Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. METHODS AND FINDINGS: In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1-9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03-1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06-1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10-8) but not glycemic progression (HR: 1.01 [95% CI 0.96-1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. CONCLUSIONS: Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.

Meaning of empowerment in peritoneal dialysis: focus groups with patients and caregivers.

BACKGROUND: While peritoneal dialysis (PD) can offer patients more independence and flexibility compared with in-center hemodialysis, managing the ongoing and technically demanding regimen can impose a burden on patients and caregivers. Patient empowerment can strengthen capacity for self-management and improve treatment outcomes. We aimed to describe patients' and caregivers' perspectives on the meaning and role of patient empowerment in PD. METHODS: Adult patients receiving PD (n = 81) and their caregivers (n = 45), purposively sampled from nine dialysis units in Australia, Hong Kong and the USA, participated in 14 focus groups. Transcripts were thematically analyzed. RESULTS: We identified six themes: lacking clarity for self-management (limited understanding of rationale behind necessary restrictions, muddled by conflicting information); PD regimen restricting flexibility and freedom (burden in budgeting time, confined to be close to home); strength with supportive relationships (gaining reassurance with practical assistance, comforted by considerate health professionals, supported by family and friends); defying constraints (reclaiming the day, undeterred by treatment, refusing to be defined by illness); regaining lost vitality (enabling physical functioning, restoring energy for life participation); and personal growth through adjustment (building resilience and enabling positive outlook, accepting the dialysis regimen). CONCLUSIONS: Understanding the rationale behind lifestyle restrictions, practical assistance and family support in managing PD promoted patient empowerment, whereas being constrained in time and capacity for life participation outside the home undermined it. Education, counseling and strategies to minimize the disruption and burden of PD may enhance satisfaction and outcomes in patients requiring PD.

Lifetime cost-effectiveness analysis of first-line dialysis modalities for patients with end-stage renal disease under peritoneal dialysis first policy.

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

Direct and indirect costs of end-stage renal disease patients in the first and second years after initiation of nocturnal home haemodialysis, hospital haemodialysis and peritoneal dialysis.

PURPOSE: To estimate the direct and indirect costs of end-stage renal disease (ESRD) patients in the first and second years of initiating peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD. METHODS: A cost analysis was performed to estimate the annual costs of PD, hospital-based HD and nocturnal home HD for ESRD patients from both the health service provider's and societal perspectives. Empirical data on healthcare resource use, patients' out-of-pocket costs, time spent on transportation and dialysis by ESRD patients and time spent by caregivers were analysed. All costs were expressed in Hong Kong year 2017 dollars. RESULTS: Analysis was based on 402 ESRD patients on maintenance dialysis (PD: 189; hospital-based HD: 170; and nocturnal home HD: 43). From the perspective of the healthcare provider, hospital-based HD had the highest total annual direct medical costs in the initial year (mean ± SD) (hospital-based HD = $400 057 ± 62 822; PD = $118 467 ± 15 559; nocturnal home HD = $223 358 ± 18 055; P < 0.001) and second year (hospital-based HD = $360 924 ± 63 014; PD = $80 796 ± 15 820; nocturnal home HD = $87 028 ± 9059; P < 0.001). From the societal perspective, hospital-based HD had the highest total annual costs in the initial year (hospital-based HD = $452 151 ± 73 327; PD = $189 191 ± 61 735; nocturnal home HD = $242 038 ± 28 281; P < 0.001) and second year (hospital-based HD = $413 017 ± 73 501; PD = $151 520 ± 60 353; nocturnal home HD = $105 708 ± 23 853; P < 0.001). CONCLUSIONS: This study quantified the economic burden of ESRD patients, and assessed the annual healthcare and societal costs in the initial and second years of PD, hospital-based HD and nocturnal home HD in Hong Kong. From both perspectives, PD is cost-saving relative to hospital-based HD and nocturnal home HD, except that nocturnal home HD has the lowest cost in the second year of treatment from the societal perspective. Results from this cost analysis facilitate economic evaluation in Hong Kong for health services and management targeted at ESRD patients.

Health-related quality of life and health utility of Chinese patients undergoing nocturnal home haemodialysis in comparison with other modes of dialysis.

BACKGROUND: To compare the health-related quality of life (HRQOL) and health utility of Chinese patients with end-stage renal disease (ESRD) undergoing nocturnal home haemodialysis (Home HD) against those patients undergoing other modes of dialysis. METHODS: Chinese ESRD patients undergoing Home HD were recruited in renal specialist outpatient clinics at three public hospitals in Hong Kong. SF-12 Health Survey (SF-12) was used to measure HRQOL and generate the SF-6D heath utility score. Mean scores of SF-12 domains, physical and mental component summary and SF-6D health utility of 41 patients undergoing Home HD were compared with available scores of patients receiving other forms of dialysis, namely, peritoneal dialysis (PD) (n = 103), hospital in-centre HD (n = 135) or community in-centre HD (n = 118). Adjusted linear regression models were used to examine the impact of mode of dialysis on the HRQOL and health utility scores, accounting for the sociodemographic and clinical characteristics. RESULTS: ESRD patients undergoing PD and community in-centre HD had better health utility, physical and mental component summary scores than the hospital in-centre HD. Adjusted analysis showed that hospital in-centre HD reported worse physical component summary and health utility scores when compared with PD and community in-centre HD. CONCLUSION: HRQOL and health utility scores of patients undergoing Home HD were similar to those undergoing PD and community in-centre HD. Better physical aspects of HRQOL and health utility was observed in PD and community-based HD than hospital in-centre HD, providing evidence for the increase in capacity of non-hospital-based HD, which provided flexibility as well as patient centredness and empowerment in Hong Kong.

Screening Algorithm for BK Virus-Associated Nephropathy Using Sequential Testing of Urinary Cytology: A Probabilistic Model Analysis.

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.

One year experience of nocturnal home haemodialysis with an alternate night schedule in Hong Kong.

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.

Patient and Caregiver Priorities for Outcomes in Peritoneal Dialysis: Multinational Nominal Group Technique Study.

BACKGROUND AND OBJECTIVES: The absence of accepted patient-centered outcomes in research can limit shared decision-making in peritoneal dialysis (PD), particularly because PD-related treatments can be associated with mortality, technique failure, and complications that can impair quality of life. We aimed to identify patient and caregiver priorities for outcomes in PD, and to describe the reasons for their choices. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on PD and their caregivers were purposively sampled from nine dialysis units across Australia, the United States, and Hong Kong. Using nominal group technique, participants identified and ranked outcomes, and discussed the reasons for their choices. An importance score (scale 0-1) was calculated for each outcome. Qualitative data were analyzed thematically. RESULTS: Across 14 groups, 126 participants (81 patients, 45 caregivers), aged 18-84 (mean 54, SD 15) years, identified 56 outcomes. The ten highest ranked outcomes were PD infection (importance score, 0.27), mortality (0.25), fatigue (0.25), flexibility with time (0.18), BP (0.17), PD failure (0.16), ability to travel (0.15), sleep (0.14), ability to work (0.14), and effect on family (0.12). Mortality was ranked first in Australia, second in Hong Kong, and 15th in the United States. The five themes were serious and cascading consequences on health, current and impending relevance, maintaining role and social functioning, requiring constant vigilance, and beyond control and responsibility. CONCLUSIONS: For patients on PD and their caregivers, PD-related infection, mortality, and fatigue were of highest priority, and were focused on health, maintaining lifestyle, and self-management. Reporting these patient-centered outcomes may enhance the relevance of research to inform shared decision-making.

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end-stage renal disease.

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.

Treatment of phosphate retention: The earlier the better?

Over the last 15 years, our knowledge and understanding of the underlying mechanisms involved in the regulation of calcium and phosphate homeostasis in chronic kidney disease have advanced dramatically. Contrary to general opinion in the 20(th) century that moderate hypercalcemia and hyperphosphatemia were acceptable in treating secondary hyperparathyroidism, the calcium and phosphate load is increasingly perceived to be a major trigger of vascular and soft tissue calcification. The current treatment options are discussed in view of historical developments and the expectations of the foreseeable future, focusing on the early treatment of hyperphosphatemia. At present, we lack indisputable evidence that active intervention using currently available drugs is of benefit to patients in chronic kidney disease stages 3 and 4.

Prophylaxis against gram-positive organisms causing exit-site infection and peritonitis in continuous ambulatory peritoneal dialysis patients by applying mupirocin ointment at the catheter exit site.

OBJECTIVE: We evaluated the effectiveness of local application of mupirocin ointment at the catheter exit site in preventing exit-site infection and peritonitis attributable to gram-positive organisms in continuous ambulatory peritoneal dialysis patients. METHODS: This prospective randomized controlled trial included 154 patients. They were randomly allocated to a mupirocin-treated group (group M) and a control group (group C). Group M included 73 patients (47.4%) who were instructed to apply mupirocin ointment to the catheter exit site once daily after the routine daily exit-site dressing. Group C included 81 patients (52.6%) who continued their usual daily exit-site care without applying mupirocin. The two groups were followed to see whether there would be any difference in the frequency of exit-site infection and peritonitis or in the infecting organisms. RESULTS: Interim data were collected at 5 months after the start of the study. Those data showed a significantly lower incidence of exit-site infection and peritonitis attributable to gram-positive organisms in group M as compared with group C. The incidence of gram-positive exit-site infection in group C was 1 episode per 36.8 patient-months; in group M, the incidence was 1 episode per infinity patient-months (0 incidence in 5 months, p < 0.05). The incidence of gram-positive peritonitis in group C was 1 episode per 40.5 patient-months; in group M, the incidence was 1 episode per 365 patient-months (p < 0.05). Mupirocin treatment had no significant effect on the incidence of exit-site infection and peritonitis attributable to other organisms. Before mupirocin treatment, we saw a trend toward higher infection rates in diabetic patients and nasal carriers of Staphylococcus aureus as compared with non diabetic patients and nasal non carriers, although the differences were not statistically significant. Mupirocin brought the infection rate attributable to gram-positive organisms to an equally low level in diabetic and non-diabetic patients, and in nasal carriers and nasal non carriers of S. aureus. No adverse effect of local application of mupirocin was reported. CONCLUSION: Local application of mupirocin ointment at the catheter exit site is a safe and effective method of preventing exit-site infection and peritonitis involving gram-positive organisms.

Setting up a continuous ambulatory peritoneal dialysis training program.

Continuous ambulatory peritoneal dialysis (CAPD) training programs have become fundamental patient education programs in renal centers providing peritoneal dialysis (PD) services. Several key topics must be addressed in setting up a CAPD training program: Health care and organizational issues, Multidisciplinary team approach, Evidence-based practice, Pre-training patient assessment, Patient training Program evaluation. The PD nurses should identify key learning objectives for patient training. The essential elements of CAPD training are the training content and schedule, training assessment, and teaching methods. Program set-up also includes establishing a back-up system and follow-up protocols, which are essential for continuity of care in renal patients. Outcomes such as rates of peritonitis and exitsite infection, unplanned readmission, and patient satisfaction are all important indicators when the results of CAPD training programs are reviewed. The development and successful implementation of a cost-effective CAPD training program has a significant impact on patient outcomes in the renal specialty.