Impact of acetate- or citrate-acidified bicarbonate dialysate on ex vivo aorta wall calcification.

Vascular calcification is highly prevalent in patients with chronic hemodialysis. Increased acetatemia during hemodialysis sessions using acetate-acidified bicarbonate has also been associated with several abnormalities, By contrast, these abnormalities were not induced by citrate-acidified bicarbonate dialysis. Moreover, citrate is biocompatible alternative to acetate in dialysis fluid. However, the effects of citrate on vascular calcification during hemodialysis had not been studied in detail. This study analyzed herein the effects of acetate- or citrate-acidified bicarbonate dialysis on vascular calcification. Citrate has been shown to inhibit calcification in urine in hemodialysis patients. Therefore, our hypothesis is that citrate-acidified bicarbonate dialysis could reduce vascular calcification. Blood samples before and after hemodialysis from patients on acetate- or citrate-acidified bicarbonate dialysis were collected in heparin-containing tubes (n = 35 and n = 25 respectively). To explore the effect of pre- and post-dialysis plasmatic bicarbonate and citrate on vascular calcification, rats aortic rings cultured ex vivo in Minimum Essential Medium containing 0.1% FBS and 45-calcium as radiotracer were used (n = 24). After 7 days of incubation aortic rings were dried, weighed and radioactivity was measured via liquid scintillation counting. Bicarbonate levels increase calcium accumulation in rat aortic wall in a dose-response manner (pH = 7.4). Moreover, citrate prevents calcium accumulation, with a mean inhibitor concentration (IC50) value of 733 µmol/L. During acetate-acidified bicarbonate dialysis, bicarbonate and citrate levels in plasma increase (22.29 ± 3.59 versus 28.63 ± 3.56 mmol/L; p < 0.001) and decrease (133.3 ± 53.6 versus 87.49 ± 32.3 µmol/L, p < 0.001), respectively. These changes in pos-hemodialysis plasma significantly (p < 0.001) alter calcium accumulation in the aortic wall (38.9% higher). Moreover, citrate-acidified bicarbonate dialysis increases post-hemodialysis citrate levels 5-fold (145 ± 79.8 versus 771.6 ± 184.3 µmol/L), reducing calcium accumulation in the aortic wall. Citrate-acidified bicarbonate dialysis reduces plasmatic calcium and pH variations during dialysis session (Δ[Ca2+] = -0.019 ± 0.089; ΔpH = 0.098 ± 0.043) respect to acetate-acidified bicarbonate dialysis (Δ[Ca2+] = 0.115 ± 0.118; ΔpH = 0.171 ± 0.078). To our knowledge, our study is the first to show that citrate protects against calcium accumulation in rat aortic walls ex vivo. Therefore, citrate-acidified bicarbonate dialysis may be an alternative approach to reduce calcification in hemodialysis patients without additional cost.

Estudio prospectivo aleatorizado multicéntrico para demostrar los beneficios de la hemodiálisis sin acetato (con citrato): Estudio ABC-treat. Efecto agudo del citrato / Prospective randomised multicentre study to demonstrate the benefits of haemodialysis without acetate (with citrate): ABC-treat Study. Acute effect of citrate

INTRODUCCIÓN: El líquido de diálisis (LD), elemento esencial en la hemodiálisis (HD), se fabrica in situ mezclando 3 componentes: agua tratada, concentrado de bicarbonato y concentrado ácido. Para evitar la precipitación de carbonato cálcico y magnésico que se produce en el LD por la adición de bicarbonato, es necesario añadir un ácido. Existen 2 concentrados ácidos según contengan acetato (LDA) o citrato (LDC) como estabilizante. OBJETIVO: Comparar el efecto agudo de la HD con LDC vs. LDA sobre el metabolismo del calcio, fosforo y magnesio, el equilibrio ácido base, la coagulación, inflamación y la estabilidad hemodinámica. MÉTODOS: Estudio prospectivo, multicéntrico, aleatorizado y cruzado, de 32 semanas de duración, en pacientes en HD trisemanal, monitor AK-200-Ultra-S o Artis, 16 semanas con LDA SoftPac(R), elaborado con 3 mmol/l de acetato, y 16 semanas con LDC SelectBag Citrate(R), con 1 mmol/l de citrato. Se incluyeron pacientes mayores de 18 años en HD durante un mínimo de 3 meses mediante fístula arteriovenosa. Se recogieron datos epidemiológicos, de diálisis, bioquímica pre- y posdiálisis, episodios de hipotensión arterial, y scores de coagulación mensualmente durante los 8 meses de estudio. Se extrajeron pre- y posdiálisis: gasometría venosa, calcio (Ca), calcio iónico (Cai), fósforo (P), magnesio (Mg) y hormona paratiroidea (PTH), entre otros. ClinicalTrials.gov NCT03319680. RESULTADOS: Se incluyeron 56 pacientes, 47 (84%) hombres y 9 (16%) mujeres de edad media: 65,3 (16,4) años, técnica HD / HDF: 20 (35,7%) / 36 (64,3%). Encontramos diferencias (p < 0,05) cuando utilizamos el LD con citrato (C) frente a acetato (A) en los valores posdiálisis de bicarbonato [C: 26,9 (1,9) vs. A: 28,5 (3) mmol/l], Cai [C: 1,1 (0,05) vs A: 1,2 (0,08) mmol/l], Mg [C. 1,8 (0,1) vs A: 1,9 (0,2) mg/dl] y PTH [C: 255 (172) vs. 148 (149) pg/ml]. No encontramos diferencias en ninguno de los parámetros medidos prediálisis. Se registraron menos episodios de hipotensión arterial durante las sesiones con el LDC; de las 4.416 sesiones de HD, 2.208 en cada grupo, cursaron con hipotensión 311 sesiones (14,1%) con LDA y 238 (10,8%) con LDC (p < 0,01). También fue menor la caída de volumen sanguíneo máximo medido por biosensor Hemoscan(R) [-3,4(7,7) vs. -5,1 (8,2)], aunque sin significación estadística. CONCLUSIÓN: La diálisis con citrato produce de forma aguda menor alcalemia posdiálisis y modifica de forma significativa el Ca, el Mg y la PTH. El LDC tiene un impacto positivo sobre la tolerancia hemodinámica

INTRODUCTION: Dialysis fluid (DF), an essential element in hemodialysis (HD), is manufactured in situ by mixing three components: treated water, bicarbonate concentrate and acid concentrate. To avoid the precipitation of calcium and magnesium carbonate that is produced in DF by the addition of bicarbonate, it is necessary to add an acid. There are 2 acid concentrates that contain acetate (ADF) or citrate (CDF) as a stabilizer. OBJECTIVE: To compare the acute effect of HD with CDF vs. ADF on the metabolism of calcium, phosphorus and magnesium, acid base balance, coagulation, inflammation and hemodynamic stability. METHODS: Prospective, multicenter, randomized and crossed study, of 32 weeks duration, in patients in three-week HD, AK-200-Ultra-S or Artis monitor, 16 weeks with ADF SoftPac(R), prepared with 3mmol/L of acetate, and 16 weeks with CDF SelectBag Citrate(R), with 1mmol/L of citrate. Patients older than 18 years were included in HD for a minimum of 3 months by arteriovenous fistula. Epidemiological, dialysis, pre and postdialysis biochemistry, episodes of arterial hypotension, and coagulation scores were collected monthly during the 8 months of the study. Pre and post-dialysis analysis were extracted: venous blood gas, calcium (Ca), ionic calcium (Cai), phosphorus (P), magnesium (Mg) and parathyroid hormone (PTH) among others. ClinicalTrials.gov NCT03319680. RESULTS: We included 56 patients, 47 (84%) men and 9 (16%) women, mean age: 65.3 (16.4) years, technique HD / HDF: 20 (35.7%) / 36 (64.3%). We found differences (p < 0.05) when using the DF with citrate (C) versus acetate (A) in the postdialysis values of bicarbonate [C: 26.9 (1.9) vs. A: 28.5 (3) mmol/L], Cai [C: 1.1 (0.05) vs. A: 1.2 (0.08) mmol/L], Mg [C: 1.8 (0.1) vs A: 1, 9 (0.2) mg/dL] and PTH [C: 255 (172) vs. 148 (149) pg/mL]. We did not find any differences in any of the parameters measured before dialysis. Of the 4,416 sessions performed, 2,208 in each group, 311 sessions (14.1%) with ADF and 238 (10.8%) with CDF (p < 0.01), were complicated by arterial hypotension. The decrease in maximum blood volume measured by Hemoscan(R) biosensor was also lower [-3.4 (7.7) vs -5.1 (8.2)] although without statistical significance. CONCLUSION: Dialysis with citrate acutely produces less postdialysis alkalemia and significantly modifies Ca, Mg and PTH. CDF has a positive impact on hemodynamic tolerance

Prospective randomised multicentre study to demonstrate the benefits of haemodialysis without acetate (with citrate): ABC-treat Study. Acute effect of citrate. / Estudio prospectivo aleatorizado multicéntrico para demostrar los beneficios de la hemodiálisis sin acetato (con citrato): Estudio ABC-treat. Efecto agudo del citrato.

INTRODUCTION: Dialysis fluid (DF), an essential element in hemodialysis (HD), is manufactured in situ by mixing three components: treated water, bicarbonate concentrate and acid concentrate. To avoid the precipitation of calcium and magnesium carbonate that is produced in DF by the addition of bicarbonate, it is necessary to add an acid. There are 2 acid concentrates that contain acetate (ADF) or citrate (CDF) as a stabilizer. OBJECTIVE: To compare the acute effect of HD with CDF vs. ADF on the metabolism of calcium, phosphorus and magnesium, acid base balance, coagulation, inflammation and hemodynamic stability. METHODS: Prospective, multicenter, randomized and crossed study, of 32 weeks duration, in patients in three-week HD, AK-200-Ultra-S or Artis monitor, 16 weeks with ADF SoftPac®, prepared with 3mmol/L of acetate, and 16 weeks with CDF SelectBag Citrate®, with 1mmol/L of citrate. Patients older than 18 years were included in HD for a minimum of 3 months by arteriovenous fistula. Epidemiological, dialysis, pre and postdialysis biochemistry, episodes of arterial hypotension, and coagulation scores were collected monthly during the 8 months of the study. Pre and post-dialysis analysis were extracted: venous blood gas, calcium (Ca), ionic calcium (Cai), phosphorus (P), magnesium (Mg) and parathyroid hormone (PTH) among others. ClinicalTrials.gov NCT03319680. RESULTS: We included 56 patients, 47 (84%) men and 9 (16%) women, mean age: 65.3 (16.4) years, technique HD/HDF: 20 (35.7%)/36 (64.3%). We found differences (p<0.05) when using the DF with citrate (C) versus acetate (A) in the postdialysis values of bicarbonate [C: 26.9 (1.9) vs. A: 28.5 (3) mmol/L], Cai [C: 1.1 (0.05) vs. A: 1.2 (0.08) mmol/L], Mg [C: 1.8 (0.1) vs A: 1, 9 (0.2) mg/dL] and PTH [C: 255 (172) vs. 148 (149) pg/mL]. We did not find any differences in any of the parameters measured before dialysis. Of the 4,416 sessions performed, 2,208 in each group, 311 sessions (14.1%) with ADF and 238 (10.8%) with CDF (p<0.01), were complicated by arterial hypotension. The decrease in maximum blood volume measured by Hemoscan® biosensor was also lower [-3.4 (7.7) vs -5.1 (8.2)] although without statistical significance. CONCLUSION: Dialysis with citrate acutely produces less postdialysis alkalemia and significantly modifies Ca, Mg and PTH. CDF has a positive impact on hemodynamic tolerance.

Catéter-fístula: una nueva alternativa en la punción de accesos vasculares / Fistula catheter: a new alternative in venous access puncture

Es imprescindible un acceso vascular adecuado para obtener una hemodiálisis óptima. El daño causado por la punción de la aguja convencional o complicaciones intradiálisis derivadas del movimiento del brazo pueden comprometer la supervivencia del acceso. Otro factor esencial en la calidad de la hemodiálisis, íntimamente relacionado con el calibre de la aguja, es conseguir un mayor flujo sanguíneo eficaz. El catéter-fístula, una nueva cánula de punción de fluoruroplástico, disminuye el daño en la pared interna del acceso y presenta un menor calibre de punción con un mayor calibre interior, lo que le permite alcanzar mayores flujos con una máxima eficacia depuradora y menores complicaciones vasculares. El objetivo de este estudio prospectivo fue comparar el uso del catéter-fístula con el uso de la aguja convencional. Se realizaron 18 sesiones de hemodiálisis con cada uno de los dispositivos en pacientes estables y con buen acceso vascular, recogiéndose en todos los casos el flujo obtenido, las presiones y otros parámetros del monitor, analíticas e incidencias. Los resultados han demostrado que la utilización del catéter-fístula disminuyó la presión arterial y la presión venosa, sin disminuir la eficacia dialítica, en consecuencia, mejoró el perfil hemodinámico. Mejoró significativamente el flujo de sangre real, el número de litros dializados y el Kt. El menor trauma mecánico producido en el acceso vascular permitió disminuir la dosis de heparina, el tiempo de hemostasia y hubo una reducción de las complicaciones vasculares: extravasación y resangrado. Siendo bien tolerada la punción, hay un leve empeoramiento en la sensación dolorosa, justificada por la inexperiencia del manejo. La mejoría en los parámetros dinámicos abren las posibilidades de conseguir mayor eficacia dialítica al hacer factible la utilización de mayores flujos sanguíneos con presiones más adecuadas (AU)

Adequate vascular access is essential in order toobtain optimal haemodialysis. The damage caused by conventional needle puncture or intradialytic complications deriving from the movement of the arm can compromise the survival of the access. Another essential factor in the quality of the haemodialysis, closely related to the calibre of the needle, is obtaining a greater efficient blood flow. The fistula catheter, a new puncture cannula made of fluoroplastic, reduces the damage to the internal wall of the access and presents a lower puncture calibre with a higher interior calibre, which allows it to reach better flows with maximum efficiency and fewer vascular complications. The aim of this prospective study was to compare the use of the fistula catheter with the use of the needle. Eighteen haemodialysis sessions were carried out with each of the devices in stable patients with good vascular access, recording in all cases the flow obtained, pressures and other monitor parameters, test results and incidents. The results have shown that the use of the fistula catheter reduced the arterial pressure and venous pressure, without reducing the dialytic efficiency, and consequently the haemodynamic profile improved. The actual blood flow, number of litres dialysed and Kt improved significantly. The lesser mechanical trauma caused in the vascular access made it possible to reduce the dose of heparin, the haemostasis time and there was a reduction in vascular complications: extravasation and rebleeding. While the puncture is well tolerated, there is a slight worsening in the feeling of pain, explained by the lack of experience in handling. The improvement in dynamic parameters opens up the possibilities of achieving greater dialytic efficiency by making it feasible to use greater blood flows with more adequate pressures (AU)