Intervention with selution SLR™ Agent Balloon for Endovascular Latent Limus therapy for failing AV Fistulas (ISABELLA) Trial: Protocol for a pilot clinical study and pre-clinical results.

BACKGROUND: The aim of this pilot clinical study is to evaluate the safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon (M.A. MedAlliance SA, Nyon, Switzerland) for improving the patency of failing arterio-venous fistulas (AVF) in hemodialysis patients. We also present herein a pre-clinical pharmacokinetic and safety evaluation of Selution™ to justify its first use in hemodialysis patients for endovascular access salvage. METHODS AND RESULTS: This is an investigator-initiated prospective single-center, non-blinded single-arm trial. Forty patients with clinically significant de novo or recurrent stenoses in a mature AVF circuit will be recruited. All stenotic lesions will be prepared with high pressure non-compliant conventional balloon angioplasty (CBA) prior to deployment of the Sustained-Release Selution™ sirolimus drug-eluting balloon. The primary efficacy endpoint is 6-month target lesion primary patency and the primary safety endpoint is freedom from localized or systemic serious adverse events through 30 days. Secondary endpoints of interest include technical and clinical success rates and circuit access patency at 3 and 6 months. Follow-up will occur for 2 years for those patients whose AVFs remain patent. Pharmacokinetic and histological animal safety studies performed with the Selution™ coating formulation showed prolonged arterial tissue retention of sirolimus with therapeutic levels up to 60 days and non-toxic and rapidly declining blood levels. Histological results in animal models demonstrated safety, freedom from intraluminal thrombus, reduction in restenosis by sirolimus elution compared to CBA, and no evidence of embolic phenomena indicative of adverse particulate effects. DISCUSSION: Long release sirolimus coated balloons may serve as a promising novel alternative therapy to paclitaxel-based technology for treating conduit stenosis secondary to neointimal hyperplasia. Pre-clinical pharmacokinetic and histological animal data are encouraging and provide suggestion of safety and efficacy in this setting. This single-center trial will provide a first step toward demonstration of efficacy and safety of this device for treatment of stenotic fistulas.

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.

Outcomes following peritoneal dialysis catheter removal with reinsertion or permanent transfer to haemodialysis.

INTRODUCTION: Long-term use of peritoneal dialysis catheter is associated with complications such as infection and malfunction, necessitating removal of catheter with subsequent reinsertion or permanent transfer to haemodialysis. This study aims to investigate the outcome in patients who underwent reinsertion. METHODS AND MATERIALS: A single-centre retrospective study was performed in Singapore General Hospital for all adult incident peritoneal dialysis patients between January 2011 and January 2016. Study data were retrieved from patient electronic medical records up till 1 January 2017. RESULTS: A total of 470 patients had peritoneal dialysis catheter insertion with median follow-up period of 29.2 (interquartile range = 16.7-49.7) months. A total of 92 patients required catheter removal. Thirty-six (39%) patients underwent catheter reinsertion. The overall technique survival at 3 and 12 months were 83% and 67%. Median time to technique failure of the second catheter was 6.74 (interquartile range = 0-50.2) months. The mean survival for patients who converted to haemodialysis and re-attempted peritoneal dialysis was comparable (54.9 ± 5.5 vs 57.3 ± 3.6 months; p = 0.75). Twelve (13%) patients had contraindication for peritoneal dialysis and were excluded from analysis. Of 11 patients who required catheter removal due to malfunction, 7 (64%) underwent catheter reinsertion and 6 (86%) patients ultimately converted to haemodialysis during study period. Of the 69 patients who had catheter removal due to infection, 29 (42%) underwent catheter reinsertion and 8 (28%) patients eventually converted to haemodialysis during the study period. CONCLUSION: Patient survival was comparable between patients who re-attempted peritoneal dialysis and patients who transferred to haemodialysis. Patients who had previous catheter removal due to infections had favourable technique survival than those due to catheter malfunction.

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.

Outcomes of arteriovenous fistula creation, effect of preoperative vein mapping and predictors of fistula success in incident haemodialysis patients: A single-centre experience.

AIM: Vascular access in haemodialysis is critical for effective therapy. We aim to evaluate the outcomes of arteriovenous fistula (AVF) creation in incident haemodialysis patients, impact of preoperative vein mapping and predictors of successful AVF maturation in our centre. METHODS: Data of End-stage Renal Disease (ESRD) patients initiated on haemodialysis from January 2010 to December 2012 in our centre were retrospectively obtained from electronic medical records and clinical notes. Demographic characteristics, medical comorbidities, perioperative details were collected, and patients were followed up until 1 January 2014. RESULTS: A total of 708 patients (median age 64, IQR 55-72) were included with mean duration of follow up of 2.3 ± 1.2 years, with access of AVF and arteriovenous graft (AVG) in 694 (98%) and 14 (2%) patients respectively. Eight patients were lost to follow-up. Successful AVF maturation was achieved in 542 patients (78%), with 1-year cumulative patency rate of 74%. Multivariate analysis revealed male gender, upper arm AVF and good postoperative thrill and pulse as predictors of successful AVF maturation. Preoperative vein mapping was performed in 42.5% (295/694) of patients, with mean vein diameter of 2.44 ± 0.82 mm. Maturation rates with and without vein mapping were 72.2% and 82.4%, respectively, (P = 0.001). In patients with vein diameters of <2 mm and ≥2 mm, there was no statistically significant difference in maturation rates (71.3% vs. 72.6%; P = 0.887) and median maturation time (66 vs. 78 days; P = 0.73). CONCLUSION: Arteriovenous fistula can be successfully created in most incident haemodialysis patients. Routine vein mapping is not necessary if veins are suitable on physical examination alone, and vein sizes of <2 mm on ultrasound is not associated with lower AVF maturation rate.

Real-time circuit pressures correlate poorly with circuit longevity in anticoagulant-free, predilution continuous venovenous hemofiltration.

BACKGROUND: Continuous venovenous hemofiltration (CVVH) in renal failure is compromised by circuit clotting. We hypothesized that adverse circuit pressures are predictive of clotting in circuits that last less than 24 h during predilution, anticoagulant-free CVVH. METHODS: This was a single-center retrospective study of 63 CVVH circuits of 13 critically ill intensive care unit patients with severe renal failure. Circuits were categorized into 'clotters' (C) or 'nonclotters' (NC), if spontaneous clotting occurred at <24 or ≥24 h from the start of CVVH, respectively. RESULTS: Effluent pressures and pre-filter pressures were more adverse in NC compared to C starting from 6 and 4 h before spontaneous clotting, respectively. Arterial pressures and return pressures were not significantly different in C versus NC. Blood flow rate settings, hemofiltration fluid replacement and effluent drainage rates in C versus NC were comparable. CONCLUSION: Real-time circuit pressure readings seem to offer only potentially limited prognostic value in predicting circuit clotting.