Conversion from Aranesp® to NESP® in dialysis patients-Exploration of dosing strategies and the feasibility of extending the dosing interval.

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

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.

Non-invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological-pathological correlation analysis.

OBJECTIVES: To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. METHODS: Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. RESULTS: A total of 40 elastography scans were carried out (median creatinine 172.5 µmol/L [interquartile range 133.8-281.8 µmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range 19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0 kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78-0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61-0.89), 0.85 (95% CI 0.75-0.95) and 0.65 (95% CI 0.53-0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively. CONCLUSIONS: Shear wave elastography can be used as a non-invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.

Enhanced Psychosocial Support for Caregiver Burden for Patients With Chronic Kidney Failure Choosing Not to Be Treated by Dialysis or Transplantation: A Pilot Randomized Controlled Trial.

BACKGROUND: Family caregivers of patients with chronic kidney failure have increased burden, as reflected by their high frequency of physical and mental disturbances. The impact of enhanced psychosocial support to caregivers of patients with chronic kidney failure remains unclear. STUDY DESIGN: Open-label randomized controlled trial. SETTING & PARTICIPANTS: All new patients referred to the renal palliative clinic were screened. Caregivers of patients who met the following criteria were recruited: (1) chronic kidney failure as defined by creatinine clearance < 15 mL/min, (2) opted for conservative management by nephrology team or patient, (3) never treated with dialysis or transplantation, and (4) able to provide informed consent. INTERVENTIONS: Random assignment to treatment with enhanced psychosocial support or standard renal care (control). Enhanced psychosocial support included counseling and psychosocial interventions by an on-site palliative care nurse and designated social worker. Each caregiver was followed up at 2- to 4-week intervals for up to 6 months. OUTCOMES: Zarit Burden Inventory (ZBI) and Hospital Anxiety and Depression Scale (HADS) in caregivers and McGill Quality of Life scores in patients of both groups were compared. RESULTS: 29 pairs of family caregivers/patients with chronic kidney failure were randomly assigned (intervention, n=14; control, n=15). Mean ages of patients and caregivers were 81.6 ± 5.1 and 59.8 ± 14.2 (SD) years, respectively. The intervention group showed significantly lower ZBI scores than the control group at 1 and 3 months (22.0 ± 5.3 vs 31.6 ± 9.5 and 21.3 ± 6.6 vs 33.4 ± 7.2; P=0.006 and P=0.009, respectively). HADS anxiety scores of caregivers who received the intervention were significantly lower than those of controls at 1 and 3 months (7.1 ± 3.2 vs 10.1 ± 2.2 and 6.5 ± 4.5 vs 11.0 ± 3.1; P=0.01 and P=0.03, respectively). Insignificant reductions in ZBI and HADS scores were found at 6 months. 19 patients died (intervention, n=10; control, n=9) during the study period. LIMITATIONS: The study is limited by a relatively small sample size and short duration. CONCLUSIONS: Enhanced psychosocial support program in patients with chronic kidney failure and caregivers resulted in an early significant reduction in caregiver burden and anxiety.

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections.

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p < 0.001). The psoriasis group also had a significantly high mean melting temperature (78.62 ± 0.20) when compared with the inactive SLE group (78.49 ± 0.29, p < 0.05) and control group (78.44 ± 0.25, p < 0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28 ± 0.21 vs 78.44 ± 0.25, p < 0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.

CT angiography versus conventional digital angiography in preoperative assessment for Chinese living kidney donors.

BACKGROUND: Computed tomography (CT) angiography is used for preoperative evaluation of living kidney donors, but its correlation with intraoperative findings during the transplant operation remains unknown. METHODS: Between April 1997 and October 2008, 34 consecutive pairs of living kidney transplants were carried out. Conventional digital angiography was employed for the preoperative assessment in the first 19 pairs, and CT angiography in the subsequent 15 pairs. The radiological reports and operative findings during kidney harvest were carefully examined and compared. RESULTS: Among the 34 cases in our cohort, we found 9 early branching renal arteries (26.4%) and 6 double renal arteries (17%). Venous and ureteral anomalies were rare, with only 1 case (2.9%) of each. CT angiography offered excellent and equal accuracy (accuracy 100%) when compared with conventional digital angiography for renal arterial anatomy. CT angiography showed superior performance compared with conventional angiography in the domain of venous and collecting system anomalies (accuracy 100% vs. 94.7%, respectively). No contrast nephropathy or allergy was documented in our series. CONCLUSIONS: CT angiography showed excellent correlations with surgical findings in the Chinese population. It is associated with minimal risk of contrast nephropathy as well as lower cost and therefore should be adopted as the standard preoperative assessment of living kidney donors.

Cost comparison between mycophenolate mofetil and cyclophosphamide-azathioprine in the treatment of lupus nephritis.

OBJECTIVE: To compare the healthcare expenditure associated with mycophenolate mofetil (MMF)-based immunosuppression in contrast to conventional therapy in patients with lupus nephritis. METHODS: Our retrospective single-center study compared the major healthcare costs during the first 24 months of treatment incurred by immunosuppressive medications, hospitalization, and complications in patients with severe lupus nephritis who had been treated with prednisolone and either MMF or sequential cyclophosphamide induction followed by azathioprine maintenance (CTX-AZA). RESULTS: Forty-four patients were studied (22 in each group). Baseline demographic and clinical measures, and remission rates after treatment, were similar between the 2 groups. Immunosuppressive drug cost was 13.6-fold higher in the MMF group (US$4168.3+/-1176.5 per patient, compared with $285.0+/-70.6 in the CTX-AZA group, mean difference $3883.2+/-251.3; p<0.001). MMF treatment was associated with a lower incidence of infections (12.0 episodes/1000 patient-months, compared with 32.4 in the CTX-AZA group; p=0.035). Combined cost of hospitalization and treatment of infections was 82.5% lower in the MMF group (mean difference -2208.7+/-1700.6; p=0.120). Overall treatment expenditure on immunosuppressive drugs, hospitalization, and treatment of infections was 1.57-fold higher in the MMF group (mean US $4635.9 compared with $2961.5 in the CTX-AZA group; p<0.001). CONCLUSION: While the cost of MMF treatment for severe lupus nephritis is much higher compared with CTX-AZA, the increased drug cost is partially offset by savings from the reduced incidence of complications.

Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin.

BACKGROUND: Usage of cyclosporin (the Hong Kong Hospital Authority's single largest item of drug expenditure) continues to increase, mainly due to increasing numbers of renal allograft patients taking it as long-term antirejection therapy. Diltiazem, an antihypertensive agent, interferes with the first pass extraction of oral cyclosporin, thus serving to conserve its dosage. AIMS: In renal transplant patients, to assess whether diltiazem co-treatment could achieve worthwhile dosage conservation of Neoral (a relatively new microemulsified cyclosporin formulation), safely. METHODS: A randomized, placebo-controlled, double-blind clinical trial was undertaken at three local hospitals. Renal transplant recipients receiving Neoral as prophylactic immunosuppression were randomized to two treatment arms. Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or >or= 60 kg, respectively. One hundred and ten eligible patients gave their informed consent, and were followed up for at least six months. The mean difference in the dollar cost in the sixth month was the primary outcome. Secondary/ancillary outcomes included changes in cyclosporin dosage and blood level, and untoward clinical events including rejection. Outcomes were evaluated by intention to treat analyses. RESULTS: During weeks 23-26 (sixth month) post randomization, diltiazem co-treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95% confidence interval (CI) of the difference being HK dollars 609 +/- 517 or pound 50 +/- 42], with no apparent excess of untoward or adverse events, complications, hospitalization, outpatient visits, or inferior quality of life. CONCLUSIONS: This diltiazem co-treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK dollars 14.3 million ( pound 1.17 million) annually, without adverse sequelae.