腎移植長期管理中的是是非非.ppt

醫(yī)道是仁，為你打call： DCD腎移植長期管理中的是與非,腎移植長期管理中的是是非非,01,02,Contents,目,錄,03,美國DDKT患者整體5年存活率僅為87.2%,OPTN/SRTR 2016 Annual Data Report: Kidney,美國國家器官獲取和移植網(wǎng)絡(luò)（OPTN）顯示，在美國成人DDKT中，不同年齡段患者的存活率不同，65歲以上的腎移植患者存活率明顯更低，患者整體上5年存活率僅為87.2%,DDKT:死亡供體腎移植；OPTN：美國國家器官獲取和移植網(wǎng)絡(luò),2011年不同年齡段成人死亡供腎受者的存活率,美國DDKT患者的移植物長期存活率仍不容樂觀,美國國家器官獲取和移植網(wǎng)絡(luò)（OPTN）顯示，美國成人DDKT中，移植后6個月的移植物功能衰竭率明顯降低，幾乎只有10年前的一半；移植后10年的移植物功能衰竭發(fā)生率變化不大,OPTN/SRTR 2016 Annual Data Report: Kidney,6個月 1年 3年 5年 10年,移植物功能衰竭率(%),2005年的移植物衰竭率為51.6%,移植腎丟失的主要原因： 心血管疾病和腎功能受損,移植腎丟失原因1,帶功死亡: 50%,慢性移植物失功：50%,心腦血管意外2 42.3%,感染 2 17.6%,腫瘤 2 9.2%,慢性移植物腎病：30-40%,其他疾?。?0-20%,CNI 毒性,原疾病 復(fù)發(fā),急排,新發(fā) 疾病,慢排 亞臨床急排,非特異性 纖維化和 小管萎縮,其他 2 30.9%,高血壓,高脂血癥,糖尿病,高尿酸血癥3,危險因素,高尿酸血癥 致腎小管損傷/壞死,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.,腎移植術(shù)后代謝相關(guān)并發(fā)癥發(fā)生率高,美國腎移植后新發(fā)糖尿病(NODAT)發(fā)生率為53%1，高血壓患病率為70-90%2，高脂血癥發(fā)病率為71%3 ，高尿酸血癥發(fā)病率為68.3%4 中國腎移植后NODAT發(fā)病率為20.3%；高血壓發(fā)病率71.7%；高脂血癥發(fā)病率47.9%5,高尿酸血癥發(fā)生率為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;中南大學(xué);2012年. 5. Lv C, et al. PLoS One. 2014 Jun 9;9(6):e99406. 6.王明睿,等.中華器官移植雜志,2016,37(12):742-747.,并發(fā)癥發(fā)生率(%),移植術(shù)后代謝相關(guān)并發(fā)癥 增加移植物失功風(fēng)險,4項研究分析了932名腎移植受者，評估了移植物丟失的因素。 結(jié)果顯示：代謝綜合征（MS）增加移植物丟失的風(fēng)險。（RR：3.06; 95CI：2.17-4.32; I 2 = 0;異質(zhì)性P= 0.72）,截至2015年11月7日的一項薈萃分析， 對MEDLINE，EMBASE和Cochrane圖書館進(jìn)行了檢索。比較MS對移植物丟失，心血管疾病死亡和全因死亡率，檢索了585項研究，納入1269例患者在內(nèi)的5項研究。目的是評估MS對腎移植后結(jié)局的影響。 MS的定義基于美國膽固醇教育計劃/成人治療專家組III（NCEP / ATPII）、國際糖尿病聯(lián)合會（IDF）或世界衛(wèi)生組織（WHO）標(biāo)準(zhǔn),MS:代謝綜合征,Pedrollo EF, et al. Transpl Int. 2016 Oct;29(10):1059-66.,移植術(shù)后代謝相關(guān)并發(fā)癥 增加CVD死亡風(fēng)險,3項研究分析了865名腎移植受者，評估了心血管事件死亡因素。 結(jié)果顯示：代謝綜合征（MS）增加心血管死亡風(fēng)險（RR：3.53; 95CI：1.27-9.85; I 2 = 0;異質(zhì)性P= 0.40）,MS:代謝綜合征；CVD：心血管疾病,截至2015年11月7日的一項薈萃分析， 對MEDLINE，EMBASE和Cochrane圖書館進(jìn)行了檢索。比較MS對移植物丟失，心血管疾病死亡和全因死亡率，檢索了585項研究，納入1269例患者在內(nèi)的5項研究。目的是評估MS對腎移植后結(jié)局的影響。 MS的定義基于美國膽固醇教育計劃/成人治療專家組III（NCEP / ATPII）、國際糖尿病聯(lián)合會（IDF）或世界衛(wèi)生組織（WHO）標(biāo)準(zhǔn),Pedrollo EF, et al. Transpl Int. 2016 Oct;29(10):1059-66.,腎移植術(shù)后受者需要心身關(guān)愛,Srifuengfung M, et al.J Nerv Ment Dis. 2017 Oct;205(10)788-792.,抑郁癥：腎移植受者抑郁的發(fā)生率為11.3-41.4%。 心身疾?。阂唤M發(fā)生發(fā)展與心理社會因素密切相關(guān)，但以軀體癥狀表現(xiàn)為主的疾病，主要特點(diǎn)包括： 心理社會因素在疾病的發(fā)生與發(fā)展過程中起重要作用 表現(xiàn)為軀體癥狀，有器質(zhì)性病理改變或已知的病理生理過程 不屬于軀體形式障礙,01,Contents,目,錄,03,02,移植后導(dǎo)致心血管死亡的危險因素,移植前因素,移植后因素,供體因素 年齡，移植物質(zhì)量，腦死亡損傷，血管疾病,受體因素 年齡，吸煙，BMI，既往糖尿病史，長期透析,免疫因素 急性排斥反應(yīng)發(fā)作,非免疫因素 CNI或類固醇的慢性影響,eGFR下降,左心室肥厚,高血壓1,移植后糖尿病1,血脂異常1,心率失常,充血性 心力衰竭,冠狀動脈 疾病,心臟瓣膜病,心血管相關(guān)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,高尿酸血癥2,腎移植受者血壓控制欠佳,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報道的波蘭的一項回顧性研究，納入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，旨在分析血壓控制率和藥物治療情況,血壓,腎移植受者（KTRs）血壓控制達(dá)標(biāo)率低于血透（HD）患者，且使用多種降壓藥比例或高于HD患者1,高血壓是移植后新發(fā) CHF和IHD的獨(dú)立危險因素,研究顯示，高血壓與移植后新發(fā)充血性心力衰竭有關(guān)，多因素分析顯示，收縮壓升高是新發(fā)充血性心力衰竭的獨(dú)立危險因素（HR=1.29，95%CI：1.101.50，P=0.001），舒張壓升高是新發(fā)缺血性心臟病的獨(dú)立危險因素（HR=1.41，95%CI：1.031.94，P=0.03）,來自加拿大的一項回顧性分析，納入638例移植時無心臟病的成人腎移植受者，旨在描述新發(fā)CHF、新發(fā)IHD與成人腎移植受者的死亡率，危險因素和相互關(guān)系,CHF：充血性心力衰竭；IHD：缺血性心臟病,Rigatto C,et al.J Am Soc Nephrol. 2002 Apr;13(4)1084-90.,發(fā)生CHF的危險比（HR）,血壓,腎移植后高血壓患者的控制目標(biāo),歐洲腎臟最佳實(shí)踐指南建議蛋白尿患者血壓控制目標(biāo)125/75 mmHg KDIGO臨床實(shí)踐指南推薦KTR患者： 診室內(nèi)血壓應(yīng)控制在140/90 mmHg 家庭自測血壓130/80 mmHg 圍手術(shù)期：目標(biāo)血壓 150/90 mmHg 術(shù)后1周：目標(biāo)血壓 140/90 mmHg 術(shù)后1個月：目標(biāo)血壓 130/80 mmHg,Glicklich D, et al. Cardiol Rev. 2017 May/Jun;25(3):102-109.,血壓,腎移植術(shù)后降壓藥合理使用,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：鈣通道拮抗劑；ACEI：血管緊張素轉(zhuǎn)換酶抑制劑；ARB：血管緊張素受體拮抗劑；BPH：良性前列腺增生,血壓,NP-CEL-2018.07-012 Valid Until 2020.07,隱匿性高血壓和夜間高血壓需加強(qiáng)重視,德國漢諾威醫(yī)學(xué)院對172例兒童移植受者進(jìn)行前瞻性病例對照研究，旨在描述兒童受者高血壓的發(fā)生情況。結(jié)果顯示：兒童移植受者高血壓普遍發(fā)生，更進(jìn)一步隱匿性高血壓和夜間高血壓發(fā)生率也高居不下，急需重視。,隱匿性高血壓：診室血壓120/70mmHg,2018 American Transplant Congress B285,血壓,原腎切除或有助于血壓控制,p0.0001,p=0.0127,p=0.0057,斯坦福大學(xué)對137例兒童腎移植受者進(jìn)行回顧性分析，旨在比較原腎切除和原腎保留對患者長期血壓控制的影響。結(jié)果顯示：原腎切除受者的長期血壓控制率更高，差異具有統(tǒng)計學(xué)意義。,2018 American Transplant Congress D158,血壓,NP-CEL-2018.07-012 Valid Until 2020.07,使用ACEi/ARB腎移植受者存活較高,2018ATC上報道的來自美國圣路易斯大學(xué)的研究：檢索了一個連接SRTR登記的新數(shù)據(jù)庫，其中有來自大型藥品索賠倉庫的AHM填寫記錄，記錄了2008-2015年的54153個腎移植受者，通過多變量Cox回歸分析抗高血壓藥物(AHM)的選擇對患者和移植結(jié)果的影響，旨在分析抗高血壓藥物對患者和移植結(jié)果的影響。 與DHP-CCB方案相比，NDHP-CCB( aHR 1.111.241.37 )和其他藥物( aHR1.441.692.00 )治療的死亡率更高； ACEi / ARB治療的患者死亡率更低( aHR 0.850.920.99 ),H. Yamout, et al. 2018 ATC.Abstract number:337,ACEi / ARB：血管緊張素轉(zhuǎn)換酶抑制劑/血管緊張素受體阻滯劑； DHP-CCB：二氫吡啶鈣通道阻滯劑； NDHP-CCB：非二氫吡啶鈣通道阻滯劑,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.,血壓,利尿劑/其他,受體阻滯劑,CCB類,非CCB類,ACE I/ARB類,死亡率,移植后新發(fā)糖尿病高發(fā),血糖,36%,1/3的無既往糖尿病腎移植受者移植后發(fā)生新發(fā)糖尿病,紐約阿爾伯特愛因斯坦醫(yī)學(xué)院一項回顧性隊列研究供納入了304例腎移植受者，旨在描述移植后受者新發(fā)糖尿病的發(fā)生情況。結(jié)果顯示: 1/3的無既往糖尿病腎移植受者移植后發(fā)生新發(fā)糖尿病，其中年齡大，BMI高，移植前心血管疾病，以及接受KDPI評分更高供腎是新發(fā)糖尿病的風(fēng)險因素,2018 American Transplant Congress A219,移植后糖尿病增加心血管發(fā)生風(fēng)險,患有移植后糖尿?。≒TDM）的患者發(fā)生心臟事件的風(fēng)險增加,一項前瞻性單中心觀察研究，納入201例連續(xù)KT受者，旨在評估新診斷的新發(fā)PTDM對主要心臟事件（心源性死亡或非致死性急性心肌梗死）和患者存活的長期影響,Conte C, et al. Acta Diabetol. 2018 Aug;55(8):763-779.,PTDM: 移植后糖尿病,無心血管事件發(fā)生率(%),血糖,移植后糖尿病管理,KDIGO指南推薦PTDM管理目標(biāo)：HbA1c 7.0-7.5,血糖,調(diào)整免疫制劑方案 激素的減量和撤除 FK轉(zhuǎn)化為環(huán)孢素 CNI/mTOR轉(zhuǎn)化為貝拉西普,高血壓者血壓控制130/80mmHg； CCB為一線推薦用藥；避免使用噻嗪類利尿劑 飲食和生活習(xí)慣改變，他汀類藥物使用。,DPP4-1 GLP-1 RA SGLT-2i Sus 胰島素,飲食控制 運(yùn)動療法 肥胖減重 行為療法,免疫抑制藥物對血糖的影響,PTDM管理：減少胰島素抵抗和保護(hù)細(xì)胞功能(改善胰島素分泌) 對于腎移植后住院患者，胰島素治療是控制移植后高血糖的首選方案 激素與CNI的使用影響血糖代謝，增加PTDM發(fā)生。,Pimentel AL, et al. Clin Chim Acta. 2015 Oct 23;450:327-32.,血糖,CNI藥物是否增加PTDM有爭議,1.Karpe KM, et al. Cochrane Database Syst Rev. 2017 Jul 21;7:CD006750.,一項薈萃分析檢索截止到2016.10.11在Cochrane腎臟和移植專科登記包含標(biāo)準(zhǔn)劑量CNI治療與CNI停藥或低劑量CNI比較的結(jié)果的RCT研究，共納入83項研究，16156例患者，評估CNI對于移植后結(jié)局的影響2,2. 2017年發(fā)表的一項數(shù)據(jù)庫研究分析，納入了6項研究，810例受者的分析表明，與CNI停藥或減量方案相比，標(biāo)準(zhǔn)劑量CNI方案PTDM發(fā)生率與之相當(dāng)(RR 0.94 95% CI 0.621.42, P=0.76, I2=0%),1.無CNI方案可降低NODAT發(fā)生率的研究已得到臨床醫(yī)生的認(rèn)可。,NODAT：移植后新發(fā)糖尿病; PTDM:移植后糖尿病,血糖,mTORi較MMF方案HbA1C升高更顯著,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,基線糖尿病患者,HbA1C變化值(1年水平-基線值)(%),P= 0.020,HbA1C變化值(1年水平-基線值)(%),N=150,N=122,N=40,N=33,血糖,2018 TTS上報道的一項縱向1年的回顧性研究，收集272例2013.6-2016.5間腎移植受者，基于他克莫司和潑尼松，聯(lián)合霉酚酸酯(MP組)或mTOR抑制劑(mTORi組)的兩組不同免疫抑制方案，研究患者總膽固醇，低密度脂蛋白，甘油三酯，HbA1c和新發(fā)糖尿病的變化，結(jié)果顯示： 與MMF/MPS患者相比，mTORi治療的患者HbA1C升高更為顯著,CsA+MPA+激素方案NODAT發(fā)生率較低,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：一項美國觀察性研究，納入SRTR數(shù)據(jù)庫中1995.1.3-2015.9.15成年KTR數(shù)據(jù)，通過Cox回歸分析，分析了與免疫抑制方案相關(guān)的NODAT移植后1年的風(fēng)險,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發(fā)生風(fēng)險不同： SRL+Tac+STac+MPA+SCSA+MPA+S SRL+Tac+SSRL+MPA+SCSA+MPA+S,血糖,移植術(shù)后血脂管理的目標(biāo)及建議,中國器官移植受者血脂管理指南（2016 版）推薦移植術(shù)后血脂管理的目標(biāo),中國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個月后， LDL-C和/或TG高于目標(biāo)值,飲食干預(yù)2-3個月后，LDL-C和/或TG高于目標(biāo)值,起始治療前，考慮急性排斥反應(yīng)等問題，優(yōu)化免疫抑制藥物以改善移植物功能,咨詢營養(yǎng)師通過飲食干預(yù)治愈,開始他汀類藥物治療，評估潛在的藥物相互作用；監(jiān)測肌酸激酶和肝轉(zhuǎn)氨酶水平,他汀治療2-3個月后，LDL-C和或TG高于目標(biāo)值,增加他汀類藥物劑量，使其耐受最大劑量，監(jiān)測是否達(dá)標(biāo)；若未達(dá)標(biāo)，則考慮聯(lián)合治療，如依折麥布 10mg/d,LDL-C和或TG達(dá)到目標(biāo)值,每年監(jiān)測血脂水平。 同時更頻繁的監(jiān)測不良反應(yīng),評估整體心血管風(fēng)險， 監(jiān)測空腹8-12h后血脂情況,LDL-C：低密度脂蛋白膽固醇；TC：膽固醇；HDL-C：高密度脂蛋白膽固醇；TG：甘油三酯,血脂,移植術(shù)后免疫抑制劑合理應(yīng)用,他汀類藥物在腎移植受者中的推薦劑量,器官移植術(shù)前己存在高脂血癥，或移植術(shù)后發(fā)生 ASCVD 的風(fēng)險評級為高危，或術(shù)后發(fā)生高脂血癥的受者 首先考慮減少和撤除激素 謹(jǐn)慎使用 mTORi；如確認(rèn)脂代謝異常與 mTORi 相關(guān)，在移植器官功能穩(wěn)定的前提下，考慮使用其他藥物，如霉酚酸（MPA）類藥物 CNI 類藥物的使用：考慮將環(huán)孢素更換為他克莫司，或采用聯(lián)合 MPA 類藥物的 CNI 減量方案 胰腎聯(lián)合移植受者應(yīng)撤除激素，使用他克莫司或環(huán)孢素聯(lián)合 MPA 類藥物的免疫抑制方案,中國器官移植受者血脂管理指南（2016 版）,血脂,既往減重手術(shù)或增加移植后排斥風(fēng)險,血脂,單因素分析： 相較于無減重手術(shù)史的實(shí)體器官受者，既往減重手術(shù)史受者的排斥發(fā)生風(fēng)險明顯增加，差異具有統(tǒng)計學(xué)意義。 （85.5% vs. 72.5%, p=0.03）,多因素分析： 對實(shí)體器官移植受者排斥發(fā)生風(fēng)險進(jìn)行多因素分析，發(fā)現(xiàn)既往減重手術(shù)受者發(fā)生排斥風(fēng)險的趨勢仍然很高。 (OR=2.09, 95% CI: 0.98-4.46, p = 0.05).,芝加哥西北大學(xué)對4363例實(shí)體器官移植受者進(jìn)行回顧性隊列研究，旨在分析減重手術(shù)對受者排斥發(fā)生的影響。,2018 American Transplant Congress 319,mTOR使用或加速高脂血癥的出現(xiàn),血脂,美國多中心隨機(jī)開放US92研究共納入613例腎移植受者，旨在確證腎移植受者使用EVR+低劑量tac和MMF+標(biāo)準(zhǔn)劑量Tac的非劣效。該研究的事后分析顯示， mTOR組不良事件發(fā)生率顯著高于MMF組，其中高脂血癥的發(fā)生時間顯著加速到平均移植后62天。,2018 American Transplant Congress A448,mTORi增加血脂風(fēng)險,David Cucchiari, et al. 2018 TTS.Abstract number:620.5,2018 TTS上報道的一項縱向1年的回顧性研究，收集272例2013.6-2016.5間腎移植受者，基于他克莫司和潑尼松，聯(lián)合霉酚酸酯(MP組)或mTOR抑制劑(mTORi組)的兩組不同免疫抑制方案，研究患者總膽固醇，低密度脂蛋白，甘油三酯，HbA1c和新發(fā)糖尿病的變化，結(jié)果顯示： mTORi組甘油三酯較MPA組顯著增加，尤其是針對基線非糖尿病患者,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,基線非糖尿病患者,P0.001,甘油三酯C變化值(1年水平-基線值)(mg/dL),N=110,N=189,血脂,高尿酸血癥增加KTR的CVD風(fēng)險,P=0.0001,P=0.044,一項回顧性研究，納入100例具有正常移植物功能的腎移植受者，分析移植后第一年的臨床生化參數(shù)，目的是評估高尿酸血癥與移植物功能障礙之間的關(guān)系以及腎移植受者心血管風(fēng)險的發(fā)展,Sofue T, et al. Drug Des Devel Ther. 2014 Feb 17;82:45-53.,尿酸,移植一年后，高尿酸血癥患者（尿酸水平6.5mg/ dL），脈搏波速度更快，左心室質(zhì)量指數(shù)更差，有更高的心血管疾病風(fēng)險,移植術(shù)后低尿酸水平預(yù)示更優(yōu)結(jié)局,設(shè)計：韓國首爾延世大學(xué)一項回顧性隊列研究，納入了1992年到2014年腎移植受者2993例，根據(jù)尿酸水平分為三組：低中高尿酸水平組分界值（女6 mg/dL）/（男7 mg/dL），并于1年和5年進(jìn)行分析，比較其長期結(jié)局。,D. Kim, et al. 2018 ATC.Abstract number:A193,尿酸,移植后尿酸水平影響早期預(yù)后,1年分析顯示：相較于中尿酸組，低尿酸水平組的發(fā)生總體器官衰竭率（OGF）、死亡刪失器官衰竭（DCGF）及復(fù)合腎臟事件的風(fēng)險更低，高尿酸水平組發(fā)生風(fēng)險更高。,尿酸,移植后尿酸水平影響長期結(jié)局,從5年分析來看，低尿酸水平組的風(fēng)險比也表現(xiàn)出了類似的趨勢，但無統(tǒng)計學(xué)差異。而高尿酸組顯著增加了三項結(jié)局的發(fā)生風(fēng)險，差異具有統(tǒng)計學(xué)意義。,尿酸,MMF較MZR顯著降低高尿酸發(fā)生風(fēng)險,MZR（咪唑立賓）較MMF發(fā)生高尿酸血癥的風(fēng)險顯著增加。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