The aim of this study is to evaluate the maturation and patency rates after endovascular treatment of non-maturing arteriovenous fistulas with percutaneous transluminal angioplasty, embolization of competitive veins, or a combination of both in a series of consecutive patients.Retrospective evaluation of patients with non-matured arteriovenous fistulas treated in our hospital was performed. Fistulography and ultrasonography was performed in all patients to evaluate the presence of stenosis and competitive veins. Significant stenoses (> 50%) were treated with balloon angioplasty and competitive veins (accessory and collateral veins) with coil embolization.A total of 78 fistulas were treated. Angioplasty and coil embolization were performed in 73 and 51 patients, respectively. No major complications occurred. In 65 out of 78 arteriovenous fistulas (83%), successful cannulation with two needles was possible after endovascular treatment. Sixty-three arteriovenous fistulas (81%) were used successfully for at least 3 months. Accessory veins were the only lesion present in 14% of the arteriovenous fistulas; coil embolization of these accessory veins resulted in 100% successful maturation. The estimated 3, 6, and 12 months postintervention assisted primary patency rates were, respectively, 73%, 55%, and 45%. The estimated 3, 6, and 12 months postintervention secondary patency rates were, respectively, 81%, 78%, and 73%.Angioplasty and coil embolization are successful and safe procedures that can convert a non-mature fistula into a mature one in more than 80% of patients. Accessory vein embolization may be more important than collateral vein embolization in the presence of stenosis.
Amphotericin B is a broad-spectrum antifungal agent that is used in the treatment of systemic fungal infections. We describe the case of a 62-year-old female patient with recent aneurysmal subarachnoid hemorrhage who was treated for suspected ventriculitis and a fungal coinfection. Instead of liposomal amphotericin B (L-AmB), 465 mg (5 mg/kg) amphotericin B deoxycholate (DOC) was inadvertently administered, leading to refractory shock with multiple organ failure and requiring mechanical ventilation. Since an overdose of amphotericin B can lead to fatal consequences and has a half-life of 15 days, plasmapheresis was started. The serum concentration decreased from 1.32 µg/mL to 0.62 µg/mL before plasmapheresis, demonstrating a mean half-life of 49 hours. After two plasmapheresis sessions, the serum concentration further dropped to 0.26 µg/mL, demonstrating a mean half-life of 17 hours. In contrast, the third plasmapheresis session had no effect on serum concentration. The patient made a full recovery, potentially facilitated by enhanced amphotericin B elimination through plasmapheresis. Positive outcomes were previously reported in two adult patients treated with plasmapheresis. However, other reports without plasmapheresis described fatal outcomes in adult patients, albeit with a twofold overdose compared to the two patients successfully treated with plasmapheresis. Moreover, plasmapheresis itself carries risks such as hypocalcemia, metabolic alkalosis, and coagulation deficits. Consequently, the role of plasmapheresis in amphotericin B overdose is still debated.
Background Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. Methods and results The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. Conclusions The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturation.
Background Arteriovenous fistulas (AVFs) for hemodialysis (HD) are often associated with better outcomes than arteriovenous grafts (AVGs). We aimed to investigate vascular access (VA) outcomes and assessed if AVF nonmaturation outweighs long-term complications of AVGs. Methods In this multicenter, retrospective cohort study in The Netherlands, 1- and 3-year primary, primary assisted, secondary, and functional patency rates were calculated, and the incidence of adverse events and procedures was assessed. Functional patency of RCAVFs, upper arm AVFs, and AVGs was compared using Cox analyses. Results In total, 1041 patients who received their first VA were included, of whom 863 had VAs that successfully matured. These patients were analyzed with a median follow-up of 25 months. The 1-year functional patency rates were 67%±2.0% for RCAVFs, 83%±2.0% for upper arm AVFs, and 85%±3.5% for AVGs. Three-year functional patency rates were 62%±2.0% for RCAVFs, 74%±2.0% for upper arm AVFs, and 69%±5% for AVGs. AVGs required more procedures per year (3.3 per year) of functional patency when compared with upper arm AVFs (1.8 per year). Conclusions The functional patency of AVFs and AVGs is comparable, although AVGs required more interventions to maintain usability for HD. The choice of VA is a trade-off between short-term advantages, favoring AVGs, and long-term advantages, favoring AVFs. Which VA is most appropriate depends on the patient’s prognosis and preferences.
Amphotericin B is a broad-spectrum antifungal agent that is used in the treatment of systemic fungal infections. We describe the case of a 62-year-old female patient with recent aneurysmal subarachnoid hemorrhage who was treated for suspected ventriculitis and a fungal coinfection. Instead of liposomal amphotericin B (L-AmB), 465 mg (5 mg/kg) amphotericin B deoxycholate (DOC) was inadvertently administered, leading to refractory shock with multiple organ failure and requiring mechanical ventilation. Since an overdose of amphotericin B can lead to fatal consequences and has a half-life of 15 days, plasmapheresis was started. The serum concentration decreased from 1.32 µg/mL to 0.62 µg/mL before plasmapheresis, demonstrating a mean half-life of 49 hours. After two plasmapheresis sessions, the serum concentration further dropped to 0.26 µg/mL, demonstrating a mean half-life of 17 hours. In contrast, the third plasmapheresis session had no effect on serum concentration. The patient made a full recovery, potentially facilitated by enhanced amphotericin B elimination through plasmapheresis. Positive outcomes were previously reported in two adult patients treated with plasmapheresis. However, other reports without plasmapheresis described fatal outcomes in adult patients, albeit with a twofold overdose compared to the two patients successfully treated with plasmapheresis. Moreover, plasmapheresis itself carries risks such as hypocalcemia, metabolic alkalosis, and coagulation deficits. Consequently, the role of plasmapheresis in amphotericin B overdose is still debated.
Abstract Objectives Radiocephalic arteriovenous fistulas (RCAVF) are the preferred vascular access (VA) for hemodialysis (HD). Cohort studies from North America revealed that nonmaturation is a significant disadvantage of RCAVFs compared to other VAs. DESIGN: This present retrospective study describes the incidence of nonmaturation of AVFs and functional failure of arteriovenous grafts (AVG) in a multicentre cohort in the Netherlands and attempts to create a prediction model for nonmaturation of RCAVFs. Furthermore, the efficacy of interventions to promote maturation as well as the variability between hemodialysis centers was evaluated. Materials Medical records from 8 hospitals from 1997 to 2016 were retrospectively evaluated for VA type, maturation/primary success and demographics and comorbidities. Methods A prediction model was created for RCAVF nonmaturation using multivariate logistic regression analysis, selecting significant predictors using backward selection. Discrimination and calibration of the model were assessed. Results 1383 AVFs and 273 AVGs were included in 1221 patients. Overall nonmaturation was 24% for RCAVFs, and 11% for upper arm AVFs. The functional failure rate for AVGs was 6%. The nonmaturation rate of contralateral RCAVFs after failure of an RCAVF was 22%. Procedures to improve RCAVF maturation were successful in 98/142 cases (69%). Predictors for nonmaturation were female gender, peripheral vascular disease, cerebrovascular disease and a cephalic vein diameter <2.5 mm, but the prediction model lacked sensitivity and specificity predicting individual RCAVF nonmaturation (C‐statistic 0.629). Conclusion Nonmaturation rates are highest for RCAVFs, but nonmaturation could not be predicted with demographic parameters.
The autologous arteriovenous fistula (AVF) for hemodialysis burdens the cardiovascular system with increased cardiac output and pulmonary artery pressure, increasing cardiovascular risk. This article reviews literature on the benefits and drawbacks of a functioning AVF after kidney transplantation and discusses the cardiovascular effects of AVF closure. Several cohort studies demonstrate a significant cardiac burden of an AVF and improvement of cardiac dimensions after AVF ligation. However, no randomized trials have been conducted on routine AVF closure after successful kidney transplantation. Therefore, clinical trials are warranted to evaluate whether the cardiovascular benefits of routine AVF closure outweigh the potential harm for patients after successful kidney transplantation.
Patients on maintenance hemodialysis (HD) require a reliable vascular access; however, only half of newly created radiocephalic arteriovenous fistulas (RCAVF) can be used for HD without additional procedures to promote maturation and up 25% fail to provide adequate vascular access for HD.1Voorzaat B.M. van der Bogt K.E.A.A. Janmaat C.J. et al.Arteriovenous fistula maturation failure in a large cohort of hemodialysis patients in the Netherlands.World J Surg. 2018; 42: 1895-1903Crossref PubMed Scopus (14) Google Scholar The need for subsequent creation of upper arm arteriovenous fistulas (AVFs) and arteriovenous grafts may decrease if maturation can be improved. Currently, no pharmacological treatments have been proven to improve clinical maturation of AVFs. Although the underlying pathophysiology of nonmaturation is incompletely understood, impaired outward remodeling and neointimal hyperplasia in the venous outflow tract seem to contribute.2Rothuizen T.C. Wong C. Quax P.H.A. et al.Arteriovenous access failure: more than just intimal hyperplasia?.Nephrol Dial Transplant. 2013; 28: 1085-1092Crossref PubMed Scopus (88) Google Scholar Studies in murine and porcine models of AVF failure revealed a pronounced inflammatory response in the venous outflow tract in the early phase after AVF surgery.3Dundon B.K. Torpey K. Nelson A.J. et al.The deleterious effects of arteriovenous fistula-creation on the cardiovascular system: a longitudinal magnetic resonance imaging study.Int J Nephrol Renovasc Dis. 2014; 7: 337-345PubMed Google Scholar Recent studies suggest that this inflammatory response impairs AVF maturation.4Bezhaeva T. de Vries M.R. Geelhoed W.J. et al.Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas.FASEB J. 2018; 32: 6293-6304Crossref Scopus (5) Google Scholar Pegylated liposomes have emerged as an attractive tool to facilitate selective delivery of drugs to inflamed tissues with a highly permeable microvasculature, where liposomes are being phagocytized by macrophages. It has a potent and long-lasting anti-inflammatory effect at sites of inflammation, while minimizing exposure of noninflamed tissues. In a murine model of AVF failure, we have demonstrated that liposomal prednisolone inhibits inflammation of the juxta-anastomotic vein and improves outward remodeling of the venous outflow tract.5Wong C. Bezhaeva T. Rothuizen T.C. et al.Liposomal prednisolone inhibits vascular inflammation and enhances venous outward remodeling in a murine arteriovenous fistula model.Sci Rep. 2016; 6: 30439Crossref PubMed Scopus (17) Google Scholar We hypothesized that maturation of RCAVFs in humans can be improved by inhibition of juxta-anastomotic inflammation using liposomal prednisolone. In the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study, we aimed to assess if liposomal prednisolone improves maturation of RCAVFs and if it can be safely administered to patients with end-stage renal disease. The design of this multicenter randomized placebo-controlled trial has been reported earlier in detail,6Voorzaat B.M. van Schaik J. van der Bogt K.E.A. et al.Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study–a randomized controlled trial.J Vasc Access. 2017; 18: S114-S117Crossref PubMed Scopus (5) Google Scholar and methods are available in the Supplementary Materials. From April 2016 through May 2018, 109 patients were planned for RCAVF creation and assessed for study eligibility. A total of 64 patients were excluded for known exclusion criteria from their medical history (n = 24), not consenting to study participation (n = 34), or late referral (n = 6, Figure 1). Of the remaining 45 patients who provided informed consent, 32 were randomized (Table 1). Reasons for dropout are shown in Figure 1. After randomization, but before treatment, 2 patients experienced clinical events constituting exclusion criteria. The remaining 30 patients received the study treatment. The trial was stopped prematurely in May 2018 because of slow enrollment.Table 1Baseline characteristics of 29 patients in the LIPMAT study by treatment groupBaseline characteristicsPlacebo (n = 13)Liposomal prednisolone (n = 16)Total (n = 29)Age, yr70 ± 8.565 ± 1267 ± 11Gender Female5 (38)1 (6)6 (21) Male8 (62)15 (94)23 (79)Race Caucasian11 (85)13 (81)24 (83) Hindustani Surinamese1 (8)2 (13)3 (10) Moroccan0 (0)1 (6)1 (3) Asian1 (8)0 (0)1 (3)Cause of renal failure Diabetes mellitus4 (31)6 (38)10 (35) Renal vascular disease5 (39)4 (25)9 (31) Glomerulonephritis3 (23)2 (13)5 (17) Interstitial nephropathy1 (8)2 (13)3 (10) Cystic kidney disease0 (0)2 (13)2 (7)Comorbidities Diabetes mellitus7 (54)7 (44)14 (48) Coronary artery disease6 (46)4 (25)10 (35) Peripheral artery disease4 (31)3 (19)7 (24) Cerebrovascular disease5 (39)4 (25)9 (31)Medication ACE inhibitor1 (8)6 (38)7 (24) Angiotensin 2 receptor blocker8 (62)5 (31)13 (45) Loop diuretic8 (62)9 (56)17 (59) Aldosterone receptor antagonist0 (0)1 (6)1 (3) Beta blocker10 (77)8 (50)18 (62) Calcium channel blocker8 (62)11 (69)19 (66) Platelet inhibitor4 (31)10 (63)14 (48) Anticoagulant2 (15)3 (19)5 (17) Vitamin D12 (92)13 (81)25 (86)ACE, angiotensin-converting enzyme; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation.Data are reported as mean ± SD or n (%). Open table in a new tab ACE, angiotensin-converting enzyme; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. Data are reported as mean ± SD or n (%). The primary end point was assessed in 29 patients. The distal cephalic diameter was 3.9 mm (95% confidence interval, 2.7–5.8 mm) in the placebo group and 3.7 mm (95% confidence interval, 3.0–5.3 mm) in the treatment group (P = 0.88). No significant results were observed for secondary end points (Table 2).Table 2Effect of liposomal prednisolone on primary and secondary end points in 29 patients in the LIPMAT studyEnd pointsPlacebomedian (IQR)Liposomal prednisolonemedian (IQR)P (Mann-Whitney U)6 wk Cephalic veinJuxta-anastomotic diameter, mm3.9 (2.7–5.8)3.7 (3.0–5.3)0.88Elbow diameter, mm5.5 (4.7–6.7)5.0 (4.0–6.1)0.47Mid upper arm diameter, mm4.0 (2.3–5.3)4.8 (4.1–5.4)0.22 Radial arteryJuxta-anastomotic diameter, mm3.6 (2.9–4.2)3.6 (3.0–4.0)0.83Flow, ml/min456 (277–688)406 (300–772)0.81 Brachial arteryFlow, ml/min523 (342–985)550 (417–1201)0.793 moCephalic vein Juxta-anastomotic diameter, mm4.2 (2.3–6.1)4.9 (3.9–5.8)0.43 Elbow diameter, mm6.2 (4.7–6.9)5.7 (4.4–6.3)0.35 Mid upper arm diameter, mm5.8 (2.8–4.5)5.7 (3.6–6.2)0.83Radial artery Juxta-anastomotic diameter, mm4.0 (2.1–5.0)3.6 (3.0–4.6)1.00 Flow, ml/min546 (110–1037)560 (334–970)0.65Brachial artery Flow, ml/min800 (434–1485)798 (479–1019)0.60IQR, interquartile range; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. Open table in a new tab IQR, interquartile range; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. At the time of assessment of the functional outcomes, 54% of AVFs in the placebo arm and 69% in the liposomal prednisolone arm were successfully used for HD (P = 0.41). Seven patients (44%) in the liposomal prednisolone arm and 4 patients (31%) in the placebo group underwent an endovascular or surgical procedure to achieve RCAVF maturation. During follow-up, in the placebo and liposomal prednisolone groups, respectively 23% and 13% of RCAVFs had failed (P = 0.45). The functional outcome could not be determined for 6 patients, because of loss to follow-up (2 patients who moved abroad) or not initiating HD (Table 3).Table 3Effect of liposomal prednisolone on functional outcomes of RCAVF in 29 patients in the LIPMAT studyFunctional outcomePlacebo (n = 13)Liposomal prednisolone (n = 16)AVF used Without procedures to improve maturation3 (23)4 (25) With procedures to improve maturation4 (31)7 (44)AVF not used Failed due to nonmaturation3 (23)2 (13) Kidney transplantation0 (0)1 (6) Did not reach ESRD1 (8)1 (6) Deceased before ESRD0 (0)1 (6)Loss to follow-up2 (16)0 (0)Values are n (%).AVF, arteriovenous fistula; ESRD, end-stage renal disease; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. Open table in a new tab Values are n (%). AVF, arteriovenous fistula; ESRD, end-stage renal disease; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. No infusion reactions were observed except for 1 subject in the liposomal prednisolone arm who was known to have symptoms of orthostatic hypotension, and experienced mild dizziness without hypotension on postural change during the infusion. The incidence of symptoms related to progressive renal failure and cardiovascular events was similar in both treatment arms (Table 4).Table 4Adverse events reported in the LIPMAT studyAdverse eventsPlacebo (n = 13)Liposomal prednisolone (n = 16)AVF-related events Angiography/angioplasty36 Revision surgery10 Coiling or ligation of collateral veins12 Hematoma or bleeding21 New AVF within 3 mo11 Nerve damage10 Edema10Infusion-related events Orthostatic symptoms (no hypotension)01Renal and metabolic Fluid overload32 Gout10 Uremia (worsening)10 Anemia (worsening)11Cardiovascular Atrial fibrillation/flutter24 Myocardial infarction12 Angina pectoris (worsening)01 Intermittent claudication (worsening)10Infectious AVF site infection01 Cellulitis (non-AVF site)01 Upper airway infection including rhinosinusitis02 Septicemia01 Dental10Other Accidental injury32 Fatigue and sleep disorders44 Liver enzyme abnormalities22 Hyperthyroidism01 Hair loss10 Intoxication01 Aspecific thoracic pain01 Constipation01 Sunburn01 Melanoma10 Gastric pain01 Hematoma non-AVF site01 Urinary catheter placement01Myocardial infarction includes non-ST-elevation myocardial infarction.AVF, arteriovenous fistula; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. Open table in a new tab Myocardial infarction includes non-ST-elevation myocardial infarction. AVF, arteriovenous fistula; LIPMAT, Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation. In the liposomal prednisolone arm, 5 infections were observed in the 3 months of follow-up. One subject was treated with antibiotics due to erythema in the AVF arm, without fever or systemic symptoms. One subject experienced 2 episodes of mild rhinosinusitis that resolved without specific treatment. One subject died 72 days after AVF surgery, because of progressive fluid overload, complicated by septicemia from a possible catheter-related infection or pneumonia. In the placebo group, 1 subject experienced a dental abscess 3 months after AVF surgery. In the LIPMAT study, we evaluated if liposomal prednisolone improves maturation of RCAVFs. The trial was terminated because of slow enrollment after inclusion of 30 of the 80 subjects initially aimed for. We present the study to investigate feasibility and to report preliminary outcomes. Liposomal prednisolone was safe and well-tolerated by patients with end-stage renal disease. No severe infusion reactions were observed and no severe infections were observed within the expected duration of effect of liposomal prednisolone. Liposomal prednisolone did not result in improved RCAVF maturation as measured by ultrasound at 6 weeks and 3 months after surgery. The 62% successful cannulation rate observed in the LIPMAT study was comparable to previous studies on functional AVF maturation.1Voorzaat B.M. van der Bogt K.E.A.A. Janmaat C.J. et al.Arteriovenous fistula maturation failure in a large cohort of hemodialysis patients in the Netherlands.World J Surg. 2018; 42: 1895-1903Crossref PubMed Scopus (14) Google Scholar,7Bleyer A.J. Scavo V.A. Wilson S.E. et al.A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis.J Vasc Surg. 2019; 69: 507-515Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Although the nonsignificant result may be a mere result of a lack of power due to the small sample size, also no trend toward any difference between the treatment and control group was observed. Apart from a lack of statistical power, several factors might explain the lack of therapeutic efficacy of liposomal prednisolone to improve AVF maturation. First, the local concentration of liposomal prednisolone in the vessel wall of the AVF might not have been sufficient to exert a strong anti-inflammatory effect. The local accumulation of liposomal prednisolone could not be examined, as the AVFs could not be sacrificed for examination. In addition, no approved formulation of the compound was available to trace the liposomes in vivo in humans. Second, the inflammatory response in the RCAVF might have been too limited to induce significant local vascular accumulation of the liposomes. Previous clinical studies revealed substantial localization of liposomal prednisolone in the atherosclerotic arterial wall.8der Valk FM van van Wijk D.F. Lobatto M.E. et al.Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration.Nanomedicine. 2015; 11: 1039-1046Crossref PubMed Scopus (93) Google Scholar As the prevalence of atherosclerosis was high in the LIPMAT subjects (Table 1), a significant proportion of liposomal prednisolone may therefore have accumulated in nontarget vessel walls instead of the AVF vein. In future studies, tissue samples of AVFs that failed early may be acquired during surgical revisions and analyzed for liposomal prednisolone content. The extent and timing of venous inflammation after AVF surgery in humans is not fully known. To avoid potential detrimental effects on wound healing, liposomal prednisolone was not administered before surgery. As most of outward remodeling of AVFs has been shown to occur within the first 4 weeks after surgery,9Robbin M.L. Greene T. Cheung A.K. et al.Arteriovenous fistula development in the first 6 weeks after creation.Radiology. 2016; 279: 620-629Crossref PubMed Scopus (65) Google Scholar we aimed to cover this interval by administering the drug at day 1 and 15 after surgery. This might have been too short, with significant inflammation persisting at 4 weeks after surgery. The LIPMAT study was the first to study an anti-inflammatory strategy to improve AVF maturation in humans. We could not demonstrate a clinically significant impact on RCAVF maturation. Future studies are needed to elucidate the role of inflammation in AVF maturation and the clinical promise of liposomal formulations of anti-inflammatory drugs to promote AVF maturation.
