1、CRRT的规范化治疗 概述连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)是指一组体外血液净化的治疗技术,是所有连续、缓慢清除水分和溶质治疗方式的总称。传统CRRT 技术每天持续治疗24 小时,目前临床上常根据患者病情治疗时间做适当调整。CRRT 的治疗目的已不仅仅局限于替代功能受损的肾脏,近来更扩展到常见危重疾病的急救,成为各种危重病救治中最重要的支持措施之一,与机械通气和全胃肠外营养地位同样重要。血液净化标准操作规程(2010 版)CRRT CRRT is any extracorpreal blood purificattion t
2、herapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours/day 所谓CRRT也就是指所有每天24小时或接近24小时的缓慢、连续清除水和溶质的治疗方法。历史1977年,Kramer等首先提出了连续性动静脉血液滤过(continuous arterio-venous hemofiltration,CAVH)1979年,Bambauer-Bishoff提出连续性静脉-静
3、脉血液滤过(CVVH)1980年,Paganini提出缓慢连续性超滤(SCUF)1984年Geronemus 提出CAVHD,1987-CVVHD1985年Ronco首次将CAVHDF应用于治疗l例败血症合并MODS患者1992年Grootendorst 提出高容量血液滤过(high volume hemofiltration,HVHF)1998年,Tetra等提出连续性血浆滤过吸附(CPFA)主要技术缓慢连续超滤(slow continuous ultrafiltration,SCUF)连续性静静脉血液滤过(continuous venovenous hemofiltration,CVVH)
4、连续性静静脉血液透析滤过(continuous venovenous hemodiafiltration,CVVHDF)连续性静静脉血液透析(continuous venovenous hemodialysis,CVVHD)连续性高通量透析(continuous high flux dialysis,CHFD)连续性高容量血液滤过(high volume hemofiltration,HVHF)连续性血浆滤过吸附(continuous plasmafiltration adsorption,CPFA)血液净化标准操作规程(2010 版)总 结急性肾损伤急性肾损伤(acute kidney in
5、jury,AKI)是指发生急性肾功能异常,包括从肾功能微小改变到最终肾衰竭整个过程。RIFLE Criteria for Acute Renal DysfunctionRiskInjuryFailureLossESRDIncreased creatinine x1.5 or GFR decrease 25%End Stage Renal Disease GFR Criteria*Urine Output CriteriaUO .3ml/kg/hx 24 hr or Anuria x 12 hrsUO .5ml/kg/hx 12 hrUO 50%Increase creatinine x3or
6、GFR dec 75%or creatinine 4mg/dl(Acute rise of 0.5 mg/dl)HighSensitivityHighSpecificityPersistent ARF*=complete loss of renal function 4 weeks Oliguria“Acute on Chronic”DiseaseBaseline0.5(44)1.0(88)1.5(133)2.0(177)2.5(221)3.0(265)Risk0.75(66)1.5(133)2.3(200)3.0(265)3.8(332)-Injury1.0(88)2.0(177)3.0(2
7、65)-Failure1.5(133)3.0(265)4.0(350)4.0(350)4.0(350)4.0(350)Creatinine is expressed in mg/dL and(mcmol/L).AKIN分层标准 Stage Serum creatinine criteria Urine output criteria 1 Increase in serum creatinine of more than or equal to 0.3 mg/dl Less than 0.5 ml/kg per (26.4 mol/l)or increase to hour for more t
8、han 6 hours more than or equal to 150%to 200%(1.5-to 2-fold)from baseline 2 Increase in serum creatinine to Less than 0.5 ml/kg per more than200%to 300%hour for more than 12hours (2-to 3-fold)frombaseline 3 Increase in serum creatinine to Less than 0.3 ml/kg per more than300%(3-fold)from hour for 24
9、 hours or baseline(or serumcreatinine of anuria for 12 hours more than or equato 4.0 mg/dl 354 mol/l with an acute increaseof at least 0.5 mg/dl 44 mol/l)适应症肾脏疾病非肾脏疾病血液净化标准操作规程(2010 版)肾脏疾病重症急性肾损伤(AKI)伴血流动力学不稳定和需要持续清除过多水或毒性物质,如AKI合并严重电解质紊乱、酸碱代谢失衡、心力衰竭、肺水肿、脑水肿、急性呼吸窘迫综合征(ARDS)、外科术后、严重感染等。慢性肾衰竭(CRF)合并急性
10、肺水肿、尿毒症脑病、心力衰竭、血流动力学不稳定等。血液净化标准操作规程(2010 版)Acute renal failureAsymptomatic,nonoliguric,adequate nutrition possible(Non)oliguric,haemodynamically stable;life-threathening hyperkalaemia(Non)oliguric,haemodynamically unstableHigh risk of bleedingNo high riskExpectative(Increasing)uraemiaIHD#UnstableCit
11、rate-CRRTCRRTStableAlgorithm for the dialytic treatment of acute renal failure according to circumstancesIHD=intermittent haemodialysis,CRRT=continuous renal replacement therapy.Delay initiation of dialytic treatment to maximise the odds of native renal recovery,#if no citrate-protocol for CRRT,hepa
12、rin-free IHD may be used as alternative treatment.非肾脏疾病 非肾脏疾病包括多器官功能障碍综合征(MODS)、脓毒血症或败血症性休克、急性呼吸窘迫综合征(ARDS)、挤压综合征、乳酸酸中毒、急性重症胰腺炎、心肺体外循环手术、慢性心力衰竭、肝性脑病、药物或毒物中毒、严重液体潴留、需要大量补液、电解质和酸碱代谢紊乱、肿瘤溶解综合征、过高热等血液净化标准操作规程(2010 版)禁忌症CRRT无绝对禁忌证,但存在以下情况时应慎用。无法建立合适的血管通路。严重的凝血功能障碍。严重的活动性出血,特别是颅内出血。血液净化标准操作规程(2010 版)Poten
13、tial indications for CRRT in the ICUNonobstructive oliguria(urine output 200 ml/12 h)or anuriaSevere acidaemia(pH 30 mmol/l)Hyperkalaemia(K+6.5 mmol/l or rapidly rising K+)*Suspected uraemic organ involvement(pericarditis/encephalopathy/neuropathy/myopathy)Bellomo and Ronco Crit Care 2000,4:339345Po
14、tential indications for CRRT in the ICUProgressive severe dysnatraemia(Na+160 or 39.5C)Clinically significant organ oedema(especially lung)Drug overdose with dialyzable toxinCoagulopathy requiring large amounts of blood products in patient with or at risk of pulmonary oedema/ARDSAny one of these ind
15、ications constitutes sufficient grounds for considering the initiation of CRRT.Two of the above criteria make CRRT highly desirable.Combined disorders suggest the initiation of CRRT even before some of the above-mentioned limits have been reached.*IHD removes potassium more efficiently than CRRT.How
16、ever,if CRRT is started early enough,hyperkalaemia is easily controlled.For example,a fulminant liver failure patient with adult respiratory distress syndrome(ARDS),an international normalized ratio 3 and spontaneous epistaxis.Unless volume is rapidly removed,as fresh frozen plasma is rapidly given,
17、the patient is very likely to develop pulmonary oedema.治疗前患者评估选择合适的治疗对象,以保证CRRT 的有效性及安全性。患者是否需要CRRT治疗应由有资质的肾脏专科或ICU 医师决定。肾脏专科或ICU 医师负责患者的筛选、治疗方案的确定等。血液净化标准操作规程(2010 版)CRRT现状调查Uchino等报道:前瞻性、观察研究结果,2000.9-2001.12,23个国家、54家ICU、1006例患者的CRRT应用情况。除1例外均采用V-V通路,CVVH占52.8%,33.1%不抗凝,平均剂量为20.4ml/kg/h,仅11.7%35m
18、l/kg/h。CRRT现状调查常用抗凝剂肝素42.9%、枸橼酸9.9%、甲磺酸萘莫司他6.1%、低分子肝素4.4%。常见并发症为低血压19%,心律失常4.3%,出血3.3%,其中应用低分子肝素者出血为11.4%医院死亡率为63.8%,存活者中有85.5%肾功能恢复Age(years)66(5174)Reasons to start CRRTGender(male)662/1006(65.8%)Oliguria/anuria 703/1002(70.2%)Premorbid renal function High urea/creatinine 531/1002(53.0%)Normal 590
19、/1006(58.6%)Metabolic acidosis 437/1002(43.6%)Chronic impairment 283/1006(28.1%)Fluid overload 368/1002(36.7%)Unknown 133/1006(13.2%)Hyperkalemia 186/1002(18.6%)SAPS II 48(3962)Immunomodulation 136/1002(13.6%)Predicted mortality(%)41.5(23.071.4)Others 70/1002(7.0%)Hospital to ICU(days)1(07)ICU morta
20、lity 555/1003(55.3%)ICU to start(days)1.2(0.44.1)Hospital mortality 641/999(64.2%)Contributing factors to ARF SMR 1.38(1.281.50)Sepsis/septic shock 504/1003(50.2%)Major surgery 377/1003(37.6%)Low cardiac output 262/1003(26.1%)Hypovolemia 201/1003(20.0%)Drug induced 176/1003(17.5%)Hepatorenal syndrom
21、e 73/1003(7.3%)Obstructive uropathy 20/1003(2.0%)Others 114/1003(11.4%)Data are presented as median and interquartile ranges(25th75th percentiles)or percentages;SAPS II,Simplified Acute Physiology score;Hospital to ICU,duration betweenhospital admission and intensive care unit admission;ICU to start
22、,duration between intensive care unit admission and study inclusion;ARF,acute renal failure;SMR,standardized mortality ratio;ICU,intensive care unit病人基本情况Intensive Care Med(2007)33:15631570CRRT mode AnticoagulationCVVH 531/1006(52.8%)Unfractionated heparin 429/1000(42.9%)CVVHDF 342/1006(34.0%)Sodium
23、 citrate 99/1000(9.9%)CVVHD 132/1006(13.1%)Nafamostat mesilate 61/1000(6.1%)CAVHD 1/1006(0.1%)Low-molecular-weight 44/1000(4.4%)Dilution site for replacement fluid heparinPredilution 509/870(58.5%)Prostacyclin 11/1000(1.1%)Postdilution 361/870(41.5%)Hirudin 9/1000(0.9%)Filter material Heparin-protam
24、ine 6/1000(0.6%)Polyacrylonitrile 457/975(46.9%)Others b 3/1000(0.3%)Polysulfone 209/975(21.4%)Combination c 7/1000(0.7%)Polyamide 164/975(16.8%)No anticoagulation 331/1000(33.1%)Cellulose triacetate 89/975(9.1%)Polymethyl-methacrylate 27/975(2.8%)Polyarylether-sulfone 14/975(1.4%)Cellulose diacetat
25、e 11/975(1.1%)Others a 4/975(0.4%)a 3 Polyester-polymer-alloy,1 ethylene-vinyl alcohol;b 2 danaparoid,1 warfarin;c 4 heparin-citrate,2 heparin-prostacyclin,1 nafamostat mesilate-low-molecular-weight heparinCRRT使用情况Intensive Care Med(2007)33:15631570Hypotension 188/1000(18.8%)Bleeding 33/997(3.3%)Ind
26、welling vascular catheter sites 13/997(1.3%)Intra-abdominal 3/997(0.3%)Gastrointestinal 3/997(0.3%)Nostril 3/997(0.3%)Sternal wound 3/997(0.3%)Others a 8/997(0.8%)Arrhythmia 43/1000(4.3%)Atrial fibrillation 24/1000(2.4%)Supraventricular tachycardia 7/1000(0.7%)Cardiac arrest 4/1000(0.4%)Bradycardia
27、3/1000(0.3%)Ventricular tachycardia 3/1000(0.3%)Atrial flutter 1/1000(0.1%)Ventricular fibrillation 1/1000(0.1%)a Intracranial,lower leg,bone marrow aspiration site,oral,and pericardial并发症Intensive Care Med(2007)33:15631570Venkataraman et al,J Crit Care,2002CRRT处方与实际完成的比较何时开始CRRT?目前没有统一的标准:“时间”、指标等均
28、不统一。Getting等报道:早期开始RRT(BUN 42.6mg/dl )比晚期(BUN 94.5mg/dl)RRT的生存率高(39%-20%)Intensive Care Med 1999;25:805-813.All Early starters:Late starters:p value (n=100)BUN 60 mg/dl (n=41)(n=59)BUN prior to CRRT(mg/dl)73.2(39.6)42.6(12.9)94.5(28.3)0.0001Serum creatinine prior to CRRT(mg/dl):nonrhabdomyolysis pat
29、ients(n=89)a 3.26(1.8)2.69(1.6)3.59(4.3)0.025Serum creatinine prior to CRRT(mg/dl)rhabdomyolysis patients only(n=11)5.94(1.2)5.73(1.06)6.50(1.8)0.387Creatinine clearance prior to CRRT(ml/min)b 15.1(19.3)17.4(26.4)13.4(11.6)0.332Albumin prior to CRRT(g/dl)c 2.61 2.76 2.50 0.049Oliguric on CRRT day 1(
30、%)46.00 56.10 39.00 0.091Heart rate(beats/min)110.0 116.8 105.3 0.001Mean blood pressure(mmHg)88.0 87.8 88.2 0.915Cardiac index(l/min per m2)5.07 4.95 5.15 0.525Stroke volume(ml)91.8 85 96.6 0.056Oxygen delivery index(ml O2/min per m2)738.8 707.6 760.4 0.239Patients meeting SIRS criteria prior to CR
31、RT(%)91.20 94.60 88.90 0.345Hospital day of CRRT initiation 15.8(23.4)10.5(15.3)19.4(27.2)24小时,无尿12小时;BUN25-30mmol/lAm J Respir Crit Care Med Vol 162.pp 191196,2000治疗模式选择临床上应根据病情严重程度以及不同病因采取相应的CRRT模式及设定参数。SCUF和CVVH用于清除过多液体为主的治疗;CVVHD用于高分解代谢需要清除大量小分子溶质的患者;CHFD适用于ARF伴高分解代谢者;CVVHDF有利于清除炎症介质,适用于脓毒症患者;CP
32、FA主要用于去除内毒素及炎症介质。血液净化标准操作规程(2010 版)CRRT 常用治疗模式比较常用治疗模式比较 SCUF CVVH CVVHD CVVHDF血流量(血流量(ml/min)50100 50200 50200 50200透析液流量(透析液流量(ml/min)1020 1020清除率(清除率(L/24h)1236 1436 2040超滤率(超滤率(ml/min)25 825 24 812中分子清除力中分子清除力 血滤器血滤器/透析器透析器 高通量高通量 高通量高通量 低通量低通量 高通量高通量置换液置换液 无无 需要需要 无无 需要需要溶质转运方式溶质转运方式 无无 对流对流 弥散
33、弥散 对流弥散对流弥散有效性有效性 用于清除液体用于清除液体 清除较大分清除较大分 清除小分子清除小分子 清除中小分清除中小分 子物质子物质 物质物质 子物质子物质CRRT剂量慢性肾衰血透的剂量要求是:kt/V1.2CRRT的治疗剂量目前尚无统一意见高容量血液滤过(HVHF)在严重感染、重症胰腺炎(SIRS)中受推崇。41%57%58%Saudan et al,Kidney Int 2006Saudan et al,Kidney Int 2006Bouman研究Bouman et al.,Crit Care Med 2002Bouman et al.,Crit Care Med 2002Bou
34、man et al.,Crit Care Med 2002Schiffl et al,NEJM 2002Schiffl研究:IHD剂量与预后关系Schiffl et al,NEJM 2002Schiffl研究:IHD剂量与预后关系Schiffl et al,NEJM 2002Schiffl研究:IHD剂量与预后关系Kellum,Nature Clin Pract Nephrol 2007治疗剂量与预后的关系Palevsky et al,NEJM 2008;349(May 20)不同治疗强度间死亡率比较RENAL研究:Randomized Evaluation of Normal versus
35、Augmented Level Replacement Therapy Study KaplanMeier Estimates of the Probability of Death.Mortality at 28 days was similar in the higher-intensity and lower-intensity treatment groups(38.5%and 36.9%,respectively),and mortality at 90 days was the same(44.7%)in both groups.N Engl J Med 2009;361:1627
36、-38.透析剂量推荐采用体重标化的超滤率作为剂量单位ml/(kgh)。CVVH 后置换模式超滤率至少达到3545 ml/(hkg)才能获得理想的疗效,尤其是在脓毒症、SIRS、MODS 等以清除炎症介质为主的情况下,更提倡采用高容量模式。血液净化标准操作规程(2010 版)血管通路 临时导管常用的有颈内、锁骨下及股静脉双腔留置导管,右侧颈内静脉插管为首选,置管时应严格无菌操作。提倡在B 超引导下置管,可提高成功率和安全性。带涤纶环长期导管若预计治疗时间超过3 周,使用带涤纶环的长期导管,首选右颈内静脉。血液净化标准操作规程(2010 版)抗凝方案普通肝素:采用前稀释的患者,一般首剂量1520m
37、g,追加剂量510mg/h,静脉注射;采用后稀释的患者,一般首剂量2030mg,追加剂量815mg/h,静脉注射;治疗结束前3060 分钟停止追加。抗凝药物的剂量依据患者的凝血状态个体化调整;治疗时间越长,给予的追加剂量应逐渐减少。血液净化标准操作规程(2010 版)抗凝方案低分子肝素:首剂量6080IU/kg,推荐在治疗前2030 分钟静脉注射;追加剂量3040IU/kg,每46 小时静脉注射,治疗时间越长,给予的追加剂量应逐渐减少。有条件的单位应监测血浆抗凝血因子Xa 活性,根据测定结果调整剂量。血液净化标准操作规程(2010 版)抗凝方案局部枸橼酸抗凝枸橼酸浓度为4%46.7%,以临床常
38、用的一般给予4%枸橼酸钠为例,4%枸橼酸钠180ml/h 滤器前持续注入,控制滤器后的游离钙离子浓度0.250.35mmol/L;在静脉端给予0.056mmol/L 氯化钙生理盐水(10%氯化钙80ml 加入到1000ml 生理盐水中)40ml/h,控制患者体内游离钙离子浓度1.01.35mmol/L;直至血液净化治疗结束。也可采用枸橼酸置换液实施。重要的是,临床应用局部枸橼酸抗凝时,需要考虑患者实际血流量、并应依据游离钙离子的检测相应调整枸橼酸钠(或枸橼酸置换液)和氯化钙生理盐水度。血液净化标准操作规程(2010 版)抗凝方案阿加曲班:一般12g/(kgmin)持续滤器前给药,也可给予一定的
39、首剂量(250g/kg 左右),应依据患者凝血状态和血浆部分活化凝血酶原时间的监测,调整剂量。无抗凝剂:治疗前给予4mg/dl 的肝素生理盐水预冲、保留灌注20 分钟后,再给予生理盐水500ml 冲洗;血液净化治疗过程每3060 分钟,给予100200ml 生理盐水冲洗管路和滤器。血液净化标准操作规程(2010 版)血滤器或血透器选择根据治疗方式选择血滤器或血透器,通常采用高生物相容性透析器或滤器。血液净化标准操作规程(2010 版)置换液电解质:原则上应接近人体细胞外液成分,根据需要调节钠、钾和碱基浓度。碱基常用碳酸氢盐或乳酸盐,但MODS 及脓毒症伴乳酸酸中毒、合并肝功能障碍者不宜用乳酸盐
40、。采用枸橼酸抗凝时,可配制低钠、无钙、无碱基置换液。血液净化标准操作规程(2010 版)碳酸氢盐置换液成份及浓度钠 135145 mmol/L钾 04 mmol/L氯 85120 mmol/L碳酸氢盐 3040 mmol/L钙 1.251.75 mmol/L镁 0.250.75 mmol/L(可加MgSO4)糖 100200 mg/dl(5.511.1 mmol/L)血液净化标准操作规程(2010 版)置换液糖:浓度通常为100200 mg/dl,无糖置换液可引起低血糖反应,高糖溶液可能引起高血糖症,不建议使用。温度:在温度较低的环境中补充大量未经加温的置换液可能导致不良反应。应注意患者的保暖
41、和置换液/透析液加温。细菌学检查:必须使用无菌置换液。高通量透析可能存在反向滤过,应使用无菌透析液血液净化标准操作规程(2010 版)置换液前稀释与后稀释模式:对于CVVH 和CVVHDF 模式,置换液既可以从血滤器前的动脉管路输入(前稀释法),也可从血滤器后的静脉管路输入(后稀释法)。后稀释法节省置换液用量、清除效率高,但容易凝血,因此超滤速度不能超过血流速度的30%。前稀释法具有使用肝素量小、不易凝血、滤器使用时间长等优点;不足之处是进入血滤器的血液已被置换液稀释,清除效率降低,适用于高凝状态或血细胞比容35者。血液净化标准操作规程(2010 版)CRRT与IHD与IHD相比,CRRT有利
42、于ARF患者肾功能的恢复CRRT对降低死亡率似乎有优势,但意见不一,目前无定论。Curr Opin Crit Care 12:538-43对急性肾衰不同地区治疗模式的选择Liao et al,Artif Organs 2003不同模式对血尿素氮的影响 CRRT(n=65)IHD(n=28)P valueTime to RRT(hr)84(80)68(60)0.52Age(yr)54.7(15.4)62.6(13.4)0.02GenderMale 45(69%)17(61%)0.43Female 20(31%)11(39%)Diagnostic groupMedical 46(71%)17(61
43、%)Surgical 12(18%)10(36%)0.23Transplant 7(11%)1(3%)APACHE II score 25.1(7.3)23.5(8.5)0.37TISS 47.8(1.3)37.6(2.0)0.0001Mechanical ventilation 65(100%)28(100%)1.0Acute lung injury 32(49%)6(21%)0.01Admission serum 289(217)410(223)0.02creatinine(moLL1)Vasoactive drugs required 40(62%)10(36%)0.02不同RRT模式病
44、人的基本情况Jacka et al.CAN J ANESTH 2005/52:3/pp 327332 CRRT IHD P value (n=65)*(n=28)*Oliguria 600 moLL1 8(12%)5(18%)0.48Urea 35 mmoLL1 11(17%)10(36%)0.05K 6 mmoLL1 3(5%)2(7%)0.62pH 5 gkg1min1 18(27%)6(18%)0.53Epinephrine 15(23%)1(3%)0.02Norepinephrine 29(44%)5(15%)0.014Cross over to alternate 18(67%)0(
45、0%)0.002mode of RRTJacka et al.CAN J ANESTH 2005/52:3/pp 327332A)ICU survival vs RRT mode Survived DiedCRRT 29(45%)36(55%)IHD 20(71%)8(29%)P=0.02B)Hospital survival vs RRT mode Survived DiedCRRT 24(37%)41(63%)IHD 14(50%)14(50%)P=0.24C)Renal recovery vs RRT mode Recovered Chronic dialysisCRRT 21(87%)
46、3(13%)IHD 5(36%)9(63%)P=0.0003Jacka et al.CAN J ANESTH 2005/52:3/pp 327332结果比较Clark et al,Blood Purif 2006肾功能的恢复Uchino et al,Int J Artif Organs 2007肾功能的恢复Bell et al,Intensive Care Med 2007肾功能的恢复Mehta et al(2002)肾功能的恢复Manns et al,Crit Care Med 2003肾功能的恢复谁管理CRRT?肾科医务人员ICU医务人员两者合作危重肾脏病专家Mehta RL,Letter
47、i JM:Current Status ofRRT for ARF.AJN 1999;19:377-82谁管理CRRT?Ronco C et al:Management of severe ARFin critically ill patients:Intl.Survey 345 ctrs.Nephrology Dial Transpl 2001;16:23037谁管理CRRT?Curr Opin Crit Care 12:538-43在ICU中谁管理RRTSome guidelines to deliver adequate CRRT on the ICU Start early:oligu
48、ria 24 hours or anuria 12 hours;uraemia25-30 mmol/l Prescribe adequate dialysis dose:daily Kt/V 1.2;UF volume35 ml/kg/h Use(semi)synthetic biocompatible high-flux membranes Use the venovenous approach,preferably internal jugular vein Maximise UF flow rate,before adding slow-dialysisVan Bommel.Renal
49、replacement therapy for acute renal failure on the intensive care unit:coming of age?Some guidelines to deliver adequate CRRT on the ICU In case of severe liver dysfunction,use bicarbonate as buffering anion Judicious use of anticoagulation to improve delivered dialysis dose Prescribe 1.2-1.4 g prot
50、ein/kg/day to improve nitrogen balance If the patient is stabilised,switch to intermittent treatmentVan Bommel.Renal replacement therapy for acute renal failure on the intensive care unit:coming of age?指导意见 严重急性肾衰患者应进行肾脏替代治疗 何时开始肾脏替代治疗尚无一致意见,但应在严重并发症出现前开始;有限的证据显示:早期开始有利于改善预后 无明确的统一的关于选择肾脏替代治疗模式的推荐意见