Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community / Epidemiología de la enfermedad de Fabry en pacientes en hemodiálisis de la Comunidad de Madrid

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. Inclusion criteria: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). Exclusion criteria: underaged patients or not agreeing or not being capable of signing the IC. Results: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. Conclusions: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient. (AU)

El objetivo del estudio ha sido realizar un mapa descriptivo de la enfermedad de Fabry (EF) en la Comunidad de Madrid, así como realizar un despistaje de la EF a todo paciente incidente durante un período de 3 años. Criterios de inclusión: Pacientes mayores de 18 años, excluyendo aquellos diagnosticados de cualquier otra enfermedad hereditaria con afectación renal diferente de la EF, que firmaran el consentimiento informado. Criterios de exclusión: pacientes menores de edad, no estar de acuerdo o no ser capaces de firmar el consentimiento informado. Resultados: Se incluyeron 3.470 pacientes (63% hombres), con una edad media de 67,9±9,7 años, de los cuales 2.357 eran pacientes prevalentes y 1.113 incidentes. En el caso de los pacientes prevalentes, el tiempo medio en hemodiálisis (HD) fue de 45,2 (DE 51,3) meses. En pacientes incidentes, la proteinuria estuvo presente en el 28,4%. No hubo diferencias estadísticamente significativas en la actividad plasmática de alfa-galactosidasa A o valores de Lyso-Gl3 al comparar las poblaciones de incidentes y de prevalentes, y tampoco entre hombres y mujeres. Se realizó estudio genético en 87 pacientes (2,5% de los pacientes): 60 varones con disminución de la actividad enzimática y 27 mujeres con una disminución de la actividad enzimática, aumento de los niveles de Lyso-Gl3 o ambos. Las variantes genéticas identificadas fueron: p.Asp313Tyr (4 pacientes), p.Arg220Gln (3 pacientes) y M290I (un paciente). Ninguna de las variantes identificadas fue patógena. Conclusiones: El 76% de los centros de HD de la Comunidad de Madrid participaron en el estudio. Este es el primer estudio epidemiológico prospectivo de EF en la población de HD de una región de España. También es la primera vez que se describen niveles de alfa-galactosidasa A y Lyso-Gl3 en HD, sin embargo, en este estudio no se han identificado pacientes con EF. (AU)

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular-weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.

Efficacy of enoxaparin in preventing coagulation during high-flux haemodialysis, expanded haemodialysis and haemodiafiltration.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are easily dialysable with high-flow membranes; however, it is not clear whether the LMWH dose should be adjusted according to the membrane type and dialysis technique. This study aimed to evaluate the influence of the dialyser on anticoagulation of the extracorporeal dialysis circuit. METHODS: Thirteen patients received the same dose of LMWH through the arterial port via three dialysis techniques: high-flux haemodialysis (HF-HD), online haemodiafiltration (HDF) and expanded haemodialysis (HDx). All dialysis was performed under similar conditions: duration, 4 h; blood flow, 400 mL/min; and dialysate flow, 500 mL/min. Antifactor Xa (aXa) activity and activated partial thromboplastin time (APTT) were measured before and after the dialysis. Clotting time of the vascular access site after haemodialysis, visual clotting score of the dialyser and any complications with the extracorporeal circuit or bleeding were registered. RESULTS: Post-dialysis aXa activity in HF-HD (0.26 ± 0.02 U/mL) was significantly different from that in HDF (0.21 ± 0.02 U/mL, P = 0.024), and there was a trend in HDx (0.22 ± 0.01 U/mL, P = 0.05). APTT post-dialysis in HF-HD (30.5 ± 0.7 s) was significantly different from that in HDx (28.2 ± 0.64 s, P = 0.009) and HDF (28.8 ± 0.73 s, P = 0.009). CONCLUSIONS: AXa activity in HDF was significantly lower than that in HF-HD, possibly because of more losses of LMWH through the dialyser. Given the higher anticoagulant loss in HDF and probably in HDx than in HF-HD, the enoxaparin dose administered may be adjusted according to the dialysis technique.

Intradialytic hypotension and relationship with cognitive function and brain morphometry.

BACKGROUND: The haemodynamic stress brought about by dialysis could justify the loss of structural and functional integrity of the central nervous system (CNS). The main objective of this study was to analyse the relationship between intradialytic hypotension (IDH) and cognitive function and brain morphometry. METHODS: The cross-sectional KIDBRAIN study (Cohort Study of Morphological Changes of the Brain by MRI in Chronic Kidney Disease Patients) included 68 prevalent patients with no history of neurological disorders (cerebrovascular disease and cognitive impairment) undergoing haemodialysis (HD). We analysed 18 non-consecutive dialysis sessions (first three of each month over a 6-month period) and various definitions of IDH were recorded. Global cognitive function (GCF) was assessed using the Mini-Mental State Examination (MMSE) and parameters of structural integrity of the CNS were obtained using volume morphometry magnetic resonance imaging analysis [grey matter (GM), white matter (WM) and hippocampus). RESULTS: A greater number of sessions with IDH were associated with less volume of WM (r = -0.359,P = 0.003) and hippocampus (r = -0.395, P = 0.001) independent of cardiovascular risk factors according to multivariable linear regression models (ß = -0.198, P = 0.046 for WM; ß = -0.253, P = 0.017 for hippocampus). The GCF by the MMSE was 27.3 ± 7.3.1 and was associated with WM volume (ß = 0.403, P = 0.001) independent of GM and hippocampus volume. Symptomatic IDH was associated with GCF (r = -0.420, P < 0.001) in adjusted analysis (ß = -0.339, P = 0.008). CONCLUSIONS: Even when asymptomatic, IDH is associated with a lower WM and hippocampus volume and reduced GCF in patients undergoing HD, thus suggesting greater vulnerability of the brain to the haemodynamic stress that may be generated by a dialysis session.

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.

Thrombotic Microangiopathy in a Kidney Transplant Patient With COVID-19.

Kidney transplant recipients are at increased risk for infection, including coronavirus disease 2019 (COVID-19), given ongoing immunosuppression. In individuals with COVID-19, complications including thrombosis and endothelial dysfunction portend worse outcomes. In this report, we describe a kidney transplant recipient who developed severe thrombotic microangiopathy with a low platelet count (12 ×109/L), anemia (hemoglobin, 7.5 g/dL with 7% schistocytes on peripheral-blood smear), and severe acute kidney injury concurrent with COVID-19. The clinical course improved after plasma exchange. Given this presentation, we hypothesize that COVID-19 triggered thrombotic microangiopathy.

Definiciones de hipotensión intradiálisis con poder predictivo de mortalidad en una cohorte de hemodiálisis / Intradialytic hypotension definitions with mortality prediction capacity in a cohort of haemodialysis patients

INTRODUCCIÓN: La hipotensión arterial intradiálisis (HAID) es una complicación frecuente que se asocia a una mayor morbimortalidad en hemodiálisis, aunque es una tarea pendiente la uniformidad de criterios respecto a su definición. El objetivo del estudio es analizar las características de distintas definiciones de hipotensión y su relación con la morbimortalidad en una cohorte de pacientes en hemodiálisis. METODOLOGÍA: Estudio observacional, con un seguimiento de 30 meses, que incluye 68 pacientes prevalentes en hemodiálisis con al menos 6 meses de tratamiento. Se recogieron parámetros de diálisis, y distintas definiciones de hipotensión, de 18 sesiones no consecutivas (las primeras 3 sesiones de cada mes de un período de 6 meses). Se definió como evento positivo de HAID si ocurría cualquier definición en más del 25% de las sesiones estudiadas. Se analizó el poder predictivo para cada definición de hipotensión (Nadir90, Nadir100, Fall20, Fall30, Fall20Nadir90, Fall30Nadir90, KDOQI, HEMO) mediante un análisis de supervivencia. Se estimó la relación con los eventos cardiovasculares no fatales y la mortalidad global mediante distintos modelos proporcionales de Cox. RESULTADOS: Encontramos definiciones de HAID que ocurrieron con una significativa mayor frecuencia (Nadir100: 339,8/1.000 sesiones; Nadir90: 172,3/1.000 sesiones) en comparación con otras (KDOQI: 98/1.000 sesiones; HEMO 129,9/1.000 sesiones). Con una media de seguimiento de 27,12 ± 6,84 meses se registraron 13 eventos mortales. Un mayor número de sesiones con HAID conforme a la definición Nadir90 fue un factor predictor de mortalidad (Log rank 5,02, p = 0,025), independiente según los modelos ajustados (HR: 3,23 [IC95%: 1,08-9,6], p = 0,035). Las definiciones Nadir100 (HR: 4,54 [IC95%: 1,25-16,4], p = 0,02) y Fall30Nadir90 (HR: 3,08 [IC95%: 1,07-8,8], p = 0,03) fueron predictores independientes de eventos cardiovasculares no fatales en los modelos ajustados. CONCLUSIONES: La hipotensión intradiálisis, incluso asintomática, tiene poder predictivo de mortalidad y eventos cardiovasculares no fatales en pacientes prevalentes en hemodiálisis

INTRODUCTION: Intradialytic hypotension (IDH) is a common complication and is associated with higher morbidity and mortality in patients on haemodialysis. However, there is a lack of uniformity in definitions of IDH. The main objective of this study is to analyse clinical and dialysis related factors with several IDH definitions, and its relationship with morbidity and mortality in a cohort of haemodialysis patients. METHODOLOGY: Observational study with a 30-month follow-up period that includes 68 prevalent patients on haemodialysis with at least six months of treatment. We analysed 18 non-consecutive dialysis sessions (first three of each month of a six-month period), and different definitions of IDH were recorded. A positive event of IDH was defined if any definition occurred in more than 25% of the sessions studied. Using survival analysis, we analysed the prediction capacity of each IDH definition (Nadir90, Nadir100, Fall20, Fall30, Fall20Nadir90, Fall30Nadir90, KDOQI, HEMO). The relationship with non-fatal cardiovascular disease and global mortality was estimated using different Cox proportional models. RESULTS: We found IDH definitions that occurred significantly more frequently (Nadir100: 339.8/1,000 sessions, Nadir90: 172.3/1,000 sessions) than others (KDOQI: 98/1,000 sessions, HEMO 129.9/1,000 sessions). We registered 13 fatal events with a mean follow-up of 27.12 ± 6.84 months. A greater number of sessions with IDH according to the Nadir90 definition was a predictive factor of mortality (Log rank 5.02, p = 0.025), independent according to adjusted models (HR: 3.23 [95% CI: 1.08-9.6], p = 0.035). The definitions Nadir100 (HR: 4.54 [95% CI: 1.25-16.4], p = 0.02) and Fall30Nadir90 (HR: 3.08 [95% CI: 1.07-8.8], p = 0.03) were independent predictors of non-fatal cardiovascular disease in adjusted models. CONCLUSIONS: Intradialytic hypotension, even asymptomatic, is a predictor of mortality and non-fatal cardiovascular disease in prevalent patients on haemodialysis

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Intradialytic hypotension definitions with mortality prediction capacity in a cohort of haemodialysis patients. / Definiciones de hipotensión intradiálisis con poder predictivo de mortalidad en una cohorte de hemodiálisis.

INTRODUCTION: Intradialytic hypotension (IDH) is a common complication and is associated with higher morbidity and mortality in patients on haemodialysis. However, there is a lack of uniformity in definitions of IDH. The main objective of this study is to analyse clinical and dialysis related factors with several IDH definitions, and its relationship with morbidity and mortality in a cohort of haemodialysis patients. METHODOLOGY: Observational study with a 30-month follow-up period that includes 68 prevalent patients on haemodialysis with at least six months of treatment. We analysed 18 non-consecutive dialysis sessions (first three of each month of a six-month period), and different definitions of IDH were recorded. A positive event of IDH was defined if any definition occurred in more than 25% of the sessions studied. Using survival analysis, we analysed the prediction capacity of each IDH definition (Nadir90, Nadir100, Fall20, Fall30, Fall20Nadir90, Fall30Nadir90, KDOQI, HEMO). The relationship with non-fatal cardiovascular disease and global mortality was estimated using different Cox proportional models. RESULTS: We found IDH definitions that occurred significantly more frequently (Nadir100: 339.8/1,000 sessions, Nadir90: 172.3/1,000 sessions) than others (KDOQI: 98/1,000 sessions, HEMO 129.9/1,000 sessions). We registered 13 fatal events with a mean follow-up of 27.12±6.84 months. A greater number of sessions with IDH according to the Nadir90 definition was a predictive factor of mortality (Log rank 5.02, p=0.025), independent according to adjusted models (HR: 3.23 [95% CI: 1.08-9.6], p=0.035). The definitions Nadir100 (HR: 4.54 [95% CI: 1.25-16.4], p=0.02) and Fall30Nadir90 (HR: 3.08 [95% CI: 1.07-8.8], p=0.03) were independent predictors of non-fatal cardiovascular disease in adjusted models. CONCLUSIONS: Intradialytic hypotension, even asymptomatic, is a predictor of mortality and non-fatal cardiovascular disease in prevalent patients on haemodialysis.

The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients.

BACKGROUND: YKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events. METHODS: We performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24-66) months, CV events were recorded. RESULTS: The mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/V urea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, ß2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009-1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009-1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224-0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554-3.172); P: 0.008]. Kaplan-Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007). CONCLUSIONS: YKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Exercise training during hemodialysis sessions: Physical and biochemical benefits.

Chronic inflammation, protein-energy wasting, and poor physical functioning are highly prevalent among patients with chronic kidney disease (CKD). These factors are associated with disability and increase of cardiovascular risk. The aim of this study is to evaluate the effects of exercise training during hemodialysis (HD) sessions on physical functioning, body composition, and nutritional and inflammatory status. We performed a prospective intervention study including patients on prevalent HD therapy. Patients were evaluated at baseline visit by Rehabilitation and Physiotherapy specialists and the exercise program was adapted to each patient's physical capacity. In addition to demographic, clinical, body composition and functional ability data, serum markers regarding nutritional and inflammatory status were collected at baseline and after 3 months of exercise training. We observed a significant improvement after 3-month follow-up in functional ability (6 minute walk test [6MWT] [403.15 ± 105.4 vs 431.81 ± 115.5 m, P < .001], sit-to-stand repetitions in 30 seconds [12.2 ± 4.2 vs 14.1 ± 5.0 repetitions, P = .003] and dynamometry [24.5 ± 11.9 vs 29.5 ± 12.5 kg, P < 0.001]), body composition with increase of body mass index (BMI) (23.7 ± 4.4 vs 24.1 ± 4.7 kg/m2 , P = 0.01) at the expense of lean tissue index (LTI) (14.9 ± 3.7 vs 16.2 ± 2.9 kg/m2 , P = 0.038) and lipid parameters with LDL-cholesterol decrease (70.2 ± 17.9 vs 64.9 ± 21.3 mg/dL, P = .03) and lower serum triglyceride levels (125.8 ± 54.0 vs 108.2 ± 44.6 mg/dL, P = .006). In addition, we found a decrease in iron (155.6 ± 148.2 vs 116.7 ± 110.8 mg, P = .029) and erythropoietin (117.5 ± 84.2 vs 99.2 ± 74.5 µg, P = .023) requirements. The implementation of exercise training programs during HD can improve physical functioning, body composition and lipid and anemia profile. Supervised exercise programs could be included as part of HD patient care to improve physical capacity in these patients.

Efficacy of Evolocumab vs low-density lipoprotein cholesterol apheresis in patients with familial hypercholesterolemia and high cardiovascular risk (EVOLAFER01).

Low-density lipoprotein (LDL) apheresis has been considered the last option to treat refractory hyperlipidemia in patients with familiar hypercholesterolemia (FH). Evolocumab is a monoclonal antibody which has shown significant reduction of low-density lipoprotein cholesterol (LDL-C) serum levels and cardiovascular events. The aim of the study was to examine the comparative impact of LDL-apheresis vs Evolocumab vs the combination of both LDL-apheresis and Evolocumab on lipid and lipoprotein parameters, and other metabolic/inflammatory measures. DESIGN OF THE STUDY: Non-randomized open case series study of 10 adult patients diagnosed with FH already on long-term LDL-apheresis therapy. The study was developed in three consecutive phases to compare LDL-apheresis, Evolocumab treatment and the combination of both. Laboratory parameters were collected pre and post LDL-apheresis and before Evolocumab administration. The primary endpoint was the reduction of LDL-C during the three phases. RESULTS: Reduction of LDL-C levels with Evolocumab were 31.4% vs LDL-apheresis from 153 ± 35 mg/dL to 105 ± 56 mg/dL (P < .001). Reduction of Lp(a) was also significantly higher with Evolocumab (45.5%) than LDL-apheresis from 36 (6-119) to 20 (3-41) mg/dL, P = .027. In addition, HDL-C and apo-A increased after Evolocumab treatment, from 41 ± 6 to 46 ± 8 mg/dL (P = .003) and from 124 ± 13 to 144 ± 25 mg/dL (P = .001), respectively. No changes in immunological or inflammatory parameters were observed and no serious adverse events were recorded. CONCLUSION: Evolocumab reduces LDL-C and Lp(a) more effectively than LDL-apheresis and combination of Evolocumab plus LDL-apheresis could be a therapeutic alternative to get lower LDL-C and Lp(a) levels in patients with very high cardiovascular risk.

La composición corporal influye en la eliminación de toxinas urémicas unidas a proteínas en la hemodiafiltración online / Body composition infuences the elimination of protein-bound uremic toxins in online hemodiafiltration

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Middle molecule elimination in expanded haemodialysis: only convective transport?

BACKGROUND: New high-retention onset dialysers have shown improved efficacy in the elimination of uraemic toxins, and their depurative capacity has been compared with high convective volumes of online haemodiafiltration. Haemodialysis (HD) using high-flux membranes leads to convective transport by internal filtration [direct filtration (DF)/backfiltration (BF)] and allows the removal of middle molecules (MMs). The aim of this study was to assess solute transport mechanisms in expanded HD (HDx). METHODS: In 14 4-h HDx sessions with Theranova-500 dialysers under similar dialysis conditions (blood flow 400 mL/min, dialysate flow 700 mL/min, dialysate temperature 35.5°C), pressures at the inlet and outlet of both dialyser compartments (P bi, P bo, P di and P do) were collected hourly to estimate DF/BF volumes by semi-empirical methods. Uraemic toxins with various molecular weights were measured pre-dialysis, at 1 h (pre-filter and post-filter) and post-dialysis to calculate molecules' reduction over time and dialyser in vivo clearances. RESULTS: Ultrafiltration was 1.47 ± 0.9 L and Kt/V 1.74 ± 0.3. Hydrodynamic data (P bi: 259 ± 39, P bo: 155 ± 27, P di: 271 ± 30, P do: 145 ± 29 mmHg and oncotic pressure 22.0 ± 3.5 mmHg) allowed the estimation of DF/BF rates. DF flow ranged from 29.5 ± 4.2 to 31.3 ± 3.9 mL/min and BF flow ranged from 25.1 ± 2.3 to 23.4 ± 2.6 mL/min. The highest calculated DF volume was 7506.8 ± 935.3 mL/session. Diffusive clearances (K d) of all solutes were higher than their convective transport (all P < 0.001) except for prolactin (23 kDa) clearances, which showed no differences. Total clearances of all solutes were correlated with their K d (ρ = 0.899-0.987, all P < 0.001) and Kt/V correlated with all reduction rates (ρ = 0.661-0.941, P = 0.010 to <0.001). DF flow was only associated with urea (ρ = -0.793, P = 0.001), creatinine (ρ = -0.675, P = 0.008) and myoglobin clearance (ρ = 0.653, P = 0.011). CONCLUSION: Results suggest that diffusive transport is a main mechanism of MM elimination in HDx. HDx offers an efficient depuration of MM without the need for high convective volumes.

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online / High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration

Antecedentes y objetivo: La hemodiafiltración onine (HDF-OL) con altos volúmenes de transporte convectivo mejora la supervivencia en los pacientes en hemodiálisis. Se ha propuesto limitar el volumen convectivo en los pacientes diabéticos por la carga de glucosa administrada con el líquido de sustitución. El objetivo del estudio fue analizar la influencia del volumen de sustitución en la evolución del perfil metabólico y la composición corporal de los pacientes diabéticos incidentes en HDF-OL. Material y métodos: Estudio observacional prospectivo en 29 pacientes diabéticos incidentes en HDF-OL posdilución. Basalmente se recogieron datos clínicos y demográficos, parámetros analíticos metabólicos, nutricionales e inflamatorios, y la composición corporal por bioimpedancia espectroscópica (BIS). Cada 4 meses se recogieron parámetros analíticos y el volumen de sustitución medio por sesión, y en 23 pacientes se realizó otra BIS al menos un año después. Se calcularon variaciones de hemoglobina glucosilada (HbA1c), triglicéridos, colesterol total, c-LDL, c-HDL, albúmina, prealbúmina y proteína C reactiva (PCR) al año, 2 años, 3 años y al final del seguimiento. Se calcularon las variaciones cuatrimestrales y anuales como periodos independientes, y se analizaron los cambios de composición corporal. Resultados: La edad al inicio fue a los 69,7±13,6 años; el 62,1% eran varones, de 72,3 ± 13,9 kg, 1,78 ± 0,16 m2, y con 48 (35,5-76) meses en diálisis. El 81,5% recibía insulinoterapia, el 7,4% antidiabéticos y el 51,9% estatinas. El volumen de sustitución medio fue de 26,9 ± 2,9L/sesión y el periodo de seguimiento (tiempo en HDF-OL) fue de 40,4 ± 26 meses. Se observó una correlación significativa entre el volumen de sustitución medio y un incremento de los niveles de c-HDL (r = 0,385, p = 0,039) y prealbúmina (r = 0,404, p = 0,003) a lo largo del seguimiento. El volumen convectivo se asoció a la reducción de los niveles de PCR al año (r = -0,531, p = 0,005), a los 2 años (r = -0,463, p = 0,046) y al final del seguimiento (r = -0,498, p = 0,007). Los pacientes con volumen de sustitución >26,9L/sesión tuvieron mayor descenso en los niveles de triglicéridos y PCR, y un aumento de las cifras de c-HDL. Estos pacientes con > 26,9 L/sesión finalizaron el estudio con niveles más altos de c-HDL (48,1 ± 9,4mg/dL vs. 41,2 ± 11,6 mg/dL, p = 0,025) y más bajos de PCR (0,21 [0,1-2,22] mg/dL vs. 1,01 [0,15-6,96] mg/dL, p = 0,001), sin diferencias al inicio.Las comparaciones entre el volumen de sustitución y los cambios analíticos por periodos cuatrimestrales [n = 271] mostraron una correlación significativa con un descenso de HbA1c (r = -0,146, p = 0,021), al igual que las comparaciones por periodos anuales [n=72] (r = -0,237, p = 0,045). Un volumen de sustitución medio anual >26,6L/sesión (29,3 ± 1,7L/sesión vs. 23,9 ± 1,9 L/sesión) se asoció a un descenso de HbA1c (-0,51 ± 1,24% vs. 0,01 ± 0,88%, p = 0,043). No se observó correlación entre el volumen de sustitución y las variaciones en el peso, IMC o parámetros de la BIS.Conclusión: No existe suficiente evidencia para limitar el transporte convectivo en los pacientes diabéticos en HDF-OL por el contenido de glucosa del líquido de sustitución

Background and objective: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.Material and methods: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed. Results: Age at baseline was 69.7±13.6 years, 62.1% were male, 72.3 ± 13.9 kg, 1.78 ± 0.16 m2, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9 ± 2.9L/session and follow-up period (time on OL-HDF) was 40.4 ± 26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r = 0.404, p = 0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r = -0.531, p = 0.005), 2 years (r = -0.463, p = 0.046), and at the end of follow-up (r = -0.498, p = 0.007). Patients with mean substitution volume > 26.9 L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with > 26.9L/session finished the study with higher HDL-c (48.1 ± 9.4 mg/dL vs. 41.2 ± 11.6 mg/dL, p = 0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p = 0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n = 271] showed a significant correlation with a reduction in HbA1c (r = -0.146, p = 0.021). Similar findings were obtained with annual comparisons [n = 72] (r = -0.237, p = 0.045). An annual mean substitution volume over 26.6 L/session (29.3 ± 1.7L/session vs. 23.9 ± 1.9L/session) was associated with a reduction in HbA1c (-0.51 ± 1.24% vs. 0.01 ± 0.88%, p = 0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters.Conclusion: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid