UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

慢性肾脏病贫血：使用促红细胞生成药物治疗的患者的目标血红蛋白/血细胞比容

Author
Jeffrey S Berns, MD
Section Editors
Steve J Schwab, MD
Gary C Curhan, MD, ScD
Deputy Editor
Alice M Sheridan, MD
Translators
程叙扬, 副教授

引言

世界卫生组织(World Health Organization, WHO)已将贫血定义为：成年男性及绝经后女性血红蛋白(hemoglobin, Hgb)浓度小于13.0g/dL；绝经前女性Hgb小于12.0g/dL[1]。按照这些标准，肾小球滤过率(glomerular filtration rate, GFR)小于25-30mL/min的患者中近90%存在贫血，很多患者Hgb水平小于10g/dL[2]。

自从重组人红细胞生成素[阿法依泊汀、EPO(Erythropoietin)]被美国食品药品监督管理局(Food and Drug Administration, FDA)批准以来，该药及其他红细胞生成刺激剂(erythropoiesis-stimulatiing agent, ESA)已经成为大多数晚期慢性肾脏病(chronic kidney disease, CKD)及终末期肾病(end-stage renal disease, ESRD)患者发生贫血时的治疗标准处理。由此，在整个2005年，CKD患者(尤其是透析患者)的Hgb和血细胞比容(hematocrit, Hct)平均水平稳步上升[3,4]。到2006年，美国90%维持长期透析的患者接受了ESA治疗，透析患者的Hgb平均水平为12.0g/dL[4,5]；所有患者中有2/3的Hgb水平在11-13g/dL之间[4]。

贫血还是肾功能减退相关的很多症状的促成因素。这些症状包括疲劳、抑郁、运动耐量降低、呼吸困难，以及对心血管的影响，如左心室肥厚(left ventricular hypertrophy, LVH)、左心室收缩功能不全等[6]。贫血还与并发症和死亡的风险增加相关，主要是由心脏病和脑卒中所致[7-10]，以及与透析前CKD患者的住院、住院时长及死亡的风险增加相关[11-14]。但这些关联尚未证明因果关系；因此这些关联现象可能反映了会促使贫血严重、对ESA反应性减低和结局更差的基础共存疾病及病情的严重性。

本专题将对肾病所致贫血患者ESA治疗的Hgb或Hct目标水平相关的研究数据进行总结。与使用EPO、达促红素及铁剂补充相关的内容参见其他专题。 (参见“非透析慢性肾脏病患者贫血的治疗”和“血液透析患者慢性肾脏病性贫血的促红细胞生成素治疗”和“达贝泊汀-α在慢性肾脏病贫血治疗中的应用”和“Treatment of iron deficiency in nondialysis chronic kidney disease (CKD) patients”和“血液透析患者中铁剂的使用”)

治疗的适应证

关于透析和非透析CKD患者贫血治疗选择的概述(包括采用ESA还是输血治疗的相对适应证)参见其他专题。 (参见“血液透析患者慢性肾脏病性贫血的促红细胞生成素治疗”，关于‘适应证’一节和“非透析慢性肾脏病患者贫血的治疗”，关于‘给药方案’一节)

             

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2016-12-08.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. World Health Organization. Nutritional Anaemias: Report of a WHO Scientific Group. Geneva, Switzerland: World Health Organization, 1968.
  2. Kazmi WH, Kausz AT, Khan S, et al. Anemia: an early complication of chronic renal insufficiency. Am J Kidney Dis 2001; 38:803.
  3. Obrador GT, Roberts T, St Peter WL, et al. Trends in anemia at initiation of dialysis in the United States. Kidney Int 2001; 60:1875.
  4. Hariharan S, Yang H. Introduction. Am J Kidney Dis. 2006; 47:S1.
  5. Centers for Medicare and Medicaid Services, Kinney R. 2005 Annual Report: ESRD Clinical Performance Measures Project. Am J Kidney Dis 2006; 48:S1.
  6. Levin A, Thompson CR, Ethier J, et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis 1999; 34:125.
  7. Jurkovitz CT, Abramson JL, Vaccarino LV, et al. Association of high serum creatinine and anemia increases the risk of coronary events: results from the prospective community-based atherosclerosis risk in communities (ARIC) study. J Am Soc Nephrol 2003; 14:2919.
  8. Abramson JL, Jurkovitz CT, Vaccarino V, et al. Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int 2003; 64:610.
  9. Sarnak MJ, Tighiouart H, Manjunath G, et al. Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study. J Am Coll Cardiol 2002; 40:27.
  10. McClellan WM, Flanders WD, Langston RD, et al. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol 2002; 13:1928.
  11. Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999; 10:610.
  12. Xia H, Ebben J, Ma JZ, Collins AJ. Hematocrit levels and hospitalization risks in hemodialysis patients. J Am Soc Nephrol 1999; 10:1309.
  13. Collins AJ, Li S, St Peter W, et al. Death, hospitalization, and economic associations among incident hemodialysis patients with hematocrit values of 36 to 39%. J Am Soc Nephrol 2001; 12:2465.
  14. Collins AJ, Ma JZ, Ebben J. Impact of hematocrit on morbidity and mortality. Semin Nephrol 2000; 20:345.
  15. http://www.fda.gov/Drugs/DrugSafety/ucm259639.htm (Accessed on July 28, 2011).
  16. Strippoli GF, Craig JC, Manno C, Schena FP. Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of randomized, controlled trials. J Am Soc Nephrol 2004; 15:3154.
  17. Volkova N, Arab L. Evidence-based systematic literature review of hemoglobin/hematocrit and all-cause mortality in dialysis patients. Am J Kidney Dis 2006; 47:24.
  18. Parfrey PS. Target hemoglobin level for EPO therapy in CKD. Am J Kidney Dis 2006; 47:171.
  19. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339:584.
  20. Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007; 369:381.
  21. Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361:2019.
  22. NKF-DOQI clinical practice guidelines for the treatment of anemia of chronic renal failure. National Kidney Foundation-Dialysis Outcomes Quality Initiative. Am J Kidney Dis 1997; 30:S192.
  23. IV. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: update 2000. Am J Kidney Dis 2001; 37:S182.
  24. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease. Am J Kidney Dis 2006; 47(Suppl 4):S1.
  25. KDOQI. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis 2007; 50:471.
  26. Chapter 1: Diagnosis and evaluation of anemia in CKD. Kidney Int Suppl (2011) 2012; 2:288.
  27. Berns JS, Elzein H, Lynn RI, et al. Hemoglobin variability in epoetin-treated hemodialysis patients. Kidney Int 2003; 64:1514.
  28. Lacson E Jr, Ofsthun N, Lazarus JM. Effect of variability in anemia management on hemoglobin outcomes in ESRD. Am J Kidney Dis 2003; 41:111.
  29. Fishbane S, Berns JS. Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin. Kidney Int 2005; 68:1337.
  30. Li S, Collins AJ. Association of hematocrit value with cardiovascular morbidity and mortality in incident hemodialysis patients. Kidney Int 2004; 65:626.
  31. Ofsthun N, Labrecque J, Lacson E, et al. The effects of higher hemoglobin levels on mortality and hospitalization in hemodialysis patients. Kidney Int 2003; 63:1908.
  32. Pisoni RL, Bragg-Gresham JL, Young EW, et al. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2004; 44:94.
  33. Li S, Foley RN, Collins AJ. Anemia, hospitalization, and mortality in patients receiving peritoneal dialysis in the United States. Kidney Int 2004; 65:1864.
  34. Robinson BM, Joffe MM, Berns JS, et al. Anemia and mortality in hemodialysis patients: accounting for morbidity and treatment variables updated over time. Kidney Int 2005; 68:2323.
  35. Messana JM, Chuang CC, Turenne M, et al. Association of quarterly average achieved hematocrit with mortality in dialysis patients: a time-dependent comorbidity-adjusted model. Am J Kidney Dis 2009; 53:503.
  36. Wolfe RA, Hulbert-Shearon TE, Ashby VB, et al. Improvements in dialysis patient mortality are associated with improvements in urea reduction ratio and hematocrit, 1999 to 2002. Am J Kidney Dis 2005; 45:127.
  37. Regidor DL, Kopple JD, Kovesdy CP, et al. Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol 2006; 17:1181.
  38. Locatelli F, Pisoni RL, Combe C, et al. Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2004; 19:121.
  39. Lu WX, Jones-Burton C, Zhan M, et al. Survival benefit of recombinant human erythropoietin administration prior to onset of end-stage renal disease: variations across surrogates for quality of care and time. Nephron Clin Pract 2005; 101:c79.
  40. Gilbertson DT, Ebben JP, Foley RN, et al. Hemoglobin level variability: associations with mortality. Clin J Am Soc Nephrol 2008; 3:133.
  41. Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med 2010; 153:23.
  42. Clement FM, Klarenbach S, Tonelli M, et al. The impact of selecting a high hemoglobin target level on health-related quality of life for patients with chronic kidney disease: a systematic review and meta-analysis. Arch Intern Med 2009; 169:1104.
  43. Vinhas J, Barreto C, Assunção J, et al. Treatment of anaemia with erythropoiesis-stimulating agents in patients with chronic kidney disease does not lower mortality and may increase cardiovascular risk: a meta-analysis. Nephron Clin Pract 2012; 121:c95.
  44. Coyne DW. The health-related quality of life was not improved by targeting higher hemoglobin in the Normal Hematocrit Trial. Kidney Int 2012; 82:235.
  45. Drüeke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355:2071.
  46. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355:2085.
  47. www.clinicaltrials.gov (Accessed on April 27, 2007).
  48. Parfrey PS, Foley RN, Wittreich BH, et al. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease. J Am Soc Nephrol 2005; 16:2180.
  49. Ritz E, Laville M, Bilous RW, et al. Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the Anemia Correction in Diabetes (ACORD) Study. Am J Kidney Dis 2007; 49:194.
  50. Moreno F, Sanz-Guajardo D, López-Gómez JM, et al. Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients. Spanish Cooperative Renal Patients Quality of Life Study Group of the Spanish Society of Nephrology. J Am Soc Nephrol 2000; 11:335.
  51. McMahon LP, Mason K, Skinner SL, et al. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant 2000; 15:1425.
  52. Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group. Am J Kidney Dis 1991; 18:50.
  53. Pickett JL, Theberge DC, Brown WS, et al. Normalizing hematocrit in dialysis patients improves brain function. Am J Kidney Dis 1999; 33:1122.
  54. McMahon LP, McKenna MJ, Sangkabutra T, et al. Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients. Nephrol Dial Transplant 1999; 14:1182.
  55. Foley RN, Curtis BM, Parfrey PS. Erythropoietin therapy, hemoglobin targets, and quality of life in healthy hemodialysis patients: a randomized trial. Clin J Am Soc Nephrol 2009; 4:726.
  56. Gandra SR, Finkelstein FO, Bennett AV, et al. Impact of erythropoiesis-stimulating agents on energy and physical function in nondialysis CKD patients with anemia: a systematic review. Am J Kidney Dis 2010; 55:519.
  57. Johansen KL, Finkelstein FO, Revicki DA, et al. Systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with erythropoiesis-stimulating agents. Am J Kidney Dis 2010; 55:535.
  58. Collister D, Komenda P, Hiebert B, et al. The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med 2016; 164:472.
  59. Churchill DN, Muirhead N, Goldstein M, et al. Probability of thrombosis of vascular access among hemodialysis patients treated with recombinant human erythropoietin. J Am Soc Nephrol 1994; 4:1809.
  60. Furuland H, Linde T, Ahlmén J, et al. A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant 2003; 18:353.
  61. Vaziri ND. Mechanism of erythropoietin-induced hypertension. Am J Kidney Dis 1999; 33:821.
  62. Berns JS, Rudnick MR, Cohen RM, et al. Effects of normal hematocrit on ambulatory blood pressure in epoetin-treated hemodialysis patients with cardiac disease. Kidney Int 1999; 56:253.
  63. Inrig JK, Barnhart HX, Reddan D, et al. Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. Am J Kidney Dis 2012; 60:390.
  64. Tonelli M, Winkelmayer WC, Jindal KK, et al. The cost-effectiveness of maintaining higher hemoglobin targets with erythropoietin in hemodialysis patients. Kidney Int 2003; 64:295.
  65. Roberts TL, Foley RN, Weinhandl ED, et al. Anaemia and mortality in haemodialysis patients: interaction of propensity score for predicted anaemia and actual haemoglobin levels. Nephrol Dial Transplant 2006; 21:1652.
  66. Kilpatrick RD, Critchlow CW, Fishbane S, et al. Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3:1077.
  67. Bradbury BD, Wang O, Critchlow CW, et al. Exploring relative mortality and epoetin alfa dose among hemodialysis patients. Am J Kidney Dis 2008; 51:62.
  68. Fishbane S, Besarab A. Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets. Clin J Am Soc Nephrol 2007; 2:1274.
  69. Szczech LA, Barnhart HX, Inrig JK, et al. Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes. Kidney Int 2008; 74:791.
  70. Singh AK. Resolved: Targeting a higher hemoglobin is associated with greater risk in patients with CKD anemia: pro. J Am Soc Nephrol 2009; 20:1436.
  71. Solomon SD, Uno H, Lewis EF, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med 2010; 363:1146.
  72. Rosner MH, Bolton WK. The mortality risk associated with higher hemoglobin: is the therapy to blame? Kidney Int 2008; 74:695.
  73. Zhang Y, Thamer M, Cotter D, et al. Estimated effect of epoetin dosage on survival among elderly hemodialysis patients in the United States. Clin J Am Soc Nephrol 2009; 4:638.
  74. Koulouridis I, Alfayez M, Trikalinos TA, et al. Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis. Am J Kidney Dis 2013; 61:44.
  75. Chaknos CM, Berns JS. Erythropoiesis-stimulating agents on trial: are higher dosages causing harm? Am J Kidney Dis 2013; 61:6.