ckdmbd规范治疗精选

1、1会计学ckdmbd规范治疗精选规范治疗精选Moe S, et al. Kidney Int. 2019;69:1945-1953.血磷升高血磷升高1羟化酶活性羟化酶活性PTHFGF-231,25(OH)1,25(OH)2 2D D升高升高1,25(OH)1,25(OH)2 2D D下降下降肾脏磷排泄肾脏磷排泄刺激抑制Martinez I,Saracho R,et al.NDT 2019,11 Suppl 3:22-28eGFR (mL/min/1.73 m2)152535455565758595105100200300400010203040iPTH (pg/mL)1,25(OH)2D3Ca

2、lcitriol (pg/mL)Stage 37.4 millionStage 25.7 millionStage 4300,000CKD Stage 15.6 million 2570targettargetMartinez et al. NDT 2019;11:22-28.N=150eGFR (mL/min/1.73 m2)152535455565758595105100200300400010203040iPTH (pg/mL)1,25(OH)2D3Calcitriol (pg/mL)Stage 37.4 millionStage 25.7 millionStage 4300,000CK

3、D Stage 15.6 million 2570targettargetMartinez et al. NDT 2019;11:22-28.N=150从CKD第3期即需监测iPTH及血清钙、磷变化 K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in CKD，2019Martinez I, et al. Am J Kidney Dis. 2019;29:496-502.*P 100 and CrCl 50-59, N = 1570255075100125150175200100+90-9980-8970-

4、7960-6950-5940-4930-3920-2910-19CrCl mL/mPTH, pg/mL23456100+90-9980-8970-7960-6950-5940-4930-3920-2910-19CrCl mL/mmg/dLIonized CalciumPTH*PhosphorusAm J Kidney Dis. 2019 Sep;52(3):519-30.*P0.05 for comparison of individual vitamin D levelvitamin D treatment groups with corresponding referent groups.

5、Wolf M et al. Kidney International. Advance online publication, August 8, 2019. 1086420Odds ratio ofall-cause mortality25-hydroxyvitamin D (ng/mL)301086420Odds ratio ofCV mortality25-hydroxyvitamin D (ng/mL)301086420Odds ratio ofall-cause mortality1,25-dihydroxyvitamin D (pg/mL)131086420Odds ratio o

6、fCV mortality1,25-dihydroxyvitamin D (pg/mL)13*RRR* 接受接受vitamin D 治疗治疗 未接受未接受 vitamin D 治疗治疗DOQIKDIGOK/DOQIDialysisAnemiaAccessNutrition (00)Dialysis (01)*Anemia (01)*Access(01)*CKD class. (02)Bone/Mineral (03) Lipids (03)Htn (04)CV (05)Diabetes (07)Hep C (08)Bone/Mineral (09)20192019*updateskidney.

7、org/professionals//welcome.htm从CKD第3期即需监测iPTH及血清钙、磷变化 K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in CKD，2019Turnover High Normal LowMineralization Normal AbnormalVolume High Normal LowSlide courtesy of Susan Ott分类原则 疾病名称病理生理分类高转换骨病低转换骨病病理解剖分类纤维性骨炎无动力骨病 软骨病病

8、因学分类甲旁亢甲旁低等 活性VD缺乏铝中毒钙钙, Vitamin D PTH高转换型高转换型低转换型低转换型Normal bone formation动力缺失型骨软化Mild纤维性骨炎铝混合型骨病300-400 pg/mLSherrard DJ, et al. Kidney Int. 1993;43:436-442.Wang M, et al. Am J Kidney Dis. 2019;26:836-844.SCI 6.418分分Kidney International (2019) 70, 13581366骨折的发生率From DOPPS高磷血症高磷血症高钙血症高钙血症Elevated C

9、a x P骨代谢异常骨代谢异常基质沉积基质沉积尿毒症毒素尿毒症毒素血管平滑肌细胞血管平滑肌细胞成骨样细胞成骨样细胞刺激因子刺激因子Cbfa-1BMP-2钙化抑制因子的缺失钙化抑制因子的缺失Fetuin-AMatrix Gla Protein血管钙化血管钙化骨丧失了对钙磷缓冲的能力骨丧失了对钙磷缓冲的能力 GRFGRF下降下降Goodman WG et al. N Engl J Med. 2000;343:1478.1.00.60.5Proportion with calcification04812162024Duration of dialysis (yrs)钙化积分: 0

10、钙化积分: 1钙化积分: 2钙化积分: 3钙化积分: 4Probability of SurvivalDuration of Follow-up (months)020406080Blacher J et al. Hypertension. 2019;38:938.1.000.750.000.250.50Comparison between curves was highly significant (x2 = 42.66, P 0.0001)动静脉内瘘动静脉内瘘(AVF)CTMSCTX-线平片椎旁动脉钙化积分线平片椎旁动脉钙化积分 Abdominal Aorta calcification

11、were measured by Plain X-Ray film via the Kauppilas method(Kauppila et al Atherosclerosis 2019;132:235-240)Raggi et al. Kidney International 2019指南将超声评价瓣膜钙化的地位提升指南将超声评价瓣膜钙化的地位提升Bi-dimensional echocardiographic studies were performed utilizing Sequoia 512 (Siemens, Erlangen, Germany) or Vivid 7 (Gene

12、ral Electric, Milwaukee, WI) equipment. Aortic and mitral valve calcification were simply assessed as present or absent without applying any quantification methodRaggi et al. Kidney International 2019升高升高 FGF-23 PTH 血磷血磷降低降低: : 活性维生素活性维生素D D 血钙血钙 冠状动脉钙化冠状动脉钙化 主动脉钙化主动脉钙化 异常钙质沉积异常钙质沉积 骨组织学异常骨组织学异常 矿化矿

13、化 转换转换 容量容量 骨密度减低骨密度减低Moe S, et al. Kidney Int. 2019;69:1945-1953.KDIGO Overview slide presentation at: /pdf/KDIGO%20Overview%20Slide%20Set.pptK/DOQIKDIGOCKD3-4维持正常值 2.7 4.6 mg/dl维持正常值2.7 4.6 mg/dlCKD5-5D3.55.5mg/dl 没有给出CKD-5D期病人的血磷水平目标值，2C级建议为“降低以达到正常值” Cannata-Andia JB. Nephrol Dial Trans

14、. 2019;17(Suppl 11):1619.Ritz EJ. J Nephrol. 2019;18;221-228.Goodman WG. Neph Dial Trans. 2019;18(Suppl 3):iii2-iii8.Binder优点缺点含铝的强效的神经毒性，骨病（骨软化）含钙的价格便宜，广泛应用高钙风险，作用不如铝制剂强盐酸思维拉姆Sevelamer减低了高钙引起的血管钙化，降低胆固醇和低密度脂蛋白作用中等，价格太高碳酸镧强效的，减低了高钙引起的血管钙化价格太高，为稀有金属，安全性有待进一步评价CaPO4PTH磷结合剂磷结合剂(含钙的含钙的)含钙的磷结合剂有升高血钙的风险Ki

15、dney Int. 2019;62:245-252.碳酸镧碳酸镧（Lanthanum） Hutchison AJ, et al. Nephron Clin Pract. 2019;102:c61-c71.Ca x P decreasedSerum phosphate decreased0501001502000497510112815401234567nCa x P (mM2) Weeks10.09.08.07.05.04.02.00.0012345913172125293337414549Modal use of lanthanum carbonate: 1,500 mg/dayModal

16、use of calcium carbonate: 3,000 mg/dayWeeks on TreatmentSerum phosphate (mg/dL)Continued-lanthanum groupCalcium groupSwitch group (calcium to lanthanum)Comparator-controlled trial6.03.01.0K/DOQIKDIGOCKD3-4钙（专家意见）3-4期：没有优先推荐CKD5-5D任何能够有效降磷的药物都，但每日使用含钙磷结合剂中活性钙应小于1500mg，如果PTH150pg/ml或出现血管钙化则需使用不含钙的磷结合剂

17、（专家意见） 对磷结合剂没有特殊推荐（2B）。如果PTH低或动力缺失性骨病或血管钙化应限制使用含钙磷结合剂 01236.05.25.04.64.8Mean P (mg/dL) (95% CI)PhosphorusMonths After Initiation of IV Vitamin DCalcitriol (n = 2,667)Paricalcitol(n = 1,697)Doxercalciferol(n = 2,010)Tentori F, et al. Kidney Int. 2019;70:1858-1865. 0123400350300250200150100M

18、ean iPTH (pg/mL) (95% CI)019.08.68.4Mean Ca (mg/dL) (95% CI)iPTHCalciumMonthsMonthsMonths110110PTH reductionCa homeostasisHypercalcaemiaHyperphosphataemiaVascular calcificationI、适应症、适应症第1月第2月第3月目的：对比常规剂量（0.25ug/天）与两种冲击剂量（2ug每周2次，4ug每周2次）对继发性甲旁亢的疗效杜学海等，肾脏病与透析肾移植杂志 2019，7（3），230-23

19、4杜学海,张凌等，肾脏病与透析肾移植杂志 2019，7（3），230-234原则上应以最小的原则上应以最小的VitD3剂量，维持血剂量，维持血PTH、Ca、P 在合适的目标范围，并避免不良反应。在合适的目标范围，并避免不良反应。分期分期 PTH目标范围目标范围钙、磷维持水平钙、磷维持水平Ca*P3期期35-70pg/ml(3.85-7.7pmol/L)8.4-9.6mg/dl(2.10-2.37mmol/L)2.7-4.6mg/dl(0.87-1.49mmol/L)4期期70-110pg/ml(7.7-12.1pmol/L)同同 上上5期期150-300pg/ml(16.5-33pmol/L)

20、8.4-10.2mg/dl*(2.10-2.54mmol/L)3.5-5.5mg/dl(1.13-1.78mmol/L)根据根据CKD的不同分期，要求的不同分期，要求PTH维持相应目标范围，同时血维持相应目标范围，同时血Ca、P维持相应的正常水平维持相应的正常水平* 血钙应以矫正钙浓度为标准血钙应以矫正钙浓度为标准 矫正钙血清总矫正钙血清总Ca 0.8(4-白蛋白浓度白蛋白浓度g/dl)* CKD5期患者期患者 血血Ca. P. 浓度应尽量接近目标值的低限为佳。浓度应尽量接近目标值的低限为佳。钙磷乘积：钙磷乘积： Ca P55mg2/dL2 (4.52mmol2/L2) K/DOQI Clin

21、ical Practice GuidelinesiPTH：60-180pg/mL Ca:8.4-10.0 mg/dL P: 3.5-6.0mg/dL JSDT guideline 2019针对CKD5期CKD分分期期监测频率监测频率PTHCaP3、4期期6月内月内 至少至少1次次/3月月6月后月后 1次次/3月月3月内月内 1次次/月月3月后月后 1次次/3月月3月内月内 1次次/月月3月后月后 1次次/3月月5期期3月内月内 至少至少1次次/月月3月后月后 1次次/3月月1月内月内 1次次/2周周1月后月后 1次次/月月1月内月内 1次次/2周周1月后月后 1次次/月月治疗的初期，治疗的初期

22、，PTH尚未达到目标范围、活性维生素尚未达到目标范围、活性维生素D剂量尚未剂量尚未稳定及目标值变化大时，监测频率需增加；稳定及目标值变化大时，监测频率需增加；反之可适当延长监测间隔时间。平均约反之可适当延长监测间隔时间。平均约1-3月检测月检测1次。次。StartcinacalcetReduce Vit D+The Goal Is Control of BothPTH150-300 pg/mLCa x P 55 mg2/dL2SHPTTraditional Therapy Trade-offPTH150-300 pg/mLCa x P 55 mg2/dL2SHPTCONTROL: Cinacalcet OpeN Label Study To Reach K/DOQI LevelsFrancisco ALM et al. Expert Opin Pharmacother. 2019;9;795-8110200400600800100012001400iPTH(pg/ml)2周p0.0014周p0.00