移植肾脏患者的特定脑膜脑炎

我们描述了肾脏移植后患者特异性（结核性）脑炎的病例。在晶状体后期不断需要的免疫抑制疗法可能会引起各种并发症，例如感染。特异性脑膜脑炎是一种很少被诊断出来的感染，在免疫功能低下的患者中更常见。

案例报告：A 30-year-old man had kidney transplantation (kidney donor was his father). He previously was two years on chronic hemodialysis treatment because of end-stagerenal disease based on diabetic nephropathy. He has diabetes type 1. The early post-transplant period duly passed with satisfactory clinical and laboratory parameters of renal function. Two months after transplantation, he presented with febrile condition, signs of septicemia and dehydration with significant neurological deficit and expressed meningeal signs. In cerebrospinal fluid we found lymphocytosis, elevated proteins and positive micobacterium tuberculosis antibodies (Hexagon method) and we suspected to specific etiology of meningitis. Performed computed tomography (CT) scan of the brain with contrast confirmed the expected finding.

由于免疫功能低下的患者的中枢神经系统感染（CNS）的预后不良，因此只有及时的诊断才能改善这组患者的生存率。肾脏移植后的治疗方案包括在9个月内预防抗结性药物（Isoniazid 300 mg）。

临床器官移植的史始于1960年代，将硫唑嘌呤引入治疗中，与类固醇一起是未来20年的基本免疫抑制疗法。在20世纪，肾脏移植成为慢性肾脏疾病末期的选择疗法。

Immunosuppressive therapy prevents rejection of the transplanted kidney, and the administration of this therapy primarily affects the success of the transplant. Immunosuppressive therapy is carried out continuously after the transplant procedure. Initial high doses are lowered during the first few weeks and maintenance therapy is continued. Immunosuppressive therapy can cause various posttransplant complications: infections, tumors, metabolic disorders, arterial hypertension, and other adverse events. One of the leading complications of immunosuppressive therapy is infection. A study by Peterson and colleagues in the early 1980s found that infections were the cause of death in 87% of kidney transplant patients [1]. During the first month after transplant surgery most infections are so called hospital infections (eg., bacteria of the genus Pseudomonas as agents for pneumonia; gram-positive bacteria that cause wound infection). Opportunistic infections usually occur from the first to six months after transplantation. According to the infectious agent, they can be divided into bacterial, viral (cytomegalovirus (CMV), Ebstein Barr virus (EBV), varicella zoster virus (VZV), hepatitis B or C virus), fungal or parasitic. The most significant viral infections are caused by cytomegalovirus and herpes virus. Infections caused by tuberculosis bacteria from different organs should also not be neglected. CNS infections are more common after kidney transplantation than in the general population: acute and chronic meningitis, brain abscess, and multifocal leukoencephalopathy. Listeria monocytogenes, criptococcus and mycobacterium tuberculosis are among the most common causes of meningitis. Specific meningoencephalitis is an inflammation of the meninges and brain parenchyma caused by mycobacterium tuberculosis, often undiagnosed and more common in immunocompromised patients (immunosuppressive therapy and HIV infection). Over a period of approximately six months the risk of infection decreases [2].

30岁的女性患者，自十岁以来患有1型糖尿病。由于糖尿病肾病和末期肾功能不全，2003年11月，慢性血液透析治疗开始了。经过两年的慢性透析治疗后，患者住院以准备肾脏移植（活出生移植），作为潜在的接受者，潜在的肾脏供体是父亲。对接受者和捐助者的必要发现和方案，其中包括生化，微生物，放射学和专业咨询发现。2005年3月，进行了现场家庭肾脏移植。术后课程进展顺利。肾脏接受者的治疗方案还包括在手术前一天开始的标准免疫抑制疗法。每天监测体重，液体摄入量，利尿作用，动脉血压（TA），体温（T°C），血环孢菌素水平和血糖。将移植后的肌酐水平归一化，血环孢菌素水平在推荐的值之内。移植肾脏的超声检查结果正常。 The patient was discharged on the 18th posttransplant day with satisfactory clinical and laboratory parameters of renal function and in good general condition.

移植后两个月，患者因发烧（38°C），发烧，头痛，听力丧失，意识障碍，虚弱，不适，呕吐和寡尿症住院。体格检查确定患者遵循目光的能力，但尚未建立口头接触。印象是它对声学刺激没有足够的反应。该患者发热，呼吸速度，缓存，水合不足，不动，给人以严重患者的印象。皮肤苍白，脸上有红色的黄斑，在小腿上交叉。心脏和肺部发现正常，TA：130/80 mmHg，中央脉冲（CP：90/min）。神经系统地位主要是在正确的末端发现总体运动功率受损，指示脑膜迹象，中央瘫痪的迹象n。面部护理，双侧眼球震颤，但颈部用前挡板收紧。准确的红细胞沉降（SE：79/100），白细胞增多（L：23），C升高的C反应性蛋白质（CRP：61），代谢性酸中毒的迹象，肌酐升高239 µmol/L，Glycemia 26 mmol/L。。尿液阳性葡萄糖和酮。 The radiographic findings of the heart and lung were neat and the sputum on BK negative, as was the urine on Lowenstein. Ultrasound findings of the transplanted kidney show edema of the cortex, stressed pyramids, and index of resistance (RI 0.76). The ELISA test for EBV, CMV, herpes simplex virus (HSV) and VZV was IgM negative, IgG positive, and the CNS profile of IgG and IgM class from serum was negative. Computed tomography (CT) of the brain with contrast shows a wider ventricular system of the third and both lateral chambers, the initial type of hydrocephalus with discretely present periventricular hypodensity as seen with hydrocephalus accutation. CT findings do not rule out possible changes by type of meningitis. A lumbar puncture is performed in consultation with the infectologist. Liquor results in increased cell count up to 168 (lymphocytes), increased protein up to 3 g/l. Direct preparation of liquor on Micobacterium tuberculosis done five times was negative, and antibodies on Micobacterium tuberculosis in liquor (Hexagon), also made five times, were positive.

怀疑急性脑膜炎。大脑的CT又进行了两次，发现表明旁腔室弱密度不太明显。脑电图（EEG）表示支持双方额叶区域的功能障碍，并且在双方的听觉诱发电位（AEP）的发现仍然没有诱发的反应。诊断为特定的脑膜脑炎，是根据植入的数据，临床图片，体格检查，实验室发现，CSF发现和CT脑进行的。包括四倍的抗结核疗法（ATL）疗法，其中包括：利福丁，异尼氏二氮二，吡嗪酰胺，乙氨核酸。开始治疗两个月后，利法丁和异念珠菌持续了4个月。电机失语症康复程序包括登录。定期检查肾脏科医生，内分泌学家和神经科医生。通过足够的环孢菌素滴定，实现了令人满意的肾移植功能（肌酐108 µmol/L）。在三个月的时间内，随着右侧的偏瘫，在右侧进行了改善的一般状况。 facialis right by cetral type, motor aphasia and impaired hearing.

糖尿病是末期末端伤衰竭的最常见原因之一。这些患者的肾脏移植是选择的方法，尽管伴随着许多并发症。这些并发症反映在因免疫抑制疗法增强感染的风险增加中，移植肾脏中肾病的复发在移植后的头十年相对较低，加剧了代谢障碍，并加剧了心血管疾病的相关风险[1，1，1，1，1,,2]。糖尿病性肾病的复发不被认为是肾脏移植的禁忌症。

在我们的患者中，末期肾衰竭是由糖尿病性肾病引起的。肾脏替代疗法（血液透析）的选择方法是肾脏移植。在患有少年糖尿病（1型糖尿病）的年轻接受者中，同时肾脏和胰腺移植是可以显着改善质量和延长寿命的第一选择方法。糖尿病是一种严重的疾病，主要是由于心血管和感染风险增加，影响了移植的结果以及发病率和死亡率。由于肾移植后糖尿病性肾病的发生率显着，因此建议严格控制糖尿病和高血压，使用血管紧张素转化酶抑制剂（ACEI）（ACEI）（ACEI）和/或血管紧张素受体受体群（ARB）来预防或减轻这种风险[3-5]。

移植后并发症显着影响发病率和死亡率。肾脏移植后的患者必须服用免疫抑制药物，以防止对移植器官排斥。最常用的三重免疫抑制疗法：钙调神经磷酸酶抑制剂（环孢菌素/他克莫司），抗磷酸药物（霉酚酸酯或硫氰酸酯）和皮质类固醇。钙调蛋白的抑制剂对肾脏具有众所周知的毒性作用，但对其有效的神经毒性作用知之甚少。环孢菌素可以是神经毒性（最多50％的移植患者）。由钙调神经磷酸酶抑制剂引起的神经系统疾病的范围从非常轻微的症状到严重变化，并带来潜在的灾难性后果。钙调蛋白抑制剂的神经系统副作用的发展受益于：高药物浓度，高镁血症，高剂量的皮质类固醇，高血压和感染[2,6]。这些变化通常是可逆的，并且在停用药物后会逆转，而不管我们患者的情况发生了什么变化或中断，患者的持久作用较少，无论对免疫抑制治疗的变化如何。

Tuberculosis (TB) is not a rare disease after kidney transplantation, and can be life-threatening. TB treatment in patients with a kidney transplant must be performed in the same way as in the general population. This means that treatment with a combination of four drugs - rifampin, isoniazid, ethambutol and pyrazinamide, must be followed for 2 months, followed by treatment with a combination of isoniazid and rifampin for 4 months. Ethambutol should not be given initially if the isoniazid resistance rate in the population is less than 4%. Because rifampin decreases plasma concentrations of calcineurin antagonists and rapamycin, the levels of these agents in the blood should be closely monitored. Rifabutin may be prescribed as an alternative to rifampin because this drug is less effective in inducing the microsomal enzymes P450. Kidney transplant candidates and renal graft recipients should be screened for latent TB infection.

潜在的结核病感染最好用300毫克的异念珠菌剂量治疗9个月[7,8]。中枢神经系统（CNS）感染通常发生在移植后的第一年，并由精神状态，头痛，发烧和局灶性神经系统暴发的疾病表现出来。不清楚的症状学通常会导致准确诊断的延迟。在临床上，中枢神经系统感染可能表现为脑膜炎，进行性痴呆和局灶性感染[9,10]。除了免疫抑制治疗外，移植后感染的趋势还导致尿emia，贫血和血液凝结受损的患者免疫反应降低[11]。特定的脑膜脑炎是一种罕见的并发症，并且经常无法诊断，并且可能留下严重的神经后遗症，例如在当前患者中：偏瘫，右颈神经面部麻痹，运动失语症和听力受损。在这种情况下，为了诊断特定的脑膜脑炎，有积极的病史，临床发现，实验室发现，CSF和脑CT。

免疫功能低下的中枢神经系统感染患者的预后较差。只有及时和及时的诊断才能提高患者的存活率。建议在肾移植后的治疗方案中应包括300 mg剂量的异尼氏酶结核的预防服用9个月。

1. Cohen J, Hopkin J, Kurtz J. Infectious complications after renal transplantation. In: Morris PJ (ed). Kidney Transplantation; Principles and Practice. WB Saunders Company, Philadelphia, London, New York, Toronto. 2002; 468-490.
2. Živčić-（-FimounćosićS，TrobonjačaZ，RačkiS。imunosupresivnoliječenjekod kod presa presa preperabubrega bubrega。Medicina。2010;4：413-23。
3. Campbell PM. Pathology of acute rejection in the renal allograft. ASHI quaterly. Third quarter. New Jersey: ASHI. 2004: 86.
4. LežaićV，RadivojevićD，BlagojevićR，éukanovićLJ。肾移植后中枢神经系统感染。移植Infect Dis 2002;4：167-168。
5. 肾脏疾病。改善全球结果（KDIGO）移植工作组。KDIGO临床实践指南肾脏移植受者的护理指南。是J移植。2009;9（补充3）：S1-155。PubMed：https://pubmed.ncbi.nlm.nih.gov/19845597/
6. Brennan DC，Bohl D.肾移植受者的感染并发症。在：Malluche HH，Sawaya BP，Hakim RM，Sayegh MH（eds）。临床肾脏病，透析和移植。2004;1-34。
7. Randhawa P，Brennan DC。移植受体中的BK病毒感染：概述和更新。是J移植。2006;6：2000-2005。PubMed：https://pubmed.ncbi.nlm.nih.gov/16771813
8. LežaićV，RadivojevićR，RadosavljevićR，BlagojevićR，SimićS等。肾移植后的结核病是否遵循普通人群中结核病的趋势？肾衰竭。2001;23：97-106。PubMed：https://www.ncbi.nlm.nih.gov/pubmed/11256535
9. Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid organ transplant recipients: impact and implications for menagement. Clin Infect Dis. 2008; 27: 1266-1277.
10. Morath C，Schmied B，Mehrabi A，Weitz J，Schmidt J等。同时在1型糖尿病中同时进行胰腺kidney移植。临床移植。2009;23 Suppl 21：115-20。PubMed：https://www.ncbi.nlm.nih.gov/pubmed/19930324
11. 乔伊斯（Joyce），Iacoviello JM，Nag S.末期肾脏疾病与糖尿病患者的终点肾脏相关的托管护理费用。糖尿病护理。2004;27：2829-2835。PubMed：https://www.ncbi.nlm.nih.gov/pubmed/15562193