J K Saravana Priya, J Padma Kumari, Rupert Secunda, C P Ramani
Microbiology, Madras Medical College, Rajiv Gandhi Government General Hospital, Chennai, IND.
Regenerative Medicine and Research, Stanley Medical College, Chennai, IND.
Cureus. 2024 Nov 26;16(11):e74483. doi: 10.7759/cureus.74483. eCollection 2024 Nov.
Introduction Cytomegalovirus (CMV) is often associated with mortality and significant morbidity following renal transplantation leading to graft rejection or dysfunction. Primary CMV infection refers to the first detection of the virus in a person who has no prior evidence of CMV exposure before transplantation. CMV has a unique property called latency. After the initial infection, CMV can enter a dormant state within the body, residing in myeloid cells without causing active disease. CMV reactivation is likely when a latent CMV infection switches to a lytic phase of replication, which can be detected using IgG avidity ELISA. Aims and objectives This study aims to assess the prevalence of primary CMV infection and reactivation in renal transplant recipients, evaluate the impact of CMV infection on graft function following transplantation, and identify the risk factors and comorbidities associated with CMV-related graft rejection. Methodology During the study period from March 2020 to November 2021, blood samples were collected from 46 CMV-positive (by PCR) renal transplant recipients, and serum was separated and stored. IgG avidity ELISA test was performed, which served as a valuable tool to differentiate primary infection from reactivation due to difference in binding strength where low binding strength (low avidity<30%) indicated primary infection and high binding strength (high avidity>40%) indicated reactivation. All these patients were followed up to study the impact of CMV on graft functions. Results The age-wise distribution of patients shows a maximum number of cases under 40 years. The gender distribution of cases shows a higher preponderance of males (76%) compared to females (24%). The clinical presentation showed CMV syndrome as the most common (50%), followed by CMV colitis (37%), CMV nephritis (9%), CMV pneumonitis, CMV esophagitis, and CMV duodenitis, each comprising 2%. After performing the IgG avidity test, CMV infection with maximum cases of reactivation (87%) followed by primary infection (13%) was observed. The investigations related to renal dysfunction such as serum creatinine showed >3 mg/dL (85% of cases), 2.1-3 mg/dL (4.33% of cases), 1.6-2 mg/dL (2% of cases), 1-1.5 mg/dL (4.33% of cases) in decreasing order. Normal urea values are seen in 9% of cases followed by the range between 24 and 55 mg/dL in 67% and >100% in 24% of cases. The graft rejection based on the biopsy report showed that acute cellular rejection (ACR) (72%) was higher followed by antibody-mediated rejection (ABMR) with 15% and then ACR + ABMR with 4%. No rejection was found in 9% of cases. Renal dysfunction showed a higher preponderance to chronic graft dysfunction (67%) followed by acute graft dysfunction (24%) and stable graft function among 9% of cases. A comparison of graft dysfunction in primary infection/reactivation was assessed, and it was found that acute graft dysfunction was more common in primary infection. In the case of reactivation, chronic graft dysfunction was more common. Conclusion This study focuses on the microbiological dimensions and the critical role of CMV antibody screening. It underscores the necessity of vigilant monitoring and prophylactic antiviral therapy to reduce CMV infection risks and enhance patient outcomes. It also highlights the use of IgG avidity testing to differentiate between primary infection and reactivation, facilitating timely and effective interventions to prevent graft dysfunction and rejection.
引言
巨细胞病毒(CMV)通常与肾移植后的死亡率和严重发病率相关,可导致移植肾排斥或功能障碍。原发性CMV感染是指在移植前无CMV暴露证据的人首次检测到该病毒。CMV具有一种称为潜伏的独特特性。初次感染后,CMV可在体内进入休眠状态,存在于髓样细胞中而不引起活动性疾病。当潜伏的CMV感染转变为复制的裂解期时,CMV可能重新激活,这可以使用IgG亲和力ELISA检测到。
目的
本研究旨在评估肾移植受者中原发性CMV感染和重新激活的患病率,评估CMV感染对移植后移植肾功能的影响,并确定与CMV相关的移植肾排斥相关的危险因素和合并症。
方法
在2020年3月至2021年11月的研究期间,从46名(通过PCR检测为)CMV阳性的肾移植受者中采集血样,分离血清并储存。进行了IgG亲和力ELISA检测,由于结合强度的差异,该检测是区分原发性感染和重新激活的有价值工具,其中低结合强度(低亲和力<30%)表明原发性感染,高结合强度(高亲和力>40%)表明重新激活。对所有这些患者进行随访,以研究CMV对移植肾功能的影响。
结果
患者的年龄分布显示40岁以下的病例数最多。病例的性别分布显示男性(76%)比女性(24%)占比更高。临床表现显示CMV综合征最为常见(50%),其次是CMV结肠炎(37%)、CMV肾炎(9%)、CMV肺炎、CMV食管炎和CMV十二指肠,各占2%。进行IgG亲和力检测后,观察到CMV感染中重新激活的病例最多(87%),其次是原发性感染(13%)。与肾功能不全相关的检查,如血清肌酐显示>3mg/dL(85%的病例)、2.1 - 3mg/dL(4.33%的病例)、1.6 - 2mg/dL(2%的病例)、1 - 1.5mg/dL(4.33%的病例),呈递减顺序。9%的病例尿素值正常,67%的病例尿素值在24至55mg/dL之间,24%的病例尿素值>100mg/dL。根据活检报告,移植肾排斥显示急性细胞排斥(ACR)(72%)较高,其次是抗体介导的排斥(ABMR),占15%,然后是ACR + ABMR,占4%。9%的病例未发现排斥。肾功能不全显示慢性移植肾功能不全占比更高(67%),其次是急性移植肾功能不全(24%),9%的病例移植肾功能稳定。对原发性感染/重新激活中的移植肾功能不全进行了比较,发现急性移植肾功能不全在原发性感染中更常见。在重新激活的情况下,慢性移植肾功能不全更常见。
结论
本研究关注CMV抗体筛查的微生物学层面及其关键作用。强调了警惕监测和预防性抗病毒治疗以降低CMV感染风险并改善患者预后的必要性。还强调了使用IgG亲和力检测来区分原发性感染和重新激活,便于及时有效地进行干预以预防移植肾功能不全和排斥。