尿毒症患者肾移植前后抑郁水平调查

目的:通过对尿毒症患者肾移植前后抑郁水平作一临床对比研究,并对与抑郁水平相关的影响因素作一分析,探讨减少尿毒症患者抑郁发生和提高其生活质量的有效方法.方法:选择于2005-01/2008-12在河南中医学院第一附属医院诊断为尿毒症的患者91例,分为3组,肾移植后移植肾功能正常组28例;等待肾移植组31例;肾移植术后出现慢性排斥反应而恢复血液透析组32例.采用Beck抑郁量表对患者进行问卷调查,包括患者的年龄、性别、婚姻状况、尿毒症病程、肾移植后慢性排斥反应发生率、移植肾功能维持正常时间和透析时间等指标.观察抑郁发生率,并做抑郁水平相关因素分析.结果:①肾功正常组患者抑郁水平明显低于血液透析组(P＜0.01);待移植组患者抑郁水平低于血液透析组(P＜0.05).②抑郁的发生与患者的年龄和性别无明显关联(P＞0.05);已婚患者抑郁的发生率和水平低于单身患者(P＜0.05);血液透析组患者抑郁水平与移植肾功能维持正常时间的长短呈负相关(r=-0.34,P＜0.05).结论:对于单身的尿毒症患者和肾移植后移植肾功能衰竭而重新血液透析的患者,给予更多的社会和心理支持是很有必要的.把更多的尿毒症患者纳入肾移植等待范围能减少抑郁的发生,减轻抑郁的发生程度,从而提岛患者的生活质量和透析效果.     

Transplantation of the kidney--optimal treatment of patients suffering from diabetes mellitus type 1 with terminal chronic renal failure

AIM: To assess long-term results of renal transplantation in patients with diabetes mellitus of type 1 (DM-1) with terminal chronic renal failure (tCRF); to detect risk factors of low survival of the patients and development of dysfunction of renal transplant. MATERIAL AND METHODS: A retrospective comparative analysis of 418 recipients of the kidney with non-diabetic nephropathies (NDN) and 113 recipients with DM-1. RESULTS: Survival of DM-1 patients with tCRF after allotransplantation of the kidney was lower than in patients with NDN. Low survival risk factors for DM-1 patients after transplantation of the kidney are: DM-1 duration up to tCRF 25 years and more, minimum 3-year history of dialysis before transplantation, age at transplantation over 45 years, persistence of anemia (hemoglobin < 110 g/l) after operation. Survival of the transplanted kidney in DM-1 and NDN patients was the same. Risk factors of dysfunction of the transplanted kidney are the following: acute crises of rejection and delayed function of the transplant, arterial hypertension > 130/80 mmHg, proteinuria > 300 mg/day. Survival of the transplanted kidney is higher in transplantation from the relative donor, does not depend on the kind and duration of previous dialysis. Causes of a decline in the function of the transplanted kidney (by the data of puncture biopsy of 34 transplants) are the following: acute rejection crises (38%), chronic transplantation nephropathy (24%), toxic nephropathy (18%), recurrent diabetic nephropathy (6%), chronic pyelonephritis (6%). Lethality in DM-1 patients after renal transplantation is 2 times higher than in patients with NDN. Death was due to cardiovascular diseases, gangrene of the lower limbs, infectious complications (in 31%, 15% and 35% cases, respectively). CONCLUSION: Transplantation of the kidney is an optimal treatment in DM-1 patients with tCRF.     

移植肾穿刺病理组织中抗体介导的排斥反应

背景:体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。目的:对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。方法:选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD(美国)活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。结果与结论:84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。     

肾小管泌氢功能检测在肾移植对抗排斥反应治疗效果中的应用

背景：移植后的急性排斥是肾移植术后的主要并发症，也是导致慢性排斥反应和移植物失功最重要的危险因素，因此，了解肾小管泌氢功能能否早期反映移植物的功能情况有重要意义。目的：观察肾移植患者术后肾小管泌氢功能，并进行监测，探讨其在移植物急慢性排斥中的作用。设计：病例-对照观察。单位：解放军济南军区总医院泌尿外科。对象：选择2000—05／2005—06解放军济南军区总医院泌尿外科连续实施肾脏移植26例患者，男16例，女10例；年龄21～58岁，平均35岁。原发病均为慢性肾小球肾炎，慢性肾功能衰竭，全部为尸肾移植。供受者均血型相同、淋巴细胞毒试验阴性。其中1例为第2次移植。所有患者对检测项目知情同意。方法：依据典型的临床表现，彩色多普勒超声及血流变化诊断患者排斥反应，16例患者未发生排斥反应为稳定组，10例发生排斥反应的患者为排斥组，排斥组根据排斥情况分为排斥前期、排斥期及恢复期。对所有患者术前及术后1周起每周1次，连续10周分别以化学清洁玻璃瓶留取晨起中段尿测定尿可滴定酸、NH4^＋和净酸水平评估肾小管泌氢功能。主要观察指标：两组患者尿可滴定酸、NH4^＋和净酸水平。结果：纳入患者26例均进入结果分析。排斥反应组排斥前期患者肾小管泌氢功能各检测值显示泌氢功能开始建立，并趋向正常，排斥期患者肾小管泌氢功能检测值均显示明显下降，与排斥前期及稳定组比较均有统计学显著性差异（P〈0．01）。恢复期患者排斥反应治疗后监测的结果显示泌氢功能恢复较快。肾小管泌氢功能总体连续观察结果显示总体恢复的不均衡性，大部分病例恢复时间从1～10周不等，平均恢复期限约6周，2例10周内未恢复，4例严重排斥者中3例治疗后泌氢功能恢复缓慢。结论：肾小管泌氢功能可弥补血清肌酐不能良好反映肾小管功能的不足，能在连续观察中对移植肾急性排斥反应的诊断，特别是对抗排斥治疗的效果判断和预后评估中作为有价值的指标。     

The prognostic significance of acute renal failure after renal transplantation in patients treated with cyclosporin

We studied 733 cadaveric renal transplant patients (747 transplants) under cyclosporin immunosuppression, to: (i) establish the risk profile for acute renal failure (ARF) after renal transplantation in a unit using many sub-optimal donors; (ii) assess the long-term prognostic relevance of ARF; and (iii) explore the synergistic prognostic significance of delayed graft function and acute rejection during the early post-transplant period. Transplanting from a non-heart-beating or elderly donor, protracted cold ischaemia, haemodialysis immediately before transplant surgery, poor HLA matching, and grafting to a hypersensitized recipient without residual renal function, all independently predicted delayed graft function. This delay had no detrimental effect on patient or graft survival, but prolonged ARF was associated with increased mortality from infection. Late markers of graft dysfunction (poor graft function, proteinuria, hypertension) were highly prevalent among grafts affected by ARF, specially in prolonged ARF. Delayed graft function and early acute rejection showed a definite, albeit not strong, additive impact on late graft survival, and also on the prevalence of late markers of graft dysfunction.      

Detection of cytomegalovirus (CMV) antigens in kidney biopsies and transplant nephrectomies as a marker for renal graft dysfunction.

Chronic rejection accounts for the greatest loss of renal allografts. HLA mismatching has been minimised by organ allocation and new immunosuppressive drugs have been employed, but the average cadaveric graft survival still does not exceed 12 years. Though the aetiology is multifactorial, one contributory factor for this condition is cytomegalovirus (CMV). Detection of CMV in kidney biopsies and sera can diagnose and monitor this inflammatory event and define its role in chronic nephropathy. Twenty five biopsies taken at the time of transplantation, 10 biopsies for graft dysfunction and tissue blocks from 20 explanted kidney grafts were collected and investigated for CMV antigens by immunohistochemistry. Tissue samples were snap frozen and cryostat sections were incubated with monoclonal antibodies for CMV antigens followed by immunoperoxidase staining. In 12 out of 20 transplant nephrectomies CMV antigens were found. Only two of these patients had clinical CMV disease. Time 0 biopsies from CMV seronegative donors (n = 11) and CMV seropositive donors (n = 14) were negative for CMV antigens. The prevalence of CMV antigens in grafts lost due to chronic rejection was 60%. These antigens were not found within the time 0 biopsies, but were detected in 30% of biopsies taken at the time of clinical graft dysfunction. CMV appears to contribute to chronic rejection even without clinical disease.     

移植肾穿刺病理组织中抗体介导的排斥反应

背景：体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。目的：对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。方法：选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD（美国）活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。结果与结论：84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。     

Imaging in renal transplantation

Renal transplantation is the best treatment option for chronic renal failure, with marked improvement in social activity, work, and family life. In addition to these obvious improvements, it is an extremely cost-effective procedure when successful. Ultrasonography plays a major role in the imaging of these patients, and ultrasound (including color Doppler) is helpful to the transplant physician in detecting graft dysfunction and peritransplant collections, some of which may be drained under ultrasound guidance. It is also helpful in the diagnosis of chronic vascular complications including transplant artery stenosis and arteriovenous fistula. It has no specific application in the diagnosis of chronic rejection.     

The critical role of plasmapheresis in ABO-incompatible renal transplantation

BACKGROUND: Thousands of patients with chronic renal failure die yearly and are unable to have a kidney transplant due to the severe shortage of donors. Therapeutic plasma exchange (TPE) is performed to remove ABO antibodies and permit ABO‐incompatible (ABO‐I) kidney transplants, but there is only limited research within this area and a lack of standardized protocols for TPE. This article reviews the literature to provide a historical perspective of TPE for ABO‐I kidney transplantation and also provides the Johns Hopkins Hospital protocol with a focus on both titers and TPE. STUDY DESIGN AND METHODS: The TPE treatment plan is based on ABO titers with the goal of a titer of 16 or less at the anti‐human globulin (AHG) phase before surgery. Pretransplant therapy consists of every‐other‐day TPE followed immediately by cytomegalovirus hyperimmune globulin. ABO antibody titers are closely monitored before and after transplantation. After transplantation, TPE therapy is performed for all patients to prevent rebound of anti‐A and anti‐B titers until tolerance or accommodation occurs. TPE is discontinued and reinstituted based on the clinical criteria of creatinine levels, biopsy results, and ABO titer. RESULTS: Fifty‐three ABO‐I kidney transplants have been completed with no episodes of hyperacute antibody‐mediated rejection (AMR) and only three episodes of AMR. One‐year death‐censored graft survival is 100 percent and patient survival is 97.6 percent. CONCLUSIONS: While randomized clinical trials are needed to evaluate the optimal method and protocol to remove ABO antibodies, the current literature and our results indicate a critical role for TPE in ABO‐I renal transplantation.     

肾移植后肾坏死与肾移植排斥反应的病理学表现与变化

背景:肾移植后受者定期行移植肾组织活检,在移植肾出现问题的早期进行正确的病理诊断,选择合适的治疗,是使移植肾长期存活的关键。目的:总结肾移植后肾坏死与肾移植排斥反应的病理学表现与变化。方法:由作者应用计算机检索维普数据库、Pubmed数据库中与肾移植后肾坏死与肾移植排斥反应有关的文献,检索时限为1998-01/2009-10。对资料进行初审,并查看每篇文献后的引文。结果与结论:共16篇文献符合标准。移植后慢性肾脏损害的病理类型包括慢性排斥反应,系膜病变,新月体肾炎,膜性肾病,Ig肾病,溶血性尿毒综合征。移植后慢性肾脏损害最常见的病理类型为慢性排斥反应,与慢性排斥反应相关的因素可能包括:供肾年龄,急性排斥反应发生率,移植肾功能延迟恢复及CMV感染。高血压和蛋白尿对移植肾的远期预后也有重要影响。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,成功率高、安全性好,对肾移植后难以根据临床化验资料作出准确判断肾脏损害及治疗方案的选择有着重要的指导意义。     

Successful renal transplantation in a patient with cold agglutinin disease

Cold agglutinin disease is a rare cause of acute graft loss after renal transplantation. A 71‐year‐old female with end stage renal failure was diagnosed to have cold agglutinin disease when investigated for recurrent clotting of hemodialysis circuits. Kidney transplantation was a major challenge due to unavoidable exposure of the transplant kidney to cold temperatures. Large volume plasma exchange given pre‐transplant and infusion of warm saline prior to anastomosis resulted in successful renal transplantation with good graft function despite initial delayed graft function. This challenging case illustrates the complete removal of cold agglutinin antibodies with therapeutic large volume plasma exchange. J. Clin. Apheresis 32:56–58, 2017. © 2016 Wiley Periodicals, Inc.     

神经肽Y在肾移植围手术期与血压的关系

目的终末期尿毒症患者血浆神经肽Y（NPY）异常升高，与血压的变化呈正相关。本研究探讨血浆NPY水平在成功肾移植围手术期的临床意义及其与患者血压的关系。方法采集116例终末期尿毒症患者手术前、术后24h、出院前1d外周静脉血标本5ml，测定血浆NPY和肌酐（Cr）水平，同时测量记录平均动脉压。对照组为20例健康志愿者。结果在成功肾移植手术后出院前1d，血Cr水平恢复正常，血浆NPY水平有明显降低，与手术前比较，有显著性差异（P〈0．05）；但又明显高于健康志愿者血浆NPY平均值，比较有显著性差异（P〈0．05）；手术后患者平均动脉压无明显降低，个别反而较手术前更高，与手术后血浆NPY水平的变化无相关性。结论终末期尿毒症患者成功接受肾移植后，在出院前1d，肾功能恢复正常情况下其血浆NPY水平明显下降，但与患者的平均动脉压无相关性。     

肾移植受者死亡原因分析

目的 分析肾移植受者死亡原因,为提高肾移植受者长期生存率提供参考.方法 回顾性分析1990年1月至2010年12月间进行的2656例同种异体肾移植手术,共死亡285例,按肾移植时的年份分为1990~1995年(A)、1996~2000年(B)、2001~2005(C)、2006~2010年(D)4组,分析比较各组死亡率变化趋势.统计不同时间段死亡例数及各死亡原因构成比,并将其分为移植肾失功能死亡组(n=181)和移植肾带功能死亡组(n=104),对两组死亡原因进行比较分析.结果 4组肾移植受者死亡率分别为:A组28.21%;B组15.57%;C组8.14%、D组3.41%,B、C、D组与A组比较,差异有统计学意义(P<0.001).27.72%(79例)患者于肾移植术后3个月内死亡,该期死亡的主要原因是慢性充血性心力衰竭、感染;15.79%(45例)患者于术后3～5年死亡,死亡的原因主要为感染、慢性充血性心力衰竭.前3位死亡原因分别是,失功能组:慢性充血性心力衰竭(74例,40.88%)、肺部感染(26例,14.36%)、药物性肝衰竭(18例,9.94%);带功能组:肺部感染(46例,44.23%)、药物性肝衰竭(21例,20.19%)、心血管意外(2例,占1.92%).结论 肾移植受者死亡率随时间的发展呈明显下降趋势,患者死亡有两个高峰期:第一个是术后3个月,第二个是术后3～5年,感染是移植肾带功能组死亡的最主要原因,因心血管疾病死亡的风险在移植肾失功的受者中显著增加,加强对肺部感染及慢性充血性心力衰竭等并发症的防治十分关键.     

移植肾穿刺活组织检查：72例的病理及临床分析

背景：肾移植后慢性排斥反应及各种移植肾病变是移植肾失功能的常见原因,但对移植肾予以准确评估往往非常困难,活检仍是目前的主要手段。目的：分析肾移植后出现合并症时移植肾穿刺活检的病理结果。方法：对72例移植肾进行肾穿刺活组织检查,并进行病理诊断及分类,结合移植后情况进行分析。结果与结论：72例中发生急性细胞介导性排斥反应35例,急性抗体介导性排斥反应12例,移植肾急性药物毒性损伤10例,慢性T细胞介导性排斥反应6例,慢性抗体介导性排斥反应2例,急性肾小管坏死4例,慢性移植肾肾病3例。移植肾组织活检的病理报告与穿刺前临床诊断的符合率在75%以上。移植肾穿刺活检未发生明显的不良反应。提示移植肾活检安全可靠,对肾移植后难以根据临床化验资料作出准确判断肾脏损害的并发症及治疗方案的选择有极为重要的指导意义。     

Plasma levels of endothelin in chronic renal failure and after renal transplantation: impact on hypertension and cyclosporin A-associated nephrotoxicity.

1. Plasma levels of endothelin were measured in 30 patients with chronic renal failure, 32 patients on chronic haemodialysis treatment and 25 renal graft recipients with stable renal graft function. 2. In patients with chronic renal failure as well as in patients on regular haemodialysis treatment, mean plasma levels of endothelin were significantly increased (4.59 +/- 2.09 pg/ml, 10.08 +/- 3.12 pg/ml, respectively) when compared with normal subjects (1.88 +/- 0.6 pg/ml, P less than 0.01, P less than 0.001, respectively). 3. In the group with chronic renal failure a positive correlation between the plasma level of endothelin and the plasma concentration of creatinine was observed (P less than 0.003). 4. Renal graft recipients on cyclosporin A with stable renal graft function had a normal plasma level of endothelin suggesting that cyclosporin A nephrotoxicity is not mediated by endothelin. 5. Hypertensive patients with chronic renal failure or on regular haemodialysis and hypertensive renal graft recipients did not differ from the corresponding normotensive population with regard to the plasma level of endothelin, demonstrating that an increased plasma level of endothelin does not play a major role in the pathogenesis of renal hypertension.     

Aminoaciduria as a marker of acute renal transplant rejection--a patient study

Over 12 months, urine samples were systematically collected from 40 children who underwent renal transplantation for the treatment of end-stage renal disease. Sequential determinations of the excretion of individual amino acids relative to that of creatinine were carried out on 15 subjects. Nine of these (including three who sustained episodes of acute rejection) retained a native kidney in-situ, while in six patients (including three who underwent an episode of acute rejection) both native kidneys had been removed. In both subgroups, the amino acid/creatinine ratios of early morning urine samples were higher shortly before clinical manifestations of acute rejection became evident than in patients who, following renal transplantation, had stable kidney function, chronic graft rejection, or acute tubular necrosis, with one exception: a patient with one native kidney in-situ in whom acute tubular necrosis developed immediately after transplantation. The amino acids showing the greatest increase included Thr, Ser, Gly, and Ala. These values fell dramatically immediately prior to the clinical episode of acute rejection, with Thr, Ala, and Phe showing the most consistent changes. These alterations in urinary amino acid excretion occurred several days before changes in urinary protein excretion or the serum concentrations of urea and creatinine, and may have a role to play in the monitoring of renal transplant recipients.     

Presence of donor- and recipient-derived DNA in cell-free urine samples of renal transplantation recipients: urinary DNA chimerism.

BACKGROUND: Previous studies have indicated that microchimerism is present in body tissues, peripheral blood, and plasma of recipients after organ transplantation. We hypothesize that donor-derived DNA may also be present in cell-free urine of renal transplant recipients and that the concentrations of urine DNA may be correlated with graft rejection. METHODS: Thirty-one female patients who had renal transplantation were enrolled in the study. In women with male organ donors, the SRY gene on the Y chromosome was used as a marker for donor-derived DNA. Real-time quantitative PCR for the SRY and beta-globin genes was carried out on cell-free urinary DNA from these patients. Serial urine samples from a female renal transplant recipient undergoing an acute rejection episode were also collected and analyzed with the beta-globin quantitative PCR system. RESULTS: SRY sequences were detected in the urine of 14 of 17 female patients with male organ donors. None of the 14 patients with female organ donors had detectable SRY sequences in urinary DNA. The median fractional concentration of donor-derived DNA was 8.7% (interquartile range, 1.9-26.4%). During the acute rejection episode, urinary concentrations of the beta-globin gene were markedly increased, with the concentrations returning rapidly to normal following antirejection treatment. CONCLUSIONS: Our results demonstrate that urinary DNA chimerism is present following renal transplantation. The measurement of urinary DNA using quantitative PCR may be useful for the diagnosis and monitoring of graft rejection.     

Spontaneous rupture of renal allografts (author's transl)]

Spontaneous rupture of an allografted kidney is not such a rare complication of kidney transplantation. In our series 5.2% of the transplanted kidneys ruptured spontaneously. The condition is an acute emergency characterized by the triad, acute abdomen, swelling in the region of the transplant and haemorrhagic shock. The aetiology of transplant rupture seems to be multifactorial, but the superimposition of an acute rejection episode on ischaemic tubular damage with acute renal failure was found to be the most important combination of events leading to transplant rupture in our patients. Exceptionally precise immunological monitoring in the early phases following transplantation and early aggressive therapy of an acute rejection crisis associated with acute renal failure should prevent allograft rupture.     

移植肾穿刺20例活组织病理检查的临床价值

背景:根据临床表现、无创性辅助检查及临床经验来判断肾移植后移植肾功能异常的原因常常会陷入困境,经皮肾穿刺活组织检查则可提供重要的循证学依据。目的:探讨移植肾穿刺活组织检查的临床意义。方法:回顾性分析20例移植肾穿刺活检病理资料及相应调整治疗后的临床结果资料。结果与结论:20例患者病理诊断为急性排斥反应7例(35%),可疑性急性排斥反应2例(10%),可疑性急性排斥反应加免疫抑制剂中毒1例(5%),免疫抑制剂中毒3例(15%),慢性移植肾肾病3例(15%),未见明确异常3例(15%),肾小管坏死1例(5%)。相应调整治疗方案后,移植肾功能恢复正常9例(45%),移植肾功能好转7例(35%),肾功能无明显变化3例(15%),肾功能轻度恶化1例(5%)。结果可见肾穿刺活组织检查对肾移植后肾功能异常的病因诊断有重要的价值,有利于指导治疗方案的调整。     

影像检查在肾移植术后并发症诊断中的应用

肾移植是治疗终末肾功能衰竭的最佳方法,而移植肾术后的并发症常导致移植肾功能损害乃至功能丧失。应用现今常用影像检查技术监测移植肾,对于肾移植术后早期发现并发症和指导治疗具有重要意义,提高了肾移植术的成功率和患者的生存率。