A single‐center experience with 200 dual kidney transplantations

This study reports on a large series of 200 dual kidney transplantations (DKTs) from expanded criteria donors (ECDs) and proposes specific ways to optimize outcomes. Data concerning 200 DKTs performed in the last 14 yr were retrospectively analyzed. Kidneys from high‐risk ECD were allocated for use in DKTs on an old‐for‐old basis after histological assessment. Different surgical techniques and immunosuppressant regimens were used over time, and the outcomes are discussed. Donors and recipients were a median 73 (70–77) and a 62 (58–67) yr old, respectively. Delayed graft function occurred in 31.5% of cases, and acute rejection in 13.5%. Patient and graft survival at five yr were 90.4% and 85.8%, respectively. Unilateral kidney placement was preferred for 75% of patients, and was associated with a low rate of surgical complications. Our current standard therapy comprising low‐dose calcineurin inhibitors (CNIs) associated with mammalian target of rapamycin inhibitors (mTOR) and steroids appears to offer the best risk/benefit profile for elderly patients undergoing DKT. In our experience, outcomes after DKT can be improved by: (i) kidney clinical–histological assessment; (ii) unilateral kidney placement; (iii) minimal use of CNI associated with mTOR.     

Determining the effect of immunosuppressant adherence on graft failure risk among renal transplant recipients

The objective was to use the United States Renal Data System (USRDS) to quantify the relationship between immunosuppressant therapy (IST) adherence and risk of graft failure among adult renal transplant recipients (RTRs). A secondary objective was to examine the relationship among select patient characteristics and IST adherence. The study sample included adult RTRs who: received primary transplant between January 1, 1999 and December 31, 2005; experienced graft survival for at least 12 months post‐transplant and had at least 12 months of data in the USRDS; utilized Medicare coverage for IST; and were prescribed cyclosporine or tacrolimus. IST adherence was measured by medication possession ratio (MPR). Pearson chi‐square tests were used to examine associations between patient characteristics and MPR quartiles. Cox proportional hazards regression was used to assess relationships among time to graft failure, MPR, and patient characteristics. Thirty‐one thousand nine hundred and thirteen RTRs met inclusion criteria. Older age, female gender, white race, deceased donors, and tacrolimus were associated with greater adherence (p < 0.001). Cox proportional hazard modeling indicated greater adherence, white race, and having a living donor were significantly associated with longer graft survival (p < 0.05). Future prospective studies should further examine the clinical significance of IST nonadherence as it relates to graft failure.     

白芍总苷治疗类风湿关节炎疗效及安全性Meta分析

目的 :系统分析评价白芍总苷治疗类风湿关节炎(RA)的疗效及安全性。方法:计算机检索中国知网、万方医学数据库、维普中文科技期刊全文数据库有关"白芍总苷"联合免疫抑制剂应用于治疗类风湿关节炎的临床疗效及安全性的随机对照研究。采用Rev Man 5.3软件进行Meta分析。结果:通过数据库检索符合要求的文献10篇,入选患者741例。有9项研究实验组临床疗效优于对照组(OR=2.97,95%CI 1.63~5.60,Z=3.54,P0.0001)。有6项研究治疗后两组晨僵时间均缩短,但实验组缩短更明显,MD(95%CI)为-0.11(-183.42~-60.03),Z=3.61,P0.0001。有8项研究治疗后两组关节肿胀个数均减少,但实验组减少更明显,MD(95%CI)为-0.12(-175.13~-62.04),Z=3.72,P0.0001。有8项研究治疗后两组红细胞沉降率水平下降,但实验组下降更明显,MD(95%CI)为-0.12(-179.43~-64.05),Z=3.84,P0.0001。有9项研究实验组不良反应发生情况优于对照组。结论:白芍总苷治疗类风湿关节炎疗效较好,安全性高。     

天然药物化学史话:雷帕霉素

天然产物化学研究在药物研发中起着非常重要的作用。微生物是新药的主要来源之一,雷帕霉素就是一种从来自复活节岛土壤微生物中得到的化合物,它的发现引领了一系列免疫与抗癌药物的问世。科学家对雷帕霉素作用靶点的研究已取得了"诺贝尔奖级别"的成果。对雷帕霉素的研发历程进行回顾,期望能够为今后相关研究提供思路与启示。     

Impact of CYP3A5 genomic variances on clinical outcomes among African American kidney transplant recipients

Little is known about the impact of CYP3A5 polymorphisms on transplantation outcomes among African American (AA) kidney transplant recipients (KTRs). To assess this issue, clinical outcomes were compared between AA CYP3A5*1 expressers and nonexpressers. This retrospective cohort study analyzed AA KTRs. Biopsy‐proven acute rejection (BPAR), delayed graft function (DGF), glomerular filtration rate (GFR), infections, and tacrolimus dosing requirements were examined in 106 immunologically high‐risk AA kidney transplant patients over a 2‐year follow‐up period. In CYP3A5*1 expressers compared to nonexpressers, the incidence of BPAR was significantly higher in the first 6 months (13% vs 0%; P = .016) compared to 24 months (13% vs 7%; P = .521). Tacrolimus total daily dose at first therapeutic level was significantly higher in CYP3A5*1 expressers (12 mg/day) compared to nonexpressers (8 mg/day; P < .001). Compared to CYP3A5*1 nonexpressers, DGF incidence was significantly higher among CYP3A5*1 expressers (27.6% vs 6.7%; P = .006). By contrast, median GFR was significantly higher in CYP3A5*1 expressers compared to nonexpressers (54.5 mL/min vs 50.0 mL/min; P = .003) at 24 months. The findings from this retrospective study suggest that AAs with CYP3A5*1 expression require 50% more tacrolimus and have an increased incidence of DGF and acute rejection.     

Selective CD28 Blockade Results in Superior Inhibition of Donor‐Specific T Follicular Helper Cell and Antibody Responses Relative to CTLA4‐Ig

Donor‐specific antibodies (DSAs) are a barrier to improved long‐term outcomes after kidney transplantation. Costimulation blockade with CTLA4‐Ig has shown promise as a potential therapeutic strategy to control DSAs. T follicular helper (Tfh) cells, a subset of CD4⁺ T cells required for optimal antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8⁺ T cells relative to CTLA4‐Ig, but the impact of CD28‐specific blockade on CD4⁺ Tfh cells is unknown. Thus, we identified and characterized donor‐reactive Tfh cells in a murine skin transplant model and then used this model to evaluate the impact of selective CD28 blockade with an anti‐CD28 domain antibody (dAb) on the donor‐specific Tfh cell–mediated immune response. We observed that the anti‐CD28 dAb led to superior inhibition of donor‐reactive CXCR5⁺PD‐1^high Tfh cells, CD95⁺GL7⁺ germinal center B cells and DSA formation compared with CTLA4‐Ig. Interestingly, donor‐reactive Tfh cells differentially upregulated CTLA4 expression, suggesting an important role for CTLA4 in mediating the superior inhibition observed with the anti‐CD28 dAb. Therefore, selective CD28 blockade as a novel approach to control Tfh cell responses and prevent DSA after kidney transplantation warrants further study.