Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy / Predictores de eventos clínicos en una cohorte de pacientes con enfermedad de Fabry en tratamiento sustitutivo enzimático

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. Study design: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120). Results: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. (AU)

El objetivo de este estudio es realizar un mapa del tratamiento actual de la enfermedad de Fabry en España, analizando el efecto de diferentes factores en el desarrollo de eventos clínicos a largo plazo. Diseño del estudio: Análisis observacional retrospectivo multicéntrico. Criterios de inclusión: pacientes diagnosticados y tratados de enfermedad de Fabry. Se recogieron datos generales en relación con el diagnóstico, síntomas y tipo mutación, tipo de tratamiento recibido, evolución renal y cardiológica. Durante un tiempo de seguimiento de 60 meses (24-120), se recogió el primer evento clínico tras el inicio de tratamiento sustitutivo enzimático definido como mortalidad, evento renal, cardiológico o neurológico. Resultados: Se incluyeron 69 pacientes (42 H, 27 M) con una edad media de 44,6±13,7 años. A los cinco años de tratamiento, el FGe y la hipertrofia ventricular izquierda se mantuvieron estables, y la albuminuria tiende a disminuir, siendo este descenso más significativo en el grupo de pacientes tratados con beta-galactosidasa (de 242 a 128mg/g (p=0,05). Veintiún pacientes sufrieron un evento clínico (30%): seis renales, dos neurológicos y 13 cardiológicos (incluidas tres muertes). Los pacientes con ERC (FGe<60) antes del inicio de tratamiento tuvieron más eventos (log-rank 12.423, p=0,001), manteniéndose la predicción si excluíamos los eventos renales (log-rank 4.086 (p=0,043) en hombres y mujeres. La peor función renal al inicio del tratamiento aumentó entre tres y siete veces el riesgo de eventos clínicos en diferentes modelos de Cox ajustados. Conclusiones: La función renal al inicio de tratamiento sustitutivo enzimático es la principal predictora de desarrollo de eventos clínicos a largo plazo, tanto en hombres como mujeres. El inicio de tratamiento sustitutivo enzimático precoz antes del desarrollo de ERC mejoraría el pronóstico. (AU)

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Una nueva generación de triacetato de celulosa adecuado para hemodiafiltración on-line / A new generation of cellulose triacetate suitable for online haemodiafiltration

Antecedentes: La hemodiafiltración on-line (HDF-OL) es actualmente la técnica de hemodiálisis (HD) más efectiva y aumenta la supervivencia. Hasta el momento presente las membranas de alta permeabilidad con baja pérdida de albúmina como las de polisulfona, poliamida y poliacrilonitrilo son las más utilizadas. Las membranas de triacetato de celulosa (TAC), limitadas inicialmente para su uso en HDF-OL, han evolucionado. El objetivo del estudio fue determinar si las membranas de nueva generación de TAC asimétrico (TACA) son más adecuadas para realizar alto transporte convectivo. Pacientes y métodos: Se estudiaron 16 pacientes, 10 hombres y 6 mujeres, en programa de HDF-OL. A cada paciente se le realizaron 4 sesiones diferentes, con HD o HDF-OL, o con filtros de TAC o TACA de 1,9 m2, aleatorizando el orden. En cada sesión se determinaron concentración de urea, creatinina, β2-microglobulina, mioglobina, prolactina, α1-microglobulina, α1-glicoproteína ácida y albúmina en suero al inicio y al final de cada sesión, para calcular el porcentaje de reducción. Así mismo, se cuantificó la pérdida de solutos y albúmina en el líquido de diálisis. Resultados: Con las membranas de TACA se consiguió un volumen de sustitución en HDF-OL significativamente superior a las membranas de TAC clásicas (32,1±3,1 vs. 19,7±4,5L; p<0,001). En términos de depuración, la eliminación de moléculas pequeñas fue similar con ambas membranas, pero, en moléculas grandes, con HDF-OL la depuración fue mayor con TACA. En HDF-OL, el porcentaje de reducción de la β2-microglobulina se incrementó un 29%, un 27,7% la mioglobina, un 19,5% la prolactina, un 49% la α1-microglobulina, y se duplicó la α1-glicoproteína ácida (p<0,01 en todas las situaciones). La pérdida de albúmina fue inferior a 2 g en todas las situaciones de estudio. Conclusión: Las membranas de TAC de nueva generación han demostrado ser eficaces para alcanzar los objetivos de HDF-OL, sin que haya una mayor pérdida de albúmina (AU)

Background: Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport. Patients and methods: A total of 16 patients (10 males and 6 females) undergoing OL-HDF were studied. Each patient underwent 4 different sessions, with haemodialysis or OL-HDF, and/or with CTA or asymmetric CTA 1.9 m2 membranes. Each session was assigned in a randomised order. Serum levels of urea, creatinine, β2-microglobulin, myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein and albumin where measured at the beginning and end of each session to obtain the reduction rate. The loss of solutes and albumin was quantified from the dialysate. Results: A significantly greater replacement volume in OL-HDF (32.1±3.1 vs. 19.7±4.5 l, P<.001) was obtained by using asymmetrical CTA membranes compared to conventional CTA membranes. Regarding uraemic toxin removal, both membranes obtained similar results for small molecules, whereas asymmetric CTA membranes achieved better results for large molecules, increasing the reduction ratio by 29% for β2-microglobulin, 27.7% for myoglobin, 19.5% for prolactin, 49% for α1-microglobulin and double for α1-acid glycoprotein (P<0.001 in all situations). The loss of albumin was less than 2g for all treatment sessions. Conclusion: Latest-generation asymmetric CTA have proven to be effective in attaining OL-HDF objectives without increased albumin loss (AU)

A new generation of cellulose triacetate suitable for online haemodiafiltration. / Una nueva generación de triacetato de celulosa adecuado para hemodiafiltración on-line.

BACKGROUND: Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport. PATIENTS AND METHODS: A total of 16 patients (10 males and 6 females) undergoing OL-HDF were studied. Each patient underwent 4 different sessions, with haemodialysis or OL-HDF, and/or with CTA or asymmetric CTA 1.9 m2 membranes. Each session was assigned in a randomised order. Serum levels of urea, creatinine, ß2-microglobulin, myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein and albumin where measured at the beginning and end of each session to obtain the reduction rate. The loss of solutes and albumin was quantified from the dialysate. RESULTS: A significantly greater replacement volume in OL-HDF (32.1±3.1 vs. 19.7±4.5 l, P<.001) was obtained by using asymmetrical CTA membranes compared to conventional CTA membranes. Regarding uraemic toxin removal, both membranes obtained similar results for small molecules, whereas asymmetric CTA membranes achieved better results for large molecules, increasing the reduction ratio by 29% for ß2-microglobulin, 27.7% for myoglobin, 19.5% for prolactin, 49% for α1-microglobulin and double for α1-acid glycoprotein (P<0.001 in all situations). The loss of albumin was less than 2g for all treatment sessions. CONCLUSION: Latest-generation asymmetric CTA have proven to be effective in attaining OL-HDF objectives without increased albumin loss.