Developing Organ Offer and Acceptance Measures: When 'Good' Organs Are Turned Down

Turndowns of offers of deceased donor kidneys for transplantation can contribute to inefficiencies in the organ distribution system and inequality in access to donated organs. Match run data were obtained for 4967 'good' kidneys placed and transplanted in 2005 after fewer than 50 offers. These kidneys were not recovered from donation after cardiac death or expanded criteria donors, or from donors with a history of substance abuse. On average, these good kidneys were not accepted until after seven offers to candidates and after offers to 2.4 programs. Models for the likelihood of acceptance found several donor and candidate characteristics to be significantly related to acceptance rates (p < 0.05). After accounting for these variables, there remained 2- to 3-fold differences among transplant programs in acceptance rates. These models could be used to identify kidney transplant centers with exceptional acceptance practices. Several strategies might be employed to increase acceptance rates for good organs.     

活体亲属肾移植手术的17例报告

目的总结活体亲属肾移植的临床经验。方法对供、受者进行全面的免疫学检查，对供者行IVU检查了解分侧肾功能，行DSA或MRA、螺旋CT血管三维成像检查了解血管的变异情况之后，开放式手术摘取供肾13例，经后腹腔镜活体供肾摘取4例，按常规方法移植给受者。免疫抑制方案为环孢素A（或FK506）、霉酚酸酯（或硫唑嘌呤、雷帕鸣）、强的松三联免疫抑制剂。结果13例开放式手术时间1．5～3．0h，平均2．0h；热缺血时间1．0～1．5min，平均1．2min；术中出血量60～200ml，平均140ml，术中及术后均未输血；术后住院7～10d，平均8d。4例后腹腔镜手术时间3．0～4．5h，平均3．5h；热缺血时间2．5～3．5min，平均2．8min；术中出血量60～100ml，平均75ml，术中及术后均未输血；术后3～5d出院。移植肾血液循环恢复后10～40s泌尿，平均20s。1例受者术后45d发生轻微的急性排斥反应，应用激素冲击3d后逆转，其余受者均无并发症。随访4～60个月，人／肾存活率为100％，移植肾功能良好。结论活体亲属肾移植安全可行，取左肾尽量靠近腹主动脉壁切断肾动脉，取右肾切取少许下腔静脉片。     

同种异体骨支撑架微创治疗股骨头坏死的临床研究

目的应用改良髓芯减压术结合同种异体骨支撑架加自体骨和脱钙骨基质（decalcified bone matrix，DBM）治疗早期股骨头坏死，探索早期股骨头坏死的微创治疗方法。方法2004年1月～2005年4月，23例24个髋关节采用经大转子下通过股骨颈钻隧道至股骨头骨坏死区，将装有自体松质骨和DBM的同种异体骨支撑架经隧道拧入骨坏死区直至软骨下骨约5mm处，隧道远端用自体髂骨填塞。观察手术前后Harris评分变化、x线影像学表现及是否需进一步治疗。结果本组所有患者均获得随访，平均随访19（12—27）个月，以最后一次随访资料作为最终评价依据。Harris评分，术前优良率为43．5％（10／23）。术后优良率为91．3％（21／23）。22侧髋关节影像学表现保持稳定，无明显并发症发生。结论同种异体骨支撑架植入结合自体松质骨和DBM治疗成人股骨头坏死，增加了股骨头负重区软骨下骨的机械支撑，成骨作用强，有利于股骨头坏死的修复与重建，同时，不破坏患者股骨头本身的血液供应，创伤小，操作简单，值得临床推广使用。     

Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum; however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and 3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT. Presented at the American Gastroenterological Association during Digestive Disease Week in Los Angeles, CA, as a poster presentation on May 23 2006. Abstract published in GastroenterologyE 2006; 130:A604.     

Neuroimaging and Neurologic Complications after Organ Transplantation

Neurologic complications are common after transplantation and affect 30-60% of transplant recipients. The etiology of most of the posttransplant neurologic disorders is related to the opportunistic infections, both systemic and involving central nervous system (CNS), toxicity of immunosuppressive medications, and the metabolic insult created by the underlying primary disease and the transplant procedure. Neuroimaging studies are one of the key tools in the evaluation and enable early diagnosis of neurologic complications in transplant patients, especially posterior reversible leukoencephalopathy syndrome, central pontine myelinolysis, intracerebral hemorrhage, and fungal and bacterial abscesses. Magnetic resonance imaging (MRI) is the preferred technique, but each of the available neuroimaging techniques offers a unique insight into the pathophysiologic mechanisms underlying neurologic complications of transplantation. The role of neuroimaging in this population includes early detection of calcineurin inhibitor neurotoxicity, opportunistic infections, neoplasia, metabolic disorders, or cerebrovascular diseases. In addition, we can monitor longitudinal progression of disease and treatment response.     

Disappearance of Tophi in Familial Juvenile Hyperuricemic Nephropathy after Kidney Transplantation

A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney.     

A ‘Weight‐Listing’ Paradox for Candidates of Renal Transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.     

Nontransplantation of Livers from Deceased Donors Who Are Able to Donate Another Solid Organ: How Often and Why It Happens

Deceased donor factors associated with poor graft outcome are well known, but how often these factors lead to livers left untransplanted is poorly defined. A nested, case-control study was conducted using the United Network for Organ Sharing (UNOS) database from 1987 to 2005. Only those donating >/=1 solid organ were included. Primary outcome was livers not transplanted (LNT, cases) versus transplanted (LT, controls). Primary variables for multivariate analysis were donor age and obesity. Covariates included donation after cardiac death (DCD), cerebral vascular accident death, viral serologies, cancer, ALT and bilirubin. There were 23 373 (26%) LNT's from 91 362 donors who donated at least one organ. Percent LNT fell over time (1987-1990: 48%; 1991-1995: 29%; 1996-2000: 21%; 2000-2005: 16%; p < 0.01). Increased age (odds ratio: 4.2, 95% confidence interval 3.6-4.9, p < 0.01) and obesity (2.1, 1.9-2.3, p < 0.01) were significantly associated with LNT across all time periods. Other significant factors included DCD and elevated ALT. For 2001-2005, population attributable risk indicate that age >40, abnormal ALT and obesity account for 32.6%, 25.3% and 9.2% of untransplanted livers, respectively. Use of expanded criteria livers has pushed LNT lower in spite of an aging and heavier donor population. Nevertheless, age and obesity still account for a significant portion of untransplanted livers.     

Immunoadsorption in Severe C4d-Positive Acute Kidney Allograft Rejection: A Randomized Controlled Trial

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.     

CD34+细胞自身移植治疗儿童难治型系统性红斑狼疮

目的探讨治疗儿童难治型系统性红斑狼疮(SLE)积极、有效的方法.方法对2例病程分别为5年和7年,狼疮肾Ⅲ级和Ⅳ级,主要表现为持续性血小板减少、蛋白尿和浆膜炎的患儿进行CD34+细胞分选的自身干细胞移植.首先经惠尔血动员、CS-3000血细胞分离机获取单个核细胞,通过CliniMACS CD34+细胞分选仪分别得到了1.7×106/kg及1.0×106/kg CD34+细胞,采集物中分别尚存2×105/kg和1×104/kg的CD3+细胞.用CTX 50 mg/kg·d×4 d+ATG(Fresennius S 5 mg/kg·d×3 d)预处理.结果两患者分别于+9 d和+7 d获粒细胞重建,自+15 d起血小板维持于正常水平.现已分别随访13月和6月,原发病症状完全消失,自身免疫相关抗体全部转阴,但细胞免疫功能仍未恢复,CD4细胞仍处于低水平.结论CD34+细胞分选的自身干细胞移植治疗儿童难治型红斑狼疮近期疗效满意.