Journal Information
Vol. 29. Issue. S1.March 2009
Pages 1-77
Vol. 29. Issue. S1.March 2009
Pages 1-77
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MANAGING ANAEMIA IN KIDNEY TRANSPLANT PATIENTS WITH CHRONIC KIDNEY DISEASE
Manejo de la anemia en la enfermedad renal crónica del paciente trasplantado renal
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María Ovidia López Olivaa, Domingo del Castillo Cabab, Gema Fernández Fresnedoc
a Servicio de Nefrología, Hospital La Paz, Madrid, Madrid, España,
b Servicio de Nefrología, Hospital Reina Sofía, Córdoba, Córdoba, España,
c Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander, Santander, España,
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Definición: La definición de anemia más extendida es la establecida por la Organización Mundial de la Salud y que posteriormente fue adoptada por la Sociedad Americana de Trasplantes, que define como anemia la concentración de hemoglobina <12 g/dl en mujeres y <13 g/dl en varones. Prevalencia de anemia postrasplante: Varía a lo largo del período postrasplante y se asocia con el grado de función del injerto renal. La relación entre niveles de hemoglobina y filtrado glomerular no se comporta de la misma manera que en la población con enfermedad renal crónica (ERC). Los resultados de los diversos estudios muestran una prevalencia elevada en los primeros meses postrasplante (<6 meses), que disminuye a partir del año postrasplante y posteriormente se incrementa relacionándose con la pérdida de función del injerto. El estudio europeo sobre manejo de la anemia mostró una prevalencia de anemia del 38,6%, y sólo el 18% de los pacientes con anemia grave estaban en tratamiento con eritropoyetina (EPO). Fisiopatología: Se produce una disminución de la síntesis de EPO o un incremento en la resistencia a la EPO. Existen múltiples factores que pueden causar anemia postrasplante. Algunos de estos factores son únicos de los pacientes trasplantados y otros son comunes a otros pacientes con ERC. Entre los factores comunes se encuentran: el grado de función renal y el déficit de hierro, y entre los factores propios del trasplante están el rechazo agudo, la medicación postrasplante, infecciones y neoplasias. Resultados clínicos: Los datos disponibles que evalúan la asociación de anemia con la morbimortalidad del paciente y la supervivencia del injerto son escasos. La mayoría de los estudios son retrospectivos y analizan experiencias de centros aislados. En ellos se demuestra una mayor mortalidad y morbilidad entre los pacientes con una hemoglobina <11 g/dl (evidencia B). Tratamiento de la anemia postrasplante: - Agentes estimulantes de la eritropoyesis (AEE) y reposición de los depósitos férricos (evidencia A). - Respuesta al tratamiento: en los pacientes trasplantados puede existir cierta resistencia al tratamiento con AEE debido al uso de medicación mielosupresora, inflamación crónica y otros factores. - Efectos adversos del tratamiento con AEE: existen pocos estudios no controlados al respecto que muestran que los AEE son eficaces y probablemente no aceleran el deterioro de función renal, pero pueden agravar la hipertensión arterial.

Definition: The definition of anemia is established by the World Health Organization and was subsequently adopted by the American Society of Transplantation, which defines anemia as hemoglobin concentration <12 g/dl in women and <13 g/dl in men. Prevalence of anemia posttransplantation: Varies throughout the posttransplantation period and is associated with the degree of renal graft function. The relationship between hemoglobin levels and glomerular filtration does not behave the same way as in the population with chronic kidney disease. The results of various studies show a high prevalence in the first months after transplantation (<6 months), which decreases from the first year posttransplantation and then increases related to loss of graft function. European study on the management of anemia showed a prevalence of anemia in 38.6% and only 18% of patients with severe anemia were treated with erythropoietin (EPO). Pathophysiology: There is a decrease in the synthesis of erythropoietin (EPO) or an increase in resistance to EPO. There are many factors that can cause anemia post-transplantation. Some of these factors are specific to transplanted patients whilst others are common to all patients with chronic kidney disease. Among the common factors there are: the degree of renal function and iron deficiency and among the factors of transplantation there are acute rejection, post-transplantation medications, infections and malignancies. Clinical Results: The available data evaluating the association of anemia with morbidity and mortality of the patient and graft survival are scarce. Most studies are retrospective and analyze experiences of individual centers. They showed a higher mortality and morbidity among patients with a hemoglobin <11 g/dl. (Evidence B) Treatment of post-transplantation anemia: - Erythropoiesis-stimulating agents (ESA) and replenishment of iron deposits (Evidence A) - Response to treatment: In transplant patients there may be some resistance to treatment with erythropoiesis- stimulating agents (ESA) due to the use of myelosuppressive medications, chronic inflammation and other factors. - Adverse effects of treatment with ESA: There are few controlled studies failed to show respect to the ESA that are effective and unlikely to accelerate the deterioration of renal function but may aggravate hypertension.

Bibliography
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Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ. Cardiovascular disease after renal transplantation. J Am Soc Nephrol 1996;7:158-65. 2. Winkelmayer WC, et al. Posttransplantation anemia: Management and rationale. Clin J Am Soc Nephrol 2008;3:S49-S55. 3. Shah N, Al-Khoury S, Afzali B, Covic A, Roche A, Marsh J, Macdougall IC, Goldsmith DJ. Posttransplantation anemia in adult renal allograft recipients: Prevalence and predictors. Transplantation 2006;81:1112-8. 4. Yorgin PD, Scandling JD, Belson A, Sánchez J, Alexander SR, Andreoni KA. Late post-transplant anemia in adult renal transplant recipient. An under-recognized problem? Am J Transplant 2002;2:429-35. 5. Winkelmayer WG, Kewalramani R, Rutstein M, Gabardi S, Vonvisger T, Chandaker A. Pharmacoepidemiology of anemia in kidney transplant recipients. J Am Soc Nephrol 2004;15:1347-52. 6. Vanrenterghem Y, Ponticelli C, Morales JM, Abramovicz D, Baboolal K, Eklund B, et al. Prevalence and Management of anemia in renal transplant recipients: a European Survey. Am J Transplant 2003;3:835-45. 7. Molnar MZ, Czira M, Ambrus C, Szeifert L, Szentkiralyi A, Beko G, et al. Anemia is associated with mortality in kidney transplanted patients: A prospective cohort study. Am J Transplant 2007;7:818-24. 8. Karthikeyan V, et al. The burden of chronic kidney disease in renal transplant recipients. Am J Kidney Dis 2003;4:262-9. 9. Roberto Marcén, Domingo del Castillo, Luis Capdevila, Ana Fernández-Rodríguez, Carmen Cantarell, Gema Fernández Fresnedo, et al. Chronic Kidney Disease after Renal Transplantation: A Spanish Multicenter Cross-Sectional Study. Am J Transplant 2008;8(s2):450. 10. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease 2006;37:s182-238. 11. Abbud-Filho M, et al. A report of the Lisbon Conference on the care of the kidney transplant recipient. Transplantation 2007;83:S1-S22. 12. Sun CH, et al. Serum erytropoietin levels after renal transplantation. New Engl J Med 1989;321:151-7. 13. Al-Uzri A, Yorgin PD, Kling PJ. Anemia in children after transplantation: Etiology and the effect of immunosuppressive therapy on erythropoiesis. Pediatr Transplant 2003;7:253-64. 14. Lin CC, King KL, Chao YW, Yang AH, Chang CF, Yang WC. Tacrolimus-associated hemolytic uremic syndrome: A case analysis. J Nephrol 2003;16:580-5. 15. Augustine JJ, Knauss TC, Schulak JA, Bodziak KA, Siegel C, Hricik DE. Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients. Am J Transplant 2004;4:2001-6. 16.Marathias KP, Agroyannis B, Mavromoustakos T, Matsoukas J, Vlahakos DV. Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Curr Top Med Chem 2004;4:483-6. 17. López-Gómez JM, Pérez-Flores I, Jofre R, Carretero D, Rodríguez-Benítez P, et al. Presence of a failed kidney transplant in patients who are on hemodialysis is associated with chronic inflammatory state and erythropoietin resistance. J Am Soc Nephrol 2004;15:2494-501. 18.Mix TC, Kazmi W, Khan S, Ruthazer R, Rohrer R, Pereira BJ, et al. Anemia: A continuing problem following kidney transplantation. Am J Transplant 2003;3:1426-33. 19. Chadban SJ, et al. Anemia after kidney transplantation is not completely explained by reduced kidney function. Am J Kidney Dis 2007;49:301-9. 20.Winkelmayer WC, Chandraker A, Brookhart MA, Kramar R, Sunder-Plassmann G. A prospective study of anaemia and long-term outcomes in kidney transplant recipients. Nephrol Dial Transplant 2006;21:3559-66. 21. Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU, et al.; European Best Practice Guidelines Working Group. Revised European Best Practice Guidelines for the Management of Anemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 2004:19(2);ii1-45. 22. Lorenz M, Kletzmayr J, Perschl A, Furrer A, Hörl WH, Sunder- Plassmann G. Anemia and iron deficiencies among long-term renal transplant recipients. J Am Soc Nephrol 2002;13:794-7. 23. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006;355:2085-98. 24. Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355:2071-84.
[2]
Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ. Cardiovascular disease after renal transplantation. J Am Soc Nephrol 1996;7:158-65. [Pubmed]
[3]
Winkelmayer WC, et al. Posttransplantation anemia: Management and rationale. Clin J Am Soc Nephrol 2008;3:S49-S55.
[4]
Shah N, Al-Khoury S, Afzali B, Covic A, Roche A, Marsh J, Macdougall IC, Goldsmith DJ. Posttransplantation anemia in adult renal allograft recipients: Prevalence and predictors. Transplantation 2006;81:1112-8. [Pubmed]
[5]
Yorgin PD, Scandling JD, Belson A, Sánchez J, Alexander SR, Andreoni KA. Late post-transplant anemia in adult renal transplant recipient. An under-recognized problem? Am J Transplant 2002;2:429-35.
[6]
Winkelmayer WG, Kewalramani R, Rutstein M, Gabardi S, Vonvisger T, Chandaker A. Pharmacoepidemiology of anemia in kidney transplant recipients. J Am Soc Nephrol 2004;15:1347-52. [Pubmed]
[7]
Vanrenterghem Y, Ponticelli C, Morales JM, Abramovicz D, Baboolal K, Eklund B, et al. Prevalence and Management of anemia in renal transplant recipients: a European Survey. Am J Transplant 2003;3:835-45. [Pubmed]
[8]
Molnar MZ, Czira M, Ambrus C, Szeifert L, Szentkiralyi A, Beko G, et al. Anemia is associated with mortality in kidney transplanted patients: A prospective cohort study. Am J Transplant 2007;7:818-24. [Pubmed]
[9]
Karthikeyan V, et al. The burden of chronic kidney disease in renal transplant recipients. Am J Kidney Dis 2003;4:262-9.
[10]
Roberto Marcén, Domingo del Castillo, Luis Capdevila, Ana Fernández-Rodríguez, Carmen Cantarell, Gema Fernández Fresnedo, et al. Chronic Kidney Disease after Renal Transplantation: A Spanish Multicenter Cross-Sectional Study. Am J Transplant 2008;8(s2):450.
[11]
National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease 2006;37:s182-238.
[12]
Abbud-Filho M, et al. A report of the Lisbon Conference on the care of the kidney transplant recipient. Transplantation 2007;83:S1-S22. [Pubmed]
[13]
Sun CH, et al. Serum erytropoietin levels after renal transplantation. New Engl J Med 1989;321:151-7. [Pubmed]
[14]
Al-Uzri A, Yorgin PD, Kling PJ. Anemia in children after transplantation: Etiology and the effect of immunosuppressive therapy on erythropoiesis. Pediatr Transplant 2003;7:253-64. [Pubmed]
[15]
Lin CC, King KL, Chao YW, Yang AH, Chang CF, Yang WC. Tacrolimus-associated hemolytic uremic syndrome: A case analysis. J Nephrol 2003;16:580-5. [Pubmed]
[16]
Augustine JJ, Knauss TC, Schulak JA, Bodziak KA, Siegel C, Hricik DE. Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients. Am J Transplant 2004;4:2001-6. [Pubmed]
[17]
16.Marathias KP, Agroyannis B, Mavromoustakos T, Matsoukas J, Vlahakos DV. Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Curr Top Med Chem 2004;4:483-6. [Pubmed]
[18]
López-Gómez JM, Pérez-Flores I, Jofre R, Carretero D, Rodríguez-Benítez P, et al. Presence of a failed kidney transplant in patients who are on hemodialysis is associated with chronic inflammatory state and erythropoietin resistance. J Am Soc Nephrol 2004;15:2494-501. [Pubmed]
[19]
18.Mix TC, Kazmi W, Khan S, Ruthazer R, Rohrer R, Pereira BJ, et al. Anemia: A continuing problem following kidney transplantation. Am J Transplant 2003;3:1426-33. [Pubmed]
[20]
Chadban SJ, et al. Anemia after kidney transplantation is not completely explained by reduced kidney function. Am J Kidney Dis 2007;49:301-9. [Pubmed]
[21]
20.Winkelmayer WC, Chandraker A, Brookhart MA, Kramar R, Sunder-Plassmann G. A prospective study of anaemia and long-term outcomes in kidney transplant recipients. Nephrol Dial Transplant 2006;21:3559-66. [Pubmed]
[22]
Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU, et al.; European Best Practice Guidelines Working Group. Revised European Best Practice Guidelines for the Management of Anemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 2004:19(2);ii1-45.
[23]
Lorenz M, Kletzmayr J, Perschl A, Furrer A, Hörl WH, Sunder- Plassmann G. Anemia and iron deficiencies among long-term renal transplant recipients. J Am Soc Nephrol 2002;13:794-7. [Pubmed]
[24]
Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006;355:2085-98. [Pubmed]
[25]
Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355:2071-84. [Pubmed]
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