The Prognostic Significance of Iliac Vessel Calcification in Renal Transplantation

BackgroundPeripheral vascular disease and major extremity amputation are common in patients with established renal failure and are associated with considerable morbidity. Several studies have shown high rates of amputation following simultaneous pancreas-kidney transplantation, but there is minimal literature on the incidence of amputation following renal transplantation. Furthermore, there is little evidence regarding the best method of predicting which patients might be at risk of developing peripheral vascular complications after transplantation.MethodsWe undertook a 5 year follow-up on the cohort of patients who were on our renal transplant waiting list 5 years ago (January 2007). At this time, it was standard practice within our unit for all patients to have routine pelvic x-rays to assess for vascular calcification of the iliac vessels at the time of activation onto the transplant waiting list. Any patients with moderate/severe calcification on x-ray, which may complicate transplantation, were referred for computed tomography angiogram (CTA) of their aorto-iliac vessels. Mortality, transplantation outcomes, and amputation rates at 5 years were correlated with the severity of calcification on preoperative imaging.ResultsOne hundred eighty-seven patients were on the waiting list for renal transplantation in January 2007 (92 men; mean age, 58.3 +/? 6.2 years). Ninety-three patients received a transplant during the subsequent 5 years. By January 2012, 82 patients had a functioning transplant, 45 remained on the waiting list (5 suspended), 40 patients had died, and 20 were alive but no longer on the waiting list. Seventy-three (39.5%) had moderate or severe calcification on plain x-ray and went on to have CTA. Of these patients, 16 (21.9%) had extensive calcification affecting all the iliac vessels and were removed from the waiting list as a result. Preoperative imaging was useful in determining the side for surgery in a further 18 patients (24.3%). Twenty-two patients developed vascular complications. Nineteen (86.4%) had moderate-severe vascular calcification on imaging. Four of the patients with vascular complications (18.2%) underwent transplantation (2 had below knee amputation (BKA) prior to transplantation; 1 developed distal ischemia on the same side as the transplantation 2 years postoperatively; 1 had bilateral above knee amputation (AKA) approximately 2 years after transplantation). Eleven (50%) of the patients with vascular complications were dead at 5 years of follow-up. Mortality and amputation rates were higher in patients with moderate-severe calcification than minimal calcification (30.1% vs 16.6%; P = .02 and 10.9% vs 1.8%; P = .003, respectively). There was no difference in rates of delayed graft function (DGF), biopsy-proven acute rejection (BPAR), or creatinine at 1 year between patients who underwent transplantation with moderate-severe calcification and those without, however, intraoperative vascular complications (26.7% vs 3%; P < .001), graft loss (28.1% vs 3.4%; P = .01), and death with a functioning transplant (9.7% vs 1.6%; P = .04) rates were higher in patients with extensive calcification compared with those without.ConclusionsPlain x-ray of the pelvis is a useful screening tool to identify those patients who may require further detailed vascular imaging prior to transplantation. Amputation rates following renal transplantation are low and peripheral vascular disease (PVD) in isolation should not preclude transplantation. Nevertheless, significant vascular calcification is predictive of mortality both with and without transplantation and graft loss in patients with a renal transplant.     

细胞质动力蛋白轻链1 在肾癌组织中的表达及其临床意义

目的:探究细胞质动力蛋白轻链1(Tctex-1)在肾癌组织中的表达及其临床意义。方法:采用免疫组化法检测136 例肾癌组织及其癌旁正常肾脏组织中Tctex-1 蛋白的表达,比较肾癌组织与癌旁正常肾脏组织中的Tctex-1 阳性表达率,并分析肾癌组织Tctex-1 阳性表达率与患者临床特征的关系。结果:肾癌组织中Tctex-1 阳性表达率为91.9%,明显高于癌旁正常肾脏组织的12.5%,差异有统计学意义(P ＜ 0.01)。肾癌组织病理分级Ⅲ、Ⅳ级的Tctex-1 阳性表达率均高于Ⅰ、Ⅱ级,临床分期Ⅲ、Ⅳ期的Tctex-1 阳性表达率高于Ⅰ、Ⅱ期,差异均有统计学意义(P ＜ 0.05)。结论:Tctex-1 在肾癌组织中高表达有助于明确诊断,可作为评估肾癌临床分期、病理分级的指标,可能对肾癌术后辅助治疗有一定的参考价值。     

Immunological Aspects of Renal Transplantation1

The major obstacle to successful organ transplantation is the immunological phenomenon of rejection. Two recent developments in transplantation biology, namely, the role of humoral antibody in graft rejection and tissue matching, are discussed in the light of the author's own experience in renal transplantation.     

Vesico-Ureteric Reflux after Renal Transplantation1

The tunnel and cuff method of ureteric implantation has been found to be an effective method in preventing vesico-ureteric reflux following cadaveric renal transplantation.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

狼疮肾炎终末期肾病患者肾移植临床分析

目的：探讨系统性红斑狼疮肾炎终末期肾病患者行肾移植术治疗的效果和可行性。方法：统计我院2004年1月～2008年12月间,原发病为终末期狼疮肾病的肾移植患者的临床资料和手术后随访情况进行分析。结果：4例患者均为女性,行移植手术时全身病情稳定,无狼疮活动;手术后均使用免疫抑制剂抗排斥反应;术后平均随访时间41.5个月;至今其中3例移植肾功能良好,未发生排异反应,1例移植肾功能异常者经移植肾病理活检证实为慢性排斥反应,4例均无狼疮肾病复发。结论：终末期狼疮肾病患者肾移植效果良好,肾移植治疗终末期狼疮肾病是有效和可行的。     

PinX1基因在肾癌组织的表达及临床意义

目的分析抑癌基因PinX1在肾癌中的表达,探讨PinX1在肾癌发生、发展和预后中的作用及临床意义。方法应用半定量逆转录聚合酶链反应(RT-PCR)检测56例肾癌组织中内源性端粒酶抑制基因PinX1及端粒酶催化亚基(hTERT)的mRNA表达水平,同时应用免疫组化方法检测PinX1蛋白表达水平,分析PinX1表达与肾癌分期、分级及临床特征之间的关系。结果 PinX1表达与肾癌组织分化、临床分期和淋巴转移之间有显著相关性(P0.05),与hTERT表达呈负相关。PinX1在肾癌和癌旁表达具有显著性差异(P0.05)。肾癌分期分级越高,PinX1表达越低,有淋巴结转移的PinX1表达要低于无淋巴结转移(P0.05)。结论 PinX1的下调可能与肾癌形成、转移过程中端粒酶激活及维持机制有关。检测PinX1的表达水平对评价肾癌恶性程度、转移潜能和预后评估均有重要的临床价值。     

Campath-1H Use in Pediatric Renal Transplantation

Campath-1H is a humanized, monoclonal antibody directed against CD52 determinants on the surface of human B- and T-cells and monocytes. Reports of Campath-1H use as induction in adult renal transplantation have been encouraging with low rejection rates and minimal adverse events. We report four high risk pediatric kidney transplant patients who received Campath-1H for unique indications with variable results. Children ranged in age from 20 months to 16 years. Immunosuppression regimens varied. Three of four patients experienced acute rejection, two of which were C4d positive. Serial flow cytometry was performed on all four patients. The patient who received only Campath-1H has an absolute lymphocyte count that remains less than 50% of baseline at 12-months post-transplant. In addition, in this patient CD3, CD4, CD8 and CD20 remain less than 50% of baseline. From this initial experience using Campath-1H in pediatric renal transplantation we conclude that; (1) the use of Campath-1H does not prevent recurrence of FSGS, (2) as seen in adults, lack of calcineurin inhibition when using Campath-1H may increase the risk of antibody-mediated rejection and (3) prolonged lymphocyte depletion remains even after a single dose of Campath-1H in children.     

Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics,Pathology, and Outcome

BackgroundRenal involvement in ANCA–associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail.MethodsIn a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value.ResultsWe included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype.ConclusionsOur findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.     

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.Kidney transplantation is the modality of choice for children with ESRD. Despite an improvement in early outcomes, long-term allograft survival remains restricted^1,2; chronic graft injury is the prime limiting survival factor and largely driven by the development of antidonor humoral responses.^3,4 Anti-human leukocyte antigen (anti-HLA) antibodies (Abs) are a major cause of acute antibody-mediated rejection and also may damage the kidney in a more indolent process, leading to chronic antibody-mediated rejection and eventual allograft loss.⁵ Nevertheless, ongoing allograft rejection in HLA identical transplant recipients and patients without detectable anti-HLA Abs to donor HLA antigens (DSA) supports an additional pathogenic role for graft injury by non-HLA antigens, such as protein kinase-ζ, and MHC class 1-related chain A (MICA).^6–9In adult renal transplantation, Terasaki¹⁰ and Terasaki and Cai¹¹ have shown that preformed and de novo post-transplant production of DSAs correlates with a higher risk of acute rejection (AR) and reduced 1-year graft survival. The impact of the humoral response has not been well studied in the pediatric transplantation. We performed quantitative analysis of post-transplant de novo Abs to HLA and MICA in children undergoing kidney transplants and questioned differences in Ab profiles with steroid avoidance.^12–14 To this end, we compared the measured humoral immune responses of pediatric kidney transplant patients in a randomized, multicenter, open-labeled study for a steroid-based (SB) or steroid-free (SF) immunosuppression protocol (SNSO1).^15,16 We conducted serial monitoring of quantitative titers of circulating for MHC classes I and II and Abs to MICA in patients with stable graft function, acute graft rejection, and chronic graft injury as evaluated by matched protocol or indicated renal allograft biopsies (Figure 1). We intended to find if there were differences in the detection of these Abs with steroid avoidance, the average time for de novo Ab detection post-transplantation, and the correlation of Ab levels with graft injury and function. Correlation of the negative impact of the peripheral and intragraft humoral responses and their specificities with adverse graft outcomes in children could develop a novel means of monitoring and titrating immunosuppression in pediatric renal transplantation.Open in a separate windowFigure 1.Study outline. This study used 440 serum samples and 440 matched blinded biopsy scores for CADI, CNIT, Banff rejection grading, and C4d stains on 440 matched protocol biopsies from the SNSO1 multicenter randomized trial of SF and SB immunosuppression in pediatric renal transplantation.^15,16 Samples and biopsies were assayed at 0 (pretransplant), 6, 12, and 24 months post-transplantation. Of 130 patients in the trial, 124 patients had at least three of four sera samples collected and were included in the analysis.     

移植肾输尿管梗阻的原因与处理方法

目的:探讨移植肾输尿管梗阻的发病原因及其处理方法。方法:报告行肾移植后发生移植肾输尿管梗阻29例的临床资料。全部经手术探查证实,包括输尿管膀胱吻合口狭窄9例,输尿管下段狭窄5例,输尿管全段闭锁2例,膀胱肌层包埋过紧1例,输尿管下段穿孔4例,输尿管全段坏死2例,输尿管下段血块堵塞1例,输尿管外周血肿压迫2例,脓肿压迫1例,移植肾输尿管结石2例。14例移植输尿管坏死患者中有10例梗阻前发生急性排斥反应。结果:患者尿路重建后移植肾功能均恢复良好,随访1年均无再次梗阻发生。结论:移植肾输尿管梗阻以输尿管狭窄和坏死最为多见,排斥反应是发生输尿管梗阻的重要病因之一。对于影像学提示梗阻而移植肾功能无明显受损的病例,应积极行移植肾活检。手术是解决移植肾输尿管梗阻最有效的方法。     

肾透明细胞癌组织中MAP1-LC3的表达及临床意义

目的：研究肾透明细咆癌组织中微血管相关蛋白1轻链3（MAP1-LC3）的表达,探讨其与肾癌生物学行为的关系。方法：采用免疫组织化学SP方法检测45例肾透明细胞癌及lO例正常肾组织中MAPlI,c3的表达情况。结果：45例肾透明细胞癌组织中．37剜MAP1-LC3表达阳性（82．2％）,与正常肾组织（40．0％）比较,其表达差异有统计学意义（P〈0．05）。结论：MAP1-LC3在肾癌组织中表达增强,这种高表达可能与肾癌的发生发展有关。     

加强肾移植的临床研究和经验总结

加强肾移植的临床研究和经验总结章咏裳肾移植是器官移植领域中开展最多的手术，据统计，１９９６年全国共施行肾移植２７９２例次，我国的肾移植总数也逾２万例次。尽管如此，在临床工作中还会遇到一些新问题，通过开展前瞻性或回顾性的临床研究和资料总结，有益于肾移植...     

Preparation of Patients for Cadaveric Renal Transplantation1

Experience with renal homotransplantation during the last six years has made it apparent that the path from the terminal stages of chronic renal failure to renal transplantation is not always smooth and can expose the patient to a series of events which have a definite morbidity and mortality. This communication describes the various problems encountered in the period leading up to transplantation. In addition. the factors thought to be significant in their development and management will Be discussed.     

Clinical Significance of Serum Visfatin in Renal Transplant Recipients

Chronic antibody-mediated rejection is the most common cause of late graft loss in renal transplant recipients. Visfatin is a pre-B cell colony-enhancing factor secreted by activated lymphocytes. We hypothesize that visfatin may play a role in the augmentation of B cell colonies and facilitate antibody-mediated rejection. Renal transplant recipients were randomly selected for the study. Fasting blood samples were obtained for the assay of visfatin. The participants were prospectively followed up for 3 years. A total of 146 patients were recruited for the study and were divided into 3 groups according to tertile of serum visfatin level. At the end of follow-up, 6 patients had graft loss, including 1 graft loss in tertile 1, 3 in tertile 2, and 2 in tertile 3 (P?=?.60). Fourteen patients experienced at least 1 episode of acute rejection, while 21 patients were diagnosed as having chronic rejection. The distribution of acute rejection was 10.2% in tertile 1, 10.2% in tertile 2, and 8.3% in tertile 3 (P?=?.94); chronic rejection occurred in 10.2%, 16.3%, and 16.7%, respectively (P?=?.59). We conclude that serum visfatin level was not correlated with either graft failure or patient mortality in a 3-year observation period.     

Delayed Graft Function in Renal Transplantation: Etiology, Management and Long-term Significance

Purpose

In cadaveric renal transplantation a period of delayed graft function postoperatively is not uncommon and often associated with a poor outcome. We reviewed the biology of reperfusion injury and delayed graft function in renal transplantation, as well as its prevention, management and long-term effects.

Materials and Methods

The medical literature covering acute tubular necrosis, delayed graft function in renal transplantation and immunology of ischemia reperfusion injury was reviewed.

Results

Delayed graft function is clearly associated with poor allograft survival, and is caused by an interaction of ischemic and immunological factors. Technical and pharmacological maneuvers can improve early function rates. The response to ischemic injury is complex, and may increase graft immunogenicity and promote the chronic proliferative changes seen in chronic allograft nephropathy.

Conclusions

Improvement in early renal function should be a primary goal in renal transplantation to enhance early and long-term results. Basic research into the injury response may yield insights into renal pathophysiology.