肾移植术后巨细胞病毒肺炎的诊治

目的：探讨肾移植术后巨细胞病毒（CMV）肺炎的诊断和治疗,方法,回顾性总结32例肾移植术后发生CMV肺炎的临床资料,通过检测外周血中CMV IgM和（或）CMV DNA,结合临床症状及胸片明确诊断,以更昔洛韦治疗,同时治疗混合感染,加强营养支持,并根据动脉血氧分压,尽早使用呼吸机,结果：27例（84．4％）治疗有效,其中26例治愈,2例好转,死亡5例,结论：对肾移植术后CMV肺炎应尽早诊断,及时应用以更昔洛为主的综合治疗。     

糖皮质激素治疗肾移植术后巨细胞病毒肺炎

目的探讨糖皮质激素在治疗肾移植术后巨细胞病毒（CMV）肺炎中的作用。方法75例患者肾移植术后并发CMV肺炎，3例CMV肺炎发生于肾移植术后1个月内，64例发生于2-6个月，8例发生于6个月以后。诊断为CMV肺炎后，均采取抗病毒为主的综合治疗措施，如停用环孢素A（或他克莫司）和霉酚酸酯等免疫抑制剂；给予更昔洛韦等抗病毒药物；选用广谱抗生素积极预防和治疗二重感染；对低氧血症明显的患者，给予高频吸氧，甚至呼吸机辅助通气；加强支持治疗。其中47例加用糖皮质激素治疗（使用激素组），给予甲泼尼龙40-80mg静脉注射，每天1-2次，体温下降后3-5d逐渐减量，根据病情调整剂量，待病情缓解或X线胸片好转后逐渐减量至停用，平均用药时间在21-28d；另28例不用糖皮质激素（未用激素组）。比较两组的治疗效果及患者存活情况。结果使用激素组的47例，治愈40例（85．1％，40／47），死亡7例（14．9％，7／47），未用激素组的28例，治愈17例（60．7％，17／28），死亡11例（39．3％，11／28），两组比较，差异有统计学意义（P〈0．05）。使用激素组治疗第1天患者的体温即有明显下降，未使用激素组在治疗第3天体温才有显著下降，两组体温恢复正常所需时间的差异有统计学意义（P〈0.01）。使用激素组治疗第1天患者的呼吸频率即较治疗前明显下降（P〈0.05），未使用激素组在治疗第3天呼吸频率才有显著下降，治疗3d时，两组患者呼吸频率的差异有统计学意义（P〈0．05）。结论肾移植后的CMV肺炎采用糖皮质激素治疗，可明显改善发热、呼吸急促等相关症状，提高治愈率，降低患者的死亡率。     

巨细胞病毒-PP65抗原监测在预防肾移植术后巨细胞病毒病中的应用

目的 探讨巨细胞病毒(CMV)-PP65抗原检测在肾移植术后CMV病预防中的应用。方法 采用免疫过氧化物酶法检测肾移植受者外周血白细胞CMV-PP65抗原，术后3个月内每周1次。结果 100例肾移植受者中42例检出CMV-PP65抗原阳性，初次检出CMV-PP65抗原的平均时间为(23．6±16．7)d，平均抗原阳性细胞数为(7．8±5．3)个／5×104白细胞。抗病毒治疗中18例抗原阳性细胞数进一步升高，平均峰值为(16．4±3．1)个。58例抗原血症阴性的受者仅1例发生CMV病。42例CMV-PP65抗原血症阳性受者抗病毒治疗后抗原血症均阴转，1例发展为CMV病，平均阴转时间为(24．6±11．3)d，平均疗程为(34．2±7．1)d。结论 CMV-PP65抗原监测可指导肾移植术后CMV病的预防性治疗。     

肾移植术后巨细胞病毒肺炎13例报告

目的：总结肾移植术后巨细胞病毒(CMV)肺炎的防治经验,探讨有效的防治措施。方法：回顾性分析13例行同种异体肾移植术后并发CMV肺炎患者的临床资料。13例均在肾移植术后2～6个月发病,均以发热、干咳起病,胸片检查均有间质性肺炎改变。13例患者中,血CMVPP65抗原阳性9例。治疗措施包括早期抗病毒治疗、撤减免疫抑制剂用量、适时使用机械通气、加强全身支持治疗等。结果：13例患者中,治愈8例(61．5%),好转3例(23．1%),死亡2例。7例术后使用更昔洛韦预防CMV感染的患者,治愈4例,好转2例,死亡1例。结论：肾移植术后加强CMV检测有利于CMV肺炎的早期诊断。术后积极预防CMV感染,早期采取以抗病毒为主的综合治疗可提高治愈率。     

肾移植术后巨细胞病毒肺炎的危险因素

分析肾移植术后巨细胞病毒（CMV）肺炎的发病和死亡危险因素．采取有效的防治措施，有利于减少术后CMV肺炎的发病和改善疾病预后。分析肾移植术后巨细胞病毒（CMV）肺炎的发病和死亡危险因素．采取有效的防治措施，有利于减少术后CMV肺炎的发病和改善疾病预后。     

肾移植术后巨细胞病毒感染的诊治体会

目的探讨肾移植术后巨细胞病毒(CMV)感染的诊疗策略。方法对2000年1月至2004年3月我院218例肾移植术后患者资料进行回顾性分析,根据实验室检查结果以及临床症状,共有57例(26%)诊断为CMV感染,24例(11%)进展为CMV肺炎,给予调整免疫抑制剂、抗感染、支持、对症处理。结果17例治愈,死亡7例。结论CMV感染应积极预防,并坚持早发现、早治疗。     

肾移植术后巨细胞病毒肺炎伴肾功能异常原因分析

目的：探讨肾移植术后早期巨细胞病毒（CMV）肺炎患者停用免疫抑制剂期间肾功能异常的原因。方法：2001年1月～2006年12月期间,肾移植术后CMV肺炎37例,在停用免疫抑制剂期间9例出现肾功能异常（肾功异常组）,28例肾功能保持正常（肾功正常组）。检测CMV肺炎发病后外周血CD4^＋细胞计数和血清肿瘤坏死因子-α（TNF-α）水平,选择同期术后3月无感染受者18例为对照（对照组）,对4例肾功能异常患者行肾穿刺活检。结果：9例患者均伴有急性呼吸窘迫综合征（ARDS）,需呼吸机辅助治疗。肾功能异常发生在停用免疫抑制剂后（8.9±3.3）d,停药的时间为（21.9±6.2）d,感染发病第7天两组外周血CD4^＋细胞计数明显较对照组低,血清TNF-α水平明显较对照组高,而肾功异常组TNF-α水平显著高于肾功正常组,组织病理学以肾小管上皮细胞变性、坏死、脱落为主要特征。结论：肾移植术后CMV肺炎患者机体免疫功能低下,停用免疫抑制剂是安全的,不会诱发急性排斥反应,炎症反应可能是移植肾功能损害的主要因素。     

肾移植术后巨细胞病毒性肺炎56例临床分析

目的：回顾分析肾移植术后巨细胞病毒性肺炎（CMV）的临床特点,探讨预防和诊治巨细胞病毒肺炎的方法,提高人肾存活率。方法：对2000年1月-2007年12月肾移植术后发生的56例CMV肺炎患者的临床特点及诊疗措施进行回顾性分析。结果：56例患者,肺炎发生在术后6个月以内37例,28例患者表现为急性呼吸窘迫综合征．经抗病毒等综合治疗后39例患者治愈,人肾存活,17例死亡,其中12例死于呼吸功能衰竭,5例死于严重混合感染。平均住院时间32天。结论：由于CMV肺炎病情凶险,强调早期预防、早期诊断及早期应用抗CMV药物等综合治疗方法,针对不同的患者采取不同的诊疗策略,适当调整免疫抑制方案、改善肺功能及加强支持治疗均能有效的促进病情的恢复,     

单用阿昔洛韦及联合更昔洛韦对肾移植术后巨细胞病毒性肺炎的预防作用

目的比较联合应用更昔洛韦、阿昔洛韦及单独应用阿昔洛韦预防肾移植术后巨细胞病毒性肺炎的效果.方法肾移植患者217例,男124例,女93例.年龄16～72岁,平均32岁.随机分为3组：单用组51例,术后第3天口服阿昔洛韦400mg,3次/d,至术后3个月;联合用药组74例,术后第3天口服阿昔洛韦400mg,3次/d至,术后3个月,术后第21天静脉滴注更昔洛韦250 mg,1次/d,持续7 d以替代口服阿昔洛韦;对照组92例未采用预防病毒治疗.比较3组间巨细胞病毒性肺炎发生率.结果217例共发生巨细胞病毒性肺炎20例,其中联合用药组4例（5.4%）,单独用药组2例（3.9%）,对照组14例（15.2%）,用药组与对照组之间比较差异有统计学意义（P＜0.05）,两用药组之间差异无统计学意义（P＞0.05）.17例（85.0%）肺炎患者经抗病毒及对症治疗治愈;3例死于呼吸衰竭.结论更昔洛韦、阿昔洛韦能显著降低肾移植术后患者巨细胞病毒性肺炎的发生率,患者依从性较好.     

HLA-G与肾移植术后巨细胞病毒活动性感染的相关性研究

目的 研究HLA-G与肾移植术后巨细胞病毒(CMV)活动性感染的相关性,分析其作用机制及意义。方法 初次肾移植受者215例,按照术后是否发生CMV活动性感染将受者分为CMV阳性组和CMV阴性组,采用流式细胞术检测膜结合型HLA-G1 (mHLA-G1)的表达,采用酶联免疫吸附试验检测可溶性HLA-G5 (sHLA-G5)的表达,采用逆转录聚合酶链法检测HLA-G mRNA的表达,采用蛋白质印迹法验证sHLA-G5的表达,采用免疫组织化学法和HE染色观察移植肾组织中HLA-G的表达,采用ROC曲线分析sHLA-G5水平预测CMV活动性感染的Cutoff值。结果 术前两组间HLA-G表达的差异无统计学意义(P＞0.05)。术后两组间外周血淋巴细胞表面mHLA-G1均呈低表达,CMV pp65阳性时亦无明显变化。CMV阳性组外周血中CD14+ mHLA-G1+细胞显著升高(P＜0.05),达到(45.53±17.32)％,转阴后下降至(10.22±5.78)％。CMV阳性组外周血中sHLA-G5表达水平明显升高(P＜0.05),其预测CMV活动性感染的最适Cutoff值为202.9μg/L,具有很高的诊断准确性。CMV阳性组受者外周血中HLA-G mRNA的表达水平均显著高于CMV阴性组(P＜0.05)。12例CMV活动性感染受者移植肾活检样本中,10例肾小管上皮细胞HLA-G表达呈阳性。结论 HLA-G在外周血中的表达显著升高和移植肾肾小管上皮细胞的阳性表达可能是保护移植肾功能的机制之一。以sHLA-G5表达水平202.9μg/L作为Cutoff阈值,具有很好的判断CMV活动性感染的价值。     

肾移植术后尿瘘的病因诊断及处理对策

目的：探讨肾移植术后尿瘘的病因诊断及处理对策，以降低肾移植术后患者尿瘘发病率及死亡率。方法：回顾性分析2003年1月～2007年12月以来行340例次肾移植术后出现尿瘘的原因及其积极正确的诊断与治疗经验，以挽救移植肾功能及患者生命。结果：340例次肾移植中，确诊尿瘘15例次，发生率为4．4％，发生时间5～24天，平均15天。根据诊断及临床特征行保守治疗和手术治疗等，恢复功能14例，治愈率为93．3％；死亡1例。死亡率为6．7％。结论：尿瘘是肾移植后主要并发症之一，发生原因各异，排斥反应及血供损伤是主要原因。加强抗排斥反应，防止血供损伤，作抗反流乳头吻合，常规内置双J管，可以减少其发生；早期诊断及个体化治疗方案是其治愈的关键。     

Kidney Disease After Heart and Lung Transplantation

Kidney disease is a commonly recognized complication of heart and lung transplantation and is associated with increased morbidity and mortality. While the spectrum of kidney disease in this population is wide-ranging, studies indicate that between 3% and 10% of these patients will ultimately develop end-stage renal disease (ESRD). This review examines the risk factors for both acute and chronic kidney injury, with a particular emphasis on the role of calcineurin inhibitor-mediated nephrotoxicity in both these settings. Against the background of current National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, we have further considered and recommended appropriate strategies for long-term management of kidney disease-related manifestations in heart and lung transplant recipients. Specific aspects addressed include retarding progressive renal injury and minimizing nephrotoxicity, as well as treatment of hypertension, hyperlipidemia and anemia. Finally, for patients in this population with advanced kidney disease, renal replacement therapy options are discussed. Based on the impact of chronic kidney disease on outcomes in both heart and lung recipients, we advocate early referral to a nephrologist for patients displaying evidence of significant renal dysfunction.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

慢性肾脏病合并肺孢子虫肺炎诊治分析

目的：提高对慢性肾脏病（CKD）患者合并肺孢子虫肺炎（PCP）的认识。方法：回顾性分析4例CKD合并PCP患者的临床症状、影像学及实验室资料,分析诊断及治疗转归情况。结果：4例临床均表现为发热、咳嗽、胸闷等,3例出现Ⅰ型呼吸衰竭,1例顽固性低氧血症。其中3例支气管肺泡灌洗液痰姬姆萨染色找到伊氏肺孢子菌,1例支气管肺泡灌洗液痰PCR检测伊氏肺孢子菌虫体DNA（＋）。4例中IgA肾病2例,肾淀粉样变性1例,膜性肾病1例。4例均应用激素治疗,有2例同时应用环磷酰胺（CTX）,激素及CTX均为常规用法、用量。4例均予卡泊芬净及复方磺胺甲唑治疗,均好转出院,无副反应。结论：PCP是接受激素和（或）CTX治疗的CKD患者肺部机会感染之一。典型的胸部X线尤其是CT征像对PCP的诊断具有重要意义,但早期胸部X线和CT征像多不典型。对接受激素和（或）CTX治疗的CKD患者,如出现发热、进行性呼吸困难,应尽早行痰或支气管肺泡灌洗液姬姆萨染色涂片找伊氏肺孢子菌或PCR检测伊氏肺孢子菌虫体DNA。卡泊芬净及复方磺胺甲唑治疗PCP效果均明确,无明显副作用,卡泊芬净可以作为治疗PCP的首选药物。     

Thrombotic Microangiopathy After Kidney Transplantation

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation that often causes graft failure. TMA may occur de novo, often triggered by immunosuppressive drugs and acute antibody‐mediated rejection, or recur in patients with previous history of hemolytic uremic syndrome (HUS). Recurrent TMA is very rare in patients who had developed end‐stage renal failure following HUS caused by Shiga‐toxin producing E. scherichia coli, whereas disease recurrence is common in patients with atypical HUS (aHUS). The underlying genetic defect greatly impacts the risk of posttransplant recurrence in aHUS. Indeed recurrence is almost the rule in patients with mutations in genes encoding factor H or factor I, whereas patients with a mutation in membrane‐cofactor‐protein gene have a good transplant outcome. Prophylactic and therapeutic options for posttransplant TMA, including plasma therapy, combined kidney and liver transplantation and targeted complement inhibitors are discussed in this review.     

Reversibility of ''Secondary Hypercalcitoninemia'' After Kidney Transplantation

Whether the increase of calcitonin (CT) concentration in patients with chronic kidney disease (CKD) is reversible or not after kidney transplantation is not known. We examined the effect of kidney transplantation on basal and pentagastrin-stimulated CT in CKD patients with elevated screening CT levels. Before transplantation, the median basal CT concentration of 17 patients was 31 pg/mL (13-76), and decreased to 8 pg/mL (4-28) at 23 months (2-34) after kidney transplantation (p < 0.00005). The maximum concentration of pentagastrin-stimulated CT was 63 pg/mL (25-110) before transplantation and decreased to 20 pg/mL (8-91) (p < 0.00005) thereafter. There was a linear association between CT and calcium as well as between phosphorus and parathyroid hormone at the time of screening. After transplantation, CT correlated with serum creatinine. Therefore, the increase of CT concentration in patients with impaired kidney function presumably reflects 'secondary hypercalcitoninemia' due to C-cell hyperactivity.     

Circulating Endothelial Progenitor Cells After Kidney Transplantation

Circulating endothelial progenitor cells (EPCs) promote vascular repair and maintain integrity of the endothelial monolayer. Reduced EPCs number has been associated with endothelial dysfunction in various cardiovascular diseases. Cardiovascular disease risk is higher in renal transplant patients (RT) than the general population. We studied EPCs number and proliferation in RT, and examined the association with other cardiovascular risk factors such as reduced glomerular filtration rate (GFR) and LDL cholesterol. EPCs concentration was determined in 94 RT and 39 control subjects (C) by flow cytometry. EPCs proliferation was also studied after 7 days in culture. EPCs concentration was significantly reduced in RT versus C (median 33.5 [5-177] vs. 53 [9-257] EPCs/10(5) PMN cells, p=0.006). EPCs proliferation was also reduced in RT versus C (mean+/-SD; 372.7+/-229.3 vs. 539.8+/-291.3 EPCs x field, p=0.003). In multiple regression analysis, GFR, HDL, LDL and body weight were independent predictors of EPCs concentration in RT (r2=0.25, p<0.001). EPCs number is reduced in RT, particularly in patients with reduced GFR. Moreover, EPCs from RT studied in vitro, showed reduced proliferation, which is a sign of functional impairment. These alterations may be involved in increased cardiovascular risk of RT.