Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Patient Decision Aid Development for Older Adults With End-Stage Kidney Disease in Singapore.

INTRODUCTION: In managing end-stage kidney disease (ESKD), older adults face a decision regarding whether to undergo dialysis or manage symptoms through kidney supportive care (KSC). This article describes the development of a patient decision aid (PDA) that is designed specifically for older adults with ESKD. METHODS: The decision context of the PDA was to choose a treatment between hemodialysis, peritoneal dialysis, and KSC. The development process used insights obtained from qualitative interviews with patients, informal caregivers, and health care providers. The PDA was then developed in English and Mandarin and was pilot-tested with patients, caregivers, and health care providers. We finalized the PDA based on feedback from pilot testing and performed a preliminary evaluation based on the International Patient Decision Aid Standards (IPDASi v4.0) criteria. RESULTS: The final PDA consists of 2 booklets and a video. During pilot testing, patients and caregivers reported high levels of ease of understanding and usefulness with ≥92.5% providing agree/strongly agree responses for the "Content"-related criteria, and ≥75% providing agree/strongly agree responses for the "Development Process and Effectiveness"-related criteria. The final PDA met 10 of 12 IPDASi v4.0 criteria. CONCLUSIONS: This PDA was found useful during pilot-testing. It will be used during renal counseling in Singapore to help older adults with ESKD and their caregivers make informed decisions on which treatment option is best for the patients.

Age and diabetes mellitus associated with worse outcomes after percutaneous coronary intervention in a multi-ethnic Asian dialysis patient population.

INTRODUCTION: There is limited literature on clinical outcomes following percutaneous coronary intervention (PCI) in Asian dialysis patients. We evaluated the angiographic characteristics and clinical outcomes of dialysis patients treated with PCI in an Asian society. METHODS: A retrospective analysis was performed of 274 dialysis patients who underwent PCI in a tertiary care institution from January 2007 to December 2012. Data on clinical and angiographic characteristics was collected. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, acute myocardial infarction (AMI) and stroke at two years. RESULTS: 274 patients (65.0% male, median age 62.0 years) with 336 lesions (81.8% Type B2) were treated. 431 stents (35.0% drug-eluting stents) with a mean diameter of 2.96 mm and mean length of 21.30 mm were implanted. The MACE rate was 55.8% (n = 153) at two years, from death (36.5%) and AMI (35.0%). In multivariable analysis, age and diabetes mellitus were significant predictors of both mortality (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.12, p < 0.001; OR 2.65, 95% CI 1.46-4.82, p = 0.001, respectively) and MACE (OR 1.06, 95% CI 1.03-1.08, p < 0.001; OR 1.84, 95% CI 1.07-3.15, p = 0.027, respectively). Left ventricular ejection fraction (LVEF) (OR 0.97, 95% CI 0.95-0.99, p = 0.006) was a significant predictor of mortality but not MACE. CONCLUSION: Asian dialysis patients who underwent PCI had a two-year MACE rate of 55.8% due to death and AMI. Age, LVEF and diabetes mellitus were significant predictors of mortality at two years.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.

Non-randomized safety and performance evaluation of the av-Guardian vascular access system.

INTRODUCTION: The ability to successfully cannulate the arteriovenous fistula reliably is a critical step in the delivery of hemodialysis therapy. The av-Guardian vascular access system (Advent Access, Singapore) is designed to overcome the technical barrier to establishing reliable blunt needle access in patients with mature arteriovenous fistula. METHODS: This was a first-in-man, prospective, non-randomized trial (registered on the Australian New Zealand Clinical Trial Registry (ACTRN12617000501347)) performed to assess the safety and feasibility of achieving repeatable successful cannulation via av-Guardian vascular access system to facilitate blunt needling in patients with mature arteriovenous fistula. The primary endpoints of the study included rate of successful hemodialysis sessions via av-Guardian vascular access system cannulation over 3 months and safety of the implants. RESULTS: A total of six patients (four patients with brachiocephalic and two with radiocephalic arteriovenous fistula) were enrolled in the study. A pair of av-Guardian vascular access system were implanted, one each at the arterial and venous cannulation sites, under local anesthesia. Overall, the rate of successful cannulation through the av-Guardian vascular access system over 3 months in 216 hemodialysis sessions was 98.1% (212/216) at the arterial site and 94.4% (204/216) at the venous site. Significantly, 90% and 85.5% of the cannulations at the arterial and venous site, respectively, were successful at first attempt. Blood flow rates within the arteriovenous fistula were unaffected by the devices. CONCLUSION: The results demonstrated the safety and feasibility of a subcutaneously implanted, extravascular device in achieving repeatable successful cannulation via a constant site, to facilitate blunt needling in matured arteriovenous fistula in limited number of patients.

Current state of vascular access in Singapore.

This article described the current state of vascular access management for patients with end-stage renal disease in Singapore. Over the past 10 years, there has been a change in the demographics of end-stage renal disease patients. Aging population and the increase in prevalence of diabetes mellitus has led to the acceleration of chronic kidney disease and increase in incidence and prevalence of end-stage renal disease. Vascular access care has, therefore, been more complicated, with the physical, psychological, and social challenges that occur with increased frequency in elderly patients and patients with multiple co-morbidities. Arteriovenous fistula and arteriovenous graft are created by vascular surgeons, while maintenance of patency of vascular access through endovascular intervention has been a shared responsibility between surgeons, interventional radiologists, and interventional nephrologists. Pre-emptive access creation among end-stage renal disease patients has been low, with up to 80% of new end-stage renal disease patients being commenced on hemodialysis via a dialysis catheter. Access creation is exclusively performed by a dedicated vascular surgeon with arteriovenous fistula success rate up to 78%. The primary and cumulative patency rates of arteriovenous fistula and arteriovenous graft were consistent with the results from many international centers. Vascular access surveillance is not universally practiced in all dialysis centers due to its controversies, in addition to the cost and the limited availability of equipment for surveillance. Timely permanent access placement, with reduced dependence on dialysis catheters, and improved vascular access surveillance are the main areas for potential intervention to improve vascular access management.

Augmented Adsorptive Blood Purification during Continuous Veno-Venous Haemodiafiltration in a Severe Septic, Acute Kidney Injury Patient: Use of oXiris®: A Single Centre Case Report.

The use of the oXiris® haemofilter during continuous veno-venous haemodiafiltration (CVVHDF) for acute kidney injury (AKI) and severe sepsis is not completely understood. Although this filter has in vitro adsorptive properties for blood-borne cytokines and other humoural mediators of sepsis, its clinical usefulness is uncertain. Given its inherent adsorptive limitation for septic mediators, we developed a CVVHDF protocol in which the oXiris haemofilter was electively changed every 12 h even though there was no clotting or adverse circuit pressures. Augmented filter membrane adsorption was conducted for 3 consecutive days. We treated a critically ill patient with severe sepsis secondary to a gram-negative bacterial infection and sepsis-associated acute kidney injury (SA- AKI) in this way. The patient required high-dose vasopressor support, required mechanical ventilation, had received 12 h of CVVHDF with conventional M100 haemofilter, was on broad spectrum antibiotics and other conventional intensive care unit (ICU) care, prior to institution of the frequent oXiris haemofilter change protocol. Following the start of elective 12 hourly oXiris filter change, the patient showed reduction in the need for vasopressor and by Day 4 of this SA- AKI frequent filter change protocol, vasopressor requirement ceased, he was extubated. He survived ICU and but not hospital stay. To this end, more clinical studies are needed.

Family dynamics in a multi-ethnic Asian society: comparison of elderly CKD patients and their family caregivers experience with medical decision making for managing end stage kidney disease.

BACKGROUND: Elderly end stage kidney patients face a decision concerning whether or not to initiate dialysis. In Asia, this decision is highly influenced by family caregivers. The objective of this paper was to understand patients' experience with and preferences for family involvement in treatment decisions, and via a series of hypothetical vignettes, to identify whether there was discordance in treatment preferences between patients and their caregivers, and how any potential conflicts were reconciled. METHODS: We conducted a survey with 151 elderly (aged ≥65) chronic kidney disease patients and their caregivers at outpatient renal clinics. The survey asked, when making treatment decisions, whom they wish makes the final decisions (i.e., preference) and who usually makes the final decisions (i.e., experience). The survey also presented a series of choice vignettes for managing patient's condition and asked respondents to choose between two hypothetical treatment profiles in each vignette. Patients and caregivers were first interviewed separately in tandem, and then were brought together to choose a treatment jointly for vignettes where the initial treatment choice differed within the dyad. We used multivariate regressions to investigate the predictors of discordance and reconciliation. RESULTS: We found that most (51%) patients preferred and experienced (64%) significant involvement from caregivers. However, 38% of patients preferred to make final decisions alone but only 27% of patients did. In the hypothetical vignettes, caregivers chose the more intensive option (i.e., dialysis) more than patients did (26% vs 19%; p < 0.01). Overall, 44% of the dyads had discordance in at least 3 vignettes, and the odds of discordance within patient-caregiver dyads was higher when caregivers chose dialysis or treatment with the higher cost (p < 0.01). In half the cases, discordance resolved in the patients' favor, and this was more likely to be the case if the patient was employed and wanted to be in charge of final decisions (p < 0.01). CONCLUSIONS: Our results highlight the important role of caregivers in decision-making but also the potential for them to overstep. Clinicians should be aware of this challenge and identify strategies that minimize the chances that patients may receive treatments not consistent with their preferences.

Prevalence of hepatitis C virus infection and the IL28B genotype polymorphism among blood donors and high-risk populations.

INTRODUCTION: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive. METHODS: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented. RESULTS: Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%. CONCLUSION: Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore.

2017 Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update Implementation: Asia Summit Conference Report.

Improving Global Outcomes (KDIGO) Clinical Practice Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) 2009 provided recommendations on the detection, evaluation, and treatment of CKD-MBD in patients CKD who are and are not undergoing dialysis. Because of the accumulation of evidence since this initial publication, the CKD-MBD Guideline underwent a selective update in 2017. In April 2018, KDIGO convened a CKD-MBD Guideline Implementation Summit in Japan with the key objective to discuss various barriers to the uptake and implementation of the CKD-MBD Guideline in 8 Asian countries/regions. These countries/regions were comparable according to their high-to-middle economic ranking assigned by the World Bank. The discussion took into account the availability of CKD-MBD medication therapies and government health policies that may influence reimbursement and practice patterns in the region. Most importantly, Summit participants developed a framework of multifaceted strategies aimed at overcoming barriers to guideline implementation. The Summit attendees suggested a shared decision-making approach between clinicians and patients in CKD-MBD management, as well as individualized care based on the treatment risk-benefit ratio. The Summit participants also discussed how KDIGO, as a guideline development organization, may work in partnership with local and national nephrology societies to provide education and facilitate implementation of the guideline by clinicians. The conclusions drawn from this Summit in Asia may serve as an important guide for other regions to follow.

Catheter-related complications and survival among incident hemodialysis patients in Singapore.

INTRODUCTION:: Hemodialysis is the main modality of renal replacement therapy in Singapore. However, a majority of the patients in Singapore are initiated on hemodialysis via a catheter. This study examines the complication rates and factors predicting catheter-related bloodstream infections and mortality rates in patients who were initiated on hemodialysis at our institution. METHODS:: This is a single-center retrospective analysis of incident hemodialysis patients who were initiated on renal replacement therapy between 1 January 2010 and 31 December 2012. Catheter-related bloodstream infection risk factors, organisms, and associated mortality were analyzed. RESULTS:: The catheter-related bloodstream infection and exit site infection incidence rates were 0.75 and 0.50 per 1000 catheter days, respectively. The mean duration to first catheter-related bloodstream infection episode was 182.47 ± 144.04 catheter days. Prolonged catheter duration was found to be a risk factor for catheter-related bloodstream infection. Compared to patients initiated on dialysis via arteriovenous fistula, initiation of dialysis via catheter is strongly associated with increased mortality (6.0% vs 14.5%; p = 0.02). In particular, the presence of diabetes mellitus and development of catheter-related bloodstream infection was associated with increased mortality ( p = 0.04 and 0.05, respectively). In addition, patients who began hemodialysis before being seen by a nephrologist were associated with decreased mortality (3.4% vs 13.0%; p = 0.03). CONCLUSION:: In conclusion, prolonged duration of catheter insertion is found to be a risk factor for catheter-related bloodstream infection in hemodialysis patients, and its development is associated with increased mortality. Early referral to a nephrologist and creation of arteriovenous fistula in pre-end-stage renal disease patients are pivotal in improving the outcomes of patients.

Impact of simulation-based learning on immediate outcomes of temporary haemodialysis catheter placements by nephrology fellows.

AIM: Traditional apprenticeship model (AM) of teaching in invasive procedures such as temporary haemodialysis catheter (THDC) insertion can result in propagation of errors and complications. Simulation-based learning (SBL) offers standardization of skills and allows trainees to repeatedly practice invasive procedures prior to performing them on actual patient. METHODS: Retrospective cohort study of first-, second- and third-year Nephrology Fellows from a tertiary teaching hospital from September 2008 to September 2015. The intervention group (n = 9) received simulation training in ultrasound-guided THDC placement. The historical control group (n = 12) received training through traditional AM. The primary and secondary outcomes were the immediate complications and success rates of THDC insertion. RESULTS: A total of 2481 THDCs were placed in 1787 patients. Success rate of internal jugular THDC placement for AM vs. SBL Fellow was 99.8% versus 100% (P = 0.90), while the success rate for femoral THDC placement was 99.6% versus 99.2% (P = 0.53). SBL Fellows reported fewer overall peri-procedure complications (8.3% vs. 11.2%, P = 0.02) and mechanical complications (1% vs. 2.4%, P = 0.02) compared to AM Fellows. The rate of reported technical difficulty was similar (7.5% vs. 9.2%, P = 0.17). After adjusting for side and site of THDC placement, body mass index and laboratory indices, THDC inserted by AM Fellows were independently associated with increased overall peri-procedure complications (OR = 1.396, 95% CI: 1.052-1.854, P = 0.02) and mechanical complications (OR = 2.481, 95% CI: 1.178-4.810, P = 0.02). CONCLUSIONS: Simulation-based learning was associated with lower procedure related complications and should be an integral component in the teaching of procedural skills in Nephrology.

Epstein-Barr virus-associated smooth muscle tumors after kidney transplantation: treatment and outcomes in a single center.

BACKGROUND: Epstein-Barr virus-associated smooth muscle tumors (EBV SMT) in adult kidney transplant recipients (KTR) are rare. The aims of this study are to document the clinical features, types of treatment given, and outcomes of KTR with EBV SMT in our institution. METHODS: Sixteen patients were identified from our institution's databases. Patients' survival, tumor outcome, and graft survival were compared between patients who remained on cyclosporine-based immunosuppressant and those who converted to sirolimus-based therapy. RESULTS: The median time of diagnosis was 9.4 yr after kidney transplantation, and majority of the patients had multifocal disease at the time of diagnosis. Overall, the patient survival rate was 75% over a mean follow-up period of five yr. Two patients with non-functioning allograft at the time of diagnosis of EBV SMT were excluded from the treatment outcome analysis. Comparing the sirolimus (n = 7) vs. cyclosporine groups (n = 7), patient survival rate was 100% vs. 42.9% (p = 0.08), graft survival 71.4% vs. 28.7% (p = 0.53), and disease-free status 42.9% vs. 14.3% (p = 0.73), respectively. CONCLUSION: Surgical resection in combination with decreasing immunosuppression or conversion to sirolimus appears to be effective in the treatment of EBV SMT in KTR.

Porous graphitic carbon shows promise for the rapid screening partial DPD deficiency in lymphocyte dihydropyrimidine dehydrogenase in Chinese, Indian and Malay in Singapore by using semi-automated HPLC-radioassay.

OBJECTIVE: Dihydropyrimidine dehydrogenase (DPD) catalyzes the degradation of thymine, uracil, and the chemotherapeutic drug 5-Fluorouracil. In general reverse-phase high pressure liquid chromatography is the standard method for separating 5-[2-(14)C]Fluorouracil and 5-[2-(14)C]Fluoro-5,6-dihydrouracil. However, the use of 100% aqueous solution (as HPLC mobile phase) may collapse the C-18 bonded phase and result in a retention time shift. The aim of this study is to develop a rapid, reproducible, sensitive method for screening partial DPD deficiency in healthy volunteers. DESIGN AND METHODS: The activity of DPD was measured using 5-[2- (14)C]Fluorouracil (5-[2-(14)C]FUra) followed by separation of substrate and product 5-[2-(14)C]FUraH(2) with a 15 x 4.6 mm I.D., 5 microm particle size (d(p)) porous graphitic carbon (PGC) column (Hypercarb(R)) and HPLC with online detection of the radioactivity. This was standardized using the protein concentration of the cytosol (NanoOrange(R) Protein Quantitation). RESULTS: Complete baseline separation of 5-[2-(14)C]Fluorouracil (5-[2-(14)C]FUra) and 5-[2-(14)C]Fluoro-5,6-dihydrouracil (5-[2-(14)C]FUraH(2)) was achieved using a porous graphitic carbon (PGC) column. The detection limit for 5-[2-(14)C]FUraH(2) was 0.4 pmol. CONCLUSIONS: By using linear gradient separation (0.1% Trifluoroacetic acid [TFA] in water to 100% Methanol) protocols in concert with PGC columns (Hypercarb(R)), we have demonstrated that a PGC column has a distinct advantage over C-18 reverse phase columns in terms of column stability (pH 1-14). This method provides an improvement on the specific assay for DPD enzyme activity. It is rapid, reproducible and sensitive and can be used for routine screening for healthy and cancer patients for partial and profound DPD deficiency before treatment with 5- FUra.