将钙调磷酸酶抑制剂转换为西罗莫司在慢性移植肾肾病中的临床治疗效果

目的 探讨慢性移植肾肾病(CAN)患者将免疫抑制方案中钙调磷酸酶抑制剂(CNI)转换为西罗莫司(SRL)的有效性及安全性.方法 选取72例经移植肾活检证实发生CAN的受者,其中35例将免疫抑制方案中CNI转换为SRL(SRL组),其余37例继续原CNI方案(CNI组).另取10例因其他原因将CNI转换为SRL治疗的受者,将45例转换为SRL的患者分为A组[血肌酐(SCr)＜120 μmol/L),B组(SCr为120～200 μol/L,且Banff分级为Ⅰ～Ⅱ级),C组(SCr为120～200 μmol/L,且Banff分级在Ⅱ级以上),D组(SCr＞200 μmol/L).随访期为24个月,检测各组随访期内的各临床指标.结果 转换治疗前,两组间SCr和肾小球滤过率(eGFR)的差异无统计学意义(P＞0.05);转换治疗后24个月内,SRL组SCr水平和eGFR较CNI组明显改善(P＜0.05),而CNI组的移植肾功能有逐渐衰退的趋势.SRL组尿蛋白及血脂明显上升(P＜0.05),而CNI组变化不大;SRL组血小板计数较CNI组明显下降(P＜0.05),两组间其他指标的差异无统计学意义(P＞0.05).A组患者各指标在转换治疗前后的变化并不大,B组患者的肾功能及蛋白尿有改善明显,C组和D组患者肾功能有不同程度衰退情况,且蛋白尿加重.结论 SRL转换治疗对于稳定及改善CAN患者的移植肾功能是有效、安全的,CAN早期进行转换(SCr＜200 μmol/L)效果明显.     

移植肾组织中补体C4d沉积在CAN的诊断和治疗中的临床意义

目的 探讨移植肾组织中补体C4d沉积在慢性移植肾肾病(CAN)的诊断和治疗中的临床意义.方法 将2000年1月至2008年8月间诊断为CAN,且已行移植肾活检,并能收集到活检后2年以上随访资料者纳入研究.符合标准者共有86例,其中男性53例,女性33例,移植时年龄18～65岁.应用免疫组织化学染色方法检测移植肾组织活检标本C4d的表达.所有患者在行移植肾穿刺诊断为CAN后均给予了常规治疗.结果 86例患者中,C4d沉积阳性者(C4d阳性组)39例,C4d沉积阴性者(C4d阴性组)47例,两组患者在性别、年龄、供肾来源、多次移植、移植时群体反应性抗体水平等各指标的比较,差异均无统计学意义(P＞0.05).活检2年后,C4d阳性组和阴性组患者的SCr水平分别为(551.5±140.4)和(443.0±133.1)μmol/L,两组比较,差异有统计学意义(P＜0.05);并且C4d阳性组患者移植肾功能丧失率(23.1%,10/39)也显著高于C4d阴性组(8.5%,4/47),两组比较,差异有统计学意义(P＜0.05).CAN治疗前,C4d阳性组发生高血压和高血脂者多于阴性组(P＜0.05);常规治疗后,剔除移植肾功能丧失者,两组间发生高血压、高血脂、高血糖和高血尿酸者差异无统计学意义(P＞0.05).结论 C4d阳性的CAN患者提示有慢性体液排斥反应的参与,临床常规治疗预后较差,若针对体液免疫反应进行干预,能够改善移植肾长期存活.     

早期糖尿病肾病TGF-β1及ET-1变化及缬沙坦联合贝那普利的干预治疗

目的:研究单用缬沙坦、贝那普刺治疗及联合应用治疗Ⅱ型糖尿病肾病(DN)早期的疗效及对转化生长因子β1 (TGF-β1)和血浆内皮素-1(ET-1)的影响.方法:将189例患者随机分为A组(贝那普利组)59例,B组(缬沙坦组)64例,C组(贝那普利+缬沙坦组)66例,分别治疗12周,检测TGF-β1、ET-1、血糖及肾功各指标;检测贝那普利与缬沙坦联合治疗前后上述指标的变化情况,比较治疗前后血压、尿蛋白及血钾和血肌酐(Cr)等的变化.结果:糖尿病肾病患者TGF-β1、ET-1均明显高于对照组(P＜0.01),TGF-β1、ET-1水平与Cr等肾功能指标呈正相关关系.贝那普利与缬沙坦联合治疗8周后,患者TGF-β1、ET-1均明显下降.结论:贝那普利与缬沙坦联合治疗与单用药相比具有更强的降尿蛋白作用,能降低糖尿病肾病早期患者的TGF-β1及ET-1水平并改善其肾功能,值得临床推广.     

雷帕霉素与他克莫司治疗慢性移植肾肾病

目的 探讨低剂量免疫抑制剂组合治疗慢性移植肾肾病的临床效果. 方法慢性移植肾肾病患者31例,均经临床及部分移植肾穿刺病理证实.术后免疫抑制方案为他克莫司(FK506)、吗替麦考酚酯(MMF)、泼尼松(Pred)三联免疫抑制治疗.调整免疫抑制剂方案为雷帕霉素(RAPA)加低剂量FK506+MMF+Pred四联方案.根据血药浓度、血常规、肝肾功能调整免疫抑制剂用量.监测血压、急性排斥反应发生率、血肌酐、肌酐清除率(GFR)、24 h尿蛋白定量.结果 31例随访12个月.28例患者SCr由治疗前(300±21)μmol/L,治疗后降至(215±38)μmol/L,GFR由治疗前(42.54±2.95)ml·s-1/1.73 m2升至(49.98±3.05)ml·s-1/1.73 m2;治疗前后SCr、GFR差异均有统计学意义(P＜0.05).3例SCr 416～464μmol/L者治疗后SCr仍进行性上升,恢复血液透析治疗.30例24 h尿蛋白定量＜0.8 g者应用RAPA后尿蛋白量并不增加,1例24 h蛋白尿由0.95g升至1.29g.人/肾存活率为100%(31/31)、90.3%(28/31).治疗过程中主要不良反应为全血细胞减少和高脂血症.结论 慢性移植肾肾病患者SCr 167～320μmol/L,24 h蛋白尿定量＜0.8 g,采用RAPA加低剂量FK506+MMF+Pred治疗安全、有效.     

CD20阳性淋巴细胞在慢性移植肾肾病组织中浸润的意义

目的 探讨肾移植术后慢性移植物肾病(CAN)组织CD20阳性淋巴细胞浸润的临床意义及其机制.方法 选择肾移植术后2年内活检证实为CAN病例为研究对象,应用免疫组织化学方法检测补体C4d的沉积和CD20阳性淋巴细胞在移植肾组织的浸润,同时分析临床随访资料.结果 人选CAN病例44例,其中CD20阳性淋巴细胞浸润13例(29.5％),CD20阴性为31例(70.5％),移植肾组织不同病理分级者中CD20阳性者所占比例的差异无统计学意义(P＞0.05).44例中,12例(27.3％)出现管周毛细血管内皮细胞(PTC)补体C4d的线性沉积,CD20阳性和阴性者中补体C4d表达阳性率的差异无统计学意义(P＞0.05).确诊为CAN时移植肾组织CD20为阴性和阳性者的肾功能分别为( 140.8±22.0)μmol/L和(183.5±25.5) μmol/L(P＜0.01),1年后分别为(165.6±37.6)μmol/L和(242.2±59.1 )μmol/L(P＜0.01).结论 CD20阳性淋巴细胞在移植肾组织的浸润与移植物的预后相关,其机制可能不是通过慢性体液免疫反应.     

头孢曲松相关急性肾后性肾功能不全的临床特点和治疗

目的 探讨头孢曲松钠治疗后发生急性肾后性肾功能不全的临床特点和治疗. 方法 回顾性分析25例使用头孢曲松钠后出现急性肾后性肾功能不全患者的临床资料.男16例,女9例.平均年龄28岁.SCr 334.9～1280.5 μmol/L,平均635.5 μmol/L,BUN 8.0 ～ 33.9 mmol/L,平均18.6 mmol/L.14例经膀胱镜放置输尿管支架治疗,11例行保守治疗(碱化尿液、解痉等),比较两组的治疗效果. 结果 在出现无尿至入院时间,输尿管支架组(1.4±0.7 d)显著短于保守治疗组(3.0+1.4 d)(P=0.045),余年龄、SCr、BUN水平差异均无统计学意义(P＞0.05).25例均恢复排尿,2～6d后复查肾功能恢复正常.两组肾功能恢复时间及住院时间比较差异均无统计学意义(P=0.963,P=0.568). 结论 头孢曲松钠治疗后发生急性肾功能不全须引起高度重视,只要及早治疗,通过保守治疗或输尿管插管治疗都能取得良好的治疗效果.     

应用血肌酐下降率预测肾移植患者术后早期肾功能恢复情况

目的 探讨肾移植术后患者SCr下降率(CRRz)与早期移植肾功能恢复情况的相关性,建立早期预测移植.肾功能恢复的标准. 方法同种异体肾移植术后患者80例.分3组:①移植肾功能立即恢复(IGF)组53例,术后5 d SCr＜265.2 gmol/L;②移植肾功能缓慢恢复(SGF)组14例,术后5 d SCr＞265.2gmol/L,但1周内不需要透析治疗;③移植肾功能延迟恢复(DGF)组13例,术后1周内需要透析治疗.比较分析3组患者CRR:值和CRRz的99%可信区间(99%CI).结果 IGF组、SGF组和DGF组患者CRR2值分别为(46.8±14.6)%、(25.6±13.5)%和(0.7±17.7)%,99%C1分别为41%～52%、15%～36%和-14%～16%.3组间CRR2值两两比较,差异有统计学意义(P≤0.01).由3组CRR2的99%CI设定IGF、SGF、DGF的早期预测标准分别为CRR2≥40%、15%＜CRR2＜40%和CRR2≤15%.结论 CRR2与术后早期移植肾功能恢复情况有较好的相关性,可用于早期预测移植术后患者发生明功能延迟恢复的风险.     

肾宁合剂治疗IgA肾病的临床观察

目的观察中药肾宁合剂治疗系膜增生性IgA肾病的疗效。方法观察2007年1月至2011年1月在武汉大学人民医院行肾穿刺活检确诊为系膜增生性IgA肾病患者40例,已除外继发性IgA肾病,随机分为研究组和对照组,其中研究组20例,给予中药肾宁合剂50 ml,3次/d,并给予对症治疗(钙通道阻滞剂和利尿剂降压治疗);对照组20例,给予贝那普利10~20 mg/d,对症治疗与研究组相同,2个月为1疗程,1个疗程后评定疗效。观察2组治疗前、后的血尿、24 h尿蛋白定量、血清胱抑素C(cystatin C,Cys-C)、血肌酐、血尿素氮及尿N-乙酰-β-D-氨基葡萄糖苷酶(N-acetyl-β-Dglucosaminidase,NAG)等指标。结果对照组有3例患者因头痛及无法忍受的咳嗽而改用其他药物,退出观察。研究组均完成疗程。2组治疗前各项指标比较,差异均无统计学意义。研究组治疗后24 h尿蛋白定量为(0.8875±0.2767)g,较治疗前的(1.6615±0.1879)g明显改善(P0.05)。对照组治疗后24 h尿蛋白定量为(0.9871±0.1385)g,较治疗前的(1.5160±0.2290)g下降(P0.05)。2组治疗后比较差异无统计学意义。2组治疗后血尿素氮及肌酐较治疗前无明显改变。对照组治疗后CysC为(0.870±0.168)mg/L,与治疗前的(1.231±0.088)mg/L比较,P0.05;研究组治疗后Cys C为(0.829±0.161)mg/L,与治疗前的(1.211±0.108)mg/L比较,P0.05,2组治疗后均较治疗前下降。对照组治疗后尿红细胞较治疗前无改变,研究组治疗后尿红细胞为(50.47±28.07)个/μl,较治疗前的(189.39±67.48)个/μl减少(P0.05)。对照组治疗后尿NAG无明显改变,研究组治疗后尿NAG为(14.35±2.37)U/L,较治疗前的(25.1±10.8)U/L下降(P0.05)。2组总有效率分别为85.0%和76.5%,差异无统计学意义。结论肾宁合剂和贝那普利均能降低尿蛋白,改善早期肾功能受损。肾宁合剂同时还能改善血尿和肾小管功能,可用于治疗系膜增生性IgA肾病。     

老年活体亲属供肾移植的安全性分析

目的 探讨老年活体亲属供肾移植供体、受体的围手术期并发症、疗效及安全性.方法 亲属活体供肾移植132例,分为老年供体组(≥55岁,43例)和中青年供体组(＜55岁,89例);对供受体的住院时间、手术前后血肌酐(SCr)、内生肌酐清除率(CCr)、肾小球滤过率(GFR)、并发症以及受体的急性排斥反应率、人/肾存活率等进行比较分析.结果 2组供者术前SCr分别为(77.67±15.21)、(83.09±15.98)μmol/L,术后7 d分别为(109.54±22.32)、(106.56±23.46)μmol/L,均在正常范围内,2组间各时间点比较差异均无统计学意义(P值均＞0.05).术后3个月2组供者SCr分别为(112.57±20.87)、(104.29±19.43)μmol/L,与术前比较分别上升44.93%和25.51%,老年供体组比中青年供体组供者scr升高更明显.差异有统计学意义(P=0.0268).2组术前CCr分别为(1.63±0.34)、(1.56±0.25)ml/s,术后10 d分别为(0.83±0.29)、(1.11±0.27)ml/s.老年供体组术后3个月CCr为(0.97±0.10)ml/s,中青年供体组为(1.16±0.17)ml/s.2组手术前后CCr变化差异无统计学意义(P＞0.05).老年供体组术后10 d的留存肾GFR为(36.58±13.26)ml/min,术后3个月增加至(52.31±12.74)ml/min,达到原双肾GFR[(73.01±20.96)ml/min]的71.65%.中青年供体组术后10 d GFR为(38.32±10.79)ml/min,术后3个月增至(56.31±12.95)m1/min,达到原双肾GFR[(78.34±20.98)ml/min]的71.88%.手术前后GFR变化差异均无统计学意义,P值均＞0.05.供者手术并发症包括术中脾脏包膜下血肿1例、降结肠破裂1例和切口脂肪液化5例.术前和术后各时间点2组受者SCr水平差异无统计学意义(P值均＞0.05).2组供者平均住院时间分别为(13.2±3.4)和(12.8±2.6)d,P=0.4563.2组受者平均住院时间分别为(23.1±11.9)和(22.3士11.4)d,P=0.6991.老年供体组受者6个月内急性排斥反应发生率为4.7%(2/43),中青年供体组为7.9%(7/89).术后1年内2组各死亡1例,中青年供体组因急性排斥反应移植肾失功1例.结论 老年活体亲属供肾可能存在一定危险性,应予以重视,但供体年龄并非独立风险因素.在严格控制老年供者的纳入标准、对供者进行全面系统评估的情况下,老年供体活体肾移植的供体和受体围手术期并发症/疗效及安全性与中青年供体比较无明显差异.     

移植肾的病理类型与肾功能及预后的关系——单中心十年经验回顾分析

目的 分析肾移植受者移植肾的病理类型和特征,及其与肾功能和预后的关系.方法 肾移植术后230例受者接受了移植肾穿刺病理活检,分析其病理表现类型和特征,比较不同病理类型和特征受者移植肾穿刺活检时的血肌酐(SCr)水平,随访受者穿刺活检后1年的移植肾功能情况,评价不同病理特征受者的预后.结果 移植术后3个月时接受了程序性肾活检的10例受者中,9例为正常肾组织,1例为移植后IgA肾病.有肾功能损害临床表现的220例受者中,病理表现为交界性改变33例,急性排斥反应(AR)45例,慢性排斥反应(CR)24例,慢性移植肾肾病(CAN)26例,移植后肾炎(PTGN)39例,以上共167例;另外,28例同时有前面两种或两种以上的病理类型表现,还有CNI肾毒性反应8例,BK病毒肾病7例,急性肾小管坏死5例.有5例受者因采集的移植肾组织过少而不能明确诊断.病理诊断为交界性改变、AR、CR、CAN和PTGN的受者,其穿刺活检时的SCr水平分别为(171±17)、(259±25)、(343±33)、(406±67)和(207±26)μmol/L,不同病理类型者的SCr水平两两比较,差异均有统计学意义(P＜0.01).穿刺活检后1年,随访到上述5种病理类型167例受者中的134例(80.2%),其中交界性改变23例、AR 36例、CR 20例、CAN 18例及PTGN37例,分别有1例(3.1%)、8例(18.2%)、8例(22.2%)、6例(33.3%)、5例(13.5%)发生移植肾功能丧失.穿刺活检后1年,上述5种病理类型移植肾功能异常受者的SCr水平与穿刺时SCr水平的差值(△SCr)分别为(-47±20.7)、(-37.3±36.9)、(25.5±24.3)、(13.5±27.7)和(25.2±17.1)μmol/L.结论 移植肾的病理改变复杂多样,结合移植肾穿刺病理活检结果和临床分析进行准确诊断,可以帮助临床选择合适的治疗方案,促进移植肾的长期存活.     

ACE-inhibitor or AT2-antagonist therapy of renal transplant recipients is associated with an increase in serum potassium concentrations.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) are frequently prescribed to renal transplant recipients with a reduced glomerular filtration rate (GFR). The aim of this study was to investigate the association of ACEI/ARB use and serum potassium levels in renal graft recipients. METHODS: We conducted an open cohort study of 2041 first renal allograft recipients, transplanted at the Medical University of Vienna between 1990 and 2003. Serum potassium levels were compared over an up to 10 years of observation period between subjects with versus without ACEI/ARB therapy using a mixed effects general linear model. The analysis was adjusted for several covariables known to influence serum potassium such as the use of diuretics, beta blockers, calcineurin inhibitor (CNI) based immunosuppression, estimated GFR, time since renal transplantation, diabetes, years on dialysis and recipient age. RESULTS: The overall adjusted estimated serum potassium difference between recipients with versus without ACEI/ARB therapy was 0.08 mmol/l (P < 0.001). The use of diuretics was associated with a 0.11 mmol/l (P < 0.001) lower potassium concentration whereas each GFR decrease by 10 ml/min led to an increase of 0.04 mmol/l (P < 0.001). CNI intake increased serum potassium by 0.06 mmol/l (P = 0.002). Furthermore, serum potassium increased by 0.17 mmol/l within the first decade after transplantation (P < 0.001) while holding the other covariables constant. No effect modification between ACEI/ARB and time since transplantation was observed. Nineteen subjects (2.4%) discontinued the ACEI/ARB therapy due to hyperkalaemia. CONCLUSIONS: In summary, relevant hyperkalaemia associated with ACEI/ARB therapy is negligible in renal transplant recipients during long-term follow-up. The hyperkalaemic effect of ACEI/ARB is balanced by the use of diuretics.     

The association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use during postischemic acute transplant failure and renal allograft survival

BACKGROUND: Postischemic acute renal transplant failure occurs in approximately one fourth of all dead donor transplantations. Uncertainty exists regarding the putative association between the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) and kidney transplant graft survival in patients with delayed allograft function. METHODS: We conducted an open cohort study of all 436 patients who experienced an acute renal transplant failure out of all 2,031 subjects who received their first kidney transplant at the Medical University of Vienna between 1990 and 2003. Actual and functional graft survival was compared between users and nonusers of ACEI/ARB using exposure propensity score models and time-dependent Cox regression models. RESULTS: Ten-year actual graft survival averaged 44% in the ACEI/ARB group, but only 32% in patients without ACEI/ARB (P=0.002). The hazard ratio of actual graft failure was 0.58 (95% confidence interval: 0.35-0.80, P=0.002) for ACEI/ARB users compared with nonconsumers. Seventy-one percent of subjects with ACEI/ARB had a functional graft at 10 years versus 64% of ACEI/ARB nonusers (P=0.027). The hazard ratio of functional graft loss was 0.48 (95% confidence interval: 0.24-0.91, P=0.025). CONCLUSIONS: Use of ACEI/ARB in patients experiencing delayed allograft function was associated with longer actual and functional transplant survival.     

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.     

Blood pressure, antihypertensive treatment, and graft survival in kidney transplant patients

Whether the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker inhibitor (ACEI/ARB) is beneficial in renal transplant recipients remains controversial. In this retrospective study on 505 renal transplant recipients, we analyzed blood pressure and graft survival according to antihypertensive treatment with ACE-I/ARB and/or calcium channel blockers (CCB) over a period of 10 years. Patients were stratified according to their blood pressure 1 year after transplantation [controlled (≤130/80 mmHg; CTR, 181 patients) and noncontrolled (>130/80 mmHg; non-CTR, 324 patients)] and according to antihypertensive treatment (ACE-I/ARB and/or CCB taken for at least 2 years). One year after transplantation, 88.4% of CTR and 96.6% of non-CTR received antihypertensive treatment ( P  < 0.05). Graft survival was longer in CTR than in non-CTR ( P  < 0.05). Importantly, graft survival was longer in patients who received long-term treatment with ACEI/ARB, CCB, or a combination of ACEI/ARB and CCB ( P  < 0.001). The beneficial effect of ACEI/ARB therapy was more pronounced in non-CTR compared with that of CTR. We conclude that blood pressure control is a key target for long-term graft survival in renal transplant patients. Long-term ACEI/ARB and CCB therapy is beneficial for graft survival, especially in patients with diabetes and/or albuminuria.     

移植肾CD20~+淋巴细胞浸润的临床意义

目的:探讨CD20+细胞在移植肾排斥反应中浸润程度与移植肾预后的关系。方法:选取93例肾移植后穿刺患者,肾活检组织标本行CD20免疫组化染色。并对病理结果行半定量分析,根据CD20+细胞在肾组织内浸润程度,分为阴性组48例(N组,CD20+细胞浸润占肾小管间质面积<10%)、中度浸润组25例(M组,CD20+细胞浸润占肾小管间质面积≥10%<50%)和重度浸润组20例(H组,CD20+细胞浸润占肾小管间质面积≥50%)。分析CD20+细胞浸润的程度与移植肾预后的相关性。随访内容包括患者穿刺活检后的临床资料,随访内容包括患者的肌酐、蛋白尿变化及移植肾的生存状况等指标。结果:三组患者在年龄、性别、组织活检时间以及移植的次数均没有明显差异(P>0.05);穿刺活检后12个月的肌酐N组[(276.79±240.78)μmol/L]低于M组[(360.16±290.30)μmol/L];M组低于H组[(466.50±330.53)μmol/L],P<0.05;CD20+浸润组的患者的4年生存率明显低于阴性组(P<0.05);穿刺活检后12个月内,N组穿刺后出现蛋白尿的概率明显低于M组和H组(P<0.05)。结论:CD20+细胞在肾移植内浸润的程度与移植肾预后有明显相关性。     

Lipid profile in chronic allograft nephropathy

Chronic allograft nephropathy (CAN) represents the cumulative and incremental damage to nephrons by time-dependent immunologic and nonimmunologic causes. Hyperlipidemia is one nonimmunologic mechanism that promotes injury and poor function in a renal transplant. The aim of our study was to determine the effect of lipid profiles on CAN among renal transplant recipients. We retrospectively evaluated 53 renal transplant recipients who were classified according to the presence of CAN: CAN+ = 28 (18 males, 10 females) constituted the study group, whereas those with stable graft function CAN- = 25 (14 males, 11 females) were the control group. Biochemical parameters included serum urea, creatinine, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a), homocysteine, and high-sensitive CRP (hs CRP). Angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) use was significantly greater among the CAN+ group compared with the controls (P = .02, P = .04). Also, higher serum creatinine levels were observed in the CAN+ group (1.49 vs 1.22 mg/dL, P = .002), whereas serum levels of total cholesterol, triglyceride, hs CRP, and albumin were similar in both groups. The levels of ApoA1, ApoB, and lipoprotein (a) were similar, whereas the LDL/HDL cholesterol ratio and homocysteine levels were significantly higher in the CAN+ group (P = .04, P = .04). In conclusion, the LDL/HDL ratio may have a positive impact on CAN and may be used as a parameter during patient follow-up.     

Renoprotective effect of early inhibition of the renin-angiotensin system in renal transplant recipients

The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.     

Angiotensin-converting enzyme inhibitors versus AT1 receptor antagonist in cardiovascular and renal protection: the case for AT1 receptor antagonist

The development of pharmacologic agents that directly inhibit the angiotensin II receptor (angiotensin receptor blocker [ARB]) has provided clinicians with an alternative to the previously available angiotensin-converting enzyme inhibitors (ACEI) to downregulate the renin-angiotensin system. This review focuses on the available data that can guide the clinician to the use of these two classes of agents vis à vis their ability to provide cardiovascular (CV) and renal protection. Although the CV protective effect of ACEI in high-risk populations is widely appreciated, whether such an effect is entirely BP independent can be questioned. Most head-to-head comparisons between ACEI and ARB have yielded comparable CV protective effects, with ARB being associated with fewer adverse effects. Likewise, several-but not all-studies have demonstrated a CV protective effect of ACEI when compared with other active agents in patients with type 2 diabetes. One study demonstrated a similar protection with ARB when compared with a beta blocker. In terms of renal protection, there are ample data to support a role for both ACEI and ARB to prevent the progression from microalbuminuria to overt albuminuria in both type 1 and type 2 diabetes. However, when progression of renal disease is used as an end point, protection has been demonstrated with ACEI only for type 1 but not type 2 diabetes. In this latter group, only ARB have been shown to slow progression to ESRD.     

Chronic allograft nephropathy and nephrotic range proteinuria

While the association between post-transplant nephrotic range proteinuria (PTx-NP) and chronic allograft nephropathy (CAN) has been described, the factors that determine graft survival in such patients are unclear. We retrospectively identified 30 patients with biopsy-proven CAN who presented with PTX-NP between 1988 and 2002. Patients were stratified into two groups according to PTX-NP onset: <1 yr vs. >1 yr post-transplantation. Both groups were comparable with respect to the degree of renal dysfunction (serum creatinine 4.3 +/- 2.5 mg/dL vs. 3.4 +/- 1.5 mg/dL) and proteinuria (4.7 +/- 1.6 gm/d vs. 5.8 +/- 3 gm/d). After a mean follow-up of 14 months post-biopsy, 87% of patients had lost their grafts in both groups (89% vs. 83%, p = NS). Overall, patients with serum creatinine 2 mg/dL (75% vs. 4%, Fisher Exact Probability p = 0.0038). Using Kaplan-Meier estimate, the 5-yr graft survival rate was 100% for patients with serum creatinine 2 mg/dL (p = 0.06). The magnitude of proteinuria beyond 3 gm/d did not influence graft survival. One-half of the patients (n = 15) received therapy with angiotensin converting enzyme inhibitors (ACEI). Graft survival, however, was not different between the patients who received ACEI compared with the patients who did not receive ACEI (13% vs. 13%). PTx-NP related to CAN was associated with poor allograft survival, irrespective of the time of onset of presentation, especially when renal function was reduced at the time of biopsy.