Sesión de hemodiálisis: la tormenta perfecta para la calcificación vascular / Haemodialysis session: The perfect storm for vascular calcification

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Sesión de hemodiálisis: la tormenta perfecta para la calcificación vascular / Haemodialysis session: The perfect storm for vascular calcification

Introducción: La calcificación vascular (CV) asociada a la enfermedad renal crónica (ERC) es un fenómeno estrechamente ligado a las alteraciones en el metabolismo mineral óseo. Existen muchos factores implicados, entre ellos los fármacos empleados en el tratamiento de la ERC. Algunos estudios in vitro señalan que las alteraciones electrolíticas y ácido básicas que tienen lugar durante la sesión de hemodiálisis (HD) pueden jugar un papel clave en el proceso de CV. Métodos: Analizamos las alteraciones electrolíticas y ácido-básicas que tienen lugar durante la sesión de HD en 26 pacientes, empleando de forma aleatorizada concentraciones de calcio en el líquido de diálisis de 1,25 o 1,5 mM. Resultados: En todos los pacientes, independientemente del baño de calcio empleado, se produce una ganancia de calcio. En el grupo de pacientes dializados con baño de calcio 1,5mM, el 100% finaliza la sesión con valores de calcio sérico > 1,3 mM, mientras que en el de 1,25mM, esto solo ocurre en el 15%. Al inicio de la sesión, esta ganancia de calcio coincide con niveles de fósforo aún no controlado. Además, en todos los pacientes se observa una alcalinización progresiva: el 50% finaliza la sesión con cifras de bicarbonato > 30mM y el 23% con pH> 7,5. Conclusiones: Durante la sesión de HD se producen cambios electrolíticos y ácido-básicos inductores de CV: ganancia de calcio y alcalinización en presencia de fósforo sérico inicialmente elevado. Son necesarios estudios con modelos cinéticos de ganancia de calcio y alcalinización diferentes a los actuales (AU)

Introduction: Vascular calcification (VC) associated to chronic kidney disease (CKD) is a complex phenomenon closely related to mineral bone metabolism disorders. Many are the factors implicated, as the drugs used in the treatment of CKD. Some in vitro studies suggest that electrolyte and acid-base disorders induced by hemodialysis (HD) may play a key role in VC. Methods: We analyzed electrolyte and acid-base disorders that occur during an HD session in 26 patients randomly assigned to 1,25 mM or 1,5 mM calcium bath. Results: There is a calcium load in all the patients, independently of calcium bath concentration or basal serum calcium levels. At the end of the session, 100% of the patients dialyzed with 1,5mMcalcium bath have calcium serum levels > 1,3 mM. However, this only occurs in 15% of the patients dialysed with 1,25 mM calcium bath. During this calcium load, phosphorus levels persist uncontrolled. Besides, there is a progressive alkalinization in all the patients. In the end of the session 50% have serum bicarbonate > 30 mM and 23% pH > 7,5. Conclusions: During HD sessions occur electrolyte and acid-base disorders that induce VC: Calcium load and alkalization in presence of elevated phosphorus levels. It is necessary to perform studies with kinetic models of calcium load and alkalinization different from the actual ones (AU)

Haemodialysis session: the perfect storm for vascular calcification.

INTRODUCTION: Vascular calcification (VC) associated to chronic kidney disease (CKD) is a complex phenomenon closely related to mineral bone metabolism disorders. Many are the factors implicated, as the drugs used in the treatment of CKD. Some in vitro studies suggest that electrolyte and acid-base disorders induced by hemodialysis (HD) may play a key role in VC. METHODS: We analyzed electrolyte and acid-base disorders that occur during an HD session in 26 patients randomly assigned to 1,25 mM or 1,5 mM calcium bath. RESULTS: There is a calcium load in all the patients, independently of calcium bath concentration or basal serum calcium levels. At the end of the session, 100% of the patients dialyzed with 1,5 mM calcium bath have calcium serum levels > 1,3 mM. However, this only occurs in 15% of the patients dialysed with 1,25 mM calcium bath. During this calcium load, phosphorus levels persist uncontrolled. Besides, there is a progressive alkalinization in all the patients. In the end of the session 50% have serum bicarbonate > 30 mM and 23% pH > 7,5. CONCLUSIONS: During HD sessions occur electrolyte and acid-base disorders that induce VC: Calcium load and alkalization in presence of elevated phosphorus levels. It is necessary to perform studies with kinetic models of calcium load and alkalinization different from the actual ones.

Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular / Oral anticoagulation in chronic kidney disease with atrial fibrillation

La presencia de fibrilación auricular en pacientes con enfermedad renal crónica (ERC) resulta un hallazgo frecuente que aumenta de forma considerable el riesgo embólico. Las escalas CHADS2 y HAS-BLED, utilizadas en la población general para valorar el riesgo/beneficio de la anticoagulación oral (ACO), infraestiman, respectivamente, los riegos de embolia y hemorragia en la ERC, haciendo complicada la indicación de ACO en estos pacientes. Con la evidencia disponible, parece indicada la ACO en ERC estadio 3, siendo controvertido su uso en estadios más avanzados. Si bien resultan prometedores los nuevos ACO, dabigatrán y rivaroxaban, aprobados para ERC estadio 3, su papel esta aún por esclarecer (AU)

Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain (AU)

Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy.

BACKGROUND: Secretory phospholipase A2 receptor (PLA2R) is the target antigen of the auto-antibodies produced in most (∼ 70%) patients with primary membranous nephropathy (pMN). The applicability of anti-PLA2R1 antibody monitoring for the prediction of MN recurrence in kidney transplant recipients still is a matter of debate. METHODS: We sought to characterize the presence and concentration of anti-PLA2R antibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 21 patients with pMN before and after transplantation to evaluate whether anti-PLA2R concentrations could predict pMN recurrence. RESULTS: The presence of pMN recurrence was significantly correlated with the existence of a positive ELISA assay at graft biopsy or with high level of anti-PLA2R1 activity before transplantation (P = 0.03). In the receiver operating characteristic analysis, anti-PLA2R levels (cut-off of 45 U/mL) during the pretransplantation period accurately predicted pMN recurrence, with a sensitivity of 85.3%, specificity of 85.1%, negative predictive value of 92%, and an area under the curve of 90.8%. This finding supports the hypothesis that anti-PLA2R cause pMN recurrence in humans and indicates the need to prove in an experimental model. Furthermore, 6 of 7 patients with recurrence were carriers of HLA DQA1* 05:01/05 and DQB1* 02:01, confirming these DQ alleles as those associated with higher anti-PLA2R levels. CONCLUSIONS: This study is the first to demonstrate pretransplantation circulating anti-PLA2R antibodies in a cohort of renal transplant recipients who prospectively developed recurrent disease. Currently, anti-PLA2R levels measured by ELISA may be a rational tool to establish the risk of MN recurrence in renal allograft recipients.

[Oral anticoagulation in chronic kidney disease with atrial fibrillation]. / Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular.

Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain.

Effect of calcium acetate/magnesium carbonate in the treatment of hyperphosphataemia in dialysis patients in real clinical practice. One year follow up / Efectos del acetato cálcico/carbonato magnésico en el tratamiento de la hiperfosfatemia en pacientes en diálisis en la práctica clínica real. Seguimiento durante un año

Background: This observational study was conducted to investigate the use and effectiveness of calcium acetate/magnesium carbonate (CaMg) in the treatment of hyperphosphataemia in dialysis patients in real-world clinical practice. Methods: 120 adult CKD patients on dialysis who received CaMg alone or in combination with other phosphate binders were followed-up for 3-12 months. Serum phosphorus, calcium, magnesium, parathyroid hormone and albumin concentration was measured at baseline and after 3, 6 and 12 months respectively. In addition, CaMg dosage, use of concurrent phosphate binders, vitamin D and cinacalcet was documented. Patients were evaluated in 2 subgroups - CaMg alone (n=79) vs. CaMg + concurrent phosphate binder (n=41). Results: In both subgroups serum phosphorus levels decreased significantly from baseline at 3, 6 and 12 months of CaMg treatment. The percentage achievement of recommended serum phosphorus targets improved after CaMg initiation. At month 6, a total of 78% were within the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range. Total corrected serum calcium increased during CaMg treatment, but mildly exceeded the upper limit of normal in three patients only. Asymptomatic significant increases in magnesium (p<0.001) were observed in the monotherapy group at 3, 6 and 12 months. A total of 80 patients (67%) experienced episodes of mild hypermagnesaemia (>2.6mg/mL, 1.05mmol/L). Conclusions: This analysis of current clinical practice shows that - consistent with findings from a randomised controlled trial - CaMg treatment leads to marked improvement in serum phosphorus levels, helping patients in trying to achieve K/DOQI and KDIGO (Kidney Disease Improving Global Outcome) targets (AU)

Antecedentes: Este estudio observacional se llevó a cabo para investigar el uso y la efectividad, en la práctica clínica real, del acetato cálcico/carbonato magnésico (CaMg) en el tratamiento de la hiperfosfatemia en pacientes en diálisis. Métodos: Se realizó un seguimiento durante 3-12 meses en 120 pacientes adultos con enfermedad crónica renal en tratamiento con diálisis que recibían monotratamiento con CaMg o en combinación con otros quelantes del fósforo. Se midieron en suero los valores de fósforo, calcio, magnesio, hormona paratiroidea y concentración de albúmina a nivel basal y tras 3, 6 y 12 meses, respectivamente. Además, se documentó la dosis de CaMg, el uso de quelantes de fósforo concomitantes, la vitamina D y el cinacalcet. Los pacientes se dividieron en 2 subgrupos: aquellos a los que solo se les administraba CaMg (n=79) frente a los que recibían CaMg y un quelante de fósforo concomitante (n=41). Resultados: En ambos subgrupos, los niveles de fósforo sérico disminuyeron de forma significativa, con respecto a los basales, a los 3, 6 y 12 meses de tratamiento con CaMg. El porcentaje de logro de los niveles recomendados de fósforo sérico mejoró tras iniciar el tratamiento con CaMg. El mes 6, un total del 78% se encontraba dentro de las recomendaciones objetivo de Calidad de los Resultados de la Insuficiencia Renal (K/DOQI). El calcio sérico total corregido aumentó durante el tratamiento con CaMg, pero superaba levemente los límites superiores normales solo en tres pacientes. Asimismo, se observaron incrementos significativos del magnesio asintomáticos (P<0,001) en el grupo de monoterapia a los 3, 6 y 12 meses. Un total de 80 pacientes (67%) sufrieron episodios de hipermagnesemia leve (>2,6 mg/mL, 1,05 mmol/L). Conclusiones: El presente análisis de la práctica clínica habitual, en consonancia con los datos obtenidos de un ensayo aleatorizado controlado, demuestra que el tratamiento con CaMg mejora de forma considerable los niveles de fósforo sérico y ayuda a los pacientes a conseguir los objetivos K/DOQI y KDIGO (mejora de los resultados globales en la enfermedad renal) (AU)

Effect of calcium acetate/magnesium carbonate in the treatment of hyperphosphataemia in dialysis patients in real clinical practice. One year follow up.

BACKGROUND: This observational study was conducted to investigate the use and effectiveness of calcium acetate/magnesium carbonate (CaMg) in the treatment of hyperphosphataemia in dialysis patients in real-world clinical practice. METHODS: 120 adult CKD patients on dialysis who received CaMg alone or in combination with other phosphate binders were followed-up for 3-12 months. Serum phosphorus, calcium, magnesium, parathyroid hormone and albumin concentration was measured at baseline and after 3, 6 and 12 months respectively. In addition, CaMg dosage, use of concurrent phosphate binders, vitamin D and cinacalcet was documented. Patients were evaluated in 2 subgroups – CaMg alone (n=79) vs. CaMg + concurrent phosphate binder (n=41). RESULTS: In both subgroups serum phosphorus levels decreased significantly from baseline at 3, 6 and 12 months of CaMg treatment. The percentage achievement of recommended serum phosphorus targets improved after CaMg initiation. At month 6, a total of 78% were within the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range. Total corrected serum calcium increased during CaMg treatment, but mildly exceeded the upper limit of normal in three patients only. Asymptomatic significant increases in magnesium (p<0.001) were observed in the monotherapy group at 3, 6 and 12 months. A total of 80 patients (67%) experienced episodes of mild hypermagnesaemia (>2.6mg/mL, 1.05mmol/L). CONCLUSIONS: This analysis of current clinical practice shows that – consistent with findings from a randomised controlled trial – CaMg treatment leads to marked improvement in serum phosphorus levels, helping patients in trying to achieve K/DOQI and KDIGO (Kidney Disease Improving Global Outcome) targets.

Ictus en pacientes en hemodiálisis: incidencia, tiempo de aparición y factores asociados / Strokes in patients on haemodialysis: incidence, onset time and associated factors

La incidencia de ictus es mayor entre los pacientes en hemodiálisis (HD) que en la población general. En este estudio observacional se analizaron los datos de los pacientes incidentes en HD en el Hospital Universitario Marqués de Valdecilla de Santander (España), durante un período de 40 años (1971-2011). El número total de pacientes que iniciaron hemodiálisis fue de 1453. El período total de seguimiento fue de 4982,22 pacientes/año. Ochenta y cuatro pacientes sufrieron un accidente cerebrovascular. La incidencia acumulada de accidentes cerebrovasculares fue de 5,8 %, con una tasa de incidencia de 1686 ictus por 100 000 pacientes-año. La tasa de incidencia en el primer año en HD fue de 1803 ictus por cada 100 000 pacientes-año, un 6,5 % superior a la media observada a lo largo de todo el período estudiado. En el resto del período, las tasas oscilaron entre 356 y 1626 ictus por cada 100 000 pacientes-año. Factores significativos relacionados con la aparición de ictus fueron: diabetes, infarto de miocardio o angina de pecho, hipertensión, arteriosclerosis/claudicación intermitente, antecedentes de accidente cerebrovascular antes de la HD y fibrilación auricular. Los niveles de hemoglobina en el grupo con ictus fueron prácticamente idénticos a los de la cohorte no ictus (11,92 ± 2,07 g/dl, en comparación con 11,68 ± 2,12 g/dl). Por último, el 60,7 % de la población ictus recibió eritropoyetina con dosis media de 9611 UI/semana, en comparación con el 51,9 % y una dosis de 9544 UI/semana en la cohorte no ictus, sin diferencias significativas entre los grupos. En conclusión, en la población en HD la incidencia de ictus es 7-10 veces superior a la población general y se asocia a factores tradicionales, pero no con niveles de hemoglobina ni dosis de eritropoyetina (AU)

The incidence of stroke is higher substantially among hemodialysis patients than in the overall population. In this observational cohort study, we analysed data from incident hemodialysis patients at Valdecilla University Hospital in Santander (Spain) during a 40-year period (1971-2011). A total number of 1453 patients were started on hemodialysis The total follow-up period was 4982.22 patients/year, with 84 patients having stroke. The cumulative incidence of stroke in our patients was 5.8%, with an incidence rate of 1686 strokes per 100 000 patient-years. The incidence rate in the first year was 1803 strokes per 100 000 patients-year, 6.5% higher than its average over the period studied. In the remaining period, the rates ranged between 356 and 1626 strokes per 100 000 patients-year. Significative factors related to stroke were: diabetes, myocardial infarction or angina, hypertension, arteriosclerosis/intermittent claudication, history of stroke before the HD and atrial fibrillation. Haemoglobin levels in the cohort stroke were virtually identical to those of the not stroke cohort (11.92±2.07g/dL, compared to 11, 68±2.12g/dL). Finally, 60.7% of the population of the stroke cohort received erythropoietin with mean dose of 9611IU/week, compared to 51.9% and a dose of 9544IU/week in the not stroke cohort, without significative differences among groups. In conclusion, in haemodialysis population the incidence of stroke is 7-10 times higher than in the general population. It is associated with well known factors for stroke but not with haemoglobin levels or erythropoietin dose (AU)

Strokes in patients on haemodialysis: incidence, onset time and associated factors.

The incidence of stroke is higher substantially among hemodialysis patients than in the overall population. In this observational cohort study, we analysed data from incident hemodialysis patients at Valdecilla University Hospital in Santander (Spain) during a 40-year period (1971-2011). A total number of 1453 patients were started on hemodialysis The total follow-up period was 4982.22 patients/year, with 84 patients having stroke. The cumulative incidence of stroke in our patients was 5.8%, with an incidence rate of 1686 strokes per 100 000 patient-years. The incidence rate in the first year was 1803 strokes per 100 000 patients-year, 6.5% higher than its average over the period studied. In the remaining period, the rates ranged between 356 and 1626 strokes per 100 000 patients-year. Significative factors related to stroke were: diabetes, myocardial infarction or angina, hypertension, arteriosclerosis/intermittent claudication, history of stroke before the HD and atrial fibrillation. Haemoglobin levels in the cohort stroke were virtually identical to those of the not stroke cohort (11.92±2.07 g/dL, compared to 11, 68±2.12 g/dL). Finally, 60.7% of the population of the stroke cohort received erythropoietin with mean dose of 9611 IU/week, compared to 51.9% and a dose of 9544 IU/week in the not stroke cohort, without significative differences among groups. In conclusion, in haemodialysis population the incidence of stroke is 7-10 times higher than in the general population. It is associated with well known factors for stroke but not with haemoglobin levels or erythropoietin dose.