肾移植长期管理中的是是非非.ppt

医道是仁，为你打call： DCD肾移植长期管理中的是与非,肾移植长期管理中的是是非非,01,02,Contents,目,录,03,美国DDKT患者整体5年存活率仅为87.2%,OPTN/SRTR 2016 Annual Data Report: Kidney,美国国家器官获取和移植网络（OPTN）显示，在美国成人DDKT中，不同年龄段患者的存活率不同，65岁以上的肾移植患者存活率明显更低，患者整体上5年存活率仅为87.2%,DDKT:死亡供体肾移植；OPTN：美国国家器官获取和移植网络,2011年不同年龄段成人死亡供肾受者的存活率,美国DDKT患者的移植物长期存活率仍不容乐观,美国国家器官获取和移植网络（OPTN）显示，美国成人DDKT中，移植后6个月的移植物功能衰竭率明显降低，几乎只有10年前的一半；移植后10年的移植物功能衰竭发生率变化不大,OPTN/SRTR 2016 Annual Data Report: Kidney,6个月 1年 3年 5年 10年,移植物功能衰竭率(%),2005年的移植物衰竭率为51.6%,移植肾丢失的主要原因： 心血管疾病和肾功能受损,移植肾丢失原因1,带功死亡: 50%,慢性移植物失功：50%,心脑血管意外2 42.3%,感染 2 17.6%,肿瘤 2 9.2%,慢性移植物肾病：30-40%,其他疾病：10-20%,CNI 毒性,原疾病 复发,急排,新发 疾病,慢排 亚临床急排,非特异性 纤维化和 小管萎缩,其他 2 30.9%,高血压,高脂血症,糖尿病,高尿酸血症3,危险因素,高尿酸血症 致肾小管损伤/坏死,1. Pascual M, et al. N Engl J Med 2002; 346(8):580-90. 2. Ojo, A. O., et al. (2000).Kidney Int.57(1): 307-313. 3. Erkmen Uyar M, et al. Transplant Proc. 2015 May;47(4):1146-51.,肾移植术后代谢相关并发症发生率高,美国肾移植后新发糖尿病(NODAT)发生率为53%1，高血压患病率为70-90%2，高脂血症发病率为71%3 ，高尿酸血症发病率为68.3%4 中国肾移植后NODAT发病率为20.3%；高血压发病率71.7%；高脂血症发病率47.9%5,高尿酸血症发生率为31.3%6,1.Sneha Palepu et al. World J Diabetes. 2015 Apr 15; 6(3): 445455. 2. Olga Charnaya, et al. Front Pediatr. 2017; 5: 86. 3. Rao NN, et al. Semin Nephrol. 2018 May;38(3):291-297. 4Kalil RS,et al.Am J Kidney Dis. 2017 Dec;70(6)762-769. 5.李冉;中南大学;2012年. 5. Lv C, et al. PLoS One. 2014 Jun 9;9(6):e99406. 6.王明睿,等.中华器官移植杂志,2016,37(12):742-747.,并发症发生率(%),移植术后代谢相关并发症 增加移植物失功风险,4项研究分析了932名肾移植受者，评估了移植物丢失的因素。 结果显示：代谢综合征（MS）增加移植物丢失的风险。（RR：3.06; 95CI：2.17-4.32; I 2 = 0;异质性P= 0.72）,截至2015年11月7日的一项荟萃分析， 对MEDLINE，EMBASE和Cochrane图书馆进行了检索。比较MS对移植物丢失，心血管疾病死亡和全因死亡率，检索了585项研究，纳入1269例患者在内的5项研究。目的是评估MS对肾移植后结局的影响。 MS的定义基于美国胆固醇教育计划/成人治疗专家组III（NCEP / ATPII）、国际糖尿病联合会（IDF）或世界卫生组织（WHO）标准,MS:代谢综合征,Pedrollo EF, et al. Transpl Int. 2016 Oct;29(10):1059-66.,移植术后代谢相关并发症 增加CVD死亡风险,3项研究分析了865名肾移植受者，评估了心血管事件死亡因素。 结果显示：代谢综合征（MS）增加心血管死亡风险（RR：3.53; 95CI：1.27-9.85; I 2 = 0;异质性P= 0.40）,MS:代谢综合征；CVD：心血管疾病,截至2015年11月7日的一项荟萃分析， 对MEDLINE，EMBASE和Cochrane图书馆进行了检索。比较MS对移植物丢失，心血管疾病死亡和全因死亡率，检索了585项研究，纳入1269例患者在内的5项研究。目的是评估MS对肾移植后结局的影响。 MS的定义基于美国胆固醇教育计划/成人治疗专家组III（NCEP / ATPII）、国际糖尿病联合会（IDF）或世界卫生组织（WHO）标准,Pedrollo EF, et al. Transpl Int. 2016 Oct;29(10):1059-66.,肾移植术后受者需要心身关爱,Srifuengfung M, et al.J Nerv Ment Dis. 2017 Oct;205(10)788-792.,抑郁症：肾移植受者抑郁的发生率为11.3-41.4%。 心身疾病：一组发生发展与心理社会因素密切相关，但以躯体症状表现为主的疾病，主要特点包括： 心理社会因素在疾病的发生与发展过程中起重要作用 表现为躯体症状，有器质性病理改变或已知的病理生理过程 不属于躯体形式障碍,01,Contents,目,录,03,02,移植后导致心血管死亡的危险因素,移植前因素,移植后因素,供体因素 年龄，移植物质量，脑死亡损伤，血管疾病,受体因素 年龄，吸烟，BMI，既往糖尿病史，长期透析,免疫因素 急性排斥反应发作,非免疫因素 CNI或类固醇的慢性影响,eGFR下降,左心室肥厚,高血压1,移植后糖尿病1,血脂异常1,心率失常,充血性 心力衰竭,冠状动脉 疾病,心脏瓣膜病,心血管相关死亡,Stoumpos S, et al.Transpl Int. 2015 Jan;28(1)10-21 Sofue T, et al. Drug Des Devel Ther. 2014 Feb 17;82:45-53,高尿酸血症2,肾移植受者血压控制欠佳,1.Zbigniew Heleniak, et al. 2018 TTS.Abstract number:P.358 2.Glicklich D, et al. Cardiol Rev. 2017 May/Jun;25(3):102-109.,2018 TTS报道的波兰的一项回顾性研究，纳入2006年59例透析患者和330例KTR；2014/2016年86例透析患者和861例KTR，旨在分析血压控制率和药物治疗情况,血压,肾移植受者（KTRs）血压控制达标率低于血透（HD）患者，且使用多种降压药比例或高于HD患者1,高血压是移植后新发 CHF和IHD的独立危险因素,研究显示，高血压与移植后新发充血性心力衰竭有关，多因素分析显示，收缩压升高是新发充血性心力衰竭的独立危险因素（HR=1.29，95%CI：1.101.50，P=0.001），舒张压升高是新发缺血性心脏病的独立危险因素（HR=1.41，95%CI：1.031.94，P=0.03）,来自加拿大的一项回顾性分析，纳入638例移植时无心脏病的成人肾移植受者，旨在描述新发CHF、新发IHD与成人肾移植受者的死亡率，危险因素和相互关系,CHF：充血性心力衰竭；IHD：缺血性心脏病,Rigatto C,et al.J Am Soc Nephrol. 2002 Apr;13(4)1084-90.,发生CHF的危险比（HR）,血压,肾移植后高血压患者的控制目标,欧洲肾脏最佳实践指南建议蛋白尿患者血压控制目标125/75 mmHg KDIGO临床实践指南推荐KTR患者： 诊室内血压应控制在140/90 mmHg 家庭自测血压130/80 mmHg 围手术期：目标血压 150/90 mmHg 术后1周：目标血压 140/90 mmHg 术后1个月：目标血压 130/80 mmHg,Glicklich D, et al. Cardiol Rev. 2017 May/Jun;25(3):102-109.,血压,肾移植术后降压药合理使用,Divac N, et al. Curr Med Chem. 2016;23(19)1941-52. Glicklich D, et al. Cardiol Rev. 2017 MayJun;25(3)102-109.,CCB：钙通道拮抗剂；ACEI：血管紧张素转换酶抑制剂；ARB：血管紧张素受体拮抗剂；BPH：良性前列腺增生,血压,NP-CEL-2018.07-012 Valid Until 2020.07,隐匿性高血压和夜间高血压需加强重视,德国汉诺威医学院对172例儿童移植受者进行前瞻性病例对照研究，旨在描述儿童受者高血压的发生情况。结果显示：儿童移植受者高血压普遍发生，更进一步隐匿性高血压和夜间高血压发生率也高居不下，急需重视。,隐匿性高血压：诊室血压120/70mmHg,2018 American Transplant Congress B285,血压,原肾切除或有助于血压控制,p0.0001,p=0.0127,p=0.0057,斯坦福大学对137例儿童肾移植受者进行回顾性分析，旨在比较原肾切除和原肾保留对患者长期血压控制的影响。结果显示：原肾切除受者的长期血压控制率更高，差异具有统计学意义。,2018 American Transplant Congress D158,血压,NP-CEL-2018.07-012 Valid Until 2020.07,使用ACEi/ARB肾移植受者存活较高,2018ATC上报道的来自美国圣路易斯大学的研究：检索了一个连接SRTR登记的新数据库，其中有来自大型药品索赔仓库的AHM填写记录，记录了2008-2015年的54153个肾移植受者，通过多变量Cox回归分析抗高血压药物(AHM)的选择对患者和移植结果的影响，旨在分析抗高血压药物对患者和移植结果的影响。 与DHP-CCB方案相比，NDHP-CCB( aHR 1.111.241.37 )和其他药物( aHR1.441.692.00 )治疗的死亡率更高； ACEi / ARB治疗的患者死亡率更低( aHR 0.850.920.99 ),H. Yamout, et al. 2018 ATC.Abstract number:337,ACEi / ARB：血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂； DHP-CCB：二氢吡啶钙通道阻滞剂； NDHP-CCB：非二氢吡啶钙通道阻滞剂,Hypertension is common among kidney transplant (KTx) recipients, but the impact of antihypertensive medication (AHM) choice on patient and graft outcomes is not well defined. We examined a novel database linking SRTR registry data for 54,153 KTx recipients with AHM fill records from a large pharmaceutical claims warehouse (2008-2015). Mutually exclusive regimens were defined hierarchically as based in: Angiotensin converting enzyme inhibitor/angiotensin receptor blockers (ACEi/ARB), dihydropyridine calcium channel blockers (DHP-CCB), non-DHP (NDHP)-CCB, beta blockers or vasodilators/others. Associations (adjusted hazard ratio, 95% LCLaHR 95% UCL) of AHM regimen in mos 7-12 post-KTx with patient and graft survival over the next 5 yrs were quantified by multivariate Cox regression including adjustment for recipient, donor and transplant factors, and clustering for center. The most common AHM after transplant were DHP-CCB, followed by beta-blockers, ACEi/ARB, and diuretics, but regimen patterns varied across transplant centers (Fig 1). In bi-level hierarchical modeling, compared to DHP-CCB-based treatment, ACEi/ARB use was more common in those with diabetes, obesity, and on mTORi-based immunosuppression. Unadjusted survival varied with AHM treatment (Fig 2). Compared to DHP-CCB regimen, adjusted mortality was higher in those managed with NDHP-CCB (aHR 1.111.241.37) and other agents (aHR1.441.692.00), but lower in patients treated with ACEi/ARB (aHR 0.850.920.99). While associations may in part reflect unobserved selection factors, these data motivate the need for controlled studies to determine optimal AHM regimens after KTx, reduce unjustified practice variation, and inform evidence-based best practices.,血压,利尿剂/其他,受体阻滞剂,CCB类,非CCB类,ACE I/ARB类,死亡率,移植后新发糖尿病高发,血糖,36%,1/3的无既往糖尿病肾移植受者移植后发生新发糖尿病,纽约阿尔伯特爱因斯坦医学院一项回顾性队列研究供纳入了304例肾移植受者，旨在描述移植后受者新发糖尿病的发生情况。结果显示: 1/3的无既往糖尿病肾移植受者移植后发生新发糖尿病，其中年龄大，BMI高，移植前心血管疾病，以及接受KDPI评分更高供肾是新发糖尿病的风险因素,2018 American Transplant Congress A219,移植后糖尿病增加心血管发生风险,患有移植后糖尿病（PTDM）的患者发生心脏事件的风险增加,一项前瞻性单中心观察研究，纳入201例连续KT受者，旨在评估新诊断的新发PTDM对主要心脏事件（心源性死亡或非致死性急性心肌梗死）和患者存活的长期影响,Conte C, et al. Acta Diabetol. 2018 Aug;55(8):763-779.,PTDM: 移植后糖尿病,无心血管事件发生率(%),血糖,移植后糖尿病管理,KDIGO指南推荐PTDM管理目标：HbA1c 7.0-7.5,血糖,调整免疫制剂方案 激素的减量和撤除 FK转化为环孢素 CNI/mTOR转化为贝拉西普,高血压者血压控制130/80mmHg； CCB为一线推荐用药；避免使用噻嗪类利尿剂 饮食和生活习惯改变，他汀类药物使用。,DPP4-1 GLP-1 RA SGLT-2i Sus 胰岛素,饮食控制 运动疗法 肥胖减重 行为疗法,免疫抑制药物对血糖的影响,PTDM管理：减少胰岛素抵抗和保护细胞功能(改善胰岛素分泌) 对于肾移植后住院患者，胰岛素治疗是控制移植后高血糖的首选方案 激素与CNI的使用影响血糖代谢，增加PTDM发生。,Pimentel AL, et al. Clin Chim Acta. 2015 Oct 23;450:327-32.,血糖,CNI药物是否增加PTDM有争议,1.Karpe KM, et al. Cochrane Database Syst Rev. 2017 Jul 21;7:CD006750.,一项荟萃分析检索截止到2016.10.11在Cochrane肾脏和移植专科登记包含标准剂量CNI治疗与CNI停药或低剂量CNI比较的结果的RCT研究，共纳入83项研究，16156例患者，评估CNI对于移植后结局的影响2,2. 2017年发表的一项数据库研究分析，纳入了6项研究，810例受者的分析表明，与CNI停药或减量方案相比，标准剂量CNI方案PTDM发生率与之相当(RR 0.94 95% CI 0.621.42, P=0.76, I2=0%),1.无CNI方案可降低NODAT发生率的研究已得到临床医生的认可。,NODAT：移植后新发糖尿病; PTDM:移植后糖尿病,血糖,mTORi较MMF方案HbA1C升高更显著,Introduction: it is widely known that immunosuppressive drugs alter lipids and carbohydrate metabolism in kidney transplant patients. The most common side effects are diabetes mellitus induced by calcineurin inhibitors and hypertriglyceridemia caused by mTOR inhibitors. However, little is known about the combination of these agents in real clinical practice and if a difference exists between patients who were already diabetics or not before transplantation. Methods: longitudinal retrospective 1-year long study in which we compared two different regimens based on tacrolimus and prednisone, one with mycophenolate (MP group) and one with an mTOR inhibitor (mTORi group). The studied population included all kidney transplanted patients in the Hospital Clnic, Barcelona, performed in a 3-year period from June 2013 to May 2016. Patients who died, lost the transplant or changed the immunosuppression before completion of follow-up were excluded, as well as patients who underwent combined kidney-pancreas transplantation (34.3% of the original population, final n=272). One-year outcomes were changes in total and LDL cholesterol, triglycerides, glycated hemoglobin (HbA1c) and incidence of de-novo diabetes. Results: considering the global population, patients doing mTORi experienced a more significant increase in HbA1C compared to patients doing MP (mTORi group +0.98 1.13% versus MP group +0.66 1.38%, p= 0.017, for the difference between baseline and 1-year values). There was a substantial increase as well in triglycerides in the mTORi group (MP +1.42 85.83mg/dl versus mTORi +23.21 95.87mg/dl, p= 0.003). When considering only diabetic patients at baseline (n=73), the increase in HbA1c at 1 year was much more pronounced in patients doing mTORi (MP +0.7 1.97% versus mTORi +1.6 1.31, p=0.020), while there was not substantially any change in triglycerides between the two groups (p=0.879). On the contrary, in patients without diabetes at baseline (n=199), the mTORi group experienced a significant increase in triglycerides (MP +1.42 85.83 mg/dl versus mTORi +23.21 95.87 mg/dl, p-value 0.003), while no difference was observed in HbA1c (p-value 0.298). There was no difference in the incidence of de-novo diabetes between groups (p=0.272). Conclusions: mTOR inhibitors are associated with higher levels of HbA1c and triglycerides 1 year after transplantation compared to mycophenolate, in a tacrolimus- and prednisone-based protocol. However, the change in HbA1c was mainly observed only in mTORi patients who were already diabetics before transplantation and there is not an increase in the incidence of de-novo diabetes. Curiously, the increase in triglycerides was confirmed only in patients who were not diabetics before transplantation. This may suggest that mTOR inhibitors can cause different metabolic abnormalities depending on the original metabolic status of the transplanted patient.,David Cucchiari, et al. 2018 TTS. Abstract number:620.5,糖尿病患者,非糖尿病患者,P= 0.017,所有患者,基线糖尿病患者,HbA1C变化值(1年水平-基线值)(%),P= 0.020,HbA1C变化值(1年水平-基线值)(%),N=150,N=122,N=40,N=33,血糖,2018 TTS上报道的一项纵向1年的回顾性研究，收集272例2013.6-2016.5间肾移植受者，基于他克莫司和泼尼松，联合霉酚酸酯(MP组)或mTOR抑制剂(mTORi组)的两组不同免疫抑制方案，研究患者总胆固醇，低密度脂蛋白，甘油三酯，HbA1c和新发糖尿病的变化，结果显示： 与MMF/MPS患者相比，mTORi治疗的患者HbA1C升高更为显著,CsA+MPA+激素方案NODAT发生率较低,A. Santos, Jr, et al. 2018 ATC.Abstract number:340,MATERIALS AND METHODS: We used an observational cohort design to study 1/3/1995-9/15/2015 adult KTR in the Scientific Registry of Transplant Recipients. With Cox regression, we analyzed the 1-year post-transplant risk of NODAT associated with the discharge immunosuppression regimens: CSA+MPA+S, SRL+MPA+S, SRL+CSA+S and SRL+Tac+S; versus the standard regimen: Tac+MPA+S. We compared NODAT risks between study regimens by estimating the differences in their hazard ratios in the Cox model. RESULTS: Recipient risk factors for NODAT (Footnote Data, Fig. 1) included: Hep C+ or CMV+ serology, higher BMI or age categories and black or Hispanic race. Compared with basiliximab, ATG or alemtuzumab immunosuppression induction was associated with a lower risk of NODAT. SRL+Tac+S was associated with a higher, CSA+MPA+S with a lower risk of NODAT than standard maintenance immunosuppression regimen (Tac+MPA+S), (Forest Plot A). Additional comparisons among maintenance regimens showed that CSA+MPA+S was associated with a lower risk of NODAT than SRL+MPA+S or SRL+Tac+S (Forest Plot-B). Among SRL regimens, SRL+MPA+S and SRL+CSA+S had comparable NODAT risks, whileSRL+Tac+S appeared to be associated with the highest NODAT risk (Forest Plot-B). CONCLUSION: The risks of NODAT in KTR on steroid-containing regimens varied according to the other component-drugs included in those regimens and these factors may be considered in tailoring immunosuppression prescription for KTR.,2018 ATC：一项美国观察性研究，纳入SRTR数据库中1995.1.3-2015.9.15成年KTR数据，通过Cox回归分析，分析了与免疫抑制方案相关的NODAT移植后1年的风险,1.35（0.99，1.85）,1.57（1.17，2.09）,0.78（0.60，1.02）,0.68（0.51，0.90）,0.50（0.39，0.64）,1.15（0.79，1.67）,不同免疫抑制方案NODAT发生风险不同： SRL+Tac+STac+MPA+SCSA+MPA+S SRL+Tac+SSRL+MPA+SCSA+MPA+S,血糖,移植术后血脂管理的目标及建议,中国器官移植受者血脂管理指南（2016 版）推荐移植术后血脂管理的目标,中国器官移植受者血脂管理指南（2016 版） Arnav Agarwal, et al. World J Transplant. 2016 Mar 24; 6(1): 125134.,移植2-3个月后， LDL-C和/或TG高于目标值,饮食干预2-3个月后，LDL-C和/或TG高于目标值,起始治疗前，考虑急性排斥反应等问题，优化免疫抑制药物以改善移植物功能,咨询营养师通过饮食干预治愈,开始他汀类药物治疗，评估潜在的药物相互作用；监测肌酸激酶和肝转氨酶水平,他汀治疗2-3个月后，LDL-C和或TG高于目标值,增加他汀类药物剂量，使其耐受最大剂量，监测是否达标；若未达标，则考虑联合治疗，如依折麦布 10mg/d,LDL-C和或TG达到目标值,每年监测血脂水平。 同时更频繁的监测不良反应,评估整体心血管风险， 监测空腹8-12h后血脂情况,LDL-C：低密度脂蛋白胆固醇；TC：胆固醇；HDL-C：高密度脂蛋白胆固醇；TG：甘油三酯,血脂,移植术后免疫抑制剂合理应用,他汀类药物在肾移植受者中的推荐剂量,器官移植术前己存在高脂血症，或移植术后发生 ASCVD 的风险评级为高危，或术后发生高脂血症的受者 首先考虑减少和撤除激素 谨慎使用 mTORi；如确认脂代谢异常与 mTORi 相关，在移植器官功能稳定的前提下，考虑使用其他药物，如霉酚酸（MPA）类药物 CNI 类药物的使用：考虑将环孢素更换为他克莫司，或采用联合 MPA 类药物的 CNI 减量方案 胰肾联合移植受者应撤除激素，使用他克莫司或环孢素联合 MPA 类药物的免疫抑制方案,中国器官移植受者血脂管理指南（2016 版）,血脂,既往减重手术或增加移植后排斥风险,血脂,单因素分析： 相较于无减重手术史的实体器官受者，既往减重手术史受者的排斥发生风险明显增加，差异具有统计学意义。 （85.5% vs. 72.5%, p=0.03）,多因素分析： 对实体器官移植受者排斥发生风险进行多因素分析，发现既往减重手术受者发生排斥风险的趋势仍然很高。 (OR=2.09, 95% CI: 0.98-4.46, p = 0.05).,芝加哥西北大学对4363例实体器官移植受者进行回顾性队列研究，旨在分析减重手术对受者排斥发生的影响。,2018 American Transplant Congress 319,mTOR使用或加速高脂血症的出现,血脂,美国多中心随机开放US92研究共纳入613例肾移植受者，旨在确证肾移植受者使用EVR+低剂量tac和MMF+标准剂量Tac的非劣效。该研究的事后分析显示， mTOR组不良事件发生率显著高于MMF组，其中高脂血症的发生时间显著加速到平均移植后62天。,2018 American Transplant Congress A448,mTORi增加血脂风险,David Cucchiari, et al. 2018 TTS.Abstract number:620.5,2018 TTS上报道的一项纵向1年的回顾性研究，收集272例2013.6-2016.5间肾移植受者，基于他克莫司和泼尼松，联合霉酚酸酯(MP组)或mTOR抑制剂(mTORi组)的两组不同免疫抑制方案，研究患者总胆固醇，低密度脂蛋白，甘油三酯，HbA1c和新发糖尿病的变化，结果显示： mTORi组甘油三酯较MPA组显著增加，尤其是针对基线非糖尿病患者,Introduction: it is widely known that immunosuppressive drugs alter lipids and carbohydrate metabolism in kidney transplant patients. The most common side effects are diabetes mellitus induced by calcineurin inhibitors and hypertriglyceridemia caused by mTOR inhibitors. However, little is known about the combination of these agents in real clinical practice and if a difference exists between patients who were already diabetics or not before transplantation. Methods: longitudinal retrospective 1-year long study in which we compared two different regimens based on tacrolimus and prednisone, one with mycophenolate (MP group) and one with an mTOR inhibitor (mTORi group). The studied population included all kidney transplanted patients in the Hospital Clnic, Barcelona, performed in a 3-year period from June 2013 to May 2016. Patients who died, lost the transplant or changed the immunosuppression before completion of follow-up were excluded, as well as patients who underwent combined kidney-pancreas transplantation (34.3% of the original population, final n=272). One-year outcomes were changes in total and LDL cholesterol, triglycerides, glycated hemoglobin (HbA1c) and incidence of de-novo diabetes. Results: considering the global population, patients doing mTORi experienced a more significant increase in HbA1C compared to patients doing MP (mTORi group +0.98 1.13% versus MP group +0.66 1.38%, p= 0.017, for the difference between baseline and 1-year values). There was a substantial increase as well in triglycerides in the mTORi group (MP +1.42 85.83mg/dl versus mTORi +23.21 95.87mg/dl, p= 0.003). When considering only diabetic patients at baseline (n=73), the increase in HbA1c at 1 year was much more pronounced in patients doing mTORi (MP +0.7 1.97% versus mTORi +1.6 1.31, p=0.020), while there was not substantially any change in triglycerides between the two groups (p=0.879). On the contrary, in patients without diabetes at baseline (n=199), the mTORi group experienced a significant increase in triglycerides (MP +1.42 85.83 mg/dl versus mTORi +23.21 95.87 mg/dl, p-value 0.003), while no difference was observed in HbA1c (p-value 0.298). There was no difference in the incidence of de-novo diabetes between groups (p=0.272). Conclusions: mTOR inhibitors are associated with higher levels of HbA1c and triglycerides 1 year after transplantation compared to mycophenolate, in a tacrolimus- and prednisone-based protocol. However, the change in HbA1c was mainly observed only in mTORi patients who were already diabetics before transplantation and there is not an increase in the incidence of de-novo diabetes. Curiously, the increase in triglycerides was confirmed only in patients who were not diabetics before transplantation. This may suggest that mTOR inhibitors can cause different metabolic abnormalities depending on the original metabolic status of the transplanted patient.,糖尿病患者,非糖尿病患者,基线非糖尿病患者,P0.001,甘油三酯C变化值(1年水平-基线值)(mg/dL),N=110,N=189,血脂,高尿酸血症增加KTR的CVD风险,P=0.0001,P=0.044,一项回顾性研究，纳入100例具有正常移植物功能的肾移植受者，分析移植后第一年的临床生化参数，目的是评估高尿酸血症与移植物功能障碍之间的关系以及肾移植受者心血管风险的发展,Sofue T, et al. Drug Des Devel Ther. 2014 Feb 17;82:45-53.,尿酸,移植一年后，高尿酸血症患者（尿酸水平6.5mg/ dL），脉搏波速度更快，左心室质量指数更差，有更高的心血管疾病风险,移植术后低尿酸水平预示更优结局,设计：韩国首尔延世大学一项回顾性队列研究，纳入了1992年到2014年肾移植受者2993例，根据尿酸水平分为三组：低中高尿酸水平组分界值（女6 mg/dL）/（男7 mg/dL），并于1年和5年进行分析，比较其长期结局。,D. Kim, et al. 2018 ATC.Abstract number:A193,尿酸,移植后尿酸水平影响早期预后,1年分析显示：相较于中尿酸组，低尿酸水平组的发生总体器官衰竭率（OGF）、死亡删失器官衰竭（DCGF）及复合肾脏事件的风险更低，高尿酸水平组发生风险更高。,尿酸,移植后尿酸水平影响长期结局,从5年分析来看，低尿酸水平组的风险比也表现出了类似的趋势，但无统计学差异。而高尿酸组显著增加了三项结局的发生风险，差异具有统计学意义。,尿酸,MMF较MZR显著降低高尿酸发生风险,MZR（咪唑立宾）较MMF发生高尿酸血症的风险显著增加。RR=1.96，95% CI (1.47, 2.61)，P0.00001,Xing S, et al.Clin Biochem. 2014 May;47(7-8):663-9.,尿酸,Objectives: Mizoribine (MZR) with its high safety and low cost has been widely used in Asia. It has been questioned whether high o