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Background The coronavirus disease 2019 (COVID-19) pandemic has put an enormous burden on health care systems worldwide. Limited access to medical care and fear of increased infective risks due to the use of immunosuppressive medication (IM) have increased concerns about IM adherence in kidney transplant recipients (KTRs). The aim of this study was to determine the various dimensions of IM nonadherence in KTRs during the COVID-19 pandemic. Methods This was a single-center, cross-sectional study using a convenient sampling approach. KTRs with follow-up in Queen Elizabeth Hospital, Hong Kong between May 1, 2020 and September 30, 2020, were invited to complete a self-reported questionnaire on IM adherence. The sociodemographic factors associated with IM adherence were extracted from medical records. Results Overall, 210 patients completed the questionnaires. The overall IM nonadherence rate was 35.2% in the 4 weeks before survey completion. None of the patients stopped taking IMs without instructions from their health care providers. The most common pattern of IM nonadherence was timing adherence (n = 63; 30.1%), followed by dose-skipping item. Among the different sociodemographic factors studied, only marital status was an independent risk factor of IM nonadherence (odds ratio, 1.97; 95% confidence interval, 1.04-3.72; P = .03). Conclusions The impact of COVID-19 on IM adherence in KTRs was not significant. All the patients continued their IM despite of the pandemic. Good family support can have a positive influence on treatment adherence in KTRs during the COVID-19 pandemic.

Introduction: Although the association between CYP3A5 gene polymorphism and tacrolimus dosing requirements was well established, the impact on how CYP3A5 genotype affects the acute rejection and long-term renal function in patients who received kidney transplants and were treated with tacrolimus remained controversial. Design: Sixty-seven Chinese patients with kidney transplants receiving de novo tacrolimus-based immunosuppressive therapy with known CYP3A5 genotype were divided into 2 groups. Those with at least 1 CYP3A5*1 allele were CYP3A5 expressers while homozygotes for the mutant allele CYP3A5*3 were nonexpressers. Instead of trough level, our center used abbreviated area under the curve for tacrolimus monitoring. Primary outcome was the long-term renal function between both groups while secondary outcomes included the weight-adjusted daily tacrolimus dose, graft survival, incidence of biopsy-proven acute rejection (BPAR), opportunistic infection, and cancer. Results: Thirty-five (52.2%) patients were CYP3A5 expressers while 32 were nonexpressers. Mean daily tacrolimus dose in the CYP3A5 expressers and nonexpressers was 0.08 (0.03) and 0.05 (0.02) mg/kg, respectively ( P < .01). Starting from 1-month posttransplant, the renal function was comparable between both groups, which persisted up to 10-year. Ten patients experienced BPAR rejection and there was no significant difference in the rejection-free survival between both groups ( P = .87). There was also no significant difference in the death-censored graft survival between both groups ( P = .86). Finally, the incidence of opportunistic infection and posttransplant cancer was similar between them. Discussion: There was no significant difference in renal function, graft survival, and acute rejection between CYP3A5 expressers and nonexpressers.

With advances in immunosuppressive therapy, there have been significant improvements in acute rejection rates and short-term allograft survival in kidney transplant recipients. However, this success has not been translated into long-term benefits by the same magnitude. Optimization of immunosuppression is important to improve the clinical outcome of transplant recipients. It is important to note that each patient has unique attributes and immunosuppression management should not be a one-size-fits-all approach. Elderly transplant patients are less likely to develop acute rejection but more likely to die from infectious and cardiovascular causes than younger patients. For those with post-transplant cancers and BK polyomavirus-associated nephropathy, reduction of immunosuppression can increase the risk of rejection. Therapeutic drug monitoring (TDM) is routinely used for dosage adjustment of several immunosuppressive drugs. It has been hoped that pharmacogenetics can be used to complement TDM in optimizing drug exposure. Among the various drug-genotype pairs being investigated, tacrolimus and CYP3A5 gives the most promising results. Different studies have consistently shown that CYP3A5 expressers require a higher tacrolimus dose and take longer time to achieve target blood tacrolimus levels than nonexpressers. However, for pharmacogenetics to be widely used clinically, further trials are necessary to demonstrate the clinical benefits of genotype-guided dosing such as reduction of rejection and drug-related toxicities. The development of different biomarkers in recent years may help to achieve true personalized therapy in transplant patients.

Introduction The coronavirus disease 2019 (COVID-19) pandemic was expected to have a negative impact on organ donation. With the differences in health care systems and lockdown policies in various regions, the pandemic's effect on organ donation and transplant service may vary. Most of the deceased donor organ referrals in our hospital came from non–intensive care units (ICUs). The objective of this study is to report our experience and quantify the effects of the COVID-19 pandemic on deceased donor organ donation in our center. Methods This was a retrospective observational study comparing the deceased donor organ donation activity during the period January 23 to November 30, 2020 with the same period in 2018 in Queen Elizabeth Hospital, Hong Kong. Results There was a 26.9% reduction in deceased donor organ donor referral in 2020 compared with 2018. No significant difference in the proportion of referrals from ICU or non-ICU areas between the 2 time periods was observed. The brain death confirmation rate was significantly higher in 2020 (40.8% vs 20.2%, P = .003). Nine patients had family consent for organ donation in 2020 (vs 7 patients in the same period in 2018). There were no significant differences in consent rate and number of recovered organs between the 2 periods. Conclusions With effective measures to limit the spread of COVID-19 in a community, it is possible to support the needs of both patients with COVID-19 and deceased donor organ donation services.

Lipoprotein glomeurulopathy (LPG) is an uncommon cause of end stage kidney disease (ESKD). The long-term outcome of kidney transplantation in patients with LPG remains largely unknown and early recurrence of LPG in the allograft kidney appears to be the rule. Here we report a young Chinese patient with ESKD due to rare coexisting LPG and fibrillary glomerulonephritis, who received deceased kidney transplantation, was diagnosed to have LPG recurrence after 20 years of post-transplant follow-up. With the longest follow-up duration after kidney transplantation in literature, our case shows that the prognosis of kidney transplantation in patients with LPG can still be good. Kidney transplantation should remain a therapeutic option for patients with ESKD due to LPG.

Aim Direct kidney involvement in B-cell lymphoproliferative disease is a rare disorder with only a few studies reported in Caucasian patients. The clinicopathological characteristics and outcome of this entity remain poorly described. Methods We retrospectively studied all adult Chinese patients who had histology-proven renal parenchymal infiltration by malignant B-cells between 1/1/2000 and 31/12/2018 at 2 tertiary hospitals in Hong Kong. Clinical, pathological and radiological data were collected from 20 patients. Follow-up data were analyzed until 31/12/2019. Results Median follow-up duration was 22 (1-171) months. Only 7 patients (35%) had established diagnosis of hematological cancer before kidney biopsy. Diffuse large B-cell lymphoma (DLBCL) was the most common subtype in our cohort (n=5, 25%). Others included low-grade B-cell lymphoma (n=11), intravascular large B-cell lymphoma (n=1), mantle cell lymphoma (n=1) and multiple myeloma (n=2). Fourteen patients (70%) presented with AKI while 12 patients (60%) had proteinuria. Seven patients (35%) had unilateral renal mass, 1 had bilateral renal masses and 1 had bilateral diffuse nephromegaly in computed tomography. Lymphomatous tubulointerstitial infiltration was the prevalent histological finding. Nine patients (45%) had coexisting renal lesions other than direct tumor infiltration. All but 1 patient received chemotherapy. Ten patients died and renal responders had a significantly better survival than non-renal responders (P=0.03). Conclusion Direct tumor infiltration can occur in a wide variety of B-cell lymphoproliferative disorders. Coexisting immunoglobulin-related nephropathy is frequently found. Renal biopsy is required for early diagnosis which allows timely and appropriate treatment. This article is protected by copyright. All rights reserved.

IntroductionDiabetic kidney disease (DKD) is a prevalent and costly complication of diabetes with limited therapeutic options, being the leading cause of end-stage kidney disease in most developed regions. Recent big data studies showed that add-on Chinese medicine (CM) led to a reduced risk of end-stage kidney disease and mortality among patients with chronic kidney disease (CKD) and diabetes. Astragalus, commonly known as huang-qi, is the most prescribed CM or used dietary herb in China for diabetes and DKD. In vivo and in vitro studies showed that astragalus ameliorated podocyte apoptosis, foot process effacement, mesangial expansion, glomerulosclerosis and interstitial fibrosis. Nevertheless, the clinical effect of astragalus remains uncharacterised. This pragmatic clinical trial aims to evaluate the effectiveness of add-on astragalus in patients with type 2 diabetes, stage 2–3 CKD and macroalbuminuria, and to identify related response predictors.Methods and analysisThis is an add-on, assessor-blind, parallel, pragmatic randomised controlled clinical trial. 118 patients diagnosed with DKD will be recruited and randomised 1:1 to receive 48 weeks of add-on astragalus or standard medical care. Primary endpoints are the changes in estimated glomerular filtration rate and urine albumin-to-creatinine ratio between baseline and treatment endpoint. Secondary endpoints include adverse events, fasting blood glucose, glycated haemoglobin, lipids and other biomarkers. Adverse events are monitored through self-complete questionnaire and clinical visits. Outcomes will be analysed by regression models. Subgroup and sensitivity analyses will be conducted for different epidemiological subgroups and statistical analyses. Enrolment started in July 2018.Ethics and disseminationThis study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West/East/Kowloon Central clusters (UW 16-553/HKEC-2019-026/REC (KC/KE)-19-0049/ER-4). We will report the findings in medical journals and conferences. The dataset will be available on reasonable request.Trial registration numberNCT03535935

A 56-year-old man, who received deceased kidney transplant 20 years ago, presented with an enlarged submandibular lymph node. Histologic examination revealed nodal marginal zone lymphoma in which the neoplastic lymphoid cells showed diffuse positivity for Epstein-Barr virus early RNA by in situ hybridization. Systemic lymphoma workup showed stage I disease. The tumor was managed as a posttransplant lymphoproliferative disorder and the immunosuppression was modified. There was no evidence of lymphoma at follow-up 6 years after excision alone. This case supports the inclusion of Epstein-Barr virus–positive nodal marginal zone lymphoma as a form of monomorphic B-cell lymphoproliferative disorder, in line with the status of its extranodal mucosa-associated lymphoid tissue lymphoma counterpart.

Background Vancomycin-resistant Enterococcus (VRE) colonization is common among patients with chronic kidney disease. However, data concerning VRE colonization among patients receiving peritoneal dialysis (PD) is lacking. The aim of this study is to evaluate the risk factors and various clinical outcomes for VRE colonization among PD patients. Methods This is a retrospective cohort study of 166 PD patients who were hospitalized between 1 August 2013 and 31 July 2014. They were screened for VRE colonization status during a major VRE outbreak in Hong Kong in 2013 and were then categorized into 2 groups: VRE-positive and VRE-negative. The primary outcome was all-cause mortality while the secondary outcomes included VRE infection, PD-related peritonitis, and length of hospitalization. Results Twenty-eight patients (16.9%) belonged to the VRE-positive group. Multivariate analysis showed that previous contact with VRE-positive patients (odds ratio [OR]: 417.86; 95% confidence interval [CI]: 17.21 – 10,147.26, p < 0.01), vancomycin use in previous 3 months (OR: 130.32; 95% CI: 5.35 – 3,176.30, p < 0.01), and old age (OR: 1.13; 95% CI: 1.02 – 1.24, p = 0.02) were the independent risk factors for VRE colonization. Patients in the VRE-positive group had significantly longer length of hospitalization, but there was no significant difference in all-cause mortality and peritonitis-free survival. Conclusion Vancomycin-resistant Enterococcus colonization is important among hospitalized PD patients. Cautious use of antibiotics and infection control measures are necessary to prevent VRE spreading, especially in high-risk patients.

// Chi Yuen Cheung 1 , Maggie Kam Man Ma 2 , Ka Foon Chau 1 , Wai Leung Chak 1 and Sydney Chi Wai Tang 2 1 Renal Unit, Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China 2 Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China Correspondence to: Sydney Chi Wai Tang, email: scwtang@hku.hk Keywords: lymphoma, posttransplant lymphoproliferative disorders, kidney transplant Received: February 22, 2017 Accepted: June 04, 2017 Published: June 30, 2017 ABSTRACT 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.

// Chi Yuen Cheung 1 , Maggie Kam Man Ma 2 , Wai Leung Chak 1 , Ka Foon Chau 1 and Sydney Chi Wai Tang 2 1 Department of Medicine, Renal Unit, Queen Elizabeth Hospital, Yau Ma Tei, Hong Kong SAR 2 Department of Medicine, Division of Nephrology, The University of Hong Kong, Queen Mary Hospital, Yau Ma Tei, Hong Kong SAR Correspondence to: Sydney Chi Wai Tang, email: // Keywords : cancer, everolimus, kidney transplant, sirolimus Received : December 12, 2016 Accepted : January 17, 2017 Published : January 30, 2017 Abstract 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.

Background. Although high tacrolimus (FK) intrapatient variability (IPV) was shown to be associated with poor graft outcome in kidney transplant recipients (KTRs), it is uncertain whether there is any association between the CYP3A5 genotype and IPV of FK concentrations. Instead of trough level, we use calculated abbreviated AUC(0-12) to investigate the impact of CYP3A5 genetic polymorphism on IPV of FK pharmacokinetics.Methods. We conducted a retrospective, single-center study of 86 adult Chinese KTRs with known CYP3A5 genotype. Coefficient of variation (CV) was used for the quantification of FK IPV. CV of dose-normalized FK AUC(0-12) was calculated and was compared between the CYP3A5 expresser group and nonexpresser group.Results. Forty-one patients (47.7%) were classified as CYP3A5 expressers while 45 were nonexpressers. No significant differences in the baseline characteristics were found between expressers and nonexpressers. CYP3A5 expressers required 1.8 times higher FK dose compared with the nonexpressers. There was no significant difference in the FK CV between CYP3A5 expressers (18.2 +/- 7.5%) and nonexpressers (16.7 +/- 5.7%) (P = .31).Conclusion. The IPV of FK exposure was not associated with CYP3A5 genotype in stable KTRs. Further studies should focus on other factors such as medication nonadherence, which may explain FK IPV.

Anticoagulant-related nephropathy (ARN), a significant but frequently undiagnosed problem in patients receiving anticoagulation, is found to be associated with increased renal morbidity and all-cause mortality. While ARN is mainly associated with warfarin use, recent case reports suggest that it may also occur in patients taking direct oral anticoagulants (DOAC). We report a patient who had a history of alcoholic liver cirrhosis and paroxysmal atrial fibrillation, and received dabigatran 110 mg twice daily for 1 year. He presented with gross hematuria and severe acute kidney injury with an international normalized ratio of 4.09. Dabigatran was stopped and he was put on temporary hemodialysis support. His renal function gradually improved when the hematuria subsided. Renal biopsy later confirmed the presence of red blood cell casts inside the renal tubules with features of IgA nephropathy. Finally, his renal function returned back to baseline level. As DOAC has been increasingly used nowadays for the treatment of various thromboembolic diatheses, regular monitoring of renal function is warranted, especially in patients with underlying glomerular diseases and coagulopathy such as chronic liver diseases.

Dialysis is the commonest modality of renal replacement therapy for patients suffering from end-stage kidney disease. Different registry studies showed that the risks of overall cancer occurrence were significantly higher in chronic dialysis patients than in the age-matched general population. However, the frequency and pattern of different cancers may vary among different geographical areas. Since chronic dialysis patients tend to have multiple comorbidities and a shorter life expectancy, routine cancer screening in all dialysis patients may not be cost-effective; rather screening should be personalized according to the patient's expected survival, candidacy for kidney transplant together with patient preferences.

The emergence of onconephrology in recent years highlights the importance of the interaction between kidney disease and cancer. Chronic kidney disease (CKD) and cancer are linked with each other in different ways bidirectionally: cancer can cause CKD, whereas CKD itself may be a risk factor for cancer. Kidney transplant recipients (KTRs) have a 2- to 3-fold increased cancer risk when compared with the general population. The elevated risk covers a wide range of cancers. Some are related to CKD, including cancers of the kidney, urinary tract and thyroid, whereas others are related to oncogenic viruses that include non-Hodgkin lymphoma, cervical cancer, nonmelanoma skin cancer and Kaposi's sarcoma. There is no standard protocol regarding how immunosuppressive drugs should be adjusted in patients who develop posttransplant cancers. However, any modification of immunosuppressive regimens should be balanced against the risk of allograft rejection or deterioration in kidney function. Cancer surveillance can be used as a strategy to improve the clinical outcome in KTRs. Although guidelines adopted in the general population have been used as the reference, a personalized approach based on individual cancer risk, life expectancy and concurrent comorbidities has to be adopted.

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.

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.

Vancomycin-resistantThis is a retrospective cohort study of 166 PD patients who were hospitalized between 1 August 2013 and 31 July 2014. They were screened for VRE colonization status during a major VRE outbreak in Hong Kong in 2013 and were then categorized into 2 groups: VRE-positive and VRE-negative. The primary outcome was all-cause mortality while the secondary outcomes included VRE infection, PD-related peritonitis, and length of hospitalization.Twenty-eight patients (16.9%) belonged to the VRE-positive group. Multivariate analysis showed that previous contact with VRE-positive patients (odds ratio [OR]: 417.86; 95% confidence interval [CI]: 17.21 - 10,147.26,Vancomycin-resistant

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.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.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.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.

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.

This cross-sectional and exploratory study aimed to compare motor performance and electroencephalographic (EEG) attention levels in children with developmental coordination disorder (DCD) and those with typical development, and determine the relationship between motor performance and the rea

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 includedage, 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. © The Author(s) 2011. This article is published with open access at Springerlink.com., published_or_final_version, Springer Open Choice, 21 Feb 2012

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.

Tacrolimus is an immunosuppressive agent that can show a wide variety of neurological side effects, including leukoencephalopathy. The prognosis is usually good with complete neurological recovery after dose reduction or cessation. However, differentiation from progressive multifocal leukoencephalopathy can sometimes be difficult. We describe the case of a 52-year-old gentleman with severe, irreversible tacrolimus-related leukoencephalopathy 4 months after kidney transplantation.

Background Post-transplant diabetes mellitus (PTDM) after renal transplantation is associated with adverse outcome on patient and graft survival. Fasting blood glucose alone will underestimate diabetes and also ignores diagnosis of impaired glucose tolerance (IGT). IGT has a strong correlation with diabetes and cardiovascular risk. Methods In this cross-sectional study, we estimate the prevalence of abnormal glucose metabolism (AGM) using oral glucose tolerance test (OGTT) and identify its predictive factors. Patients who received kidney transplantation in our centre without pre-transplant diabetes were recruited. OGTT was performed in patients with fasting glucose levels between 5.6 and 6.9 mmol/L for at least two occasions 6 months post-transplantation. Results Of 119 patients recruited, 31 had OGTT performed. The prevalence of PTDM, IGT and IFG was 21.8 (26/119)%, 6.7 (8/119)% and 3.4 (4/119)% respectively. Thus the overall prevalence of AGM was 31.9%. Age (P = 0.003), body mass index (P = 0.032), hepatitis B seropositivity status (P = 0.01), CMV infection (P = 0.02) and acute rejection (P = 0.002) were all associated with development of AGM. Using multivariate analysis, only older age at transplant (OR 1.09), history of acute rejection (OR 3.40) and hepatitis B seropositivity (OR 3.13) were significantly associated with the development of AGM. Conclusion AGM is common in our renal transplant recipients.

SUMMARY: Aims: To evaluate the efficacy and safety of a tacrolimus-based immunosuppressive regimen with and without induction therapy using daclizumab in first cadaveric renal transplant recipients. Methods: Since January 2001, we studied the effect of daclizumab in a non-randomized and prospective study of 36 sequential first cadaveric renal transplant recipients. They were compared with a historical control group of 21 sequential first cadaveric renal transplant recipients without induction therapy. All patients received tacrolimus, azathioprine and corticosteroids as concomitant immunosuppressive therapy. Daclizumab was given at 1 mg/kg infusion 2 h before transplantation and then every 14 days for four more doses. Outcomes measured included incidence of acute rejection, patient survival, graft survival, annualized change in creatinine clearance (CrCl), cardiovascular risk profile, infection and malignancy. Results: Fewer biopsy proven acute rejections were observed in the induction treatment group: 11.1% (4/36) versus 19% (4/21) but the rejection free survival was similar (P = 0.37). The patient survival and graft survival were comparable. The renal function was similar in both groups. There were also no significant difference in infection, malignancy and cardiovascular risk profile in both groups. Conclusion: Adding daclizumab to a tacrolimus-based therapy is safe but cannot further improve clinical efficacy.

To evaluate the prevalence of chronic kidney disease (CKD) in Chinese HIV-infected population.This was a cross-sectional point prevalence study. All Chinese HIV-infected patients who were followed up in a tertiary referral center in Hong Kong were recruited. Spot urine was saved for each patient to calculate urine protein-to-creatinine ratio (urine P/Cr). Those with urine P/Cr0.3 would have 24-h urine collection to determine the exact amount of proteinuria. Glomerular filtration rate (GFR) was estimated using MDRD formula. CKD was defined as GFR60 ml/min/1.73 m2 and/or urine P/Cr0.3. Baseline demographic and clinical data were extracted from patients' records.In total 322 patients were recruited. The mean age was 45.2 +/- 11.7 years. The duration of follow up was 6.0 +/- 4.0 years. There were 264 male and 58 female patients. The prevalence of hypertension, diabetes mellitus and CKD were 7.4%, 10.6% and 16.8%, respectively. Eighteen patients (5.6%) had GFR60 ml/min/1.73 m2 while 44 patients (13.7%) had spot urine P/Cr0.3. Among those with urine P/Cr0.3, 38 patients had 24-h urine collection. Using univariate analysis, CKD was found to be significantly (P0.05) associated with age, hypertension, diabetes, use of indinavir, lower CD4 count and peak viral load. Multivariate logistic regression revealed older age (P0.001), lower CD4 count (P = 0.02) and use of indinavir therapy (P = 0.04) were associated with development of CKD.CKD is prevalent in Chinese HIV-infected patients. Patients with CKD were more likely to be older, associated with use of indinavir and CD4 nadir less than 100 cells/mul.

Tacrolimus, an immunosuppressant used after organ transplantation, has a narrow therapeutic range and its pharmacokinetic variability complicates its daily dose assessment. P-glycoprotein (P-gp), encoded by the adenosine triphosphate-binding cassette B1 (ABCB1) and the cytochrome (CYP) 3A4 and 3A5 enzymes appears to play a role in the tacrolimus metabolism. In the present study, two different renal transplant recipient groups were used to examine the influence of ABCB1 and CYP3A polymorphisms on the daily tacrolimus dose and several pharmacokinetic parameters. In total 63 Caucasian renal transplant recipients divided into 26 early [median (range) of the days since transplantation - 16 (3-74)] and 37 late [median (range) of the days since transplantation - 1465 (453-4128)] post-transplant recipients were genotyped for ABCB1 and CYP3A polymorphisms. The pharmacokinetic parameters of tacrolimus were determined for all renal transplant recipients and correlated with their corresponding genotypes. A significant difference in allele frequencies of the CYP3A4*1B (P = 0.028) and CYP3A5*1 (P = 0.022) alleles was observed between the early and late post-transplant recipient groups. Significantly higher dose-normalized trough levels (dnC(0)), dose-normalized area under the curve (dnAUC(0-12)), and dose-normalized maximum concentration (dnC(max)) were observed for carriers of the CYP3A5*3 variant allele in both renal transplant patient groups. Except for the daily tacrolimus dose (P = 0.025) no significant differences were observed for carriers of the CYP3A4*1B variant allele. Neither the individual ABCB1 polymorphisms nor the ABCB1 haplotypes were associated with any pharmacokinetic parameter. We noticed that patients carrying a CYP3A5*1 allele require a twofold higher tacrolimus dose compared with homozygous carriers of the CYP3A5*3 variant allele to maintain the target dnAUC(0-12). Therefore, genotyping for the CYP3A5*3 variant allele can contribute to a better and more individualized immunosuppressive therapy in transplant patients.

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.

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) 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.

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.

Background Osteopenia and bone loss are major complications after renal transplantation. Clinical data in the Asian population are lacking. Methods We prospectively studied the changes in bone mineral density (BMD) of 31 cadaveric renal allograft recipients using dual energy X-ray absorptiometry (DEXA) within 2 weeks after transplantation and then at 1 year post transplantation. Results One year after transplantation, the mean bone mineral reduction at the lumbar spine was 6.3 ± 4.9% (osteopenia in 32.2% of patients and osteoporosis in 6.5%). For the femoral neck, there was a 4.3 ± 5.5% decrease in BMD (osteopenia in 38.7% of patients and osteoporosis in 3.2%). For total hip, there was a 4.8 ± 3.6% decrease in BMD (osteopenia in 25.8% of patients and osteoporosis in 3.2%). Decrease in BMD at the femoral neck and total hip correlated with the cumulative dosage of steroid (femoral neck: r = −0.36, p = 0.048; total hip: r = −0.4, p = 0.026). Compared with patients without rejection, patients with a history of acute rejection received higher cumulative doses of steroid, and sustained a greater decrease in BMD at the femoral neck and total hip: median percentage (interquartile range) decrease in femoral neck BMD was 7.7% (−12.8 to −6.3) versus 4.4% (−6.5 to −0.065), p = 0.016; decrease in total hip BMD was 8.2% (−11.22 to −6.7) versus 3.4% (−6.92 to −1.4), p = 0.03. There was no correlation between BMD changes and cumulative dosage of cyclosporine A, azathioprine, tacrolimus, duration of dialysis, changes in body mass index, creatinine or parathyroid hormone levels. Conclusion Reduction of BMD after renal transplantation is common. The cumulative dosage of prednisolone correlates with bone loss at the femoral neck and total hip. Patients with a history of acute rejection suffered from more bone loss after 1 year compared to patients without rejection.

We report herein two patients who presented with bilateral hydronephrosis attributed to lupus cystitis with two totally different clinical consequences. Both had systemic lupus erythematosus complicated with nephritis and nephrotic range of proteinuria. During the investigation of their proteinuria, they were noted to have a dilated collecting system. The site of obstruction was localized at the vesicoureteric obstruction by excretory urogram. The hydronephrosis resolved spontaneously in one patient before the commencement of any medical therapy, whereas in the other patient, there was no response to steroid therapy. Augmentation enterocystoplasty was thus performed. Reversible hydronephrosis caused by vesicoureteric junction obstruction in patients with systemic lupus erythematosus has been reported. Immune-mediated vasculitis involving the ureter and bladder mucosa was the postulated pathogenic mechanism. The condition usually showed good clinical response upon immunosuppressive therapy. We conclude that systemic lupus erythematosus-associated interstitial cystitis can have a spectrum of different prognoses.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease nowadays. Certain cancers are more common in patients with diabetes mellitus. However, there are no data concerning the cancer pattern in patients with DN. The aim of this study is to investigate the site-specific cancer risk and mortality in these patients. A retrospective cohort study of 5643 DN patients between 2000 and 2015 was conducted in 2 large hospitals in Hong Kong. Incidence and mortality of various cancers were compared with those of general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively. With 24,726 person-years follow-up, 250 cancers were diagnosed. Overall cancer incidence was similar between DN patients and the general population (SIR 1.05, 95% confidence interval [CI] 0.92–1.19). However, certain site-specific cancers are increased in DN patients: the highest risk was observed for laryngeal cancer (SIR 3.03, 95% CI 1.11–6.60), followed by cancers of liver (SIR 1.96, 95% CI 1.35–2.76) and colorectum (SIR 1.92, 95% CI 1.53–2.37), but the risk of prostate cancer was lower (SIR 0.48, 95% CI 0.21–0.95) in the males with DN. The SMR of all cancers was 1.17 (95% CI 1.01–1.37). For individual specific site, only colorectal cancer carried a significant higher mortality risk (SMR 2.45, 95% CI 1.82–3.23). Our data suggested that DN is associated with increased incidence of cancers of colorectum, liver, and larynx but decreased incidence of prostate cancer. Moreover, there is increased mortality of colorectal cancer in patients with DN.

Summary Alcoholic ketoacidosis is an important cause of double gap metabolic acidosis. The differential diagnosis includes toxic alcohol (such as methanol and ethylene glycol) ingestion. We report a patient with alcoholic ketoacidosis. He had a history of excessive alcohol intake and presented with repeated vomiting, loss of appetite and hypovolemic shock. Laboratory results revealed high anion gap metabolic acidosis, increased serum osmolal gap, ketonemia, lactic acidosis and acute renal failure. He was successfully treated with hemodialysis, and hydration with glucose and thiamine. 酒精性代謝酮酸中毒是雙重間隙代謝性酸中毒的重要成因，其鑑別診斷為有毒酒精(如甲醇、乙二醇)的攝入。以下個案是一位酒精性代謝酮酸中毒患者，具過度攝入酒精的習慣，入院時呈現重複嘔吐、無食慾、及低血容積性休克。化驗結果顯示高陰離子間隙之代謝性酸中毒、高血清滲透間隙、酮血症、乳酸中毒、及急性腎衰竭。在接受血液透析、合併葡萄糖與硫胺素補充療法後，病人反應良好。

Angelica Radix, the roots of the genus Angelica, has been used for more than 2,000 years as a traditional medicine in Eastern Asia. The Chinese Pharmacopoeia records more than 100 herbal formulae containing Angelica roots. There are two common sources of Angelica roots, Angelica sinensis from China and A. gigas from Korea. The two species of Angelica roots differ in their chemical compositions, pharmacological properties and clinical efficacy. 1H-NMR metabolic profiling has recently emerged as a promising quality control method for food and herbal chemistry. We explored the use of 1H-NMR metabolic profiling for the quality control of Angelica Radix. Unlike previous work, we performed the metabolic profiling on hot water extracts, so as to mimic the clinically relevant preparation method. Unsupervised principle component analyses of both the full spectral profile and a selection of targeted molecules revealed a clear differentiation of three types of Angelica roots. In addition, the levels of 13 common metabolites were measured. Statistically significant differences in the levels of glucose, fructose and threonine were found between different sources of Angelica. Ferulic acid, a marker commonly used to evaluate Angelica root, was detected in our samples, but the difference in ferulic acid levels between the samples was not statistically significant. Overall, we successfully applied 1H-NMR metabolic profiling with water extraction to discriminate all three sources of Angelica roots, and obtained quantitative information of many common metabolites.

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.

Danggui Buxue Tang (DBT) is one of the simplest traditional Chinese medicine (TCM) decoctions, first described in China in 1247 AD. DBT is composed of 2 herbs, Astragali Radix (AR) and Angelica Sinensis Radix (ASR), boiled together in a 5 : 1 ratio. Clinically, DBT is prescribed to women as a remedy for menopausal symptoms. Here,H-NMR metabolic profiling was conducted for DBT and the water extracts of AR or ASR, to evaluate the potential of this chemical profiling method for quality control of the herbal decoction. Principal component analysis (PCA) showed that DBT could be readily distinguished from the water extracts of its constituent herbs by the metabolic profiles. More interestingly, the metabolic profile of DBT was not a simple sum of that of AR and ASR. Asparagine was found at significantly higher concentration in DBT than that in either AR or ASR extract, contributing mainly to the discrimination of DBT sample. In addition, we employed the same method to profile a commercial DBT powder, verifying its authenticity as compared to our prepared DBT. This study is the first to employH-NMR metabolic profiling for the quality control of traditional Chinese medicine decoctions.

We report a gentleman suffering from purpuric skin rash mimicking vasculitis associated with impaired renal function. He was found to have positive cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in the serum, but the test for anti-proteinase 3 antibodies (PR3-ANCA) was negative. Blood culture and echocardiogram confirmed the diagnosis of Streptococcal Oralis infective endocarditis. The renal biopsy did not show any features of vasculitis or crescentic glomerulonephritis. His skin rash subsided and renal function normalized after treatment of the infective endocarditis with appropriate antibiotics. Therefore, we conclude that for those patients presenting with features of vasculitis and a positive ANCA test, other causes, such as infective endocarditis, should be considered.