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1、CKDMBDCKDMBD中国中文中国中文CKD-MBD (mineral and bone disorder)Renal osteodystropy: 骨代谢CKD-MBD：骨代谢和血管钙化病变肾病骨病发生的机制副甲状腺荷尔蒙分泌亢进活性维他命D的不足尿中磷的排泄降低肠管Ca吸收的下降血中P的浓度上升血中Ca的浓度低下肾衰竭肾衰竭Trade-off hypothesisGutierrez OM CJASN 2010; 5:1710-1716现在的想法CKDKidneyP排泄低下 SerumP上昇 BoneFGF-23 Kidney尿细血管P再吸收低下Kidney1,25(OH)D3合成低下消化
2、管Ca 吸收低下副甲状腺PTH上升SerumCa低下SerumP維持 CKD进行消化管P 吸收低下SerumP上升 CKD-MBD的发展CKDPFGF 231,25(OH)D3CaPTHCKD-MBD的对策CKDPFGF 231,25(OH)D3CaPTHP吸附药Active VDCinacalcetActive VDGuidelines for CKD-MBD, Stage 5d Origin YearCa, mg/dLP, mg/dLCa x PPTH pg/mLCARI20008.810.46.8Pref5.671.923x limitEDTA20018.811.02.54.655EBP
3、G20023.55.555150300K/DOQI200310.2Pref8.49.53.55.555150300UK20028.810.45.64x limitJSDT20068.410.03.56.060180PTH管理目标值K/DOQI: 150300, JSDT: 60180 pg/mLCalcimimetics: Cinacalcet-HCL俗名：Cinacalcet Hydrochloride化学名：N-(1R )-1-(Naphthalen-1-yl)ethyl-3- 3-(trifluoromethyl)phenylpropan-1-amine monohydrochlorid
4、e分子式：C22H22F3NHCl分子量：393.87结构式：Cinacalcet HCLLindberg JS, et al., JASN 2005; 16: 800lRandomized, double blind, HD: 260, PD 34, vs Placebo i-PTHCa x PCinacalcet-HCL：对于生存率的影响Block GA et al., KI 2010; 78:578-589lUSRD: 2004年 19186 pts: cinacalcet 5976l观察期间：26个月lAll-cause, CVD死亡率低下Cinacalcet-HCL：对于生存率的影响
5、Block GA et al., KI 2010; 78:578-589l名族l性别l年龄l透析史lBMIl原有病l合并症lAlbuminlCalPlPTHlHglKt/VlAccessCKD-MBD管理liPTH：K/DOQI 150300, JSDT 60180 pg/mLCinacalcet HCL +少量VD (目标投入量：血清Ca的维持）+透析液Ca浓度(3.0mEq/L,可能的话2.5mEq/L)控制可能l控制：吸附剂困难Relativeriskofdeathincreasesasserumphosphorusconcentrationsincrease(N =40,538)对高P
6、血症死亡率的影响Note: 1 mg/dL = 0.32 mmol/L. Data subject to multivariable adjustment. Redrawn from: Block GA et al. J Am Soc Nephrol 2004;15:220818 K/DOQI 3.5-5.5mg/dLDOPPSTentori F et al., AJKD 2008; 52:519nDOPPS,I, II, III; HD 25,588 ptsAdjusted: facility effect, age, sex, race, BMI, time with ESRD, como
7、rbid conditions, Hb, albumin, nPCR, spKt/V, PTX, vitamin D, sCa,PTH. 14-4243-5253-6061-7273-1322.01.51.00.5REFERENCE1.061.081.001.131.34*P0.01RRRelative mortality risk by CaPORelative mortality risk by CaPORelative mortality risk by CaPO4 44 product quintiles (N=2669). product quintiles (N=2669). pr
8、oduct quintiles (N=2669). The vertical bars indicate the 5% to 95% confidence intervals.The vertical bars indicate the 5% to 95% confidence intervals.The vertical bars indicate the 5% to 95% confidence intervals.Am J Kidney Dis: 1998: 31: 607-617CaPO4 Product Quintile (mg2/dl2)与死亡相关的因子PopulationAttr
9、ibutableRiskPercentBlock G, J Am Soc Neph 15: 2208-2218, 2004105150(%)20LowURR65AnemiaHb11AllMineralsHighPO41.65.0HighCa2.510.0HighPTH60600Population Attributable Risk PercentHD: 40,538, FMC-NACannata-Andia, J. B. et al. J Am Soc Nephrol 2006;17:S267-S273透析患者与一般人的大动脉钙化病变的研究Age, gender match动脉钙化与心血管死
10、亡有关ArterialCalcificationsandCardiovascularRiskinEnd-StageRenalDiseaseBlacher J et al., Hypertension (2001) 38: 938钙化进展与值Stompr TP et al.,AJKD2004；44：517-28In univariate analysis, CaSc did not show a significant correlation with any of the tested parameters of lipid profile, cytokines, or acute-phase
11、 proteins. No correlation was found between CaSc and age, dialysis vintageRPCalcium 0.12 0.37Phosphate 0.44 0.0005Ca P product 0.38 0.003iPTH 0.10 0.42PD patients 61, CAC score 0 and 12 monthsCAC score increase on the age in 39 Children and Young Adults CAC score increase on the age in 39 Children a
12、nd Young Adults CAC score increase on the age in 39 Children and Young Adults with HDwith HDwith HDGoodman WG et al : NEJM.Vol342(20) ; 1478-1483, 2000Calcification ScoreAge (years)10,0001,000100101005101520253035Ca和P代谢的治疗目标变化P Ca PTH 昔今PTHCaPGuidelines for CKD-MBD, Stage 5d Origin YearCa, mg/dLP, m
13、g/dLCa x PPTH pg/mLCARI20008.810.46.8Pref5.671.923x limitEDTA20018.811.02.54.655EBPG20023.55.555150300K/DOQI200310.2Pref8.49.53.55.555150300UK20028.810.45.64x limitJSDT20068.410.03.56.060180PB磷吸附能CaCO3(g)Ca acetate(g)Sevelamer(g)Lanthanum(g)Ca含有400mg250mg磷吸附磷吸附 (mg/ )44mg50mg33mg115mg3g能吸附的磷的量132mg1
14、50mg吸附300mg磷所需要的量7.0g6.0g9.1g37片2.6gSherman RA AJKD 54;18-23,2009 421History of Phosphate Binders 20002000199019901980198019701970LanthanumLanthanumAluminumAluminum GelCa-based PB SevelamerSevelamerSevelamerCa-based PB20092009LanthanumCa-based PBAluminum Active Vitamin DCinacalset HClSevelamer-carbo
15、mateFerric iron-IIIPhosphate binderMetallAL(OH)3lCaCO3, Ca-acetatelLanthanum carbonatelZenenex (Ferric iron-III-citrate)AMG223 (amine-polymer) SBR759 (Ferric iron-III+polymer)colestilan Sevelamer HCl, carbonatePolymer市场上销售的吸附剂lAl(OH)2l碳酸，醋酸lSevelamerlLanthanum carbonate Al(OH)2n1970-1990, 强有力的磷吸附剂n1
16、980后半脑病(多数的原因为透析液中的AL)骨钙化的前沿沉淀：低回转骨(Adynamic bone) n1902在日本成为禁忌高血症多发：胃钙化碳酸n1980末n吸附作用：中程度Active VD + 碳酸Ca 胃钙化Al(OH)2, 3g/day碳酸Ca+1D3非含Ca的吸附剂, Sevelamer HCLSlatopolsky et al., KI 1999; 55: 299-307 Sevelamer作用机制n消化管内一部分成为正电荷状态、与负电荷的磷酸和离子、氢结合Sevelamer HCL (RenaGel)吸附效果与醋酸吸附效果与醋酸相同、无高相同、无高血症血症胆汁酸吸附胆汁酸吸附
17、LDL-C低下低下-1024681012678910606570758085Ca, P (mg/dl)Ca x Pwash outRenagelwashoutCaPCa x PSlatopolsky et al., KI 1999; 55: 299-307 吸附剂的临床评价 to Mortalityto Calcification 死亡率 PB ans Survival in low P HD, ArMORR studyIsakova T et al., JASN 2009; 20: 388nObservation study, new HD, 10,044 ptsnPhosphate bin
18、der vs non PB in low serum P ptsn使用使用吸附剂后生存率良好吸附剂后生存率良好P5.6mg/dLALLPBNon PBRR：0.90p0.40RR：0.72p0.03RR：0.70p0.02RR：0.63p0.002RR：0.75p0.0Sevelamer-HCl and calcium-based binders on mortality: Dialysis Clinical Outcomes Revisited (DCOR) studySuki WN et al., KI 2007; 72: 1130nRandomized 2103, HD pts, Fol
19、lowed up: 20 months. nSevelameror a calcium-based PB (70% CA or 30% CCB),nOnly 1068 patients completed the study n死亡率上无差别死亡率上无差别n65岁以上的高龄者岁以上的高龄者 sevelamer-HCl therapy（非（非Ca-PB)有效有效 MortalityAge 65yrPhosphate Binders in CKD: A Systematic Review Navaneethan SD, et al., AJKD 2009; 54: 619n生存率Sevelamer
20、 vs Ca-ABRiC 2009,Bleyer 1999CARE-2 2008,Ferreira 2008Hervas 2003,Qunibi 2004Sevelamer vs Ca-PBRIND 2007, Treat to Goal 2002DCOR 2007TotalFavorssevelamerFavorsCa-PBSummery of clinical studies n使用Non Ca-PB、 与Ca-PB相比、估计能抑制血管钙化的进展n对生存率的影响、从研究或观察时间来看都较短、现在还不清楚。KDIGO 2009 Research recommendations n通过PB降低
21、血磷的预后（死亡、心血管病、骨痛、骨折）是否改善了？nLanthanum carbonate 在CKD 5D上能改善血管碳化？n使用非Ca-PB来推迟血管钙化能否得到良好的生存？n通过透析处方的改变能否改善CKDMBD的预后？Lanthanum carbonate确认6年的安全性关于安全性Finn WF et al. Clin Nephrol 2006;65:191202 频率最高的副作用为胃肠不适（恶心、呕吐、腹泻） Lanthanum carbonate在临床上对肝功能和血液学上无异常。 肝功能/胆道系统的异常与控制组一样。 无证据表明损害红血球。 高Ca血症的频率少4.3% Lanthanum carbonate vs 8.4% standard therapy透析患者的FGF-23变化nFGF-23低下血清 Ca低下血清低下PTXnFGF-23上升血清上升Calicitoriol使用Ca-PB高Ca透析液的使用 FGF-23：surrogate marker in CKD 5D ?“谢谢您您。 。”结束语结束语谢谢大家聆听！谢谢大家聆听！44
