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Problema de salud AUGE N° 64

Prevención de la Progresión de la Enfermedad Renal Crónica

Juicio del Panel y Evidencia

En personas con enfermedad renal crónica (etapa 3 – 4) con anemia, el Ministerio de Salud sugiere utilizar eritropoyetina por sobre no utilizarla (recomendación condicional basada en certeza baja de los efectos).
Comentarios del Panel de Expertos:
►El panel considera que un objetivo ideal de hemoglobina en personas con enfermedad renal puede ser 10 a 13 g/dl.
►Para que la eritropoyetina tenga una mayor efectividad, es necesario que las personas tengan depósitos adecuados de fierro (ferritina > 100 µg/L y saturación de tranferrina mayor a 30%).
►En la actualidad, los costos derivados de la suplementación de eritropoyetina y fierro, así como la falta de disponibilidad de laboratorios para medir la cinética de fierro y ferritina en atención primaria, constituyen una barrera para la implementación de esta recomendación.

El Panel de Expertos analizó y debatió cada uno de las preguntas de la “Tabla de la evidencia a la decisión”, considerando tanto la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes. Una vez consensuada la postura del panel respecto a las preguntas, emitieron un juicio seleccionando la opción de respuesta que mejor representaba la opinión del conjunto (destacada con color). Finalmente cuando el panel emitió su juicio sobre todas las preguntas, se emitió la recomendación.

A continuación se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.

 1.- ¿El problema es una prioridad?
No Probablemente no Probablemente sí Varía No lo sé

El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.

 2.- ¿Qué tan significativos son los efectos deseables anticipados?
Trivial Pequeño Moderado Grande Varía No lo sé

Moderados: El equipo elaborador de la Guía estimó que los efectos deseables de «usar eritropoyetina» en comparación a «no usar» son moderados, considerando la evidencia, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud.

Evidencia de investigación

Eritropoyetina para enfermedad renal crónica etapa con anemia.

Pacientes

Personas con enfermedad renal crónica (etapa 3 – 4) con diagnóstico de anemia secundaria.

Intervención

Eritropoyetina.

Comparación

No usar eritropoyetina.

Desenlaces

Efecto relativo

(IC 95%)

Estudios/

pacientes

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

SIN

eritropoyetina

CON

eritropoyetina

Diferencia

(IC 95%)

Mortalidad

RR 0,60

(0,13 a 2,88)

4 ensayo /182 pacientes

37

por 1000

22

por 1000

Diferencia: 15 menos

(32 menos a 70 más)

⊕⊕◯◯1,2

Baja

Eritropoyetina podría disminuir la mortalidad, pero la certeza de la evidencia es baja.

Progresión a diálisis

El desenlace progresión a diálisis no fue medido o reportado.

Función renal (GFR ml/min)

7 ensayos / 283 pacientes

10 ml/min

8 ml/min

DM: 2 ml/min  menos

(1,15 a 3,08 menos)

⊕⊕◯◯1,2

Baja

Eritropoyetina podría acelerar la progresión de la insuficiencia renal, pero la certeza de la evidencia es baja.

Transfusiones

RR 0,32

(0,12 a 0,83)

3 ensayos / 111 pacientes

260 por 1000

83 por 1000

Diferencia: 177 menos

(44 a 229 menos)

⊕⊕⊕◯1

Moderada

Eritropoyetina probablemente disminuye el riesgo de transfusiones.

Efectos adversos

RR 0,86

(0,28 a 2,59)

4 ensayos / 223 pacientes [ref]

85 por 1000

73 por 1000

Diferencia: 12 menos

(61 menos a 136 más)

⊕◯◯◯1,2

Muy baja

Eritropoyetina podría asociarse a menos efectos adversos. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
DM: Diferencia de medias.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN eritropoyetina está basado en el riesgo del grupo control en los estudios. El riesgo CON eritropoyetina (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
1 Se disminuyó un nivel de certeza de evidencia por riesgo de sesgo, ya que en la mayoría de los ensayos no está clara la generación de secuencia de aleatorización ni ocultamiento de ésta.
2 Se disminuyó un nivel de certeza de evidencia por imprecisión ya que cada extremo del intervalo de confianza conlleva una decisión diferente. En el caso de efectos adversos, el intervalo de confianza es muy amplio.
Fecha de elaboración de la tabla: Octubre, 2018.

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Búsqueda y Síntesis de Evidencia

 3.- ¿Qué tan significativos son los efectos indeseables anticipados?
Grande Moderado Pequeño Trivial Varía No lo sé

Pequeños: El equipo elaborador de la Guía estimó que los efectos indeseables de «usar eritropoyetina» en comparación a «no usar» son pequeños, considerando la evidencia, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud.

Evidencia de investigación

Eritropoyetina para enfermedad renal crónica etapa con anemia.

Pacientes

Personas con enfermedad renal crónica (etapa 3 – 4) con diagnóstico de anemia secundaria.

Intervención

Eritropoyetina.

Comparación

No usar eritropoyetina.

Desenlaces

Efecto relativo

(IC 95%)

Estudios/

pacientes

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

SIN

eritropoyetina

CON

eritropoyetina

Diferencia

(IC 95%)

Mortalidad

RR 0,60

(0,13 a 2,88)

4 ensayo /182 pacientes

37

por 1000

22

por 1000

Diferencia: 15 menos

(32 menos a 70 más)

⊕⊕◯◯1,2

Baja

Eritropoyetina podría disminuir la mortalidad, pero la certeza de la evidencia es baja.

Progresión a diálisis

El desenlace progresión a diálisis no fue medido o reportado.

Función renal (GFR ml/min)

7 ensayos / 283 pacientes

10 ml/min

8 ml/min

DM: 2 ml/min  menos

(1,15 a 3,08 menos)

⊕⊕◯◯1,2

Baja

Eritropoyetina podría acelerar la progresión de la insuficiencia renal, pero la certeza de la evidencia es baja.

Transfusiones

RR 0,32

(0,12 a 0,83)

3 ensayos / 111 pacientes

260 por 1000

83 por 1000

Diferencia: 177 menos

(44 a 229 menos)

⊕⊕⊕◯1

Moderada

Eritropoyetina probablemente disminuye el riesgo de transfusiones.

Efectos adversos

RR 0,86

(0,28 a 2,59)

4 ensayos / 223 pacientes [ref]

85 por 1000

73 por 1000

Diferencia: 12 menos

(61 menos a 136 más)

⊕◯◯◯1,2

Muy baja

Eritropoyetina podría asociarse a menos efectos adversos. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
DM: Diferencia de medias.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN eritropoyetina está basado en el riesgo del grupo control en los estudios. El riesgo CON eritropoyetina (y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
1 Se disminuyó un nivel de certeza de evidencia por riesgo de sesgo, ya que en la mayoría de los ensayos no está clara la generación de secuencia de aleatorización ni ocultamiento de ésta.
2 Se disminuyó un nivel de certeza de evidencia por imprecisión ya que cada extremo del intervalo de confianza conlleva una decisión diferente. En el caso de efectos adversos, el intervalo de confianza es muy amplio.
Fecha de elaboración de la tabla: Octubre, 2018.

Referencia

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Búsqueda y Síntesis de Evidencia

 4.- ¿Cuál es la certeza general de la evidencia sobre efectos?
Muy baja Baja Moderada Alta Ningún estudio incluido

Baja: Existe cierta incertidumbre respecto del efecto de «mantener terapia dual por 1 año» en comparación a «mantener monoterapia por 1 año».

Evidencia de investigación

Desenlaces

Importancia

Certainty of the evidence
(GRADE)

Mortalidad

CRÍTICO

⨁⨁◯◯
BAJA
a,b

Transfusiones

IMPORTANTE

⨁⨁⨁
MODERADO
a

Progresión a diálisis – no reportado

 

Función renal (GFR ml/min)

CRÍTICO

⨁⨁⨁
MODERADO
a

Efectos adversos

IMPORTANTE

◯◯◯
MUY BAJA
a,b

a. Se disminuyó un nivel de certeza de evidencia por riesgo de sesgo, ya que en la mayoría de los ensayos no está clara la generación de secuencia de aleatorización ni ocultamiento de ésta.
b. Se disminuyó un nivel de certeza de evidencia por imprecisión ya que cada extremo del intervalo de confianza conlleva una decisión diferente. En el caso de efectos adversos, el intervalo de confianza es muy amplio.

 5.- ¿Hay incertidumbre importante o variabilidad sobre qué tanto valora la gente los desenlaces principales?
Incertidumbre o variabilidad importantes Posiblemente hay incertidumbre o variabilidad importantes Probablemente no hay incertidumbre ni variabilidad importantes No hay variabilidad o incertidumbre importante

No hay variabilidad o incertidumbre importante: En función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud, el equipo elaborador de la Guía consideró que no existe incertidumbre o variabilidad importante respecto a lo que escogería una persona informada de los efectos deseables e indeseables de «usar eritropoyetina» y «no usar».

Evidencia de investigación

Un estudio prospectivo, multicéntrico, abierto, no aleatorizado incluyó a 1.557 adultos con anemia renal crónica <> sin diálisis para evalura la eficacia y la seguridad de eritropoyetoina en estos pacientes.
Se administró Epoetin alfa 10,000 Us por vía subcutánea una vez por semana durante 16 semanas.
La seguridad y eficacia se evaluaron mediante cambios en la calidad de vida relacionada con la salud (evaluación de escala lineal analógica (LASA) y cuestionario de enfermedad renal (KDQ)
Todos los parámetros de calidad de vida mejoraron significativamente desde el inicio (p <0,0001). Las puntuaciones medias de LASA para energía, actividad y calidad de vida general aumentaron desde el inicio hasta la finalización del estudio El tratamiento con epoetina alfa una vez a la semana fue bien tolerado, similar al reportado con dosis tres veces por semana.

Referencias

Provenzano R, Garcia-Mayol L, Suchinda P, Von Hartitzsch B, Woollen SB, Zabaneh R, et al. Once-weekly epoetin alfa for treating the anemia of chronic kidney disease. Clin Nephrol. 2004 Jun;61(6):392–405.

Búsqueda y Síntesis de Evidencia

 6.- El balance entre efectos deseables e indeseables favorece la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía No lo sé

Favorece la intervención: Considerando que la intervención es «usar eritropoyetina» y la comparación es «no usar», el equipo elaborador de la Guía opinó que el balance entre efectos deseables e indeseables claramente favorece «usar eritropoyetina».

 7.- ¿Qué tan grandes son los recursos necesarios (costos)?
Costos extensos Costos moderados Costos y ahorros despreciables Ahorros moderados Ahorros extensos Varía No lo sé

Costos moderados: El equipo elaborador de la Guía consideró que los costos de «usar eritropoyetina» son moderados si se compara con los costos de «no usar», en función de los antecedentes, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.

Evidencia de investigación

A continuación se muestran los precios referenciales de las prestaciones sanitarias de “usar eritropoyetina y no usar eritropoyetina”, de modo que el equipo elaborador de la Guía se pudiese pronunciar al respecto y no debe ser utilizado para otros fines.

Ítem

Precio Eritropoyetina1

Eritropoyetina Ampolla 2000 UI

$ 1.129 cada ampolla

Eritropoyetina Ampolla 4000 UI

$ 1.790 cada ampolla

El porcentaje de cobertura del seguro de salud sobre el precio de la(s) prestación(es) sanitaria(s), dependerá del tipo de seguro de cada paciente.
Referencias:
1 .Precio promedio compra centralizada CENABAST

Búsqueda y Síntesis de Evidencia

 8.- ¿La costo-efectividad de la intervención beneficia la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía Ningún estudio incluido

Favorece la intervención. Considerando que la intervención es «usar eritropoyetina» y la comparación es «no usar», el equipo elaborador de la Guía opinó que claramente la alternativa más costo-efectiva es «usar eritropoyetina».

Evidencia de investigación

No se realizó la búsqueda de estudios que abordaran la costo-efectividad ya que usar eritropoyetina no es considerado una intervención de alto costo (Anual $2.418.399 y Mensual $201.533).*

Referencia
*Ministerio de Salud – Decreto 80: Determinar umbral nacional de costo anual al que se refiere el artículo 6° de la ley 20.850. Santiago; 2015 Nov

 9.- ¿Cuál sería el impacto en equidad en salud?
Reducido Probablemente reducido Probablemente ningún impacto Probablemente aumentado Aumentado Varía No lo sé

Reducida: El equipo elaborador de la Guía consideró que la equidad en salud se reduciría si se recomendase «usar eritropoyetina», dado que identificó grupos o contextos que actualmente tiene barreras de acceso importantes, ya sea en términos económicos, geográficos u otros.

Consideraciones Adicionales

El panel de expertos considera que en la medida que la eritropoyetina este financiado podria aumentar la equidad.

 10.- ¿La intervención es aceptable para las partes interesadas?
No Probablemente no Probablemente sí Varía No lo sé

Probablemente sí: El equipo elaborador de la Guía consideró que «usar eritropoyetina» probablemente SÍ es aceptable para las partes interesadas (profesionales de la salud, gestores de centros de salud, directivos de centros de salud, pacientes, cuidadores, seguros de salud, otros).

 11.- ¿Es factible implementar la intervención?
No Probablemente no Probablemente sí Varía No lo sé

Probablemente sí: El equipo elaborador de la Guía consideró que «usar eritropoyetina» probablemente SÍ es factible implementar, contemplando la capacidad de la red asistencial, los recursos humanos disponibles a nivel país, recursos financieros, etc.

Consideraciones Adicionales

El panel de expertos informa que en la atención primaria la medición de ferritina y gases venosos no se realiza