Risk factors associated with coronary artery calcification should be examined before kidney transplantation

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.     

Overview of transplantation immunology and the pharmacotherapy of adult solid organ transplant recipients: focus on immunosuppression

A review of transplantation immunology is discussed with emphasis on alloantigen presentation, T-lymphocyte activation and proliferation, and the immune effector mechanisms responsible for allograft rejection. Immunosuppressive pharmacology is introduced beginning with conventional medications (cyclosporine, azathioprine, and corticosteroids) followed by a discussion of drugs recently approved by the US Food and Drug Administration (mycophenolate mofetil, tacrolimus, and the interleukin-2 receptor antagonists). In addition, drugs that are used in the treatment of transplant rejection or as rescue therapy are discussed (muromonab-CD3, antithymocyte globulin, mycophenolate mofetil, tacrolimus, and corticosteroids). Throughout, implications for nurses involved in the pharmacotherapy of transplant recipients are discussed.     

Organ transplantation and pregnancy

Organ transplantation in reproductive-age women increases in frequency each year. In the presence of stable graft function and stable maintenance immunosuppressive regimens, patients are more likely to have successful outcomes. It is reasonable to advise recipients to wait at least 2 years after transplant to become pregnant. Most pregnancies do not affect graft function significantly, while they are sometimes associated with obstetric complications such as spontaneous abortions, premature deliveries, low birth weight, intrauterine growth retardation, hypertension, infection, etc. in recipients. Immunosuppressive medications can be used safely during pregnancy, and they are necessary in order to prevent maternal and fetal complications secondary to graft rejection. Successful management of the pregnant recipients requires a multidisciplinary team.     

配偶供肾移植后微嵌合体发生与急性排斥反应

背景:微嵌合作为移植物与受者之间的双相细胞移动的标志,在移植免疫耐受中的作用日益受到重视。目的:探讨夫妻生活与嵌合体的发生,与肾移植后急性排斥反应及其他相关性的研究。方法:将接受肾脏移植的女性受者(有过生育史的女性除外)分为丈夫活体供肾组、无关男性尸体供肾组,并设立接受妻子活体供肾的对照组。STR方法检测女性受者体内男性供者来源的Y染色体反映微嵌合体的存在,与急性排斥反应发生的关系,并比较配偶间供肾效果的差异。结果与结论:尽管配偶间供肾移植存在供者年龄偏大以及人类白细胞抗原错配率较高的因素,但与接受无关男性尸肾移植的女性受者相比,接受丈夫活体供肾移植的女性更易检测出微嵌合体,而且肾移植后恢复情况好,急性排斥反应发生率低。而与接受妻子供肾的丈夫相比,接受丈夫供肾的妻子肾移植效果好。说明夫妻间长期相处导致女性接受丈夫体液的机会多,由此产生免疫耐受对于肾移植后人/肾的相容性好,急性排斥反应小。     

超声心动图用于监测肾移植术后左心室结构和功能变化进展

肾移植是治疗尿毒症的首选方式。常规心血管疾病危险因素,肾功能不全相关改变及免疫抑制药物等均可增加肾移植术后左心功能不全风险;尽早识别及干预肾移植术后左心室功能障碍有助于改善患者生活质量和提高生存率。本文就多种超声心动图技术用于监测肾移植术后左心室结构和功能变化研究进展进行综述。     

Pregnancy in organ transplant recipients

Pregnancy in women who are renal transplant recipients carries risks of hypertension and worsening of renal function for the mother and risks of prematurity, growth retardation, and infection in the infant. The risks for mother and child are greater if the transplant recipient has moderate renal insufficiency or hypertension prior to conception; even in patients with moderate renal insufficiency, birth of a viable infant is the rule. Pregnancy should not be discouraged in renal transplant recipients, but both mother and fetus should be carefully followed through the pregnancy and neonatal period. The restoration of fertility should be included as a benefit of transplant in discussions with young women deciding between dialysis and transplant for treatment of renal failure.     

Ezetimibe reduces low-density lipoprotein cholesterol (LDL-C) in renal transplant patients resistant to HMG-CoA reductase inhibitors

Hyperlipidemia is common after renal transplantation. On the basis of current lipid guidelines, the majority of renal transplant recipients should have plasma low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL. Even with statin (HMG-CoA [3-hydroxy-3-methylglutaryl CoA] reductase inhibitor) therapy, a significant number of renal transplant recipients have LDL-C levels >100 mg/dL. We report that ezetimibe, a novel inhibitor of intestinal cholesterol absorption, was well tolerated and effectively reduced the LDL-C level to <100 mg/dL in our cohort of renal transplant recipients with persistently elevated LDL-C levels during treatment with maximally tolerated statin medications.     

Risk factors and pathogenetic mechanisms of left ventricular hypertrophy in progressive chronic kidney disease and after transplantation of the kidney

AIM: To specify the trend in the incidence of left ventricular hypertrophy (LVH) at a predialysis stage of chronic kidney disease (CKD) in the course of its progression from stage III to stage V and after transplantation of the kidney (TK); to study correlations between homeostatic disorders caused by CKD progression and myocardial remodeling; to define the role of some hemodynamic and nonhemodynamic factors in formation of LVH. MATERIAL AND METHODS: The study enrolled 128 patients (58 males and 70 females, age 18-55 years, mean age 42 +/- 11 years) at a predialysis stage of CKD (group 1) and 225 recipients of renal allotransplant--RRA (group 2, 140 males and 85 females, age 18-69 years, mean age 43 +/- 12 years). General clinical examination, biochemical and immunological blood tests, echocardiography were made. RESULTS: At a predialysis stage of CKD, LVH was diagnosed in 56% patients. Incidence of LVH was directly related with age of the patients (p = 0.001), blood pressure (p < 0.001), duration of arterial hypertension (p = 0.004), severity of anemia (p = 0.017), the level of C-reactive protein (p = 0.003), blood phosphorus concentration and inversely correlated with glomerular filtration rate--GFR (p = < 0.001), albumin level (p = 0.023) and blood Ca (p < 0.001). LVH was followed up for 12 months in 35 patients with predialysis CKD. Factors of LVH progression and factors hindering its regression were systolic blood pressure, Hb and Ca in the blood. In group 2 of RRA incidence of LVH was 53%. Significant factors of LVH risk after transplantation were age (p = 0.002), hypertension (p = 0.005) and anemia (p = 0.04). Moreover, LVH closely correlated with proteinuria (p < 0.03), transplant dysfunction (p = 0.002) and posttransplantation ischemic heart disease (p < 0.037). Changes in LVH were analysed in 30 RRA. Frequency of LVH decreased for 2 years after transplantation (from 56 to 32%) but 36-60 and more months after transplantation it increased (46 and 64%, respectively). Transplant dysfunction was the leading factor hindering LVH regression after transplantation. CONCLUSION: The same mechanisms are involved in LVH pathogenesis after transplantation and at a predialysis stage of CKD. The significance of initial renal lesion signs--minimal proteinuria and hypercreatininemia--was higher after renal transplantation than in patients with CKD.     

Problems in the long-term renal allograft recipient

Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients are still significant. Cardiovascular disease accounts for much of the mortality in long-term survivors; screening before the transplant procedure and adequate control of hypertension should help improve patient survival. Many of the gastrointestinal complications are due to overimmunosuppression and sepsis. Adequate management must include withdrawal of all immunosuppressive medications in order to save the patient's life. Liver disease is usually of viral origin; patients with chronic active hepatitis or cirrhosis should remain on dialysis. Chronic rejection is the major cause of graft loss in long-term survivors; it is unresponsive to antirejection treatment and its progression may be mediated by nonimmunologic mechanisms. Correctable problems such as renal artery stenosis and ureteral obstruction should be ruled out before a late deterioration in graft function is disregarded as chronic rejection. Post-transplant diabetes, osteonecrosis, cataracts, and nephrotoxicity are directly related to the various immunosuppressive drugs currently used. The lowest dose compatible with graft acceptance should help reduce the incidence of these nonfatal but significant complications. Recurrence of disease is a common histologic finding in many transplant recipients but, except for a few diseases such as HUS, FSGS, and oxalosis, it usually does not lead to graft failure. Successful transplantation restores fertility in many uremic patients. Adequate counseling on contraception is imperative in order to avoid unwanted pregnancies and to delay parenthood for at least 1 year. Current immunosuppressive agents are not teratogenic, no dose adjustments are necessary, and an ill-advised decrease in medication may precipitate a rejection episode. Premature delivery is the major problem in these patients and can be avoided by maintaining adequate graft function and controlling hypertension and infections. It is evident from this review that most of the long-term morbidity and mortality seen in renal allograft recipients are due to overimmunosuppression with sepsis or to side effects of the individual drugs, steroids being a common denominator in almost all cases. New immunosuppressive protocols must aim not only to improve patient and graft survival but also to avoid the many complications that limit the full rehabilitation of these patients.     

拉萨维持性血液透析患者肾移植意愿调查研究

目的了解拉萨地区维持性血液透析患者的肾移植意愿及其影响因素。 方法选择2019年4月5日至2019年4月12日期间在西藏自治区人民医院血液净化中心进行维持性血液透析的患者102例参加的横断面调查。所使用的问卷是根据之前发表的文献进行编制，使用多元Logistic回归分析确定肾移植意愿的影响因素。 结果入选患者98例了解肾移植（96.1%），35例维持性透析患者有肾移植意愿（34.3%）。调整了混杂因素后，潜在受者的年龄的增长（比值比为0.9，95%CI：0.8~0.9，P<0.001）、已婚状态（比值比为0.1，95%CI：0~0.5，P=0.010）、糖尿病肾病（比值比为0，95%CI：0~0.2，P=0.001）均是肾移植意愿的负面影响因素，并发现41岁是肾移植意愿降低的一个关键转折点。较高的受教育程度（比值比为8.2，95%CI：2.9~22.7，P<0.001）是促进选择肾移植的因素。在职状态（比值比为3.1，95%CI：0.9~10.9，P=0.085，交互作用检验P=0.0133）可能是促进选择肾移植的因素。与肾小球肾炎患者相比，多囊肾患者（比值比为6.0，95%CI：1.0~35.9，P=0.050，交互作用检验P=0.0007）与肾病综合征患者（比值比为1.8，95%CI：0.4~8.4，P=0.485，交互作用检验P=0.0007）可能更愿意选择接受肾移植。 结论在拉萨地区的维持性血液透析患者中，除年龄的增长外，潜在受者对肾移植预后较为落后和偏差的认知是不愿意选择肾移植的重要原因。我们建议开发基于多学科和新媒体的标准化、患者可理解、和基于循证的CKD患者肾脏替代治疗信息系统，以促进西藏CKD患者获得正确的各种肾脏替代治疗预后的信息，以便促进患者能够做出获益更大的治疗决定。     

Hepatitis C and Treatment in Patients with Chronic Kidney Disease

Hepatitis C virus (HCV) is associated with increased mortality and morbidity in patients with chronic kidney disease (CKD). The early detection and treatment of Hepatitis C associated with kidney disease is paramount to preventing the progressive loss of kidney function. HCV treatment until the advent of direct acting anti-viral agents (DAAs) was limited to interferon and ribavirin. Interferon and ribavirin treatment resulted in only modest success but with frequent adverse events and poor tolerability. Furthermore, interferon and ribavirin could not be used in certain patient populations including those with advanced CKD, were on dialysis, or those who have received a kidney transplant. DAAs have now made treatment possible in these sub-groups with a sustained viral response (SVR) of 90–100% and minimal side effects. DAAs have helped increase transplant rates by allowing for the use of HCV positive kidneys in recipients who are HCV negative. Although the choice of DAAs should be carefully considered and based on patient characteristics, concomitant medications, and HCV genotype.     

Risks and benefits of kidney and pancreas transplantation for diabetic patients

Type 1 diabetic patients with end-stage renal disease can choose dialysis or transplantation for renal replacement therapy. For patients choosing transplantation, a kidney from a living related donor is associated with longer allograft and patient survival. When a living donor is not available, then a combined cadaveric kidney and pancreas transplant can be considered. The addition of a pancreas transplant incurs greater morbidity and may require higher levels of immunosuppression. However, there may be substantial benefits, including improvement in quality of life and stabilization of neuropathy. Patients with type 1 diabetes younger than 45 years with little or no atherosclerotic vascular disease are ideal candidates for a combined kidney and pancreas transplant. Patients who do not meet these criteria but who have life-threatening hypoglycemia may also wish to consider pancreas transplantation, but have an increased risk of serious complications. The risks and benefits of combined kidney and pancreas transplantation are outlined in this review and should be carefully considered by potential transplant recipients and their physicians.     

肾移植患者依从性现状调查及影响因素分析

目的探讨肾移植患者依从性现状及其影响因素,为护理人员更好地开展健康教育,提高肾移植患者依从性提供依据。方法采用自行设计肾移植患者依从性问卷对886例在上海市6家肾移植中心进行随访的肾移植患者进行依从性及其影响因素调查。结果患者用药依从性影响因素有文化程度、经济负担（P〈0．01,P〈0．05）;生活习惯依从性影响因素有移植时间、年龄、肾移植类型、婚姻状态、家庭类型、付费方式和经济负担（P〈0．01,P〈0．05）;自我监测依从性影响因素有移植时间和肾移植类型（P〈0．01,P〈0．05）;随访依从性影响因素有付费方式和肾移植类型（P〈0．01,P〈0．05）。结论肾移植患者的依从性受各种因素影响,护理人员应根据依从性的影响因素针对性地进行健康教育,以提高患者的依从性。     

神经肽Y在肾移植围手术期与血压的关系

目的终末期尿毒症患者血浆神经肽Y（NPY）异常升高，与血压的变化呈正相关。本研究探讨血浆NPY水平在成功肾移植围手术期的临床意义及其与患者血压的关系。方法采集116例终末期尿毒症患者手术前、术后24h、出院前1d外周静脉血标本5ml，测定血浆NPY和肌酐（Cr）水平，同时测量记录平均动脉压。对照组为20例健康志愿者。结果在成功肾移植手术后出院前1d，血Cr水平恢复正常，血浆NPY水平有明显降低，与手术前比较，有显著性差异（P〈0．05）；但又明显高于健康志愿者血浆NPY平均值，比较有显著性差异（P〈0．05）；手术后患者平均动脉压无明显降低，个别反而较手术前更高，与手术后血浆NPY水平的变化无相关性。结论终末期尿毒症患者成功接受肾移植后，在出院前1d，肾功能恢复正常情况下其血浆NPY水平明显下降，但与患者的平均动脉压无相关性。     

Urinary tract infection in renal transplant recipients

Urinary tract infection (UTI) is common in renal transplant recipients. Frequency of UTIs depend on many factors such as age, female gender, kidney function, co-morbidity, type and amount of immunosuppression, urological instrumentation and/or the follow-up period (short term or long term) after kidney transplantation. UTI may worsen graft and patient survival. A significant proportion of renal transplant recipients with UTIs may develop acute pyelonephritis (APN), which is an independent risk factor for deterioration of graft function. Renal transplant recipients with UTIs are often clinically asymptomatic as a consequence of immunosuppression. UTI, however, may progress to APN (particularly in the early post-transplant period), bacteraemia and the full blown picture of urosepsis. Strategies for long term prophylaxis and antimicrobial treatment of UTI in renal transplant recipients are discussed.     

肾移植后糖尿病酮症酸中毒18例

背景：随着免疫抑制剂的应用,肾移植受者的内分泌和糖类、脂类代谢也发生了变化,肾移植后糖尿病酮症已成为影响患者移植后短期及长期存活率的一项严重并发症,直接影响到人肾存活。目的：分析肾移植后糖尿病酮症酸中毒发病的相关因素,总结肾移植后糖尿病酮症酸中毒的救治方法,降低死亡率。方法：回顾性分析2003/2009郑州人民医院肾移植科收治的18例肾移植后糖尿病酮症酸中毒患者的临床资料,既往肾移植前有糖尿病病史者2例,均为2型糖尿病;无糖尿病病史者16例。酮症发生的时间为肾移植后3d～2.5年。早期临床表现为倦怠乏力、肌肉酸痛、发热等。随着病情的发展很快出现脱水和神经系统症状及体征。对症给予小剂量胰岛素,补液,纠正电解质酸碱平衡失调,去除诱因以及针对并发症等治疗。结果与结论：治疗成功13例,人/肾存活良好,成功率72%;3例死亡,1例死于感染性休克,2例死于多器官功能衰竭,病死率17%;2例患者救治成功,但移植肾功能丧失,恢复血液透析。提示肾移植后糖尿病酮症酸中毒是与抗排斥药物及移植肾功能密切相关的严重的肾移植后并发症,临床表现不典型,处理不当易致严重后果,需引起临床足够重视。     

Immunosuppressive drug monitoring of sirolimus and cyclosporine in pediatric patients

Sirolimus is primarily used as a rescue agent in pediatric transplant recipients, particularly in cases of cyclosporine or tacrolimus toxicity. Preliminary data indicate a higher apparent oral clearance in younger children (4-10 years of age). Various drug interactions have been described between sirolimus and drugs that are substrates/inhibitors or inducers of CYP3A and the P-glycoprotein transporter. Close monitoring of trough sirolimus blood levels is therefore recommended for pediatric transplant recipients. In de novo adult kidney transplant recipients on triple therapy with cyclosporine, corticosteroids and sirolimus, a therapeutic window of 4-12 microg/l is recommended for sirolimus trough concentrations determined by HPLC or LC/MS-MS. In maintenance adult patients after conversion to a calcineurin inhibitor-free regimen, sirolimus trough concentrations of 5-10 microg/l are proposed in combination with mycophenolate mofetil. These therapeutic ranges may also serve as a guide for pediatric renal transplant recipients. The concept of C2 monitoring still needs to be critically evaluated in pediatric patients. The crucial importance of achieving an adequate cyclosporine exposure early after transplantation has been demonstrated for adult transplant recipients. A cyclosporine concentration taken 2 h after dosing is a good surrogate marker of the AUC0-4h in adults. Various clinical studies have shown that in pediatric patients, the C2 concentration shows a substantially better correlation with cyclosporine exposure compared to the trough level (C0). In an outcome study with pediatric renal transplant recipients, it could be demonstrated that the AUC(0-4h) was a predictor of acute rejection in the first 3 weeks after transplantation, whereas C2 levels showed no significant association. Abbreviated AUC strategies may be preferable for optimization of CsA exposure in pediatric patients.     

移植肾穿刺病理组织中抗体介导的排斥反应

背景:体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。目的:对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。方法:选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD(美国)活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。结果与结论:84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。     

移植肾穿刺病理组织中抗体介导的排斥反应

背景：体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。目的：对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。方法：选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD（美国）活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。结果与结论：84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。