Effect of preoperative exercise on vascular caliber and maturation of arteriovenous fistula: the physicalfav trial, a randomized controlled study.

BACKGROUND AND OBJECTIVES: Autologous arteriovenous fistula (AVF) is the best vascular access for hemodialysis. Distal forearm radiocephalic fistula is the best option, although the primary failure rate ranges from 20% to 50%. The main objective of the PHYSICALFAV trial was to evaluate the effect of preoperative isometric exercise on vascular caliber, percentage of distal arteriovenous fistula, and primary failure rate. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicenter, prospective, randomized, controlled trial (RCT). A total of 138 patients were randomized 1:1 to the exercise group (exercises combining a handgrip device and an elastic band for 8 weeks) or the control group (no exercise) and followed up with periodic Doppler ultrasound (DU) examinations. RESULTS: After 8 weeks of preoperative isometric exercise, in the exercise group, significant increases were detected in venous caliber (2.80 ± 0.95 mm vs 3.52 ± 0.93 mm [p < 0.001]), arterial caliber (2.61 ± 0.82 mm vs 2.74 ± 0.80 mm [p = 0.008]), arterial peak systolic velocity (66.34 ± 19.2 cm/s vs 71.03 ± 21.5 cm/s [p 0.043]), and maximum strength (28.35 ± 9.16 kg vs 32.68 ± 10.8 kg [p < 0.001]). Distal radiocephalic fistulas were performed in 75% of the exercise group patients compared with 50.8% in the control group (p = 0.030). The global primary failure rate was very low in both groups (7% exercise group vs 14% control group [p = 0.373]). CONCLUSION: Isometric preoperative exercise can improve vascular caliber and increase the possibility of performing distal arteriovenous fistula, with no significant differences in primary failure rate.

Rationale and design of the PHYSICALFAV trial: a randomized controlled trial to evaluate the effect of preoperative isometric exercise on vascular calibre and maturation of autologous arteriovenous fistulas.

BACKGROUND: A good vascular access (VA) is vital for haemodialysis (HD) patients. HD with an autologous arteriovenous fistula (AVF) is associated with higher survival, lower health care costs and fewer complications. Although a distal forearm AVF is the best option, not all patients are good candidates for this approach and the primary failure rate ranges from 20% to 50%. The optimal AVF depends mainly on the anatomical and haemodynamic characteristics of the artery and the vein chosen for the anastomosis. These characteristics can be modified by performing physical exercise. VA guidelines suggest that isometric exercises should be performed both before and after the AVF is created. While the literature contains few data on the potential efficacy of preoperative exercise, small observational studies point to an improvement in venous and arterial calibre. Postoperative exercise also seems to improve maturation, although there is no consensus on the appropriate exercise protocol. METHODS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicentre, prospective, controlled, randomized trial designed to evaluate the usefulness of preoperative isometric exercise (PIE) in pre-dialysis patients or in prevalent HD patients who are candidates for a new AVF. Patients are randomized 1:1 to the PIE group (isometric exercises for 8 weeks) or the control group (no exercise). The main endpoint is whether the rate of primary failure is lower in the PIE group than in the control group. RESULTS: The trial has already started, with 40 patients having been enrolled as of 21 March 2018; 26.5% of the estimated sample.

Adding access blood flow surveillance reduces thrombosis and improves arteriovenous fistula patency: a randomized controlled trial.

PURPOSE: Stenosis is the main cause of arteriovenous fistula (AVF) failure. It is still unclear whether surveillance based on vascular access blood flow (QA) enhances AVF function and longevity. METHODS: We conducted a three-year follow-up randomized, controlled, multicenter, open-label trial to compare QA-based surveillance and pre-emptive repair of subclinical stenosis with standard monitoring/surveillance techniques in prevalent mature AVFs. AVFs were randomized to either the control group (surveillance based on classic alarm criteria; n = 104) or to the QA group (QA measured quarterly using Doppler ultrasound [M-Turbo®] and ultrasound dilution [Transonic®] added to classic surveillance; n = 103).The criteria for intervention in the QA group were: 25% reduction in QA, QA<500 mL/min or significant stenosis with hemodynamic repercussion (peak systolic velocity [PSV] more than 400 cm/sc or PSV pre-stenosis/stenosis higher than 3). RESULTS: At the end of follow-up we observed a significant reduction in the thrombosis rate in the QA group (0.025 thrombosis/patient/year in the QA group vs. 0.086 thrombosis/patient/year in the control group [p = 0.007]). There was a significant improvement in the thrombosis-free patency rate (HR, 0.30; 95% CI, 0.11-0.82; p = 0.011) and in the secondary patency rate in the QA group (HR, 0.49; 95% CI, 0.26-0.93; p = 0.030), with no differences in the primary patency rate between the groups (HR, 0.98; 95% CI, 0.57-1.61; p = 0.935).There was greater need for a central venous catheter and more hospitalizations associated with vascular access in the control group (p = 0.034/p = 0.029).Total vascular access-related costs were higher in the control group (€227.194 vs. €133.807; p = 0.029). CONCLUSIONS: QA-based surveillance combining Doppler ultrasound and ultrasound dilution reduces the frequency of thrombosis, is cost effective, and improves thrombosis free and secondary patency in autologous AVF.

Application of a pattern of incremental haemodialysis, based on residual renal function, when starting renal replacement therapy. / Aplicación de una pauta de hemodiálisis incremental, basada en la función renal residual, al inicio del tratamiento renal sustitutivo.

INTRODUCTION: The interest in the preservation of residual kidney function on starting renal replacement therapy (RRT) is very common in techniques such as peritoneal dialysis but less so in haemodialysis (HD). In our centre the pattern of incremental dialysis (2 HD/week) has been an option for a group of patients. Here we share our experience with this regimen from March 2008. MATERIAL AND METHODS: We included incident patients with residual diuresis >1,000ml/24h, clinical stability, absence of oedema, absence of hyperkalaemia >6.5 mEq/l and phosphoremia >6mg/dl, with acceptable comprehension of dietetic care. Exclusion criteria were: Clinical instability, no dietary or medical compliance and the afore mentioned laboratory abnormalities. RESULTS: A total of 24patients were included in incremental technique. The mean age at start of RRT was 60 (15 years. The average time on incremental technique was 19 (18 months (range: 7-80), with a mean time on dialysis of 31 (23 months (range: 12-86). The reasons for transfer to thrice-weekly HD were: in 6patients due to laboratory tests, in 2patients for heart failure events, one for poor compliance and 3for receiving a kidney graft. The residual diuresis decreased in the first year from 2,106 (606ml/day to 1,545 (558 (P=.17) with the urea clearance and calculated residual renal function, basal 5.7 (1.5vs. 3.8 (1.9ml/min per year (P=.01) and basal 8.9 (2.4vs. 6.9 (4.3 per year (P=.28), respectively. CONCLUSIONS: Incremental HD treatment, with twice-weekly HD, may be an alternative in selected patients. This approach can largely preserve residual renal function at least for the first year. Although this pattern probably is not applicable to all patients starting RRT, it can and should be an initial alternative to consider.

Aplicación de una pauta de hemodiálisis incremental, basada en la función renal residual, al inicio del tratamiento renal sustitutivo / Application of a pattern of incremental haemodialysis, based on residual renal function, when starting renal replacement therapy

Introducción: El interés por preservar la función renal residual una vez iniciado un tratamiento renal sustitutivo (TRS) es notorio en técnicas como la diálisis peritoneal pero es menor en hemodiálisis (HD). En nuestro centro la pauta de diálisis incremental (2HD/semana) ha sido una opción posible para un grupo de pacientes. Mostramos nuestra experiencia con dicha pauta desde marzo de 2008. Material y métodos: Incluimos a pacientes incidentes con diuresis residual >1.000ml/24 h, estabilidad clínica, ausencia de edemas, ausencia de hiperpotasemia >6,5mEq/l y de fosforemia >6mg/dl, con aceptable comprensión de los cuidados dietéticos. Fueron criterios de exclusión: la inestabilidad clínica, el no cumplimiento dietético ni médico y las alteraciones analíticas referidas. Resultados: Veinticuatro pacientes han sido incluidos en la técnica incremental. La edad media al inicio de TRS fue de 60 (15 años. El tiempo medio en técnica incremental fue de 19 (18 meses (rango: 7-80), con una permanencia media en TRS de 31 (23 meses (rango: 12-86). Los motivos de cambio a 3HD/semana fueron: 6pacientes por parámetros analíticos, 2 por episodios de insuficiencia cardiaca, uno por mal cumplimiento terapéutico y 3 por recibir un injerto renal. La diuresis residual desciende en el primer año de 2.106 (606ml/día a 1.545 (558 (p=0,07) junto con el aclaramiento de urea y la función renal residual calculada, basal de 5,7 (1,5 vs. 3,8 (1,9ml/min al año (p=0,01) y basal de 8,9 (2,4vs. 6,9 (4,3 al año (p=0,28), respectivamente. Conclusiones: La HD incremental, con 2 sesiones de HD/semana, puede ser una alternativa en un grupo seleccionado de pacientes. Esta modalidad puede preservar la función renal residual en buena medida, al menos durante el primer año. Aunque probablemente no sea aplicable a todos los pacientes que inician TRS, puede y debe ser una alternativa inicial que considerar (AU)

Introduction: The interest in the preservation of residual kidney function on starting renal replacement therapy (RRT) is very common in techniques such as peritoneal dialysis but less so in haemodialysis (HD). In our centre the pattern of incremental dialysis (2 HD/week) has been an option for a group of patients. Here we share our experience with this regimen from March 2008. Material and methods: We included incident patients with residual diuresis >1,000ml/24h, clinical stability, absence of oedema, absence of hyperkalaemia >6.5 mEq/l and phosphoremia >6mg/dl, with acceptable comprehension of dietetic care. Exclusion criteria were: Clinical instability, no dietary or medical compliance and the afore mentioned laboratory abnormalities. Results: A total of 24patients were included in incremental technique. The mean age at start of RRT was 60 (15 years. The average time on incremental technique was 19 (18 months (range: 7-80), with a mean time on dialysis of 31 (23 months (range: 12-86). The reasons for transfer to thrice-weekly HD were: in 6patients due to laboratory tests, in 2 patients for heart failure events, one for poor compliance and 3 for receiving a kidney graft. The residual diuresis decreased in the first year from 2,106 (606ml/day to 1,545 (558 (P=.17) with the urea clearance and calculated residual renal function, basal 5.7 (1.5vs. 3.8 (1.9ml/min per year (P=.01) and basal 8.9 (2.4vs. 6.9 (4.3 per year (P=.28), respectively. Conclusions: Incremental HD treatment, with twice-weekly HD, may be an alternative in selected patients. This approach can largely preserve residual renal function at least for the first year. Although this pattern probably is not applicable to all patients starting RRT, it can and should be an initial alternative to consider (AU)

The impact of access blood flow surveillance on reduction of thrombosis in native arteriovenous fistula: a randomized clinical trial.

PURPOSE: The usefulness of access blood flow (QA) measurement is an ongoing controversy. Although all vascular access (VA) clinical guidelines recommend monitoring and surveillance protocols to prevent VA thrombosis, randomized clinical trials (RCTs) have failed to consistently show the benefits of QA-based surveillance protocols. We present a 3-year follow-up multicenter, prospective, open-label, controlled RCT, to evaluate the usefulness of QA measurement using Doppler ultrasound (DU) and ultrasound dilution method (UDM), in a prevalent hemodialysis population with native arteriovenous fistula (AVF). METHODS: Classical monitoring and surveillance methods are applied in all patients, the control group (n = 98) and the QA group (n = 98). Besides this, DU and UDM are performed in the QA group every three months. When QA is under 500 ml/min or there is a >25% decrease in QA the patient goes for fistulography, surgery or close clinical/surveillance observation. Thrombosis rate, assisted primary patency rate, primary patency rate and secondary patency rate are measured. RESULTS: After one-year follow-up we found a significant reduction in thrombosis rate (0.022 thrombosis/patient/year at risk in the QA group compared to 0.099 thrombosis/patient/year at risk in the control group [p = 0.030]). Assisted primary patency rate was significantly higher in the QA group than in control AVF (hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.05-0.99; p = 0.030). In the QA group, the numbers unddergoing angioplasty and surgery were higher but with no significant difference in non-assisted primary patency rate (HR 1.41, 95% CI 0.72-2.84; p = 0.293). There was a non-significant improvement in secondary patency rate in the QA group (HR 0.510, 95% CI 0.17-1.50; p = 0.207). CONCLUSIONS: The measurement of QA combining DU and UDM shows a reduction in thrombosis rate and an increased assisted primary patency rate in AVF after one-year follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02111655.

Endothelin-1 potentiation of coronary artery contraction after ischemia-reperfusion.

Hearts from Sprague-Dawley rats were perfused at constant flow and then exposed to 30 min global zero-flow ischemia followed by 15 min reperfusion. After ischemia-reperfusion, coronary arteries were dissected from the heart and segments 2 mm long were prepared for isometric tension recording in organ baths. Stimulation of the arteries with 5-hydroxytryptamine (10(-6) M) produced contraction, which was potentiated by treatment with endothelin-1 (3x10(-10); 10(-9) M). This potentiation was lower in the arteries from hearts after ischemia-reperfusion (for 3x10(-10) M, 15+/-5%; P>0.05; for 10(-9) M, 37+/-7%, P<0.01, n=5) than after control (for 3x10(-10) M, 34+/-4%; P<0.01; for 10(-9) M, 50+/-6%, P<0.01, n=5), and the potentiation was reduced by the inhibitor of nitric oxide synthesis l-NAME (10(-4) M), the antagonist of endothelin ET(A) receptors BQ123 (10(-6) M) and the antagonist of endothelin ET(B) receptors BQ788 (10(-6) M), but not by the cyclooxygenase inhibitor meclofenamate (10(-5) M). These results suggest that endothelin-1 at low concentrations potentiates coronary vasoconstriction, and this effect is reduced after ischemia-reperfusion, mediated by endothelin ET(A) and ET(B) receptors and dependent on nitric oxide release.

Mechanisms of the protective effects of urocortin on coronary endothelial function during ischemia-reperfusion in rat isolated hearts.

1 Urocortin is a vasodilator peptide related to corticotrophin-releasing factor, which may protect endothelial function during coronary ischemia-reperfusion (I-R). The aim of this study was to study the mechanisms of this protective effect. 2 Hearts from Sprague-Dawley rats were isolated and perfused at constant flow and then exposed to 15 min global zero-flow ischemia, followed by 15 min reperfusion. The relaxation to acetylcholine (10 nM-10 microM) was recorded after pre-constriction of the coronary vasculature with U46619 (100-300 nM) in ischemic-reperfused or time-control hearts. 3 After I-R, the coronary relaxation to acetylcholine was reduced and this reduction was attenuated by treatment with urocortin (10 pM), administered before ischemia and during reperfusion. 4 This urocortin-induced improvement of the relaxation to acetylcholine was not modified by tetraethylammonium (10 mM), blocker of Ca2+ dependent-potassium channels; glibenclamide (10 microM), blocker of K(ATP) channels; N(w)-nitro-L-arginine methyl ester (L-NAME, 100 microM), blocker of nitric oxide synthesis; or meclofenamate (10 microM), blocker of cyclooxygenase, but it was abolished by chelerythrine (3 microM), blocker of protein kinase C (PKC). 5 These results suggest that urocortin may protect coronary endothelial function during I-R by activation of PKC.

Effect of ischemia duration and nitric oxide on coronary vasoconstriction after ischemia-reperfusion.

The effects of the duration of ischemia on coronary vasoconstriction after ischemia-reperfusion were analysed in rat hearts. After 15, 30 or 45 min of global zero-flow ischemia and 15 min reperfusion, the coronary response to endothelin-1 (10(-10)-10(-7) M) and the thromboxane A2 analogue 9,11-dideoxy-1a,9a-epoxymethanoprostaglandin F2alpha (U46691, 10(-8)-10(-6) M) was recorded. Vasoconstriction induced by endothelin-1 only increased after short 15 min periods of ischemia. In contrast, the vasoconstriction induced by U46619 remained unmodified by short ischemias but was reduced after longer periods of ischemia (30 and 45 min). Inhibition of nitric oxide synthesis with the Nw-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) augmented the vasoconstriction induced by endothelin-1 in non-ischemic hearts, but not following ischemia. Similarly, L-NAME increased the vasoconstriction induced by U46619 to a greater extent in non-ischemic hearts than following ischemia. These results suggest that ischemia-reperfusion inhibits nitric oxide production, causing an increased coronary response to endothelin-1 after brief ischemias. Longer ischemias may non-specifically inhibit coronary vasoconstriction and reduce nitric oxide production.