1、血液透析之慢性併發症台北慈濟醫院腎臟內科 洪思群醫師2009-05-10腎性貧血q 腎性貧血的成因及後果q 紅血球生成素q 腎性貧血的治療目標q 紅血球生成素反應不良的因素q 鐵缺乏的診斷與治療q 營養不良、發炎與腎性貧血q 腎性貧血的輔助療法 ImbalanceReduces O2 levels in bloodEPONormal blood oxygen levelsStimulus: HypoxiaImbalanceIncreases O2-carrying ability of blood紅血球生成的調控腎性貧血 - 紅血球生成素不足慢性腎病各期的貧血盛行率Kausz AT, et a
2、l. Dis Manage Health Outcomes 10:505-513, 2002 Obrador GT, et al. J Am Soc Nephrol 10:1793-1800, 1999腎性貧血的後果貧血之末期腎臟病患有較高之死亡率1.331.121.000.961.251.111.000.9700.20.40.60.811.21.4 27%27% to 30%30% to 33%33% to 500N = 333Number of PatientsDose of EPOGEN (U/kg TIW)病患對紅血球生成素的反應Phase 3, multicenter, clinic
3、al trial of HD patients (N = 333). This study was designed to evaluate the safety and efficacy of EPOGEN in patients with uncomplicated anemia. Doses were initiated at 300 or 150 U/kg TIW. When the patients Hct reached 35%, they were placed on the maintenance phase of the protocol and reduced to 75
4、U/kg TIW. The Hb target range for this study was Hct 32%38% (Hb 10.712.8 g/dL). The EPOGEN package insert recommends the Hb not exceed 12 g/dL. Eschbach JW, et al. Ann Intern Med. 1989;111:992-1000. EPO反應不良的原因q Major Iron deficiency Inflammation/Infection Malnutrition Underdialysis q Minor Hyperpara
5、thyroidismAluminum toxicityBlood loss (often occult)Hemolysis B12/Folate deficiency Marrow disorders Hemoglobinopathy PRCA associated with anti-EPO Ab ACEI 血管形成不良 angiodysplasia 腎性貧血q 腎性貧血的成因及後果q 紅血球生成素q 腎性貧血的治療目標q 紅血球生成素反應不良的因素q 鐵缺乏的診斷與治療q 營養不良、發炎與腎性貧血 q 腎性貧血的輔助療法 造血需要紅血球生成素和鐵Hematopoietic Stem Cel
6、lBFU-ECFU-EErythroblastsReticulocytesErythrocytes (RBCs)(Time to maturity = 12 days)Bone MarrowCirculationIron DependentEPO DependentFerritin Iron Transferrin Iron 鐵在人體的吸收與分布細胞之運鐵蛋白循環NKF-K/DOQI 2006 Anemia of Chronic Kidney Disease鐵劑的治療目標q Ferritin (儲鐵蛋白儲鐵蛋白) 200 ng/ml q TSAT (運鐵蛋白飽合度運鐵蛋白飽合度) 20% 診斷
7、鐵缺乏的準則q 絕對絕對鐵缺乏鐵缺乏 TSAT 20% & serum ferritin 200 ng/ml Increased blood loss; decreased iron absorptionq 功能性鐵缺乏功能性鐵缺乏 TSAT 200 ng/ml RBC production by EPO outstrips iron supplyq 網狀內皮系統阻斷網狀內皮系統阻斷 (RE blockade) TSAT 500 ng/ml Acute or chronic inflammation鐵劑給予之劑量絕對絕對鐵缺乏鐵缺乏Parenteral Iron Therapy 1000 mg
8、 given over 8-10 HD treatments to achieve and maintain K/DOQI targets If No Response A second course of IV iron should be tried (guideline 8 opinion)NKF-K/DOQI Clinical Practice Guidelines for the treatment of CRF AJKD 2001; 37(suppl 1)診斷鐵缺乏的準則q 絕對絕對鐵缺乏鐵缺乏 TSAT 20% & serum ferritin 200 ng/ml Increas
9、ed blood loss; decreased iron absorptionq 功能性鐵缺乏功能性鐵缺乏 TSAT 200 ng/ml RBC production by EPO outstrips iron supplyq 網狀內皮系統阻斷網狀內皮系統阻斷 (RE blockade) TSAT 500 ng/ml Acute or chronic inflammation鐵劑給予之劑量功能性鐵缺乏功能性鐵缺乏Parenteral Iron Therapy 25 to 125 mg once per week in order to provide 250 to 1000 mg withi
10、n 12 weeks (guideline 8 opinion)NKF-K/DOQI Clinical Practice Guidelines for the treatment of CRF AJKD 2001; 37(suppl 1)681012140481216Hemoglobin (g/dl)All 37 patients entered study iron replete with Hb 8.5 g/dl * P0.05 vs. EPO+IV iron* P0.005 vs. EPO+IV ironEPO onlyEPO+Oral IronEPO+IV Iron*WeeksMacd
11、ougall et al. Kidney Int 1996鐵劑給予之途徑EPO doseU/kg/wk6 monthsSunder-Plassmann et al. J Am Soc Nephrol 1994 靜脈鐵劑降低EPO使用量IV Fe TherapyYear of National Dialysis Surveillance19951996199719981999Epo Use (% patients)020406080100Mean Hematocrit (%)26272829303132Epo UseHematocrit26.827.227.528.028.982.778.076
12、.577.574.0Taiwan Soc Nephrol Annual Report 2003 台灣慢性血液透析病患EPO用量和Hct之趨勢變化SerumSerumSerumTSATTSATPercent of Patients0204060801001995199619971998199951413229273236404546172327262727232119187377798182ferritin 800 g/l 20%台灣慢性血液透析病患Ferritin和TSAT之趨勢變化Taiwan Soc Nephrol Annual Report 2003 Cost effective Fre
13、e radical Infection 使用鐵劑的正反兩面效應IronDrueke, T. et al. Circulation 106:2212-17, 2002接受鐵劑劑量與頸動脈厚度之相關性Kalantar-Zadeh K, J Am Soc Nephrol 16: 3070-3080, 2005接受鐵劑劑量與死亡率之相關性NKF-K/DOQI 2006 Anemia of Chronic Kidney Disease鐵劑的治療目標上限q Ferritin (儲鐵蛋白儲鐵蛋白) 500 ng/ml q TSAT (運鐵蛋白飽合度運鐵蛋白飽合度) 50% J Am Soc Nephrol
14、18: 975-984, 2007Ferritin: 500-1200TSAT 25%高Ferritin之血液透析病患對鐵劑補充仍有反應診斷鐵缺乏的準則q 絕對絕對鐵缺乏鐵缺乏 TSAT 20% & serum ferritin 200 ng/ml Increased blood loss; decreased iron absorptionq 功能性鐵缺乏功能性鐵缺乏 TSAT 200 ng/ml RBC production by EPO outstrips iron supplyq 網狀內皮系統阻斷網狀內皮系統阻斷 (RE blockade) TSAT 500 ng/ml Acute o
15、r chronic inflammationHepcidin (肝泌抑菌素)J Am Soc Nephrol 18:394-400, 2007 腎性貧血q 腎性貧血的成因及後果q 紅血球生成素q 腎性貧血的治療目標q 紅血球生成素反應不良的因素q 鐵缺乏的診斷與治療q 營養不良、發炎與腎性貧血 q 腎性貧血的輔助療法 MIA 症候群Cytokines(IL-6 and TNF-a)MalnutritionInflammationAtherosclerosisAnaemiaStenvinkel P et al. Nephrol Dial Transplant 15: 95360, 2000Fac
16、tors affecting erythropoiesisFactors Affecting ErythropoiesisEffect of Pentoxifylline Treatment on Ex Vivo TNF Production by CD3+ T Cells J Am Soc Nephrol 2004Effect of Pentoxifylline Treatment on Hb Levels Cooper et al. J Am Soc Nephrol 2004腎性貧血q 腎性貧血的成因及後果q 紅血球生成素q 腎性貧血的治療目標q 紅血球生成素反應不良的因素q 鐵缺乏的診斷與治療q 營養不良、發炎與腎性貧血 q 腎性貧血的輔助療法 Tarng et al. Nephrol Dial Transplant 2001維他命C可增加鐵的可利用率 腎性貧血的輔佐療法 維他命Cq Hemoglobin 5.5 g/dlq Creatinine 12 mg/dlq Ferritin 75 ng/mlq TSAT 12%應該如何治療?55 y/o female, general malaise, poor appetite, shortness of breath
