1、. 肝肾综合症,HEPATORENAL SYNDROME,HEPATORENAL SYNDROME 肝肾综合征,Renal abnormalities 肾脏异常 - Marked renal vasoconstriction 肾血管强烈收缩 - Marked reduction of GFR 肾小球滤过率明显降低 - Impaired sodium and water excretion 钠水排泄能力损伤 Circulatory abnormalities 循环异常Arterial hypotension. Low systemic vascular resistance动脉性低血压。全身血管
2、阻力降低Normal/reduced cardiac output心输出量正常/降低Marked activation of vasoconstrictor systems血管收缩系统明显激活,Degree of renal vasoconstriction in HRS,International Ascites Club, Hepatology 1996,HEPATORENAL SYNDROME CLINICAL TYPES 肝肾综合征临床分型,Type 1 Rapidly progressive renal failure: doubling of the initial serum c
3、reatinine concentration to a level greater than 2.5 mg/dL in less than 2 weeks迅速进展型肾功能衰竭：血清肌酐浓度最初加倍增长最终高于2.5mg/dL，这段时间 少于2周。Clinical presentation: acute renal failure 临床表现：急性肾功能衰竭Type 2 - Stable renal failure 稳定型肾功能衰竭Clinical presentation: refractory ascites 临床表现：难治性腹水,肝肾综合征: 国际腹水协会诊断标准,主要标准 肾小球滤过率低
4、（血清肌酐1.5mg/dL或24小时肌酐清除率40mL/min）2. 未出现休克、进行性细菌感染、体液丢失及正使用肾毒性药物治疗3. 在停止使用利尿剂和血浆扩容治疗后肾功能无持续性改善4. 蛋白尿500mg/日，超声检查未见阻塞性尿路病变或肾实质病变,Arroyo et al., Hepatology 1996,肝肾综合征: 国际腹水协会诊断标准,血清肌酐133 mol/L (1.5 mg/dl).2. 停止使用利尿剂和使用白蛋白(1 g/kg/日， 最多 100 g/日).扩容治疗后2天，血清肌酐水平无改善( 1.5mg/dl) 3. 未出现休克，或近期使用过肾毒性药物4. 无肾实质病变(蛋
5、白尿500mg/日)，无微小血尿和/或超声波肾脏异常发现,Salerno F et al., Gut 2007,Major differences,Renal failure with ongoing bacterial infection, but in the absence of septic shock is considered HRS. Treatment can be started without waiting for resolution of infection. Plasma volume expansion should be performed with album
6、in rather than saline Minor diagnostic criteria were removed as they added little to the diagnosis of HRS.,Gins P et al., Lancet 2003,肝肾综合征的诊断,肾衰竭 (serum creatinine 1.5 mg/dL) 血清肌酐1.5mg/dL,肾毒性药物（NSAIDS）,体液耗竭,休克,短暂性/持续性-进展性,肾毒性,急性小管坏死,肾前性肾衰竭,生化参数,肝肾综合征,超声发现肾脏异常,肾实质病变,感染征象,蛋白尿和/或血尿,临床征象,肾脏超声检查,感染诱导的肾功
7、能衰竭,肝肾综合征的发病机制及治疗原则,肝肾综合征,肝硬化,内脏动脉扩张,动脉有效血容量降低,脑血管收缩,维持动脉有效血容量,肾血管收缩,肱/股血管收缩,血管收缩系统激活,门脉高压,肝移植,心功能损伤,Initial management checklist for patients with HRS,Admission to monitored care unit Central line placement is helpful but not mandatory Complete blood tests Exclude ongoing infection Abdominal ultras
8、ound to examine the liver and kidneys 24 hr urine collection: Urine sodium Urine volume Urine sediment,Diagnostic paracentesis Albumin, cell count , culture in blood culture bottles Plasma expansion with albumin to rule out prerenal renal failure Nutrition consultation Evaluation for orthotopic live
9、r transplantation,PREVENTION OF HRS,Renal failure from SBP can be prevented with IV albumin: 1.5 gr/kg at diagnosis and 1gr/kg 48 hours later Norfloxacin 400mg/day (selected patients) Plasma expansion after therapeutic taps.,肝肾综合征血管收缩药物治疗,Vasopressin analogues (加压素类似物) - Terlipressin 特利加压素 Ornipress
10、in 鸟氨酸加压素Alfa-adrenergic agonists (-肾上腺素激动剂) - Norepinephrine 去甲肾上腺素 Midodrine 米多君Other (其它) - Octreotide 奥曲肽,Angeli P et al., Hepatology 1999 Duvoux C et al., Hepatology 2002 Ortega R et al., Hepatology 2002 Wong F et al., Hepatology 2004,肝肾综合征血管收缩剂疗法,HRS的诊断,Albumin (白蛋白) 20-40 g/ day,Albumin (白蛋白)
11、 50 g/day,Albumin (白蛋白) IV 1 g /Kg,Midodrine (米多君) p.o. 2.5- 37.5 mg/day Octreotide (奥曲肽) 300-600 g/day,12,3,6,9,0,Days,15,Terlipressin IV bolus (特利加压素单次静脉注射) 0.5-2 mg / 4-6 h,3,6,7,0,Days,12,3,6,9,0,Days,15,Norepinephrine (去甲肾上腺素) 0.5-3 mg/h,治疗目标：血清肌酐低于1.5mg/dL,Terlipressin,Initial dose: 0.5 to 1 m
12、g every 4 -6 hours Increase in a stepwise fashion to 1-2 mg every 4-6 hours every 3 days if a significant reduction in serum creatinine level ( 25% of the pre-treatment value or 1mg/dL) is not observed during a 3-day period. The recommended dose of albumin is 1 g/kg followed by 20-40 g/day.,In most
13、cases renal function starts to improve within 5 - 6 days. Side effects : approximately 10% (cramps, diarrhea, ischemic events). HRS improves in 40-60% of patients Low recurrence upon discontinuation of therapy,肝肾综合征对治疗的反应,Martn-LLah M et al., EASL 2007,Prosthesis,TIPS,Who? Bili 130mEq/L MELD 18 Age 65 Loculated ascites No cardiac disease No pulmonary hypertension No HCC,Wong F et al, Hepatology 2004,肝肾综合征和TIPS,肾小球滤过率,米多君 奥曲肽 白蛋白,时间,肝肾综合征,特利加压素+白蛋白 或 奥曲肽+米多君+白蛋白或 去甲肾上腺素+白蛋白,考虑 TIPS: Child-Pugh Score 评分 12, Bili 3, 无肝性脑病、无心肺疾病,肝移植评估,第一步,第二步,评估反应,肝移植,无反应,第三步,
