肾移植术后人类微小病毒B19感染致纯红细胞再生障碍性贫血2例并文献复习

目的探讨肾移植术后人类微小病毒(HPV)B19感染致纯红细胞再生障碍性贫血(纯红再障)的诊断和治疗特点。方法总结南方医科大学南方医院器官移植科收治的2例肾移植术后HPV B19感染致纯红再障的病例,结合文献复习讨论该病的临床特点、诊断方法、治疗过程及预后。结果两例肾移植受者术后早发严重贫血且进行性加重,输血治疗无效。排除导致贫血的其他原因,综合骨髓穿刺活检、荧光聚合酶链反应(PCR)检测HPV DNA等方法诊断为HPV B19感染致纯红再障。经调整免疫抑制方案、静脉注射用免疫球蛋白(IVIG)等治疗后2例患者贫血症状明显改善。结论对于肾移植术后早期不明原因、进行性加重的贫血患者,特别是伴随网织红细胞缺乏者,应考虑HPV B19感染致纯红再障的可能性。骨髓穿刺及荧光PCR检测结果是诊断纯红再障的主要依据,免疫抑制剂减量和应用IVIG治疗是主要治疗措施。经治疗后,患者预后较好,但易复发。     

Human parvovirus B19 infection in organ transplant recipients

We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.     

Parvovirus B19-induced anemia in renal transplantation: a role for rHuEPO in resistance to classical treatment

Human parvovirus B19 (PVB 19) is responsible for pure red cell aplasia in immunocompromised patients, and particularly solid organ recipients. Intravenous immunoglobulins (IVIG) have been shown to be efficient to achieve the correction of anemia in association with the reduction of immunosuppression. We report a case of kidney transplant recipient with PVB 19-induced anemia that did not respond to recombinant human erythropoietin (rHuEPO) and to a first course of IVIG. After discontinuation of rHuEPO, a second course of IVIG was successful with the resolution of anemia. We discuss the role of rHuEPO that may facilitate PVB 19 replication in erythropoietin-sensitive human erythroid progenitor cells.     

Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice

Clinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High‐level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2‐5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.     

肝移植术后人类细小病毒B19感染的二代测序筛查及其相关危险因素分析

目的  总结肝移植术后人类细小病毒(HPV)B19感染的筛查方法并分析相关危险因素。方法  回顾性分析86例受者的临床资料。根据二代测序(NGS)结果  分为HPV B19感染组和对照组, 分析HPV B19感染患者的临床特点、治疗方案及预后, 采用单因素和多因素Logistic回归向前LR逐步法分析HPV B19感染的危险因素。结果86例受者中9例受者肝移植术后2周左右出现不明原因发热伴进行性贫血, NGS检测提示HPV B19阳性, 诊断为HPV B19感染引起的纯红细胞再生障碍性贫血(PRCA)。所有患者给予静脉注射用免疫球蛋白(IVIG)治疗及免疫抑制方案调整后, 血红蛋白水平明显回升。多因素分析结果显示, 患者术后7 d外周血清球蛋白水平低[比值比(OR)=0.749, P=0.040]、年轻患者(OR=0.937, P=0.038)是肝移植术后HPV B19感染的独立危险因素。结论  对于肝移植术后早期出现不明原因的血红蛋白水平下降的相对年轻患者, 需考虑HPV B19感染。NGS筛查是早期诊断HPV B19感染的有效方法。患者术后7 d外周血清球蛋白水平低和年龄(年轻患者)可能是其发生的独立危险因素。     

Central nervous system vasculitis secondary to parvovirus B19 infection in a pediatric renal transplant patient

Central nervous system (CNS) vasculitis secondary to chronic parvovirus B19 (B19) infection presenting with recurrent neurological findings is a very rare disorder during childhood. Here we report a 12-year-old boy with a renal transplant who had chronic B19 infection with skin eruptions and recurrent episodes of encephalopathy with focal neurological deficits. B19 DNA was detected in blood, bone marrow, and skin biopsy specimens. Repeat cranial magnetic resonance (MR) imaging during each episode of encephalopathy showed variable focal findings, and MR angiography revealed vasculitic changes with narrowing of the cerebral arteries. We hypothesized that the CNS vasculitis might be associated with the chronic B19 infection. At the time of his fourth presentation with the same clinical findings, we administered intravenous immunoglobulin (IVIG) (1 g/kg per day, 2 consecutive days), which we continued for 6 months, at monthly intervals. IVIG therapy resulted in remission and has been effective not only for the clearance of B19, but also for the improvement of clinical and radiological findings of CNS vasculitis. We suggest that chronic B19 infection should be considered in immunocompromised patients with suspected CNS vasculitis. IVIG should be considered as a part of the treatment.     

乙型肝炎免疫球蛋白预防肾移植后新发乙型肝炎

目的 探讨肾移植受者应用小剂量乙型肝炎免疫球蛋白(HBIG)预防术后新发乙型肝炎的安全性和有效性.方法 回顾性分析单中心2007年1月至2010年6月间肾移植受者的资料,将术前无乙型肝炎的138例受者作为试验组,术前肌肉注射小剂量HBIG,术后定期监测乙型肝炎表面抗体(HBsAb)滴度,根据其滴度调整术后应用HBIG的剂量,持续应用1年或1年以上.将2004年1月至2006年12月间术前无乙型肝炎的196例肾移植受者作为对照组,不采用乙型肝炎预防措施.观察两组移植后新发乙型肝炎的发病率,并记录急性排斥反应发生情况、受者和移植肾1年存活率.结果 随访12个月,试验组仅1例(0.7％)于术后6个月出现新发乙型肝炎,对照组11例(5.6％)出现新发乙型肝炎,其中2例因爆发性肝功能衰竭而死亡.两组新发乙型肝炎发病率的差异有统计学意义(P＜0.05).术后6个月内,试验组有19例(13.8％)发生急性排斥反应,对照组有34例(17.3％)发生急性排斥反应,两组急性排斥反应发生率的差异无统计学意义(P＞0.05).试验组受者1年存活率为97.8％(135/138),移植肾1年存活率为(96.4％,133/138);对照组受者1年存活率为(91.8％,180/196),移植肾1年存活率为(90.3％,177/196).两组受者和移植肾1年存活率的差异有统计学意义(P＜0.05.P＜0.05).结论 小剂量HBIG用于肾移植后预防新发乙型肝炎是安全、有效的.     

Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression

The current outbreak of Coronavirus Disease 2019 (COVID‐19) has raised great concern worldwide, but its impact on transplant recipients is unknown. We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID‐19 pneumonia. This is a 52‐year‐old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non‐transplanted COVID‐19 patients. Following a treatment regimen consisting of reduced immunosuppressant use and low dose methylprednisolone‐based therapy, the COVID‐19 pneumonia in this long‐term immunosuppressive patient was successfully recovered. This effectively treated case has reference value for the future treatment of other transplant patients with COVID‐19 pneumonia.     

Clinical implications of quantitative real time-polymerase chain reaction of parvovirus B19 in kidney transplant recipients – a prospective study

This prospective study was designed to investigate the clinically significant level of parvovirus B19 viral load using quantitative real-time (RT) polymerase-chain reaction (PCR) in kidney transplantation (KT) recipients. One hundred forty-three adult recipients who underwent their first KT between November 2003 and October 2005 were enrolled. Six blood samples (the first taken preoperatively, subsequent samples taken every 4 weeks for 20 weeks) were taken from each patient for parvovirus B19 DNA RT-PCR analysis. All recipients were diligently followed for 1 year post-transplant. One hundred sixty-eight of the 715 (23.5%) postoperative samples were positive for parvovirus B19 PCR. Eighty-four of the 143 KT recipients (58.7%) showed at least one positive PCR. Sixteen of the 143 (11.1%) KT recipients had sustained severe anemia (SSA) with hemoglobin lower than 7.0 g/dl, after 4 weeks post-transplant. The incidence of SSA in recipients with a titer higher than 1 × 10⁶ copies/5 μl whole blood was significantly higher than those with a negative or low titer ( P  <   0.001, positive predictive value 84.6%, negative predictive value 96.2%). In conclusion, a high titer of parvovirus B19 DNA higher than 1 × 10⁶ copies/5 μl whole blood in KT recipients was related with SSA after 4 weeks post-transplant.     

肾移植受者人类微小病毒B19感染临床诊疗技术规范(2022版)

肾移植受者长期使用免疫抑制剂,导致其免疫功能低下,容易伴发各种病原体感染。近年来随着人类微小病毒B19(HPV-B19)感染的检测技术发展和肾移植手术的增多,肾移植术后HPV-B19的感染率呈逐年上升的趋势,是导致术后纯红细胞再生障碍性贫血(PRCA)的重要原因之一,影响移植肾功能恢复,甚至导致移植肾损伤或预后不良。为了进一步规范肾移植受者HPV-B19感染的诊断和治疗,中华医学会器官移植学分会和国家肾脏移植质控中心组织专家,从HPV-B19病原学、流行病学特点、临床表现、诊断、预防、治疗、存在的问题及展望等方面,制订肾移植术后HPV-B19感染的临床诊疗规范,以期为我国肾移植术后HPV-B19感染的规范化防治提供指导。     

Efficacy of conventional immunosuppressive therapy in related and unrelated living renal transplantation

BACKGROUND: The application of antibody induction therapy in adult living-related kidney transplantation remains under discussion. The purpose of this study was to compare the outcome of living-related (LRT) and unrelated renal transplant recipients (LURT) using standardized immunosuppressive protocols. From October 2000 to October 2004, 72 adult LRT (TX) were performed at our institution. Thirty-nine LRT (group A) and 33 LURT (group B) recipients received a standardized immunosuppressive therapy consisting of tacrolimus (Tac), steroids and mycophenolate mofetil (MMF) without antibody induction therapy. This prolective analysis included immediate graft function, rejection rate and loss of the transplanted organ. The incidence of post-operative good graft function (>90%) was similar for both groups, as well as the rejection rate showed 57.8% for patients of group A and 58.8% for patients of group B (p < 0.5). However, the number of rejections (>1 rejection) was significantly higher in group B (11.8%) compared to patients in group A (4.4%). No difference concerning loss of transplanted kidney was observed for both groups. Conventional Tac, MMF and steroid-based immunosuppression therapy is equivalent in efficacy of therapy in living-related and unrelated renal transplants. In our opinion, induction therapy in patients without immunologic risk factors has no favourable effect.     

肾移植后微小病毒B19感染导致纯红细胞再生障碍性贫血八例

目的 探讨肾移植后微小病毒B19感染导致的纯红细胞再生障碍性贫血(PRCA)的诊断及其治疗.方法 2011年8月至2012年3月间共诊断肾移植后微小病毒B19感染导致的PRCA患者8例.采用转换免疫抑制剂、输注丙种球蛋白、加大激素用量、停用骨髓抑制药物及必要时联合膦甲酸钠抗病毒等综合措施进行治疗.在治疗前后对其临床表现、实验室检查、病理检查、转归等进行回顾与总结分析.结果 8例初次诊断时间为移植后(53±15)d(32～86 d),期间肾功能稳定.治疗前血红蛋白最低值为(58±9.3)g/L(50～73 g/L),综合治疗后所有患者均治愈,治疗起效时间为(22±13)d(8～47 d),治疗后1个月和3个月的血红蛋白分别为(106.8±22.3)g/L和(116.0±20.7)g/L.患者随访(222±93)d,血红蛋白水平稳定.结论 对肾移植后微小病毒B19感染导致的PRCA,采用转换免疫抑制剂、输注丙种球蛋白、加大激素用量、停用骨髓抑制药物,必要时联合应用膦甲酸钠抗病毒等综合措施治疗有效.     

Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation.

BACKGROUND: Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. METHODS: Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. RESULTS: Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb)<12 g/dl, females Hb<11 g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 micromol/l vs 131.0 micromol/l, P<0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P<0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8%, P=0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R=-0.29, P<0.001), but not between EPO levels and eGFR (R=0.02, P=0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. CONCLUSION: Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia.     

Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients

Human parvovirus B19 (B19) infection has been known to cause chronic anemia, pure red cell aplasia (PRCA), glomerulopathy, and allograft dysfunction in kidney transplant (KT) recipients. The aim of this study was to evaluate the incidence and clinical significance of B19 infection in KT recipients. A total of 537 serum samples from 167 KT recipients were included in the present study. The incidence of B19 infection was based on either qualitative polymerase chain reaction (PCR) or quantitative PCR with LightCycler Parvovirus B19 Quantitation kit. Clinical significance of B19 infection was investigated by a retrospective review of hemoglobin (Hb) levels and the results of kidney and bone marrow biopsies. The overall PCR positive rate was 18.3% (98/537), and 52 of 167 (31.1%) KT recipients showed at least one positive PCR. In addition, 20 of 167 subjects (12.0%) showed PCR-positivity more than two consecutive times, and they had significantly lower Hb levels than those with negative or one positive PCR (p < 0.0001). Furthermore, two patients suffered from PRCA, which was confirmed by bone marrow biopsy. However, B19 infection did not seem to affect the graft outcome. In conclusion, the B19 infection in KT recipients was not uncommon and was associated with low Hb levels and PRCA after KT.