Therapeutics of Clinical Drugs 臨床藥物治療學 腎性貧血的評估與治療 嘉義基督教醫院藥劑科藥師許育瑋 蔡佩芬 林慧娟 摘要 (chronic kidney disease, CKD) (erythropoietin, EPO) chronic kidney disease anemia erythropoiesis stimulating agents 壹 前言 (chronic kidney disease, CKD) CKD 貳 貧血的發生原因 (hemoglobin, Hb) 1 5 2 參 慢性腎臟病與貧血之關連性 (hypoxia inducible factor, HIF) (erythropoietin, EPO) EPO erythroid colony-forming units (CFU-Es) CFU-Es 294 藥學雜誌第 117 冊 55
臨床藥物治療學 Therapeutics of Clinical Drugs () EPO EPO 3 2000 2006 20072006 CKD Hb < 13.5 g/dl Hb < 12.0g/dL 一 貧血的評估 15 圖一紅血球生成的調控機轉 CKD egfr 15 ml/min/1.73 m 2 33%67% 90% 4 EPO 5 肆 腎性貧血的評估與治療目標 (NKF/KDOQI) 1997 CKD CKD E P O (CBC) (absolute reticulocyte count) (ferritin) (serum transferring saturation, TSAT) (reticulocyte hemoglobin content, CHr) TSAT ferritin ferritin < 25 ng/ml < 12 ng/ml TSAT < 16% 3 二 Hb 的治療目標 Hb > 11 g/dl Hb 13 g/dl KDOQI 2006 56 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4
CKD Hb > 11 g/dl (erythropoiesis stimulating agents, ESA) CKD Hb 13 g/dl 3 KDQOI 2007 ESA Hb 11-12 g/dl ESA CKD Hb > 13 g/dl 6 2011 6 FDA CKD ESA CKD Hb < 10 g/dl ESA CKD Hb 11 g/ dl CKD Hb 11 g/dl 7 () Hb 10-11 g/dl 表一 KDOQI 與 FDA 之指引比較 Hb KDOQI 2000 3 < 12.0 g/dl < 11.0 g/dl 11-12 g/dl TSAT (%) Ferritin (ng/ml) 50 20 100 < 13.5 g/dl < 12 g/dl KDOQI 2006 3 11 g/dl Hb > 13 g/dl KDOQI 2007 6 FDA 2011 7 -- -- 11-12 g/dl Hb > 13 g/dl 10-11 g/dl TSAT (%) 20 -- -- Ferritin (ng/ml) HD-CKD 200 HD-CKD 100 > 500 伍 腎性貧血的藥物治療選擇 ESA ESA Hb CKD ESA Hb ESA ESA ESA Hb ESA () ESA 4 Hb 0.5-1.0 g/dl 1-2 10000/ ul ESA ESA EPO (antibody-mediated pure red cell aplasia, PRCA) 3 一 Epoetin Epoetin Epoetin- Epoetin- 294 藥學雜誌第 117 冊 57
臨床藥物治療學 Therapeutics of Clinical Drugs 3 表二 2006 年 KDOQI 對腎性貧血的治療建議 ESA 的使用 Hb ESA Hb ESA 1. ESA Hb Hb 2. Hb ESA 3. 4. ESA ESA 5. ESA ESA 1. ESA CKD ESA 2. (SC) ESA 3. (IV) ESA ESA 1. ESA CKD ESA 2. ESA 鐵劑的使用 1. ESA 2. ESA ESA 3 Hb ESA CKD ESA 1. Serum ferritin > 200 ng/ml TSAT > 20% ( CHr > 29 pg/cell) 2. Serum ferritin > 100 ng/ml TSAT > 20% Ferritin Serum ferritin > 500 ng/mlesa Hb TSAT 1. 2. iron dextran 其他的輔助治療 L-CarnitineL-Carnitine CKD Vitamin CVitamin C CKD Androgens Androgens CKD ESA 58 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4
輸血 Hb Hb ESA 抗性的評估 ESA 1. ESA Hb ESA Hb 2. Epoetin 500 IU/kg/ Hb 11 g/dl PRCA ESA > 4 PRCA 1. Hb 0.5-1.0 g/dl/ ( ) 1-2 / 2. ( ) 3. ( ) < 10000/uL Epoetin- Epoetin- ( 4-1119-25 ) 2-3 Epoetin 1/3 15-50% 8 二 Darbepoetin-α Darbepoetin- 2001 FDA ESA Darbepoetin- Epoetin Epoetin 3 9 0.45 mcg/kg1 Hb 1 1 mcg Darbepoetin- 200 IU Epoetin 10 Epoetin 2-3 Darbepoetin 1 Epoetin 1 Darbepoetin- 2 1 11 三 Continuous Erythropoiesis Receptor Activator (CERA) CERA FDA 2007 11 ESA Epoetin- polyethylene glycol (PEG) 130 12 0.6 mcg/ kg 2 Hb 12 CERA EPO PRCA ESA EPO ESA CERA 11 四 Peginesatide Peginesatide FDA 2012 3 ESA EPO (pegylated dimeric peptide) EPO 10 294 藥學雜誌第 117 冊 59
臨床藥物治療學 Therapeutics of Clinical Drugs 1次的便利性外 由於其與 EPO 的結構不 同 理論上並不會與 EPO 抗體產生交叉反 應 其臨床效益應並不會被 EPO 抗體所中 和 是在患者產生 PRCA 後或許仍能使用的 13 ESA 不過可惜的是 Peginesatide 因上市 後的過敏反應問題而於2013年2月底進行全 14 球的自願性回收 陸 結論 貧血是 CKD 患者最常見的併發症之 一 若未積極加以矯正 患者除了可能出現 相關的併發症外 更會影響預後 生活品質 與心臟 等功能 目前在 CKD 患者的貧血 治療藥物仍以鐵劑及 ESA 為首要 由於各 ESA 的臨床效益差異不大 可依患者需求選 擇合適給藥頻率之藥物 然而 畢竟每次的 藥物注射對患者的生理及心理都是壓力與負 擔 若未來能有更長效與安全的製劑可供選 擇 相信對患者而言應是一大福音 參考資料 1. 2. 60 李文欽 張舜智 黃忠餘等 慢性腎臟病與貧血 腎 臟與透析2007; 19: 81-88 Iron deficiency anaemia: assessment, prevention, and control. A guide for programme managers. Geneva, World Health Organization, 2001(WHO/NHD/01.3). THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 KDOQI: KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 2006;47(Suppl 3):S11-145. 4. 黃俊德 吳明儒 徐國雄 血液透析病人之貧血 腎 臟與透析2012; 24: 195-200 5. Tarng DC: Cardiorenal anemia syndrome in chronic kidney disease. J Chin Med Assoc 2007; 70(10):424-9. 6. 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(3):471-530. 7. FDA Drug Safety Communication: Modified dosing recommendations to improve the safe use of ErythropoiesisStimulating Agents (ESAs) in chronic kidney disease. Available at: http://www.fda.gov/drugs/drugsafety/ ucm259639.htm 8. Deicher R, Hörl WH: Differentiating factors between erythropoiesis-stimulating agents: a guide to selection for anaemia of chronic kidney disease. Drugs 2004;64(5):499509. 9. Locatelli F, Del Vecchio L: Optimizing the management of renal anemia: challenges and new opportunities. Kidney Int Suppl 2008;111:S33-7. 10. Hörl WH: Differentiating factors between erythropoiesisstimulating agents: an update to selection for anaemia of chronic kidney disease. Drugs 2013;73(2):117-30. 11. NESP MIRCERA 藥品中文仿單 12. Fishbane S: Anemia in chronic kidney disease: status of new therapies. Curr Opin Nephrol Hypertens 2009;18(2):112-5. 13. Macdougall IC, Rossert J, Casadevall N, et al: A peptidebased erythropoietin-receptor agonist for pure red-cell aplasia. N Engl J Med 2009;361(19):1848-55. 14. Affymax and Takeda Announce a Nationwide Voluntary Recall of All Lots of OMONTYS (peginesatide) Injection, Available at:http://www.fda.gov/safety/recalls/ ucm340893.htm 15. HIF-Erythropoiesis, Available at:http://www.fibrogen. com/erythropoiesis 3.
腎性貧血的評估與治療 Evaluation and Management for Anemia in Chronic Kidney Disease Yu-Wei Hsu, Pei-Fen Tsai, Hui-Chuan Lin Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital Abstract Anemia is a undesirable complication that develops in most patients with Chronic Kidney Disease (CKD), several factors including chronic bleeding, inflammation, nutritional deficiencies or hyperparathyroidism are associated with anemia in CKD patients. Insufficient erythropoietin production by the kidney is generally considered as a major cause of renal anemia. Erythropoiesis stimulating agents (ESAs) increase the production of erythropoietin through direct or indirect action on the erythropoietin receptor. Currently available ESAs showed a similar efficacy on hemoglobin level achievement and played the prominent role on anemia management in CKD. For CKD patients, early assessment and management for anemia improves not only the quality of life but prognosis of patients. 第 29 卷第 4 期 藥學雜誌 第117冊 61