急性肾损伤

null急性肾损伤急性肾损伤急性肾功能衰竭急性肾功能衰竭1951年Homer W. Smith 1951年首次在他的The Kidney–Structure and Function in Health and Disease一书中的“Acute renal failure related to traumatic injuries”章节提出急性肾功能衰竭(acute renal failure )概念。 但没有确切的生化指标的定义；至今仍没有一个统一的，据统计多达数十种之多。急性肾功能衰竭急性肾功能衰竭急性肾功能衰竭是指肾小球滤过功能在数小时至数周内迅速降低而引起的以水、电解质和酸碱平衡失调及以邯郸废物蓄积为主要特征的一组临床综合征。按尿量多寡分为少尿型和非少尿型，少数ARF患者可无症状，仅在常规生化检查中才发现血尿素氮（BUN）和血清肌酐（Scr）升高。 标准；血肌酐浓度升高44.2µmol/L（0.5mg/dl）(实用内科学)急性肾损伤急性肾损伤由于肾衰标准的不统一，给临床、科研以及规范的制定等带来了极大困难。 据报道：急性肾功能衰竭占ICU病人的1%～25%，死亡率达15% ～ 60%也有报道为40% ～90% 2004年， ADQI（Acute Dialysis Quality Initiative）提出急性肾损伤概念以及RIFLE 诊断及分层标准。 急性肾损伤(acute kidney injury，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一个过程。 急性肾损伤急性肾损伤2005年 AKIN(Acute Kidney Injury Network)专家（包括危重病、肾脏病以及成人和儿童AKI专家）在荷兰的阿姆斯特丹召开会议，提出AKI的诊断和分层的标准。 与RIFLE相比较有如下特点：1.时间窗为48小时;2.把血肌酐升高≥ 0.3mg/dl列入标准;3.把AKI分为1、2、3期，不用R、I、F的分层法;4.任何需要RRT治疗的病人都归入3期;5.把‘Loss’ and ‘End-stage kidney disease’从分层系统中去除而作为结果处理。 null急性肾损伤临床特点： 是一个连续的过程 包括肾功能的轻微改变到肾功能衰竭 Scr并不能早期、精确反应肾功能变化 一些损伤标志物可能具有早期诊断的价值 病因及发病：多种病因引起的临床综合征如：感染、创伤、中毒、药物、肾灌注不足、血管收缩等等。炎症反应在其发病机制中起重要作用。null肾损伤的生物标志物NGAL 肾损伤分子- 1 Cyr61 低分子蛋白 白介素18 其他 nullNGAL中性粒细胞明胶酶相关脂质运载蛋白(Neutrophil Gelatinase - Associated Lipocalin，NGAL) ，是lipocalin家族的新成员。在人类许多组织(如肾脏、肺)上均呈低达状态，但当上皮细胞受到刺激时会显著高表达。损伤的肾小管上皮细胞表达的NGAL可诱导肾小管间质中浸润的中性粒细胞发生凋亡以保护肾组织免受炎细胞的侵害。 研究发现NGAL能在肾损伤发生后的数小时内（Scr水平还没有明显的变化时）检测到null肾损伤分子- 1肾损伤分子- 1 (kidney injury molecule – 1， KIM -1)是一种跨膜蛋白，在正常的肾组织中几乎不表达，但在缺血及肾毒性损伤后的人和啮齿动物的近曲小管上皮细胞中呈高表达状态。 研究发现KIM - 1蛋白可以在缺血性肾损伤后12h内在病人的尿中检测到，升高的程度远远高于其他原因引起的肾损伤患者 同时对区分近端小管损伤有较高的特异性nullCyr61Cyr61 (cysteine-rich protein 61)是一种分泌性蛋白。 Muramatsu等研究证明Cyr61在肾脏局部缺血后迅速在近曲小管中产生并分泌于尿液中。3～6h能在尿中测得，6～9h达到峰值，此后迅速降低。 由于持续时间短，临床应用中它的时间点难以把握。null低分子蛋白低分子蛋白：包括胱抑素C(cystatin C)、α1 -微球蛋白、β2 - 微球蛋白和视黄醇结合蛋白(RBP)。几乎完全被肾小球滤过，不被肾小管重吸收和分泌。 血液中低分子蛋白值的升高可以看作近曲小管细胞受损的标志。它比血清肌酐更准确、灵敏的反映出肾功能的变化，同时也可以帮助判断预后，评估是否需要RRT治疗。 其中cystatin C的灵敏性和稳定性等高于其他几个低分子蛋白，是一个理想的肾小球滤过率指标。 null白介素18白介素18（IL – 18）：实验证明，在缺血性肾损伤中， IL - 18能在近端小管被大量检测到；尿中IL - 18在已经确诊AKI的病人中有90%的特异性和敏感度。并且缺血性ATN患者在Scr值尚未明显增高前就能检测出高价的尿IL - 18值。 Parikh等对接受心肺转流术的患者进行研究，发现最终发生AKI的患者术后4～6h内便能测得尿IL -18,，12h达到峰值，48h后仍保持高水平。而Scr则在术后48～72h才能升高nullSSATSSAT ( Spermidine / spermine N – acetyltransferase， SSAT)在急性缺血性肾损伤中能早期大量地表达，且能作为区分肾小管损伤和肾实质损伤的标志物nullRIFLE Criteria for Acute Renal DysfunctionRiskInjuryFailureLossESRDIncreased creatinine x1.5 or GFR decrease > 25%End Stage Renal Disease GFR Criteria*Urine Output CriteriaUO < .3ml/kg/h x 24 hr or Anuria x 12 hrsUO < .5ml/kg/h x 12 hrUO < .5ml/kg/h x 6 hrIncreased creatinine x2 or GFR decrease > 50% Increase creatinine x3 or GFR dec >75% or creatinine 4mg/dl (Acute rise of 0.5 mg/dl) High SensitivityHigh SpecificityPersistent ARF** = complete loss of renal function > 4 weeks Oligurianull“Acute on Chronic” DiseaseCreatinine is expressed in mg/dL and (mcmol/L). AKIN诊断标准AKIN诊断标准An abrupt (within 48 hours) reduction in kidney function absolute increase in serum creatinine of more than or equal to 0.3mg/dl (≥ 26.4 μmol/l) a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline) a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours).AKIN分层标准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 μmol/l) or increase to hour for more than 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 hours or baseline(or serumcreatinine of anuria for 12 hours more than or equato 4.0 mg/dl [≥ 354 μmol/l] with an acute increaseof at least 0.5 mg/dl [44 μmol/l])两个标准的比较两个标准的比较Lopes等比较了RIFLE标准和AKIN标准对AKI发生率、分级以及医院死亡率的影响。 对象为葡萄牙里斯本de Santa Maria 医院ICU2003.2- 2006.12，共662例。 结果: AKIN标准对诊断AKI具有更高的敏感性，但对医院死亡率判断两者没有差别。Crit Care Med 2008 Lopes et al.nullIncidence of acute kidney injury stratified by the Risk, Injury, Failure, Loss of Kidney Function, End-stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN) definition/classification schemes RIFLE classification AKIN classification None 372 (56.2%) None 328 (49.5%) Risk 97 (14.7%) Stage 1 140 (21.1%) Injury 73 (11%) Stage 2 67 (10.1%) Failure 120 (18.1%) Stage 3 127 (19.2%) Any category 290 (43.8%) Any stage 334 (50.4%)Crit Care Med 2008 Lopes et al.nullPatients with acute kidney injury classified by creatinine criteria or urine output criteria, or both criteria Creatinine (%) Urine output (%) Creatinine + urine output (%) RIFLE classification Risk 85.5 5.2 9.3 Injury 68.5 6.8 24.7 Failure 44.2 5 50.8 Any category 64.1 5.6 30.3 AKIN classification Stage 1 87.1 3.6 9.3 Stage 2 73.1 7.5 19.4 Stage 3 42.5 4.7 52.8 Any category 67.4 4.8 27.8Crit Care Med 2008 Lopes et al.nullMortality according to acute kidney injury stratified by the Risk, Injury, Failure, Loss of Kidney Function, End-stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN) definition/classification schemes RIFLE classification AKIN classification None 11% None 8.5% Risk 30.9% Stage 1 30.7% Injury 32.8% Stage 2 32.8% Failure 55% Stage 3 53.5% Any category 41.3% Any stage 39.8%Crit Care Med 2008 Lopes et al.RIFLE标准的应用RIFLE标准的应用Hoste等报道应用RIFLE标准的单中心研究结果：2000.7.1—2001.6.30，一年时间，美国匹茨堡大学医学中心，7个ICU（120张病床）5383例病人。 入ICU 的第一天有 1182 patients (21.9%) 存在AKI，ICU 住院过程中 3,617 patients (67.2%) 发生AKI 根据RIFLE分级，R、I、F级医院死亡率分别为8.8%、11.4%、26.3%。没有AKI者死亡率为5.5%Critical Care Vol 10 No 3 Hoste et al.nullMaximum Risk 670 (12%) Maximum Injury 1436 (27%) Critical Care Vol 10 No 3 Hoste et al.nullEvolution of ARF by RIFLEPreliminary data Hoste et al. Crit Care 8 (Suppl 1): P81, 2004. nullOutcomes for all patients and for patients classified according to the maximum Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE) class No acute kidney injury Risk Injury Failure All injury (n = 1,766) (n = 670) (n = 1,436) (n = 1,511) (n = 5,383) Renal replacement therapy* 1 (0.1%) 0 (0%) 4 (0.3%) 214 (14.2%) 219 (4.1%) Hospital LOS after reaching maximum RIFLE class (days)* 5 (3–10) 5 (3–10) 7 (4–14) 11 (5–23) 7 (3–14) ICU LOS (days)* 3 (2–4) 3 (2–6) 5 (3–10) 9 (4–21) 4 (2–9) Hospital LOS (days)* 6 (4–10) 8 (5–14) 10 (6–19) 16 (9–31) 9 (5–19) Hospital mortality* 97 (5.5%) 59 (8.8%) 163 (11.4%) 398 (26.3%) 717 (13.3%)Critical Care Vol 10 No 3 Hoste et al.nullOstermann研究Ostermann研究Ostermann 等应用RIFLE标准回顾性1989至1999，英国和德国的22家ICU，Riyadh Intensive Care Unit Program 资料库，41,972 病人的资料，结果发现： 符合AKI标准的有15,019例(35.8%) ，根据 RIFLE 分级，R为7,207例(17.2%) ，I为4,613例(11%) ，F为 3,199例(7.6%) 。有 797例(2.3%) 入ICU时处ESKD阶段，依赖RRT治疗。Crit Care Med 2007 Vol. 35, No. 8结果分析结果分析医院死亡率：无AKI患者死亡率为8.4% ，AKI患者分别为20.9%（R），45.6%（I）和 56.8%（F）。与无AKI 相比较OR为2.11 （R）， 5.15 （I） 和 8.27 （F） 有 1,836 例患者接受RRT 治疗，1,473 例(80.2%) 为CRRT，95例 (5.2%) IHD，12 例 (0.7%)腹膜透析， 243 例(13.2%)CRRT和IHD， 12 patients (0.7%)先CRRT后续腹膜透析Crit Care Med 2007 Vol. 35, No. 8null Characteristics and outcome depending on degree of renal function No AKI(n 26,153) Risk(n 7,207) Injury(n 4,613) Failure(n 3,199) Age, yrs Mean 57.3 66.5 67.3 63.7 95% CI 57.2–57.5 66.2–66.7 66.9–67.7 63.2–64.2 SD 16.01 12.9 13.2 14.5 Range 16–99 16–99 16–97 16–96 APACHE II score at admission to ICU Median 11 15 19 22 Range 1–64 1–44 1–62 1–52 No. of associated failed organs at admission to ICU Median 0 0 1 1 Range 0–5 0–6 0–6 0–6 Maximum no. of associated failed organ systems Median 1 1 1 2 Range 0–5 0–6 0–6 0–6 Outcome ICU mortality, n (%) 1,307 (5.0) 1,057 (14.7) 1,686 (36.5) 1,523 (47.6) Hospital mortality, n (%) 2,204 (8.4) 1,505 (20.9) 2,104 (45.6) 1,816 (56.8) Survivors’ ICU length of stay,days Median 1 2 3 6 Range 1–112 1–270 1–219 1–193 Nonsurvivor’s ICU length of stay, days Median 2 2 3 5 Range 1–90 1–73 1–110 1–104null Impact of renal replacement therapy (RRT) Without RRT With RRT p Incidence, Hospital Incidence, Hospital No. (%) Mortality, No. (%) No. (%) Mortality, No. (%) No AKI (n 26,153) 26,085 (99.7) 2,190 (8.4) 68 (0.3) 14 (20.6) .0007 Risk (n 7,207) 7,126 (98.9) 1,449 (20.3) 81 (1.1) 56 (69.1) .0001 Injury (n 4,613) 4,207 (91.2) 1,791 (42.6) 406 (8.8) 313 (77.1) .0001 Failure (n 3,199) 1,918 (60) 1,071 (55.8) 1,281 (40) 745(58.2) .21Crit Care Med 2007 Vol. 35, No. 8Bagshaw研究Bagshaw研究Bagshaw等发表了一个多中心、大样本的。从AustralianNewZealand Intensive Care Society Adult Patient Database中，提取澳大利亚57个ICU，2000.1.1-2005.12.31间，120 123 例患者的资料（住ICU≥24小时）。应用RIFLE标准进行AKI分析。 AKI发生率为36.1%；RIFLE 分级：Risk 16.3%,，Injury 13.6% Failure 6.3%。 医院粗死亡率 ： Risk 17.9%， Injury 27.7% ， Failure 33.2% 。Nephrol Dial Transplant (2008) 23: 1203–1210null Incidence of AKI stratified by RIFLE criteria RIFLE category (%) SCr criteria only UO criteria only Both None 83 620 (69.6) 106 500 (88.7) 76 728 (63.9) Risk 17 184 (14.3) 5869 (4.9) 19 547 (16.2) Injury 13 253 (11.0) 5724 (4.8) 16 344 (13.6) Failure 6066 (5.1) 2010 (1.7) 7504 (6.3) Any RIFLEcategory 36 503 (30.4) 13 603 (11.4) 43 395 (36.1)Nephrol Dial Transplant (2008) 23: 1203–1210nullnull Clinical outcomes stratified by RIFLE category Clinical outcome None (n = 76 728) Risk (n = 19 547) Injury (n = 16 344) Failure (n = 7504) P Crude mortality (%) Creatinine criteria only 9.8 18.2 29.8 32.2 <0.001 Urine output criteria only12.1 28.8 33.5 40.8 <0.001 Both 8.9 17.9 27.7 33.2 <0.001 ICU Length of stay (days) Dead [median (IQR)] 4.1 (2.1–8.6) 4.0 (2.1–8.2) 3.7 (1.9–8.0) 3.4 (1.9–7.9) <0.001 Alive [median (IQR)] 2.1 (1.6–3.9) 2.7 (1.7–5.0) 3.3 (1.9–6.6) 3.9 (2.1–7.7) <0.001 Hospital length of stay (days) Dead [median (IQR)] 10.4 (4.6–23) 9.9 (4–3.22) 8.6 (3.4–20.3) 9.0 (3.4–20.3)<0.001 Alive [median (IQR)] 10.6 (6.9–19.1) 13 (7.9–23.7) 15.7 (9.0–29) 17.9 (9.9–32.8)<0.001 Discharge location of survivors (%) Home 85.3 80.8 77 75.3 <0.001 Transfer to other hospital 9.9 12.2 14.5 17 <0.001 Rehabilitation/ long-term care 4.8 7.0 8.5 7.7 <0.001 Nephrol Dial Transplant (2008) 23: 1203–1210sepsis与AKI sepsis与AKI Bagshaw 等进行亚组分析，sepsis病例33,375 (27.8%)。其中14,039例(42.1%) 合并AKI (septic AKI)，AKI病例中sepsis占32.4% 。 Septic AKI ，根据RIFLE分级：R、I、F分别为38.5%、 38.8% 和 22.7% 。 与nonseptic AKI 比较，疾病的严重程度重，死亡率高，住院时间长。Critical Care Vol 12 No 2 Bagshaw et al.null Summary of acute physiology and laboratory parameters by sepsis and AKInullIncidence of AKI stratified by RIFLE criteria and by an admission diagnosis of sepsis RIFLE category Nonseptic (n = 86,748) Septic (n = 33,375) None (%) 66.2 57.9 Risk (%) 16.3 16.2 Injury (%) 12.6 16.3 Failure (%) 5.0 9.6 Any RIFLE category (%) 33.8 42.1Critical Care Vol 12 No 2 Bagshaw et al.nullCritical Care Vol 12 No 2 Bagshaw et al.nullCritical Care Vol 12 No 2 Bagshaw et al.nullSecondary outcomes in ICU patients stratified by sepsis and AKI Clinical outcome None Sepsis, no AKI Nonseptic AKI Septic AKI P (n = 57,392) (n = 19,336) (n = 29,356) (n = 14,039) ICU length of stay (days) Dead (median [IQR]) 3.9 (2.1–8.1) 4.6 (2.3–9.5) 3.7 (1.9–7.7) 3.9 (2.0–8.8) 0.0001 Alive (median [IQR]) 2.1 (1.6–3.8) 2.4 (1.6–4.8) 2.8 (1.8–5.2) 3.8 (2.0–7.6) 0.0001 Hospital length of stay (days) Dead (median [IQR]) 10.2 (4.4–23.0) 10.6 (4.8–23.0) 9.0 (3.7–20.2) 9.5 (3.7–20.9) 0.0001 Alive (median [IQR]) 10.2 (6.9–18.2) 11.8 (6.7–22.7) 13.9 (8.1–25.1) 16.7 (9.5–30.9) 0.0001 Discharge location of survivors (%) Home 86.7 81 79.9 75.6 <0.0001 Transfer to other hospital 4.5 5.9 7.3 8.5 <0.0001 Rehabilitation /long-term care 8.8 13.1 12.8 15.9 <0.0001Critical Care Vol 12 No 2 Bagshaw et al.nullCritical Care Vol 12 No 2 Bagshaw et al.nullCritical Care Vol 12 No 2 Bagshaw et al.治疗治疗原发病的治疗 肾脏保护及防止或减轻肾损伤 抗炎治疗 肾脏替代治疗RRTRRT适应症 模式 时机 剂量 终止时机nullATN研究:the Veterans Affairs/National Institutes of Health (VA/NIH) Acute Renal Failure Trial NetworknullPalevsky et al, N Engl J Med 2008;359:7-20.ATN研究:the Veterans Affairs/National Institutes of Health (VA/NIH) Acute Renal Failure Trial NetworknullRENAL研究：Randomized Evaluation of Normal versus Augmented Level Replacement Therapy StudynullN Engl J Med 2009;361:1627-38.RENAL研究：Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Study小结小结急性肾损伤是指多种原因引起的急性肾功能异常，包括从肾功能微小改变到最终肾衰竭整个一个过程。 RIFLE诊断分级系统实用性较高，逐步得到普遍的认可，但尚有待于进一步的完善。 肾损伤生物标志物有可能成为早期诊断以及预后判断的指标null