesis and protein synthesis. Interference with c-MYC at E8.5 prematurely decreased ribosome biogenesis, while persistent c-MYC expression in cortical progenitors increased transcription of protein biosynthetic machinery and enhanced ribosome biogenesis, as well as enhanced progenitor proliferation leading to subsequent macrocephaly. These findings indicate large, coordinated changes in molecular machinery of forebrain precursors during early brain development., Competing Interests: KC, MS, RF, EF, HM, MJ, AS, MS, BL, ML No competing interests declared, (© 2018, Chau et al.)

Aim: Anxiety and depression are prevalent among patients with end stage renal failure. However, data concerning their role in the subsequent peritonitis and hospitalization was scarce. The aim of this study was to examine the prevalence of psychological problems in our Chinese peritoneal dialysis (PD) patients and its association with subsequent clinical outcome., Methods: This was a single-centre prospective cohort study. All patients newly started on PD between 1 September 2012 and 31 December 2014 were recruited. Hospital Anxiety Depression Scale was used to categorize the patients into high score group (HSG) and low score group (LSG). Higher score reflects higher emotional distress., Results: A total of 132 patients were recruited. Seventy-five patients (55%) were categorized as HSG. Higher overall peritonitis rate and Gram-positive organism associated peritonitis rate were observed in HSG (P = 0.012 and P = 0.016, respectively). The hospitalization rates in HSG and LSG were 1.20 episodes per patient-year and 1.05 episodes per patient-year respectively. Both high CCI (OR 1.33, 95% CI 1.10-1.62, P < 0.01) and HSG (OR 3.17, 95% CI 1.27-7.93, P = 0.01) were independent risk factors for PD peritonitis., Conclusion: Anxiety and depression were also common among Chinese PD patients. Those in HSG were more likely to develop PD peritonitis. These psychological symptoms deserved early detection. Further studies are needed to investigate whether intervention can improve the clinical outcome of these patients., (© 2016 Asian Pacific Society of Nephrology.)

Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n = 613). HLA typing of 563 Chinese deceased renal donors was used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA (freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors. The cPRA based on historical donor filtering was the percentage of filter out count over total number of donors (cPRA (filter)). Values of cPRA (freq) and cPRA (filter) showed almost perfect agreement with Lin's correlation coefficient equal to 1.000. SD of bias was 0.6 cPRA point. Limit of agreement was 0.9 to -1.5 points difference. Furthermore, the poor agreement between our in-house cPRA and values from other online calculators indicated the necessity to use local population data for accurate cPRA calculation. Built-in donor filtering method was more practicable for Hong Kong due to factors such as cost and flexibility. An on-going donor pool can reflect population allele frequencies and permits efficient periodic update of cPRA., (© 2017 Steunstichting ESOT.)

Objective: To investigate the impact of mammalian target of rapamycin (mTOR) inhibitor conversion together with minimization of calcineurin inhibitor on allograft outcome and patient survival in kidney transplant recipients with post-transplant cancers., Methods: A retrospective study of all kidney transplant recipients diagnosed to have post-transplant cancers between the period 1/1/1994 and 30/6/2015. Patients were divided into 2 groups: mTOR inhibitor group and non-conversion group. Outcome included allograft function, patient survival, graft survival, acute rejection and cancer recurrence., Results: 115 patients (56 in mTOR inhibitor group and 59 in non-conversion group) were analyzed. Median follow up was 28 months (range: 1 month - 20 years). The allograft function at 1-year remained similar between both groups. There was no significant difference in the patient survival, graft survival and rejection free survival between both groups. More patients in the non-conversion group developed recurrence of cancers than mTOR inhibitor group but statistically not significant., Conclusions: Use of mTOR inhibitors together with calcineurin inhibitor minimization offer a reasonable option in kidney transplant recipients who developed post-transplant cancers in view of stable renal function, low rejection rate and low cancer recurrence rate.

Objective: To characterize the posttransplant lymphoproliferative disorders (PTLD) including the Epstein-Barr virus (EBV) status, histological subgroups, site of occurrence and the clinical outcome in the Chinese kidney transplant recipients., Methods: A retrospective cohort study of 1, 227 adult kidney transplant recipients who were followed up in two transplant centers in Hong Kong over two decades., Results: 23 (1.9%) patients developed PTLD. Median duration from transplant to PTLD was 104 (5-252) months. Six patients (26.1%) had early PTLD and 17 (73.9%) had late PTLD. Ten (43%) developed PTLD >10 years after transplant. All patients in early PTLD group were EBV-positive. In the late PTLD group, 60% were EBV-negative and 40% EBV-positive. More than 90% of cases were monomorphic PTLD with majority being diffuse large B cell lymphoma. Bone marrow was the most common extranodal site. The overall treatment response rate was 52.2 %. None of the patients developed rejection or relapse after PTLD. At a median follow-up of 9 (1-79) months after PTLD, 18 patients died. Patient survival was 48% at 1 year and 30% at 3 years and death-censored allograft survival was 82% at 1year and 73% at 3 years., Conclusion: Late PTLD is common. Careful adjustment of immunosuppression, close monitoring of patients, increased awareness and early detection of the disease are essential., Competing Interests: CONFLICTS OF INTEREST The author declare no conflicts of interest.

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal gastrointestinal neoplasms. However, GISTs occurring in kidney transplant recipients, including their treatment and outcome, are rarely described in literature. We hereby report two kidney transplant recipients with GISTs. Our first patient was diagnosed with high-risk epithelioid gastric GIST 2 years after kidney transplant. He received everolimus after resection and remained disease-free for 2 years before liver metastasis was confirmed. Imatinib therapy was planned but he died of fulminant pneumonia shortly. Our second patient was diagnosed with spindle cell GISTs in the mesentery 1 year after kidney transplant. Only partial response was obtained with imatinib as new lesions continued to develop. Withdrawal of cyclosporine and introduction of sirolimus resulted in complete shrinkage of existing tumors and no new lesions. He remained disease-free for more than 10 years. Combination therapy consisting of imatinib and inhibitors of mammalian target of rapamycin (mTORi) seems to be safe and effective in kidney transplant recipients. However, therapeutic drug monitoring of mTORi is essential to avoid nephrotoxicity. Further trials addressing the optimal dosage of imatinib and mTORi in kidney transplant recipients are recommended., (© 2016 John Wiley & Sons Australia, Ltd.)

Introduction: The number of actual donors per million population is the most commonly used metric to measure organ donation rates worldwide. It is deemed inadequate, however, because it does not take into account the potential donor pool. The aim of this study was to determine the true potential for solid organ donation from deceased brain-dead donors and the reasons for non-donation from potential donors in the Chinese community., Methods: Medical records of all hospital deaths between 1 January and 31 December 2014 at a large regional hospital in Hong Kong were reviewed. Those who were on mechanical ventilation with documented brain injury and aged ≤75 years were classified as possible organ donors. The reasons why some potential organ donors did not become utilised organ donors were recorded and evaluated., Results: Among 3659 patient deaths, 121 were classified as possible organ donors. The mean age of the possible organ donors was 59.4 years and 72.7% of them were male. The majority (88%) were from non-intensive care units. Of the 121 possible organ donors, 108 were classified as potential organ donors after excluding 13 unlikely to fulfil brain death criteria. Finally 11 patients became actual organ donors with an overall conversion rate of 10%. Reasons for non-donation included medical contra-indication (46%), failure to identify and inform organ donation coordinators (14%), failure of donor maintenance (11%), brain death diagnosis not established (18%), and refusal by relatives (11%)., Conclusions: It is possible to increase the organ donation rate considerably by action at different stages of the donation process. Ongoing accurate audit of current practice is necessary.

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., Competing Interests: The authors have declared that no competing interests exist.

Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways., Competing Interests: Michael Seiler, Silvia Buonamici, Peter G. Smith are employees and shareholders of H3 Biomedicine. Catherine J. Wu is co-founder and scientific advisory board member of Neon Therapeutics, Inc. All other authors have no conflicts of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Emergence of multidrug-resistant bacteria is important in solid organ transplant recipients, because it can jeopardize patient and graft survival. Methicillin-resistant Staphylococcus aureus (MRSA) infections are not rare in kidney transplant recipients. On the other hand, infections related to community-associated MRSA (CA-MRSA) strains are seldom reported in the literature. Herein, we report the first patient, to our knowledge, with CA-MRSA renal graft abscess who was successfully treated with drainage and parenteral antibiotics., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Different studies in the past have shown that the risk of cancer development is increased in chronic dialysis patients. However, data concerning the cancer risk in Asian dialysis patients was scarce. More importantly, there was lack of information about the cancer-specific mortality in dialysis patients., Methods: A multicenter retrospective cohort study of 6,254 patients who started either chronic peritoneal dialysis or hemodialysis between 1994 and 2014 in 4 renal units in Hong Kong. Patterns of cancer incidence and mortality in our dialysis patients were compared with those of the general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively., Results: With 14,887 person-years of follow-up, 220 cancers were recorded. The SIR of all cancers was 1.44 (95% CI 1.26-1.65). A trend of an increased SIR was observed in young patients and within the first year of dialysis. Colorectum was the most common site of cancer (20%) while kidney cancer carried the highest risk (SIR 12.28, 95% CI 8.44-17.08). The SMR of all cancers was 0.91 (95% CI 0.72-1.13) and only kidney cancer had higher cancer mortality risk (SMR 4.92, 95% CI 1.80-10.70). SMR was highest in young patients and then decreased with age., Conclusions: The incidence of cancers in our chronic dialysis patients was elevated. Our findings of substantially increased risks in young patients, particularly in relation to kidney cancer, suggest that we can adopt a more individualized approach to cancer screening in chronic dialysis patients., (© 2016 S. Karger AG, Basel.)

After neural tube closure, amniotic fluid (AF) captured inside the neural tube forms the nascent cerebrospinal fluid (CSF). Neuroepithelial stem cells contact CSF-filled ventricles, proliferate, and differentiate to form the mammalian brain, while neurogenic placodes, which generate cranial sensory neurons, remain in contact with the AF. Using in vivo ultrasound imaging, we quantified the expansion of the embryonic ventricular-CSF space from its inception. We developed tools to obtain pure AF and nascent CSF, before and after neural tube closure, and to define how the AF and CSF proteomes diverge during mouse development. Using embryonic neural explants, we demonstrate that age-matched fluids promote Sox2-positive neurogenic identity in developing forebrain and olfactory epithelia. Nascent CSF also stimulates SOX2-positive self-renewal of forebrain progenitor cells, some of which is attributable to LIFR signaling. Our Resource should facilitate the investigation of fluid-tissue interactions during this highly vulnerable stage of early brain development., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report a patient suffering from end-stage renal disease (ESRD) because of lupus nephritis presented with exhausted vascular access after multiple arteriovenous grafts creation and hemodialysis catheters insertion. A rare percutaneous transrenal approach was finally used for the insertion of dialysis catheter. After 2 years, this hemodialysis catheter was complicated by blockage but was successfully replaced by a new catheter via the same site. Our report shows that the transrenal route of hemodialysis catheter insertion can provide a glimpse of hope for those ESRD patients with exhausted vascular access., (© 2015 International Society for Hemodialysis.)

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis-stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in-center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty-six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD., (© 2014 International Society for Hemodialysis.)

A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell-type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system., (Copyright © 2015 the authors 0270-6474/15/354903-14$15.00/0.)

Background: Current data concerning the relationship between renal function and clinical outcome among stroke patients treated with intravenous thrombolytic therapy are conflicting. Our aim is to analyze whether the clinical outcome of Chinese ischemic stroke patients treated with thrombolytic therapy is affected by the presence of renal dysfunction., Methods: Chinese patients who received intravenous thrombolytic therapy for acute ischemic stroke were recruited. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m(2). The primary outcome was independent function (modified Rankin Scale, mRS, 0-2) at 3 months, while secondary outcomes included early improvement of the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h, symptomatic intracerebral hemorrhage (ICH) within 36 h of treatment and 30-day mortality., Results: A total of 199 patients were recruited, of whom 51.3% had renal dysfunction. There were no significant differences in functional independence at 3 months, NIHSS improvement at 24 h post-thrombolysis and 30-day mortality between patients with or without renal dysfunction. Multivariate analysis showed that eGFR as a continuous variable was not an independent risk factor for symptomatic ICH., Conclusion: Chinese ischemic stroke patients with renal dysfunction who received thrombolytic therapy had clinical outcomes similar to those without renal dysfunction.

Background: Incorporating urinary cytology in BK virus (BKV) screening algorithm potentially reduces the screening cost for BK viral nephropathy. We aimed to evaluate the test performances and screening cost of sequential 2-stage screening consisting of urine cytology followed by BKV serum quantitative polymerase chain reaction (PCR)., Methods: Ninety-five kidney transplant recipients who had BKV serum quantitative PCR/urine cytology tested and verified with histopathology (the reference gold standard) were included. A probabilistic model was constructed to evaluate the test performance and screening cost of 2-stage screening, and was compared with screening with urine cytology or serum viral load alone., Results: At a viral load threshold of ≥104 copies/ml, the sensitivity and specificity of quantitative PCR alone were 83% (95% CI 69-96) and 91% (95% CI 83-97), respectively. The sensitivity and specificity of urine cytology alone were 91% (95% CI 79-100) and 74% (95% CI 60-91), respectively. Sequential 2-stage screening resulted in loss in sensitivity but a net gain in specificity (viral load threshold ≥104 copies/ml - sensitivity, 75% (95% CI 60-91); specificity, 98% (95% CI 95-99)). Two-stage screening also had superior positive predictive value and is cost effective when BKV-associated nephropathy prevalence is below 94%., Conclusions: Our study had demonstrated a favorable test performance and cost efficiency of 2-stage BKV screening., (© 2016 S. Karger AG, Basel.)

Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian brain. However, it is unknown whether phosphorylation at any of the previously identified sites on MeCP2 can be induced by signals other than neuronal activity in other cell types, and what functions MeCP2 phosphorylation may have in those contexts. Here we show that in neural progenitor cells isolated from the adult mouse hippocampus, cell cycle-linked phosphorylation at serine 421 on MeCP2 is directly regulated by aurora kinase B and modulates the balance between proliferation and neural differentiation through the Notch signalling pathway. Our findings suggest MeCP2 S421 phosphorylation may function as a general epigenetic switch accessible by different extracellular stimuli through different signalling pathways for regulating diverse biological functions in different cell types.

Both lipoprotein glomerulopathy (LPG) and fibrillary glomerulonephritis (FGN) are rare causes of end-stage renal disease (ESRD), and the literature concerning the outcome of kidney transplant in patients with LPG or FGN is scarce. We report a patient who suffered from ESRD with coexisting FGN and LPG and received deceased kidney transplant >10 years ago did not reveal any clinical features of disease recurrence during follow-up. Our case shows that the prognosis of patients with LPG component who received kidney transplant can be good. Kidney transplantation remains a viable therapeutic option for patients with ESRD secondary to FGN with LPG.

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

Heparin-induced thrombocytopenia (HIT) is a potentially fatal clinical condition which can develop after exposure to unfractionated or low-molecular-weight heparins. Even small doses of heparin such as heparin flushes in hemodialysis catheter can induce the development of HIT. However, the true incidence of heparin lock-related HIT is unknown. We report a 58-year-old woman with acute kidney injury because of obstructive uropathy who developed HIT after heparin-free hemodialysis. She was found to have severe thrombocytopenia with deep vein thrombosis of left lower limb and arterial thrombosis of the right anterior and middle cerebral arteries. The heparin-platelet factor 4 antibody was positive and she was put on plasmapharesis. However, her condition further deteriorated and succumbed shortly. Heparin lock solution in the hemodialysis catheter was believed to be the cause of HIT in our patient., (© 2014 International Society for Hemodialysis.)

Background: Data on the outcomes of older adults receiving peritoneal dialysis (PD), especially those who are dependent and have multiple comorbidities, are scarce., Methods: In a retrospective cohort study, we compared older adults (≥65 years) with stage 5 chronic kidney disease receiving PD (PD group) with those receiving conservative management (conservative group). Baseline characteristics (demographics and clinical, functional, socioeconomic, and laboratory parameters) were collected, and study outcomes (patient survival, emergency hospitalization, institutionalization, and palliative and end-of-life care) were compared between groups., Results: We included 199 eligible participants aged 65-90 years (mean ± standard deviation 73.8 ± 5.4 years; 157 in the PD group and 42 in the conservative group). The PD group had a longer survival (median [interquartile range]: 3.75 [2.49-5.25] vs 2.35 [1.13-3.71] years, p < .001), lower emergency hospitalization rates (1.63 [0.82-2.92] vs 3.51 [1.06-7.16] per person-year, p < .01) and hospital days (16.17 [6.29-43.32] vs 38.01 [6.75-76.56] days per person-year, p = .03), and no increased risk of institutionalization compared with the conservative group. Age (hazard ratio [HR] for 1-year increase 1.06, 95% confidence interval [CI] 1.02-1.10), modified Charlson's Comorbidity Index (HR 1.36, 95% CI 1.18-1.56), impairment in basic activities of daily living (HR 2.11, 95% CI 1.28-3.46), and emergency dialysis (HR 1.67, 95% CI 1.11-2.53) were independent predictors of mortality in the PD group., Conclusion: PD is a viable treatment option in older adults with stage 5 chronic kidney disease. Age alone should not preclude dialysis. Comprehensive geriatric assessment can prognosticate and facilitate shared decision making to commence dialysis in older adults.

Saline to freshwater invasions have become increasingly common in recent years. A key hypothesis is that rates of freshwater invasions have been amplified in recent years by increased food concentration, yet this hypothesis has remained unexplored. We examined whether elevated food concentration could enhance freshwater tolerance, and whether this effect evolves following saline to freshwater invasions. We examined physiological response to salinity and food concentration in a 2 × 2 factorial design, using ancestral brackish and freshwater invading populations of the copepod Eurytemora affinis. We found that high food concentration significantly increases low-salinity tolerance. This effect was reduced in the freshwater population, indicating evolution following the freshwater invasion. Thus, ample food could enable freshwater invasions, allowing subsequent evolution of low-salinity tolerance even under food-poor conditions. We also compared effects of food concentration on freshwater survival between two brackish populations from the native range. Impacts of food concentration on freshwater survival differed between the brackish populations, suggesting variation in functional properties affecting their propensity to invade freshwater habitats. The key implication is that high food concentration could profoundly extend range expansions of brackishwater species into freshwater habitats, potentially allowing for condition-specific competition between saline invaders and resident freshwater species.

Vascular calcification in children with long-standing dialysis is a unique phenomenon. Hyperphosphataemia and hyperparathyroidism are the major pathogenic risk factors. We describe a young patient with end-stage renal disease diagnosed since childhood and underwent prolonged dialysis therapy. He was admitted for recurrent episodes of acute joint pain. Investigations confirmed diffuse periarticular, vascular, and intracardiac calcifications which were rarely seen in the young population. He underwent parathyroidectomy and incidentally found to have a co-existing papillary carcinoma of thyroid. After parathyroidectomy, serial X-rays showed resorption of these calcifications.

Manystudies have shown that kidney transplant recipients have a higher incidence of cancers when compared with general population. However, most data on the posttransplant malignancies (PTM) are derived from Western literature and large population-based studies are rare. There is also lack of information about the posttransplant cancer-specific mortality rate. We conducted a population-based study of 4895 kidney transplants between 1972 and 2011, with data from the Hong Kong Renal Registry. Patterns of cancer incidence and mortality in our kidney transplant recipients were compared with those of the general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively. With 40 246 person-years of follow-up, 299 PTM was diagnosed. The SIR of all cancers was 2.94 (female 3.58 and male 2.58). Non-Hodgkin lymphoma (NHL), kidney, and bladder cancers had the highest SIRs. The overall SMR was 2.3 (female 3.4 and male 1.7) and the highest SMR was NHL. The patterns of PTM differ among countries. Increases in cancer incidence can now translate into similar increases in cancer mortality. NHL is important in our kidney transplant recipients. Strategies in cancer screening in selected patient groups are needed to improve transplant outcomes., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: To present and discuss the epidemiological and clinical aspects, as well as therapeutic options and outcome of de novo renal cell carcinoma (RCC) of the native kidneys in a series of Chinese renal transplant recipients., Patients and Methods: A retrospective, cohort study examining all renal transplant recipients with the diagnosis of RCC of native kidney followed up in two major regional hospitals in Hong Kong between January 2000 and December 2009. Clinical data included age, gender, cause of renal failure, symptoms at presentation, duration of transplantation, immunosuppressive therapy, and history of acquired cystic kidney disease (ACKD). Laboratory, radiographic, operative, and pathology reports were used to assess the tumor extent., Results: Among the 1,003 renal transplant recipients recruited, 12 transplant recipients had a nephrectomy for a total of 13 RCC. The prevalence of de novo RCC was 1.3%. The mean age at diagnosis of RCC was 48.4 years, and the median time from transplantation to diagnosis was 6.1 years. ACKD was found in 6 (50%) of the patients. All patients except one were asymptomatic. pT1 disease was found in ten patients with a mean tumor size of 3.2 cm. All patients were treated successfully with radical nephrectomy. After a median follow-up of 38 months, two patients (16.7%) died. One died of sepsis, and the other died of metastatic carcinoma., Conclusions: With increasing data showing a better prognosis if RCC is detected early by screening, it is time to consider screening all kidney transplant recipients for ACKD and RCC.

DNA methylation-dependent epigenetic mechanisms underlie the development and function of the mammalian brain. MeCP2 is highly expressed in neurons and functions as a molecular linker between DNA methylation, chromatin remodeling and transcription regulation. Previous in vitro studies have shown that neuronal activity-induced phosphorylation (NAIP) of methyl CpG-binding protein 2 (MeCP2) precedes its release from the Bdnf promoter and the ensuing Bdnf transcription. However, the in vivo function of this phosphorylation event remains elusive. We generated knock-in mice that lack NAIP of MeCP2 and found that they performed better in hippocampus-dependent memory tests, presented enhanced long-term potentiation at two synapses in the hippocampus and showed increased excitatory synaptogenesis. At the molecular level, the phospho-mutant MeCP2 protein bound more tightly to several MeCP2 target gene promoters and altered the expression of these genes. Our results suggest that NAIP of MeCP2 is required for modulating dynamic functions of the adult mouse brain.

Genetic reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) could offer replenishable cell sources for transplantation therapies. To fulfill their promises, human iPSCs will ideally be free of exogenous DNA (footprint-free), and be derived and cultured in chemically defined media free of feeder cells. Currently, methods are available to enable efficient derivation of footprint-free human iPSCs. However, each of these methods has its limitations. We have previously derived footprint-free human iPSCs by employing episomal vectors for transgene delivery, but the process was inefficient and required feeder cells. Here, we have greatly improved the episomal reprogramming efficiency using a cocktail containing MEK inhibitor PD0325901, GSK3β inhibitor CHIR99021, TGF-β/Activin/Nodal receptor inhibitor A-83-01, ROCK inhibitor HA-100 and human leukemia inhibitory factor. Moreover, we have successfully established a feeder-free reprogramming condition using chemically defined medium with bFGF and N2B27 supplements and chemically defined human ESC medium mTeSR1 for the derivation of footprint-free human iPSCs. These improvements enabled the routine derivation of footprint-free human iPSCs from skin fibroblasts, adipose tissue-derived cells and cord blood cells. This technology will likely be valuable for the production of clinical-grade human iPSCs.

Aim: Nocturnal home haemodialysis (NHHD) was started in Hong Kong in 2006. The experience of 1 year of NHHD with an alternate night schedule in two local centres is reported., Methods: The clinical parameters of 14 patients who had completed 1 year of NHHD were retrospectively analyzed. All patients were receiving an alternate night schedule (3.5 sessions/week) for 6-8 h/session., Results: After 1 year of NHHD, haemoglobin levels increased from 9.6±1.6 g/dL before NHHD to 11.4±2.2 g/dL (P<0.05) despite a reduction in erythropoietin dose requirement from 120.6±44.3 to 59.4±74.6 U/kg/week (P<0.05). Four patients (29%) were able to stop taking erythropoietin after NHHD. Serum phosphate levels reduced from 2.33±0.41 to 1.59±0.29 mmol/L (P<0.01) and calcium phosphate product decreased from 5.29±0.96 to 3.74±0.90 mmol2/L2 (P<0.01). Phosphate binder dose was greatly reduced and eight patients (67%) were able to stop taking phosphate binders. The number of antihypertensive medications tended to reduced from 2.5±1.3 to 1.6±1.5 (P=0.067) with four patients (29%) able to stop antihypertensives. Left ventricular mass index decreased from 186±62 to 168±60 g/m2 (P=0.463) although this was not statistically significant. Weekly spKt/V during conventional haemodialysis was 3.63±0.95 while that during NHHD was three times higher at 11.09±6.44 (P<0.01). The quality of life indexes also showed improvement., Conclusion: This 1 year experience of alternate night NHHD demonstrates benefits in terms of anaemia control, erythropoietin requirement, serum phosphate and calcium phosphate product reduction, blood pressure control, haemodialysis adequacy and quality of life. NHHD with an alternate night schedule is a promising dialytic therapy for patients receiving chronic haemodialysis in this locality., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

We report the first case of Streptococcus gordonii-related continuous ambulatory peritoneal dialysis (CAPD) peritonitis. He is a 69-year-old man with end-stage renal failure due to chronic glomerulonephritis who had been put on CAPD for 1 year. He was successfully treated with a 2-week course of cefazolin. This case highlights the emerging threat that S. gordonii can be the source of infection in patients on CAPD.

Objectives: To define the risk factors for delayed graft function and study the impact of such delays on renal function and long-term allograft survival in renal transplant recipients., Design: Single-centre retrospective study., Setting: Regional hospital, Hong Kong., Patients: Records of 118 Chinese renal transplant recipients from 1 July 1997 to 31 July 2005 were reviewed, and categorised into delayed and immediate graft function groups., Results: Delayed graft function was observed in about 19% of patients, for which cold ischaemic time was an important independent predictor. For each additional hour of cold ischaemic time, the odds ratio increased for delayed function by 0.002 (95% confidence interval, 0.001-0.003; P=0.03). Multivariate analysis revealed that neither cold ischaemic time nor delayed graft function was associated with acute rejection. On the other hand, at 1 year both delayed graft function (odds ratio=18.5; 95% confidence interval, 2.6-130.5; P=0.003) and donor age (1.2; 1.1-1.3; P=0.003) were related to a glomerular filtration rate of less than 30 mL/min. When renal function between patients with and without delayed graft function during the first 3 years was compared, it was significantly better in those without delayed graft function. However, there was no significant difference in death-censored graft survival between delayed graft function and immediate graft function groups., Conclusions: Delayed graft function has a significant adverse effect on graft function at 1 year. Limiting cold ischaemic time is important as it is an independent predictor of delayed graft function.

Aim: There is limited data concerning the impact of recipient body mass index (BMI) on graft outcome in Asian renal transplant recipients. The aim of this study is to identify whether obesity (BMI > or =25 kg/m(2)) and overweight (BMI > or =23 kg/m(2)) can predict graft outcome., Methods: This is a single-centre retrospective study. All patients who received kidney transplantation between 1997 and 2005 were recruited. Patients were categorized according to two different designated BMI cut-off values., Results: One hundred and thirty-one patients were recruited with a median follow-up duration of 73 months. If a BMI cut-off value of 25 kg/m(2) was used, 86.3% patients were classified as non-obese and 13.7% as obese. Obesity was significantly associated with poor renal graft function and decreased patient and graft survival. On the other hand, 34.3% patients were classified as overweight and 65.7% patients as normal if a BMI cut-off value of 23 kg/m(2) was used. Overweight was significantly associated with a lower glomerular filtration rate only. Cox regression analysis showed that obesity (odds ratio (OR) = 3.09), acute rejection (OR = 5.68), pre-transplant diabetes mellitus (OR = 3.21) and age of recipient (OR = 1.06) were all significant independent risk factors associated with graft failure., Conclusion: Recipient BMI > or =25 kg/m(2) is a significant predictive factor for long-term renal graft outcome in the Asian population.

Aim: The first prospective, randomized trial with paired kidney analysis was conducted to compare the efficacy and safety of tacrolimus with cyclosporine-based immunosuppressive therapy in renal transplant recipients. This paper reports the long-term follow-up results of the authors' previously published study, with the main focus on graft survival and renal function., Methods: Chinese patients transplanted in our centre between June 1998 and June 2005 with their first deceased renal transplant were included. Patients were included if both kidneys were received by the authors' centre, thus allowing a paired analysis. Patients were randomized to receive triple immunosuppressive therapy with either tacrolimus or Neoral cyclosporine, concomitantly with prednisolone and azathioprine therapy., Results: Seventy-six patients received cadaveric kidneys from 38 donors. Each pair of kidneys was randomly assigned to a separate group (38 subjects/group). The mean follow-up duration was 6.1 +/- 1.8 years. The mean calculated creatinine clearance was significantly higher in patients receiving tacrolimus-based therapy. The rate of biopsy-proven acute rejection was lower in the tacrolimus group (18.4% vs 42.1%, P = 0.03). The patient and graft survival were comparable in both treatment arms. Significantly fewer patients on tacrolimus-based therapy developed hypercholesterolaemia (P = 0.05). However, there was no significant difference in the development of post-transplant diabetes mellitus, hypertension, opportunistic infection and malignancy between both groups., Conclusion: Using the immunosuppressive regimen, tacrolimus-based therapy provided adequate immunosuppression with better renal function and less acute rejection, as compared with cyclosporine-based therapy.

Lipoprotein glomerulopathy is a rare kidney disease in which lipoprotein thrombi are seen in the glomerular capillaries. Most of these patients are found in Japan and East Asian countries. The presenting symptoms include proteinuria, an abnormal plasma lipoprotein profile that resembles type III hyperlipoproteinaemia, and a marked increase in serum apolipoprotein E concentration. Previous studies have suggested that lipoprotein glomerulopathy might be related to APOE gene mutation. No effective therapeutic regimen has been established for lipoprotein glomerulopathy. We report the first case of biopsy-proven lipoprotein glomerulopathy in Hong Kong in a patient who presented with nephrotic syndrome and dyslipidaemia. DNA analysis revealed apolipoprotein E Kyoto together with a novel apolipoprotein E mutation, apolipoprotein E (Asp230Tyr) Hong Kong. There was significant improvement in the clinical parameters and resolution of symptoms after the introduction of statins. Further studies will be needed to clarify the role of apolipoprotein E Hong Kong and its interaction with apolipoprotein E Kyoto in the pathogenesis of lipoprotein glomerulopathy.

Objective: To investigate the prevalence of metabolic syndrome in Chinese renal transplant recipients, using two different sets of diagnostic criteria., Design: Cross-sectional study., Setting: Regional hospital, Hong Kong., Patients: All Chinese patients who received solitary living-related or cadaveric kidney transplantation from 1 July 1997 to 31 December 2005 in our hospital with follow-up of more than 6 months were recruited. The diagnosis of metabolic syndrome was made according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria and the International Diabetes Federation criteria., Results: Using the modified (Asian) NCEP-ATPIII criteria, a total of 39 (32%) of 121 patients had metabolic syndrome, which included 20/69 (29%) of the males and 19/52 (37%) of the females. Using the International Diabetes Federation criteria, metabolic syndrome was diagnosed in 26% of the patients, 22% in males and 31% in females. In our patients, the most common component of metabolic syndrome was hypertension and the least common was low high-density-lipoprotein-cholesterol level. Low high-density-lipoprotein-cholesterol levels were significantly more common in female patients., Conclusion: This study shows that there is a high prevalence of metabolic syndrome in our Chinese renal transplant recipients.