【作者】 黄忠；

【导师】 赵占正；

【作者基本信息】 郑州大学 ， 肾脏病学， 2013， 硕士

【摘要】 终末期肾脏病(end-stage renal disease, ESRD)已经逐步成为本世纪影响人类社会健康状况的一种重大的疾病之一。据统计我国乙型肝炎病毒相关性肾炎(hepatitis B virus associated glomerulo-nephritis,HBV-GN)的发病率占肾小球肾炎的8.9%-20%。在我国城乡居民中,慢性肾脏病(chronic kidney disease, CKD)和终末期肾脏病的患病率呈现逐年升高的趋势,同时,中国是乙肝大国,慢性肝脏疾病(chronic liver disease,CLD)的患病率也在逐年上升,导致临床上终末期肾脏病合并晚期肝硬化(hepatocirrhosis HC)的患者越来越多见。这类患者的治疗已经成为临床工作中的一大难题。目前,ESRD的主要肾脏替代治疗方法有血液透析(hemodialysis,HD)、腹膜透析(peritoneal dialysis, PD)及肾移植。鉴于发展中国家经济发展水平落后的基本国情,以及肾移植肾脏来源的有限性,导致肾移植开展和普及困难。因此,绝大多数终末期肾脏病患者接受了透析治疗。PD较HD具有许多优点,逐渐成为ESRD患者主要的肾脏替代治疗方法之一,越来越被尿毒症患者所接受。尽管如此,目前我国的肾脏病透析患者中,主要为血液透析患者。ESRD伴有晚期肝硬化的患者,因为晚期肝硬化的病理生理特点,有一定的特殊性,对于选择何种透析方式,国内外学者们各持己见。我国有学者研究了17例尿毒症并血吸虫性肝硬化患者行血液透析治疗获得良好疗效,提倡血液透析用于此类患者疗效良好。有学者认为腹透治疗此类患者存在许多问题：接受腹膜透析后营养不良和低蛋白血症可能加重；腹膜透析治疗效果可能不理想,透析不充分,水钠潴留；腹膜腔感染所致腹膜透析超滤衰竭。肝硬化患者进入失代偿期以后,门静脉高压、腹膜腔大量积液和低白蛋白血症会导致全身血容量减少,甚至出现低血压,且血透是在体外循环下才能进行,对血流动力学的影响巨大,这样一来,可能使机体的有效循环血容量进一步减低,同时,由于血液透析时内环境渗透压在短时间迅速的改变,可能导致脑细胞水肿,增加肝性脑病的发生风险,且血液透析时使用抗凝剂,以及体外循环下的血小板、血小板活性的损伤,使得肝硬化患者的出血倾向加重,可能导致血透在此类患者中的应用受到了很多限制。相比而言,腹透具有许多优点,如无需使用体外循环和抗凝剂,患者无需至医院,可以在家自己换液操作,不影响社会活动,另外腹膜透析通过腹膜透析管的作用,还可以起到引流和治疗腹水的作用。Paul、De Vecchi等认为腹透可有效的保护残余肾功能,蛋白丢失量能够长期维持在较低水平,且效果不被终末期肝病所影响,是这类患者较理想的透析方式。国外有学者认为自从美国Baxter公司提供双联腹膜透析液系统的应用之后,腹膜腔感染率已明显降低到40个病人月以上,和非肝硬化腹透患者相似。有人对比分析了30例肝硬化腹透患者与60例非肝硬化腹透患者的溶质清除率情况,发现前者的尿素清除率和肌酐清除率显著高于后者,其超滤能力也高于后者,说明对这类患者行腹膜透析治疗从溶质清除方面来说是合适的。目前对于此类患者选择何种的透析方式存在争议,到底哪一种透析方式更加优胜。为此,本研究通过比较肝硬化失代偿期合并终末期肾病行血液透析和腹膜透析治疗的临床疗效,探讨治疗该类患者较理想的透析方法。方法收集2004年5月至2012年8月在郑州大学第一附属医院肾内科行HD和PD治疗的ESRD伴晚期HC患者的临床资料,定期随访(随访时间自患者开始透析至死亡或2012年8月31日止,即透析龄),并完善随访检查,排除糖尿病、严重心功能衰竭、消化道大出血、二期以上肝性脑病(含二期)、严重肺部感染、腹膜炎、脑出血、恶性肿瘤等。共30例入选。PD组14例,使用Baxter提供的双涤纶套腹透管和乳酸盐双联腹透液行持续性不卧床腹膜透析(continuous ambulatory peritoneal dialysis CAPD).剂量6000～8000ml/d;HD组16例,使用费森尤斯透析器,均为常规碳酸氢盐透析,每周2-3次,每次4～5h。2组患者均为维持性透析治疗,在透析过程中,根据病情辅助性的应用降压、降脂、降磷、活性维生素D、促红细胞生成素(Erythropoietin,EPO)、铁剂等药物,并依据相关指标调整用量。收集患者透析前、透析6个月和12个月后的相关临床资料、生存质量评分(根据KDQOL-SFTM1.2生存质量评分表,通过问卷得出结果,分数越高代表该项目中患者情况越好)、并发症、转归等。数据采用x±s表示,组间比较计量资料用两独立样本的t检验和计数资料用x2检验,应用SPSS17.0统计软件分析,P<0.05为差异有统计学意义。结果1.一般情况：HD组16例,男9例,女7例,透析初始年龄34～68岁,平均(48.64±10.13)岁,其中3例透析不满1年死亡、5例透析不满2年死亡、3例透析不满3年死亡,5例患者透析时间超过3年,透析龄7-42个月,平均(25.25±11.74)月；PD组14例,男8例,女6例,透析初始年龄36～68岁,平均(45.56±9.74)岁,其中1例透析不满1年死亡、1例透析不满2年死亡、2例透析不满3年死亡,10例患者透析时间超过3年,透析龄11～44个月,平均(33.00±10.20)月。两组间在性别、病因、开始透析时平均年龄差异无统计学意义(P>0.05),PD组透析龄大于HD组(P<0.05)。2.透析前临床指标比较：透析前两组患者合并症情况、血小板、白蛋白、残余肾小球滤过率(glomerular filtration rate,GFR)等临床指标比较差异无统计学意义(P>0.05)。3.透析6个月后临床指标、生存质量评分比较：HD组体质量、总胆固醇、β2微球蛋白高于PD组,尿素氮、肌酐、24h尿量、血小板计数、GFR氐于PD组,两组间比较差异有统计学意义(P<0.05)。PD组肾脏病对日常生活的影响8项、工作状况2项、社交质量3项、社会功能2项得分比HD组高,差异有统计学意义(P<0.05)。HD组发生低血压、抽搐风险比PD组高,差异有统计学意义(P<0.05)。4.透析1年后临床指标、生存质量评分比较：HD组体质量、总胆固醇、p2—微球蛋白高于PD组,尿素氮、肌酐、24h尿量、血小板计数、GFR低于PD组,两组间比较差异有统计学意义(P<0.05)。PD组症状与不适12项、肾脏病对日常生活的影响8项、工作状况2项、社交质量3项、患者满意度1项、社会功能2项、体能10项、精力状况4项得分比HD组高,差异有统计学意义(P<0.05)。HD组发生皮下及消化道出血、低血压、抽搐风险比PD组高,差异有统计学意义(P<0.05)。5.转归与死因比较：所有入组患者除死亡外均无退出透析或转变透析方式。HD组透析满1年时患者存活数13例,透析满2年时仍存活的患者有8例,透析满3年时仍存活的患者有5例；PD组相应为13例、12例、10例。2组透析满1年存活率比较差异无统计学意义(x2=0.87,P>0.05),透析满2年存活率比较差异有统计学意义(x2=4.29,P<0.05),透析满3年存活率比较差异有统计学意义(x2=4.82,P<0.05)。HD组死亡原因主要为出血,其次为心脑血管并发症；PD组死亡原因主要为腹膜炎,其次是出血和心脑血管并发症。结论对于ESRD伴晚期HC患者行CAPD和HD治疗,前者相比后者能更好地治疗肝硬化腹水、较好地保护残余肾功能和清除毒素、对凝血功能影响小、生存质量相对较高、并发症少、长期存活率高,若无明显腹透禁忌,可选择CAPD作为此类患者的初始透析方式。更多还原

【Abstract】 Background and ObjectiveEnd-stage renal disease (ESRD) has become one of the major diseases which effects human health in the21st century.In chaina, the morbidity rates of chronic kidney disease(CKD) and ESRD are increasing year by year.At the same time, the morbidity rate of chronic liver disease(CLD) is increasing year by year. So ESRD patients with advanced hepatocirrhosis (HC) are more and more. The treatment for these patients has become a thorny problem in our clinical work. There are three main renal replacement therapy that are used in clinical practice including hemodialysis(HD)、peritoneal dialysis(PD) and kidney transplant. China is the biggest developing country, The level of economic development is backward,and limited source of transplant kidneys,so there are many difficulties for the development and popularization of kidney transplant.So the majority of patients with ESRD accept dialysis treatment. PD has many advantages to compare to HD,for example easy operation, to better protect the residual renal function, less impact on hemodynamics and coagulation function and so no. It has become one of the main modality of renal replacement therapy and more and more accepted by patients with ESRD. Nevertheless, the majority of dialysis patients accepted hemodialysis. ESRD patients with advanced cirrhosis, because the pathophysiological features of advanced cirrhosis, dialysis treatment is different from other dialysis patients, for the choice of dialysis modality, domestic and overseas scholars have the different views.Chinese scholars observed17patients with uremia and schistosomal cirrhosis who were given hemodialysis treatment, the clinical efficacy was marked. They suggested that peritoneal dialysis should not be used as the preferred method of treatment for such patients. Some scholars believe that there are many problems if PD is used for such patients:aggravate malnutrition and hypoalbuminemia, the clinical efficacy is not ideal, inadequate dialysis, retention of water and sodium, peritoneal dialysis ultrafiltration failure is caused by the peritoneal cavity infection.For decompensated cirrhosis patients, portal hypertension,massive ascites, hypoproteinemia and can cause systemic hypovolemia, even occur hypotension, And hemodialysis is accomplished in extracorporeal circulation,it influence hemodynamics, thus, effective circulating blood volume further reduced.At the same time, internal environment’s osmotic pressure rapidly change in short time during hemodialysis,it can cause brain cell edema and increase the risk of hepatic encephalopathy.besides, use of anticoagulants, platelet destruction under extracorporeal circulation, and then the bleeding tendency aggravated, so hemodialysis is limited. In contrast, PD do not need extracorporeal circulation and anticoagulants, by home dialysis their social activities are affected, by peritoneal dialysis catheter ascites can be drained constantly. Paul, DeVecchi et al concidered PD can effectively protect residual renal function, protein loss can be maintained at a low level for a long time, the clinical efficacy is affected by end-stage liver disease. Some foreign scholars thought that since the double peritoneal dialysis catheter system was used, the peritoneal cavity infection rate has decreased to lower than40patient-months,it was similar with that of non cirrhotic patients.It was reported a comparative analysis of30cases of liver cirrhosis patients with PD and60cases of non-cirrhotic patients with PD found the solute clearance rate and ultrafiltration capacity of liver cirrhosis patients were significantly higher than that of non-cirrhotic patients. This shows that PD is suitable for this kind of patients.Which dialysis is more superior? In our study we compared the clinical efficacy of peritoneal dialysis and hemodialysis in patients with ESRD and decompensated liver cirrhosis, in order to define an optimal dialysis modality.MethodsThe analysis included data from30patients with ESRD and decompensated liver cirrhosis who had undergone dialysis for at least6months (between May2004and August2012) at the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University. The patients were divided into an HD group (n=16) and a PD group (n=14). None of the selected cases had severe heart failure, diabetes mellitus or therioma and so on.Continuous ambulatory peritoneal dialysis (CAPD) was undertaken using double cuff peritoneal dialysis tubes and lactate peritoneal dialysis solution (Baxter, America). During this procedure the patients received6to8L of peritoneal dialysis solution over a period of24h. Hemodialysis was undertaken using the dialyzer machines (Fresenius,Germany). The patients received bicarbonate hemodialysis for4or5h, two or three times a week. During the hemodialysis sessions the patients were given antihypertensive, lipid lowering and phosphorus reducing drugs, together with active vitamin D, erythropoietin and iron supplements and so on. The dosages were adjusted according to the patient’s condition.All cases were followed up from the beginning of dialysis untikl death or until31August2012. The surviving patients had received dialysis therapy for over3years. Demographic and clinical data (dialysis duration, blood pressure, laboratory evaluations, urine volume and so on) recorded for6to12months were analyzed for all patients. The incidence of peritonitis and other complications was analyzed together with survival data. Quality of life was recorded using the Kidney Disease Quality of Life Short Form (KDQOL-SF version1.2) questionnaire survey.Statistical analysis was undertaken using SPSS version17.0software. Results are reported as means and standard deviations (Mean±SD). Between group differences were analyzed by independent two-sample t-tests and chi square tests. Values of P <0.05were considered statistically significant.Results5Study populationThe study population included16patients (nine men and seven women) who began HD at a mean age of48.6years (range:34to68years) and who had undergone dialysis for a mean of25.3months (range:7to42months). The PD group comprised14patients (eight men and six women) who began dialysis at a mean age45.6years (range:36to68years) and who had undergone dialysis for a mean of33.0months (range:11to44years). In HD group,3cases died when dialysis for less than1year,5cases died when dialysis for less than2years,3cases died when dialysis for less than3years,5cases undergoing dialysis for more than3years; In PD group,1cases died when dialysis for less than1year,2cases died when dialysis for less than2years,3cases died when dialysis for less than3years,8cases undergoing dialysis for more than3years.There were no significant difference between the two groups with respect to pre-dialysis demographic or clinical parameters.2. Outcome of dialysisAfter6and12months of dialysis, body weight, blood levels of2-microglobulin and total cholesterol were significantly higher in patients undergoing HD than in those undergoing PD (P<0.05). In addition, blood urea nitrogen, serum creatinine, residual urine volume, platelet count and glomerular filtration rate (GFR) were all significantly lower in the HD group than in the PD group (P<0.05).3. Quality of life assessmentsAt both6and12months, quality of life evaluations of’the effects of kidney disease’,’work status’,’quality of social interaction’and’social functioning’were significantly higher in the PD group than in the HD group (P<0.05), At12months scores for ’patient satisfaction’,’physical functioning’,’role physical’and ’symptom/problem items’ were also significantly higher in the PD group than in the HD group (P<0.05).4. ComplicationsThe incidence of repeated hypotension and convulsion at6and12months was significantly higher in the HD group than in the PD group (P<0.05). At12months, the incidences of subcutaneous and archenteric hemorrhage were also significantly higher in the HD group (P<0.05).At12months,three patients in the PD group (23.1%) each developed three episodes of bacterial peritonitis, which was equivalent to one event every52patient-months, The peritonitis were cured by use of antibiotics.5. Patient survival The1-year survival rate in patients continuing the same mode of dialysis for1year was81.3%in the HD group and92.9%in the PD group. The corresponding2-and3-year survival rates were significantly higher in the PD group (85.7%and71.4%, respectively) than in the HD group(50.0%and31.3%;P<0.05).In group HD, the major causes of death were hemorrhage, followed by cardiovascular and cerebrovascular complications; group PD, the major causes of death were peritonitis, followed by hemorrhage and cardiovascular and cerebrovascular complications.ConclusionsTaken together our findings suggest that PD has many advantages over HD for patients with ESRD and co-existing advanced liver cirrhosis. PD provides better the treatment of ascites induced by cirrhosis, better the protection of residual renal function,more complete toxin removal and less impairment of coagulation function than HD. Its use is also associated with a better the quality of life, fewer complications, and increased long-term survival.更多还原