Personalized immunosuppression after kidney transplantation.

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.

Clinicopathological features of Chinese patients with B-cell lymphoproliferative disorders and kidney infiltration.

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 January 2000 and 31 December 2018 at two tertiary hospitals in Hong Kong. Clinical, pathological and radiological data were collected from 20 patients. Follow-up data were analysed until 31 December 2019. RESULTS: Median follow-up duration was 22 (1-171) months. Only seven patients (35%) had established diagnosis of haematological 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, one had bilateral renal masses and one 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 tumour infiltration. All but one patient received chemotherapy. Ten patients died and renal responders had a significantly better survival than non-renal responders (p = .03). CONCLUSION: Direct tumour 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.

An update on cancer after kidney transplantation.

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.

Oncology in nephrology comes of age: A focus on chronic dialysis patients.

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.

Prevalence and impact of anxiety and depression in Chinese peritoneal dialysis patients: A single centre study.

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.

Cancer Incidence and Mortality in Chronic Dialysis Population: A Multicenter Cohort Study.

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.

Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry.

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.

Metabonomic analysis of water extracts from different angelica roots by ¹H-nuclear magnetic resonance spectroscopy.

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.

Methicillin-resistant Staphylococcus aureus nasal carriage among patients on haemodialysis with newly inserted central venous catheters.

BACKGROUND: Although methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is common among end-stage kidney disease patients undergoing haemodialysis, few studies were focused on MRSA nasal carriers among haemodialysis patients with central venous catheters (CVCs). The aim of this study is to evaluate the risk factors, various clinical outcomes and effect of decolonization for MRSA nasal colonization among patients on haemodialysis via CVCs. METHODS: This was a single-centre non-concurrent cohort study of 676 patients who had new haemodialysis CVCs inserted. They were all screened for MRSA colonization via nasal swabs and were categorized into two groups: MRSA carriers and MRSA noncarriers. Potential risk factors and clinical outcomes were analysed in both groups. All MRSA carriers were given decolonization therapy and the effect of decolonization on subsequent MRSA infection was also performed. RESULTS: Eighty-two patients (12.1%) were MRSA carriers. Multivariate analysis showed that MRSA carrier (OR 5.44; 95% CI 3.02-9.79), long-term care facility resident (OR 4.08; 95% CI 2.07-8.05), history of Staphylococcus aureus infection (OR 3.20; 95% CI 1.42-7.20) and CVC in situ > 21 days (OR 2.12; 95% CI 1.15-3.93) were independent risk factors for MRSA infection. There was no significant difference in all-cause mortality between MRSA carriers and noncarriers. The MRSA infection rates were similar between MRSA carriers with successful decolonization and those who had failed/incomplete decolonization in our subgroup analysis. CONCLUSION: MRSA nasal colonization is an important cause of MRSA infection among haemodialysis patients with CVCs. However, decolonization therapy may not be effective in reducing MRSA infection.

Development and validation of the Chinese oral anticoagulants knowledge tool (C-OAKT): A pilot study.

Objective: To develop and validate an oral anticoagulant knowledge tool for Chinese-speaking patients treated with warfarin or direct oral anticoagulants (DOACs) in Hong Kong. Method: This pilot validation study consisted of the following three phases: (1) the development of a knowledge tool and content validity assessment; (2) a pilot study of 200 participants, consisting of 100 patients taking warfarin or DOACs, 50 pharmacists, and 50 members of the general public; and (3) known-group validity and reliability assessments. Results: A 19-item "Chinese Oral Anticoagulants Knowledge Tool (C-OAKT)" was developed with a scale content validity index of 0.95. The mean score for known-group validity was significantly higher in the pharmacist group than the patient groups, and the patient groups scored significantly higher than the general public (mean ± standard deviation [SD] = 90.00 ± 7.11 vs. 51.55 ± 17.49 vs. 19.0 ± 15.42, respectively; p < 0.001). The mean score was higher for patients who attended a pharmacist-managed anticoagulant therapy management clinic (PAC) than for non-PAC patients (mean ± SD = 56.80 ± 13.60 vs. 46.30 ± 9.43; p = 0.004). An analysis of internal consistency showed a Cronbach's alpha value of 0.86. Conclusion: The results of the pilot validation study suggested that the C-OAKT is a valid and reliable instrument for assessing patients' knowledge of oral anticoagulants in ambulatory care settings. Innovations: This is the first validated Chinese version of an anticoagulant knowledge assessment tool. This tool will be utilized in public hospitals in Hong Kong, and will facilitate future research exploring the relationship between anticoagulant knowledge and patient-related outcomes.

Unusual late presentation of lipoprotein glomerulopathy recurrence in a Chinese kidney transplant recipient.

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.

Streptococcus gordonii peritonitis in a patient on CAPD.

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.

Immunosuppressive Medication Adherence in Kidney Transplant Recipients During the COVID-19 Pandemic: A Cross-Sectional Study in Hong Kong.

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.

Impact of COVID-19 Pandemic on Organ Donation in Hong Kong: A Single-Center Observational Study.

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.

Optimal body mass index that can predict long-term graft outcome in Asian renal transplant recipients.

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.