Anemia y erc
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Fisiopatologia y tratamiento de la ANEMIA asociada a la Enfermead renal.
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Anemia y erc
- 1. Presentadora: Dra. Silvana Alcalá Ferrara Asesora: Dra. Maria Lara 9/24/2015 1
- 2. 1. Introducción 2. Diagnóstico de Anemia • Definición según K/DOQI – KDIGO- NICE • Estudio de la Anemia: exclusión de otras causas • Evaluación de los depósitos de Hierro 3. Terapia con Hierro • Indicaciones, Dosis, Tipos, Efectos Adversos 4. Agentes Estimulantes de la Eritropoyesis • Indicaciones, Dosis, Tipos, Efectos Adversos, mecanismos de resistencia 5. Coadyuvantes No Férricos • Ac. Ascórbico, Complejo B, Ac. Fólico, Pentoxifilina, Estatinas 6. Nuevas Terapias • Peginesatide 7. Objetivos de Corrección 8. Anemia Y Transplante Renal 9. Conclusiones
- 3. Richard Bright (1836): • 1° en Observar Anemia como complicación de Falla Renal Robert Christison: • Describió la Anemia Renal Goldwasser, Miyake, and Kung (1977): • Identificó y purificó la EPO Joseph Eschbach (1985): • 1° en Aplicar EPO en humanos
- 4. • Anemia Hiporregenerativa. • Normocítica • Normocrómica • M.O: hipoplasia eritroide sin alteraciones de la serie blanca ni plaquetas. 9/24/2015AJKD-MAY 2006
- 5. Todo mayor de15 años o < 13gr/dl o < 12gr/dl 9/24/2015Kidney International Supplements 2012 Entre 12 – 14 años < 12 gr/dl Entre 5 – 11 años < 11,5 gr/dl Entre 0,5 – 4 años < 11 gr/dl
- 6. 9/24/2015Winstrobe´s Clinical Hematology. 2009 • Hemoglobinopatías hereditarias • Sangre Oculta en Heces • Parasitosis Intestinales • Bilirrubina, LDH • Coombs • Déficit de Vit B12 • Déficit de Folato
- 7. 9/24/2015Winstrobe´s Clinical Hematology. 2009 • Fármacos inhibidores de Absorción de Fe+ • Afectación de Médula ósea o Infiltración Neoplásica o Micosis sistémicas o Mielodisplasia • PCR • Aluminio Sérico • Hiperparatiroidismo
- 8. • Aspirado de M.O • Hierro sérico • Ferritina • Transferrina (Capacidad total de Fijación de Hierro) • % Saturación de Transferrina • VCM • HCM • CMHC • Porcentaje de GR hipocrómicos • Reticulocitos Fe+ sérico x 100 Cap. de unión de Fe Winstrobe´s Clinical Hematology. 2009
- 9. • TSAT <20% / ND: Ferritina<100ng/ml / D: Ferritina <200ng/ml • Adultos: TSAT < 30% y Ferritina < 500ng/ml (500 mcg/l) o Que reciben AEE, para disminuir dosis. o En los que no se desee iniciar AEE • Niños: TSAT < 20% y Ferritina < 100ng/ml (100 mcg/l) • Evaluar depósitos de hierro c/3 meses cuando uso de AEE • Evaluación mas frecuente cuando: o Cambia dosis de AEE, o Sospecha perdida de sangre, o Monitoreo de respuesta a hierro, o Otras condiciones de depleción Berns et al., Up-to-date, March 2013 KDIGO Clinical Practice Guideline for Anemia in CKD 2012 INDICACIONES
- 10. Orales Intravenosos 9/24/2015KDIGO 2012 / Coyne et al., JASN, 2007/ Schiesser et al., NDT, 2006 10 • Menor Costo • No Hospital dependiente • Absorción Variable • Efectos Gastrointestinales • Sulfato/Fumarato/Gluconato /Polimaltosado Presentaciones • Mayor Costo • Hospital dependiente • Segura Absorción • Reacciones Adversas mas severas • Mayor respuesta Terap. • Dextrano/Gluconato/Sacarosa
- 12. – HIERRO DEXTRANO 1000 MG DIVIDIDAS EN 10 SESIONES HD 25 A 100 MG/SEMANA REACCION ANAFILACTICA: Hipotensión, sincope, sibilancias, Disnea, Rubor. – GLUCONATO FERRICO DE SODIO HD: 1000 mg DIVIDIDAS EN 8 SESIONES (125 mg DOSIS) Niños: 1-1,5mg/kd/dosis ESCASO EFECTO ADVERSO – Hierro oral Sulfato ferroso Adultos 300 mg 3 veces/día (200mg de Fe elemental/dia) Niños: 2-6mg/kg/día Gastrointestinales: Estreñimiento, Dispepsia, Distensión, Diarrea. Recomendaciones de práctica clínica de la SLANH para el tratamiento de la Anemia en el paciente con ERC Dosis/ Efectos Adversos (Provenzane et al., JASN, 2009) (Schiesser et al., NDT, 2006)
- 13. • Evitar la administración de Hierro Parenteral a pacientes con procesos infecciosos sistemicos activos. • Evitar TSAT > 50% / Ferritina > 800ng/ml (800 mcg/l) 9/24/2015Footer Text 13 Precauciones
- 14. • Fatiga • Dolor Articular. Predominante en manos • Disfunción Erectil • Perdida de Peso • Dolor Abdominal • Palpitaciones 9/24/2015Footer Text 14 Síntomas
- 15. 9/24/2015Footer Text 15 Tratamiento • Deferoxamina • Deferiprone • Deferasirox
- 16. • Adultos ERC-ND: uso con Hb <10g/dl . • Evaluar Hb cada 3 meses • VSC • Adultos ERC-D: Hb<10g/dl • Evaluar Hb mensualmente • Via IV o VSC en HD. VSC en DP • Niños: Mantener Hb entre 11-12 g/dl 9/24/2015KDIGO Anemia 2012 / Jeffery et al., Up-To-date, March 2013 16 INDICACIONES
- 18. VIV VSC 7 19 9 24 25 49 134 137 9/24/2015Footer Text 18
- 19. Henrich et al., Up-To-Date, March 2013 Ventajas de la VSC sobre VIV • Mejoría de relación costo-efectividad • Vida media mas larga • Menor incidencia de HTA • Ideal para pacientes SIN acceso vascular
- 20. • La respuesta varía y depende de: • Respuesta limitada por (Ifudu et al., Am J Kidney Dis, 2000)
- 21. • No se ha demostrado Superioridad de algún AEE sobre otro. • Cualquiera, AEE de acción corta o larga pueden ser usados siendo elegidos según su disponibilidad, costo, personal médico y paciente Berns et al., Up-To-Date, March 2013/ KDIGO guidelines for Anemia 2012
- 22. Monitoreo durante tratamiento Monitoreo mensual con ajuste de dosis si es requerido Incremento ideal Hb 1 a 2 g/dl/mes Aumento < 1 g/dl = aumentar AEE 50% Aumento > 2 g/dl = Disminuir AEE 50% o cesar uso 9/24/2015Footer Text 22
- 23. Conversión de AEE de acción corta la AEE Larga 9/24/2015Footer Text 23
- 24. • No usar 13 de rutina para mantener Hb > 11,5 g/dl • No usarse intencionalmente para mantener hb > 13gr/dl • Evitar aumento de Hb > 2g/dl por Mes • Paciente con antecedentes oncológicos, ECV. 9/24/2015Footer Text 24 PRECAUCIONES
- 25. Objetivos de Hemoglobina • CREATE, 2006 Europa: epoetin beta. ERC-ND o no diferencias en regresion de VI, mortalidad CV. o Mayor mejoria de calidad de vida en grupo de Hb elevada • CHOIR, 2006 Norte america: Epoetin alfa ERC-ND o Normalización de la Hb se asocia a un incremento del riesgo de eventos cardiovasculares • TREAT, 2009:ERC-ND por DM placebo vs dabapoetina. o Mayor riesgo de ictus • Normal Hct trial 2012. epoetin alfa o ERC-HD + IC y/o Cardiopatía isquémica o Mayor mortalidad cardiovascular y trombosis de acceso venoso 9/24/2015Footer Text 25
- 26. 9/24/2015Footer Text 26 Mecanismos de resistencia
- 27. • No aumento de Hb con respecto a basal luego de un mes. • Evitar aumentos escalonados repetitivos mas allá del doble de la dosis inicial según el peso (KDIGO, Kidney Int, 2012) HIPORESPUESTA
- 28. 1. Hipertensión Arterial Etiología • 20-30% • Altas dosis de AEE • Historia Personal de HTA • Disminución de producción de Oxido Nítrico • Aumento de calcio intracitosólico • Aumento de la sensibilidad vascular alfaadrenérgica • Activación del sistema RAA • Tromboxano / prostaciclina elevadas en tejido vascular (Kraphfet al., CJASN, 2009)
- 29. 1. Hipertensión Arterial Prevención y Tratamiento • Monitoreo Cercano • Aumento lento de Hto • Objetivo de Hb entre 10-11g/dl • Remoción de Volumen • Anti Hipertensivos: Betabloqueantes, vasodilatadores, calcioantagonistas, IECAs (Novak et al., Pharmaco Therapy, 2003)
- 30. 2. Aplasia Pura de Glóbulos Rojos • No frecuente • Suero de Pacientes inhiben crecimiento de células progrenitoras Eritroides en cultivos de MO • IgG contra EPO exógena tiene reacción cruzada contra EPO endógena • Polysorbato como agente estabilizante. • Almacenamiento y/o manejo inadecuado (Hermeling et al., Pharm Res, 2003)
- 31. Diagnóstico • Descenso de Hb 0.5-1 g/dl/semana. • Plaquetas y Leucocitos normales • Transferrina y Ferritina elevadas. (Casadevall et al., Eur J Haematol, 2004) Aplasia Pura de Glóbulos Rojos
- 32. Aplasia Pura de Glóbulos Rojos Tratamiento • Transfusiones para anemia sintomática • Descontinuar AEE • Inmunosupresión o Metilprednisolona, Ciclofosfamida, Rituximab • Reinstauración de AEE puede llevar a anafilaxia, o Tolerancia en pacientes con bajos titulos AntiEpo • Sustituir AEE por Peginesatide Rossert et al., NDT, 2005/Praditpornsilpa, et al Clinc Nephrl 2012
- 33. • L-carnitina: Mecanismo desconocido (Hothi et al., NDT, 2006) • Vitamina C: Aumenta la liberación de Fe+ desde Ferritina. Riesgo de oxalosis (Sirover et al., Ren Fail, 2008) • Pentoxifilina: Beneficios en Anemia resistente a EPO. (Cooper et al., JASN, 2004) • Estatinas: Efecto antiinflamatorio y antioxidante (Chiang et al., Am J Nephrol, 2009) • No recomendados (KDOQI, Am J Kidney Dis, 2006/ KDIGO 2012 ) • La vitamina B12 y el ácido fólico deben ser utilizados rutinariamente en los pacientes ERC-HD SLANH, 2009/ Hörl WH. NDT, 2002
- 34. • Elevación exitosa de Hb • Evitar mientras sea posible, • Uso según en la clínica • Complicaciones (Berns et al., Up-To-Date, 2013)/KDIGO 2012
- 35. • Péptido sintético estructuralmente diferente a EPO que activa su receptor. • EMERALD I y II compararon peginesatide Vs AEEs en 1418 Pacientes ERC-D con seguimiento de 52 semanas. o Seguridad cardiovascular similar o No inferior para mantener Hb (Fishbane et al., NEJM, 2013) Peginesatide
- 36. • PEARL I y II en ERC-ND o Aumento de eventos CV con peginesatide. • FDA : uso en paciente en diálisis • Retirado del mercado debido a serias reacciones de hipersensibilidad. 0.2% incluso muerte en 0.02%. Peginesatide Valliant and Hofmann. International Journal of Nanomedicine. Ago 2013/ Berns et al., Up-To-Date, March 2013
- 37. • Común • Frecuentemente Subtratada • Incidencia 40% al año del transplante. • Receptores de Transplante que reinician dialisis tienen hemoglobina mas baja en comparación con ERC no transplantados (8.9 Vs 10.2 gm/dl). • En general, la anemia es un marcador de mala evolución, en relación con una mala función renal (Arias et al., Kidney Int, 2002)/Sociedad Española de Trasplante
- 38. Postrasplante inmediato 6-12 meses > 12 meses • Anemia Pretrasplante • Cirugía • Funcion retardada del injerto • Suspención de AEE • Rechazo del Injerto • Inmunosupresión • Edad del Donante • Función Renal • Extraciones Sanguineas • Inmunosupresión • Función del Injerto • IECA/ARAII • Inflamación • Inmunosupresión
- 39. Factores de Riesgo • Género Femenino. • Raza no blanca. • Hipoalbuminemia. • Receptor menor de 45años. • Donante Mayor de 60 años (Shah et al., Transplantation, 2006)
- 40. • Antimetabolitos (Aza, MMF, MPS) Causan supresión medular (Imaogene-Dyedeji et al., JASN, 2006) • SIR causa anemia tempranamente, pero ese efecto aminora a traves del tiempo. (Fishbane et al., Kidney Int, 2009) • CNIs no causan supresión medular. • SIR + CNIs puede causar anemia, HUS. (Kim et al., Transplant Proc, 2003)
- 41. Tratamiento • AEE si Hb menor a 10 gm/dl. • Transfusiones son una preocupación. • mantener Hb 10-12 gm/dl. • Monitoreo estricto de la presión arterial • El paciente trasplantado debe seguir las mismas recomendaciones que se aplican en pacientes renales no trasplantados (Mehrotra et al., JASN, 2012)/Sociedad Española de Trasplante
- 42. • Para los pacientes en ERC, los valores de hemoglobina, dosis de AEE, dosis de Hierro, en el cual exista balance óptimo entre el beneficio clínico y los riesgos potenciales no son conocidos, por lo cual la prescripción y fijación de objetivos es complicada y debe ser indivisualizada según las caracteristicas de cada paciente. 9/24/2015Footer Text 42
- 43. 9/24/2015Footer Text 43 Gracias!! La Paz, por encima de todas las cosas, debe ser deseada, pero la Sangre a veces debe ser derramada para obtenerla en términos ecuánimes y duraderos. Andrew Jackson
Editor's Notes
- Reducción de la masa Eritroide. Anemia Hiporregenerativa. Reducción tasa de generacón de la masa Eritroide. Sin alteración en el volumen: Normocitica. Sin alteración de la hemoglobina corpuscular: Normocròmica. Distribución Eritrocitaria normal. Espiculaciones en la membrana del eritrocito. La Medula Ósea: hipoplasia eritroide sin alteraciones de la serie blanca ni plaquetas.
- Hierro: 60 a 170 mcg/dL TIBC: 240 a 450 mcg/dL Saturación de transferrina: 20-50% Ferritina 30-300ng/ml
- Hierro: 60 a 170 mcg/dL TIBC: 240 a 450 mcg/dL Saturación de transferrina: 20-50% Ferritina 30-300ng/ml The two most widely available tests for assessing iron status are the TSAT and serum ferritin level. A very low serum ferritin (o30 ng/ml [o30 mg/l]) is indicative of iron deficiency.16 Except in this circumstance, the TSAT and serum ferritin level have only limited sensitivity. Carencia real absoluta de hierro: hierro serico bajo, ferritina baja, transferrina alta, saturación baja Functional Iron deficiency: respond to iron therapy. Adequate iron stores with inability to mobilize to support erythropoiesis. Inflammatory Iron block: does not respond to iron therapy. Occurs in patients with refractory anemia due to underlying inflammatory state. Hierro serico bajo, transferrina baja (su produccion es inhibida en estados inflamatorios), saturación normal o alta. Ferritina normal o aumentada (Bernz et al., Up-to-date, March 2013)
- Déficit de Fe+ es causa de no respuesta a EPO In patients with CKD-associated anemia, iron supplementation is intended to assure adequate iron stores for erythropoiesis, correct iron deficiency, and, in patients receiving ESA treatment, prevent iron deficiency from developing. Iron supplementation, particularly with intravenous iron, can enhance erythropoiesis and raise Hb levels in CKD patients with anemia even when TSAT and ferritin levels are not indicative of absolute iron deficiency, and even when bone marrow studies reveal adequate iron stores.38–40 Iron treatment, particularly when administered intravenously, has also been consistently demonstrated to improve the erythropoietic response to ESA treatment. For any individual patient the optimal balance of Hb level, ESA dose, and iron dose at which clinical benefit is maximized and potential risk is minimized is not known. Prescribing iron therapy for CKD patients is complicated by the relatively poor diagnostic utility of serum ferritin and TSAT tests to estimate body iron stores or for predicting a Hb response to iron supplementation.23,30 Even examination of bone marrow iron stores, considered the ‘gold standard’ for assessment of iron stores, does not predict erythropoietic responsiveness to iron supplementation in patients with CKD with a high degree of accuracy. Most CKD patients with serum ferritin levels 4100 ng/ml (4100 mg/l) have normal bone marrow iron stores,16–21 yet many such patients will also have an increase in Hb concentration and/or reduction in ESA dose if supplemental iron is provided
- The need to consider trends in iron status tests are highlighted by consideration of a patient with decreasing TSAT and ferritin levels which may signify the presence of gastrointestinal bleeding or excessive dialysis-associated blood loss. As another example, an increasing TSAT and ferritin level may indicate excessive iron supplementation and a need to decrease or discontinue iron administration. Finally, an increase in ferritin level accompanied by a decrease in TSAT and Hb level suggests inflammation-mediated reticuloendothelial blockade
- IV iron may be provided as a single large dose or as repeated smaller doses depending on the specific IV iron preparation used (with the highest single dose varying by specific formulation). It is common practice to provide an initial course of IV iron amounting to approximately 1000 mg; this may be repeated if an initial dose fails to increase Hb level and/or allow a decrease in ESA dose and if the TSAT remains r30% and serum ferritin remains r500 ng/ml (r500 mg/l). In patients with Hb below the desired level who are receiving relatively high ESA doses, or in whom discontinuation of ESA therapy is preferred (for instance a CKD patient with malignancy), a therapeutic trial of additional IV iron (i.e., a single course of up to 1000 mg over a period of several weeks which can be repeated as needed) may be undertaken in patients with serum ferritin levels 4500 ng/ml (4500 mg/l) after due consideration of potential acute toxicities and long-term risks . Serum ferritin and TSAT levels should not be measured until at least one week has elapsed since the most recent prior IV iron dose. Oral iron is typically prescribed to provide approximately 200 mg of elemental iron daily (for instance ferrous sulfate 325 mg three times daily; each pill provides 65 mg elemental iron). The suggestion for oral iron supplementation in children is 2–6 mg/kg/day of elemental iron in 2–3 divided doses.he recommendation for initial ferric gluconate therapy is 1.5 mg/kg for eight doses for irondeficient pediatric CKD 5HD patients and 1 mg/kg per week for iron-replete pediatric CKD 5HD patients, with subsequent dose adjustments made according to TSAT and/or ferritin levels. SLANH: 300mg/semana luego 20mmg/mensual
- Iron is essential for the growth and proliferation of most pathogens including many bacteria, viruses, fungi, parasites and helminthes, and also exerts subtle effects on immune function and host responses towards microbes.97 There is theoretical and experimental evidence to suggest that iron administration may worsen an existing infection but clinical evidence is lacking. In animal models, iron overload results in an impaired control of infections, specifically with intracellular bacteria or fungi.98–101 In humans, tissue iron overload has been considered as a risk factor for the acquisition of certain infections and for an unfavorable clinical course of the infection. Data in CKD patients are conflicting.102–104 Since current evidence cannot provide a clear answer as to whether specific CKD patient groups are at increased risk for infection, or of having a poorer outcome with infection when anemia is treated with IV iron, the Work Group suggests that IV iron not be administered when patients have an active systemic infection.
- Box 1 Primary (hereditary) hemochromatosis is due to an inherited defect of iron metabolism. Secondary hemochromatosis is almost always due to a hereditary or acquired disorder of erythropoiesis and/or the treatment of such a disorder with blood transfusions. Go to: Iron overloading due to blood transfusions The most important cause of secondary hemochromatosis is chronic transfusion therapy. Every unit of erythrocytes that is transfused contains about 200 to 250 mg of iron as a component of the red heme pigment (box 2). When the erythrocytes are broken down by the macrophage system, iron is freed from heme and stored in the body. As the normal daily loss of iron in sweat and in shed cutaneous and mucosal epithelial cells is only about 1 mg, a single unit of erythrocytes corresponds to about 200 daily rations of iron. Because excess iron cannot be eliminated from the body, it necessarily follows that chronic transfusion therapy brings the body’s iron balance very far out of equilibrium. Box 2 Calculation of iron balance in transfusion therapy (example) Donated blood contains about 0.5 mg iron per mL erythrocyte concentrate. A 400 mL unit of donated erythrocytes contains about 200 mg of iron. Transfusion of 100 units therefore involves loading with 20 g of iron. Total body iron is normally 3 to 4 g. Go to: Clinical consequences The clinical and pathological findings of iron overload in secondary hemochromatosis are similar to those seen in hereditary hemochromatosis. Hepatomegaly and splenomegaly may be present, the latter due to increased sequestration of erythrocytes in the spleen. Hepatic function is usually still normal, or only mildly impaired, at the time of diagnosis. Patients with thalassemia often develop finely nodular hepatic cirrhosis three or four decades into the course of their illness. Further consequences of iron overload include decreased glucose tolerance or overt diabetes mellitus, as well as cardiac arrhythmias and heart failure (1). Patients with MDS may have such a short life expectancy because of their bone marrow disease that certain consequences of iron overload, such as hepatic cirrhosis, do not have time to become severe. Go to: The pathophysiology of iron toxicity The dictum "Only the dose keeps any substance from being a poison" (Paracelsus) is true of iron as well. Its toxicity in high doses comes from its ability to react with molecular oxygen, transferring electrons to it to create intermediate oxygen species, which, in turn, in the presence of iron, cause yet other highly reactive radicals to come into being. These can then attack lipids, proteins, and DNA, inducing cellular damage that ultimately becomes clinically manifest as organ dysfunction. Iron is not dangerous if it is held in the storage molecule ferritin or bound to the transport protein transferrin. Once the storage and transport capacities of these molecules are exceeded, however, non-transferrin-bound iron (NTBI) begins to appear in the blood plasma. The redox-reactive part of NTBI, known as labile plasma iron (LPI), is rapidly taken up into cells by endocytosis. When the intracellular pool of LPI becomes too large, it can no longer be disposed of by the cell’s antioxidative mechanisms, and the formation of radicals ensues. Go to: Diseases causing secondary hemochromatosis The spectrum of iron-loading anemias encompasses both hereditary and acquired disorders of erythropoiesis. The congenital diseases in this category include the various types of thalassemia as well as sickle-cell anemia, pyruvate kinase deficiency, the various types of congenital dyserythropoietic anemia (CDA), hereditary spherocytosis, and X-linked sideroblastic anemia (XLSA) (box 3). Iron overloading is especially severe in homozygous ß-thalassemia.
- Box 1 Primary (hereditary) hemochromatosis is due to an inherited defect of iron metabolism. Secondary hemochromatosis is almost always due to a hereditary or acquired disorder of erythropoiesis and/or the treatment of such a disorder with blood transfusions. Go to: Iron overloading due to blood transfusions The most important cause of secondary hemochromatosis is chronic transfusion therapy. Every unit of erythrocytes that is transfused contains about 200 to 250 mg of iron as a component of the red heme pigment (box 2). When the erythrocytes are broken down by the macrophage system, iron is freed from heme and stored in the body. As the normal daily loss of iron in sweat and in shed cutaneous and mucosal epithelial cells is only about 1 mg, a single unit of erythrocytes corresponds to about 200 daily rations of iron. Because excess iron cannot be eliminated from the body, it necessarily follows that chronic transfusion therapy brings the body’s iron balance very far out of equilibrium. Box 2 Calculation of iron balance in transfusion therapy (example) Donated blood contains about 0.5 mg iron per mL erythrocyte concentrate. A 400 mL unit of donated erythrocytes contains about 200 mg of iron. Transfusion of 100 units therefore involves loading with 20 g of iron. Total body iron is normally 3 to 4 g. Go to: Clinical consequences The clinical and pathological findings of iron overload in secondary hemochromatosis are similar to those seen in hereditary hemochromatosis. Hepatomegaly and splenomegaly may be present, the latter due to increased sequestration of erythrocytes in the spleen. Hepatic function is usually still normal, or only mildly impaired, at the time of diagnosis. Patients with thalassemia often develop finely nodular hepatic cirrhosis three or four decades into the course of their illness. Further consequences of iron overload include decreased glucose tolerance or overt diabetes mellitus, as well as cardiac arrhythmias and heart failure (1). Patients with MDS may have such a short life expectancy because of their bone marrow disease that certain consequences of iron overload, such as hepatic cirrhosis, do not have time to become severe. Go to: The pathophysiology of iron toxicity The dictum "Only the dose keeps any substance from being a poison" (Paracelsus) is true of iron as well. Its toxicity in high doses comes from its ability to react with molecular oxygen, transferring electrons to it to create intermediate oxygen species, which, in turn, in the presence of iron, cause yet other highly reactive radicals to come into being. These can then attack lipids, proteins, and DNA, inducing cellular damage that ultimately becomes clinically manifest as organ dysfunction. Iron is not dangerous if it is held in the storage molecule ferritin or bound to the transport protein transferrin. Once the storage and transport capacities of these molecules are exceeded, however, non-transferrin-bound iron (NTBI) begins to appear in the blood plasma. The redox-reactive part of NTBI, known as labile plasma iron (LPI), is rapidly taken up into cells by endocytosis. When the intracellular pool of LPI becomes too large, it can no longer be disposed of by the cell’s antioxidative mechanisms, and the formation of radicals ensues. Go to: Diseases causing secondary hemochromatosis The spectrum of iron-loading anemias encompasses both hereditary and acquired disorders of erythropoiesis. The congenital diseases in this category include the various types of thalassemia as well as sickle-cell anemia, pyruvate kinase deficiency, the various types of congenital dyserythropoietic anemia (CDA), hereditary spherocytosis, and X-linked sideroblastic anemia (XLSA) (box 3). Iron overloading is especially severe in homozygous ß-thalassemia.
- Evaluar todas las posibles causas de anemia previo al inicio de AEE Adultos ERC-ND: uso con Hb <10g/dl dependiendo de necesidad de transfusión, síntomas atribuibles a anemia, estado férrico Evaluate iron states and correct deficiency. Search for treatable causes (hemolysis, nutritional deficiency as B12, folate). The minimum interval between ESA dose adjustments is 2 weeks because the effect of most dose changes will not be seen within a shorter interval. In anemic children with CKD there are no RCTs examining the effects of ESA administration on hard outcomes. Therefore, any suggestion for Hb targets in this subgroup of CKD patients has to rely on results obtained in the adult CKD patient population and on clinical experience in the pediatric setting. The upper and lower Hb targets are opinion-based, in keeping with the lack of pediatric specific evidence. There are a number of factors unique to children that make exclusive reliance on evidence in adults inappropriate such as age-specific variation of normal Hb concentrations as well as QoL, growth, developmental, and psychological differences between children and adults.58 Limited data suggest that children with CKD and a Hb less than 9.9 g/dl (99 g/l) are at increased risk for mortality,139 left ventricular hypertrophy,140,141 and/or decreased exercise capacity142 compared to those with a Hb greater than 9.9 g/dl (99 g/l). When evaluated as a continuous variable, hematocrit (Hct) was linked directly to measures of improved health and physical functioning in a health based QoL questionnaire administered to a pediatric CKD population
- Alfa y Beta[editar] Las dos primeras versiones del fármaco fueron la epoetina alfa y epoetina beta. Ambas son comercializadas por la empresa farmacéutica estadounidense Amgen. Aunque ambas variantes tienen una farmacocinética similar, la epoetina beta tienen una metabolización más lenta, llegando a necesitar en caso de utilizarse la vía intravenosahasta un 20% más de tiempo que la epoetina alfa para su eliminación total del organismo (la diferencia es menor cuando se utiliza la vía subcutánea).1 Así, la vida media de la epoetina en el organismo es de 6-8 horas, en contraste con las ESAs de generaciones posteriores, con una vida media significativamente mayor.2 Delta (Dynepo)[editar] Existe también una versión posterior, la epoetina delta (Dynepo). Esta sustancia activa el gen de la eritropoyetina, y al contrario de las versiones anteriores (producidas por células de animales) es producida por células humanas. Darbepoetina alfa es un fármaco estimulador de la eritropoyesis (ESA) de segunda generación; se trata de la versión sintética (recombinante) de la eritropoyetina (EPO), unahormona humana natural producida por los riñones. La darbepoetina, igual que su equivalente natural (EPO), estimula la eritropoyesis, es decir, la producción de eritrocitos(también llamados glóbulos rojos o hematíes). Se produce por tecnología ADN recombinante en células de hamster chinos, y se diferencia de la eritropoyetina natural en que contiene dos cadenas más de oligosacaridos. Laproteína está formada por 165 aminoácidos. Su vida media en el organismo es de unas 26 horas, en contraste con las 6-8 horas de vida media de las distintas epoetinas (ESA de primera generación). La Farmacocinética de la Darbepoetina es más compleja y más larga que la EPO normal, porque en su estructura hay cinco cadenas de carbohidratos unidas por un grupo amida y hay mucha mas siaoproteina. Esto permite una mejor administración de medicamento en los enfermos de insuficiencia renal crónica.
- Differentiating factors between erythropoiesis-stimulating agents: a guide to selection for anaemia of chronic kidney disease. Deicher R1, Hörl WH. Author information Abstract Endogenous erythropoietin (EPO) consists of a central polypeptide core covered by post-translationally linked carbohydrates. Three of the four currently available erythropoiesis stimulating agents (ESA)--epoetin-alpha, epoetin-beta and epoetin-omega- are composed of an identical amino acid sequence, but glycosylation varies as a result of type- and host cell-specific differences in the production process. Epoetin-alpha and epoetin-beta resemble each other with respect to molecular characteristics and pharmacokinetic data, although epoetin-beta has a higher molecular weight, a lower number of sialylated glycan residues and possibly slight pharmacokinetic advantages such as a longer terminal elimination half-life. A serious adverse effect of long-term administration of ESA is pure red cell aplasia. This effect has been observed predominantly with subcutaneous use of epoetin-alpha produced outside the US after albumin was removed from the formulation. In comparison with the intravenous route, subcutaneous administration of epoetin has been reported to have a dose-sparing effect in some studies. Epoetin-beta has been the subject of studies aimed at proving efficacy with a reduced administration frequency but results are not unequivocal. Epoetin-omega is produced in a different host cell than all other erythropoietic agents, hence glycosylation and pharmacokinetics are different. Small-scale clinical studies found epoetin-omega to be slightly more potent than epoetin-alpha. Epoetin-delta is a recently approved agent produced by human cells that are genetically engineered to transcribe and translate the EPO gene under the control of a newly introduced regulatory DNA sequence. However, epoetin-delta is not yet on the market and few data are available. The erythropoietin analogue darbepoetin-alpha carries two additional glycosylation sites that permit a higher degree of glycosylation. Consequently, in comparison with the other epoetins, darbepoetin-alpha has a longer serum half-life and a higher relative potency, which further increases with extension of the administration interval. Dosage requirements of darbepoetin-alpha do not appear to differ between the intravenous and subcutaneous routes of administration. The less frequent administration of darbepoetin-alpha in comparison to the other epoetins may reduce drug costs in the long term, but the variability in dosage or dosage frequency required within a single patient is high. Further studies should be aimed at defining predictors of the individual demand for erythropoietic agents, thereby allowing nephrologists to prescribe a cost-effective, individualised regimen.
- Ventajas de la VSC sobre VIV Mejoría de costo-efectividad Vida media mas larga Menor incidencia de HTA Ideal para pacientes SIN acceso vascular
- Sexo femenino, Obesidad, ECV aumenta resesistencia La Respuesta depende de la frecuencia y ruta de administración. Con la VSC, la frecuencia no es tan importante como con VIV Respuesta puede estar limitada por bajas reservas de hierro, fibrosis medular, infecciones y dialisis inadecuada
- Other Studies: PATRONUS study: IVMIRCERA Vs IVdarbepoetin alfa. (Carrera et al., NDT, 2010) Mircera superior efectividad 1 dosis mensual que darbapoetina 1 vez mensual CORDATUS study: CERA/Month. Vs Dabapoetina. Igual de eficaz menos riesgo de sobrepasar niveles optimos (Roger et al., NDT, 2011) CAPRI study: CERA/M for PD patients. (Gonzalez et al., Ren Fail, 2013)
- When converting a patient from one ESA to another the pharmacokinetic and pharmacodynamic characteristics of the new ESA need to be taken into consideration. The manufacturers have provided conversions from epoetinalfa or epoetin-beta to darbepoetin-alfa or CERA. Note that the conversion ratios from epoetin to darbepoetin are non-linear.
- When converting a patient from one ESA to another the pharmacokinetic and pharmacodynamic characteristics of the new ESA need to be taken into consideration. The manufacturers have provided conversions from epoetinalfa or epoetin-beta to darbepoetin-alfa or CERA. Note that the conversion ratios from epoetin to darbepoetin are non-linear.
- In anemic children with CKD there are no RCTs examining the effects of ESA administration on hard outcomes. Therefore, any suggestion for Hb targets in this subgroup of CKD patients has to rely on results obtained in the adult CKD patient population and on clinical experience in the pediatric setting. The upper and lower Hb targets are opinion-based, in keeping with the lack of pediatric specific evidence. There are a number of factors unique to children that make exclusive reliance on evidence in adults inappropriate such as age-specific variation of normal Hb concentrations as well as QoL, growth, developmental, and psychological differences between children and adults.58 Limited data suggest that children with CKD and a Hb less than 9.9 g/dl (99 g/l) are at increased risk for mortality,139 left ventricular hypertrophy,140,141 and/or decreased exercise capacity142 compared to those with a Hb greater than 9.9 g/dl (99 g/l). When evaluated as a continuous variable, hematocrit (Hct) was linked directly to measures of improved health and physical functioning in a health based QoL questionnaire administered to a pediatric CKD population Higher target is associated with increased risks for: Stroke (RR 1.5, 95% CI 1.03-2.21). Hypertension (RR 1.67, 95% CI 1.31-2.12). Vascular thrombosis (RR 1.33, 95% CI 1.16-1.53). (Palmer et al., Ann Intern Med, 2010)
- Cardiovascular Risk Reduction in Early Anemia Treatment with Epoetin Beta (CREATE, 2006) and Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR,2006) trials to present their findings, which, according to meeting organizers, have important medical and policy implications for all nephrologists (Drüeke TB et al. N Engl J Med. 2006;355:2071-2084. Singh AK et al. N Engl J Med. 2006;355:2085-2098). The studies showed no cardiovascular benefit from treating predialysis patients to normal hemoglobin levels observed in healthy individuals, and they reinforce the need to treat to "subnormal" hemoglobin levels as indicated in current treatment guidelines. This message was reiterated in the FDA alert that followed the publication of the CHOIR results CREATE, 2006 europa: epoetin beta. no diferencias en regresion de VI, mortalidad CV. Mayor mejoria de calidad de vida en grupo de hemoglobina elevada CHOIR, 2006 Norte amercica: pacientes no dialisis. normalización de la Hb se asocia a un incremento del riesgo de eventos cardiovasculares TREAT, 2009:pacientes diabeticos no dialisis. placebo vs dabapoetina. Mayor riesgo de ictus Normal hematocrit trial 2012. epoetin alfa pacientes con insuficiencia cardiaca y cardiopatia isquemica. Mayor mortalidad cardiovascular y trombosis de acceso venoso
- Deficiencia absoluta o funcional de hierro Inflamación/malnutrición Infecciones Pérdidas crónicas de sangre Hiperparatiroidismo Intoxicación por aluminio Hemoglobinopatías (talasemia, drepanocitosis) Deficiencia de ácido fólico o vitamina B12 Neoplasias, quimioterapia o radioterapia Mieloma múltiple Hemólisis Fármacos (IECAs, inmunosupresores, citotóxicos)
- No aumento de Hb con respecto a basal luego de un mes de tratamiento con dosis adecuada para su peso En pacientes con hiporespuesta evitar aumentos escalonados repetitivos mas allá del doble de la dosis inicial segun el peso
- Almacenamiento y/o manejo inadecuado (exposición a altas temperaturas) puede promover respuesta inmune
- Descenso de Hb 0.5-1 g/dl/semana. Requerimiento transfusional semanal. Cuenta de reticulocitos disminuida. (menor a 10,000 mm3) Anticuerpos Anti EPO Plaquetas y Leucocitos normales Transferrina y Ferritina elevadas. Reacción Urticarial en sitios de administración de EPO
- Objective is to: Enhance EPO response. Reduce the economic impact. Address EPO hyporesponsiveness. (Berns et al., Up-To-Date, March 2013) Oxalosis Enfermedad enzimática de transmisión hereditaria que produce un acúmulo de oxalato en las vísceras y en el riñón. Se manifiesta por una nefrocalcinosis y una litiasis renal que, con el tiempo, evoluciona hacia una insuficiencia renal.
- No Usar para un valor de Hb determinado Disminución de Sintomas Mejoría de la calidad de vida Complicaciones Sensibilización inmunológica Sobrecarga de hierro Sobrecarga de volumen. Reacciones de hipersensibilidad Transmisión de Infecciones
- Estudios fase III
- Peace, above all things, is to be desired, but blood must sometimes be spilled to obtain it on equable and lasting terms. Andrew Jackson Age does not protect you from love. But love, to some extent, protects you from age. Anais Nin Change your opinions, keep to your principles; change your leaves, keep intact your roots. Victor Hugo Read more at http://www.brainyquote.com/quotes/authors/v/victor_hugo.html#qWspqp5AZ2jAZFVh.99 Read more at http://www.brainyquote.com/quotes/keywords/blood_2.html#YZViOeLWdkfHJpUU.99
- Hierro e infecciones, hierro presentaciones comerciales, cambio a MICera
- La elevación del hematocrito también se en el 10-15% de los pacientes que recibieron un trasplante renal, luego de transcurridos 24 meses. Este aumento tiene una multitud de causas , y se asocia con una gran morbilidad. Una revisión de 53 casos de eritrocitosis posterior al trasplante renal reportó un incremento de los eventos tromboembólicos (18,9%) comparado con receptores de trasplante renal sin hematocrito elevado (0 %), aunque este resultado no coincide con todos los estudios. Ensayos aleatorizados prospectivos demuestran que estos pacientes suelen responder bien a los inhibidores de la enzima convertidora de angiotensina o a los bloqueantes de los receptores de angiotensina, lo que lleva a una reducción del hematocrito dentro de los 3 meses. En estos se deben tomar medidas para evitar la deshidratación, como el uso prudencial de los diuréticos y la rehidratación en caso de diarrea o vómitos. Los pacientes que no responden a los inhibidores de la enzima convertidora de angiotensina o la bloqueantes de los receptores de angiotensina pueden ser tratados mediante una flebotomía para descender el hematocrito a menos de 0,45, pero en este caso, la deficiencia de hierro se puede convertir en un problema. Como sucede en todos los casos de eritrocitosis, se puede hacer tratamiento de reemplazo del hierro en forma cautelosa , pero hematocrito debe ser estrechamente supervisado