The risk of cytomegalovirus recurrence after kidney transplantation

Recurrent cytomegalovirus (CMV) infections commonly occur after kidney transplantation. We studied the impact of secondary prophylaxis and other factors on the risk of CMV recurrence. All kidney transplant recipients between 2004 and 2009 in our institution were analyzed (N = 254). Patients with CMV infection were included (N = 62). CMV infections were diagnosed with quantitative PCR. CMV D+/R- recipients received 6 months valganciclovir prophylaxis, after which DNAemia was monitored. After treatment, secondary prophylaxis with valganciclovir was given at the clinician's discretion for 2-26 weeks and CMV DNAemia was monitored. Altogether 43 reactivations and 19 primary infections occurred. Antiviral treatment with valganciclovir or ganciclovir was given to 45 patients; 34/62 (55%) patients received secondary prophylaxis for mean 62 days (range 14-180 days). CMV recurrence occurred in 14/43 (33%) seropositive patients and in 4/19 (21%) patients after primary infection. In logistic regression, delayed graft function (OR 3.4) and high viral load (>100 000 copies/ml) at initial diagnosis (OR 5.9) predicted recurrence. Use or length of secondary prophylaxis, CMV serostatus, level of immunosuppression, HLA mismatch, antiviral treatment, or time to clearance of viremia during treatment did not predict recurrence of CMV. CMV recurrences occur commonly despite secondary prophylaxis. High viral load at diagnosis predicted the risk of recurrent CMV infection.     

Impact of a Polymorphism in the IL-12p40 Gene on the Outcome of Kidney Transplantation

A number of factors interfere with the outcome of renal transplantation. Revealing genetic factors that impact on graft outcome may have consequences for clinical practice. Interleukin-12 (IL-12), by stimulating interferon gamma (IFNγ) production, plays a crucial role in immune responses against both graft and viral agents. An A-to-C single nucleotide polymorphism (SNP) within the 3′-untranslated region (3′UTR) of the IL-12p40 gene has been reported to be both functionally and clinically relevant. Since the impact of this SNP on kidney graft outcome has never been reported, we investigated the impact of the 3′UTR polymorphism on clinical events after transplantation among 253 kidney recipients transplanted between 1995 and 2003. The polymorphism was genotyped using the restriction fragment length polymorphism method. Our results showed that the 3′UTR polymorphism affected neither graft survival (P = .768) nor the occurrence of delayed graft function (DGF; P = .498). C allele carriers in our study displayed more acute rejections in the first year than patients with the A/A genotype, but it did not reach statistical significance (P = .108). In contrast, the C allele appeared to be a significant risk factor for cytomegalovirus infection (odds ratio = 1.77; P = .027). In conclusion, IL12B 3′UTR polymorphism did not affect graft survival, DGF, or acute rejection episodes, but had an impact on the occurrence of cytomegalovirus infection.     

The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.     

Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival

BACKGROUND: The impact of cytomegalovirus (CMV) infection and disease on long-term outcome after kidney transplantation is still unsettled. METHODS: Between 1994 and 1997, 397 consecutive first kidney graft recipients and 74 retransplants were included in the study and followed prospectively until December 31, 2001. CMV infection (CMV pp65 antigenemia) and CMV disease were recorded once weekly during the first 100 days after transplantation. No CMV prophylaxis or preemptive therapy was given. In a multiple Cox proportional hazard model allowing time-dependent covariates, the effects of asymptomatic CMV infection and CMV disease, recipient age and gender, retransplantation, living donor, panel-reactive cytotoxid antibodies, acute rejection, and graft loss were tested on overall mortality beyond 100 days post-transplantation. In a similar analysis, the effect of asymptomatic CMV infection and CMV disease plus other factors were tested on death censored graft loss beyond 100 days. RESULTS: Median (range) follow up time was 66.6 (<1-86.9) months. The incidence of CMV infection and disease during the first 100 days was 62.8% and 23.4%, respectively. The number of total deaths was 96 (20%), 82 occurred after the first 100 days. Independent risk factors for overall mortality beyond 100 days were asymptomatic CMV infection, RR = 2.90 (95% CI 1.61-5.22) (P= 0.001), CMV disease, RR = 2.50 (95% CI 1.31-4.79) (P= 0.006), both compared to no infection or disease, recipient age, RR = 1.066 per year (95% CI 1.048-1.084) (P < 0.001), and graft loss in the whole study period RR = 7.88 (95% CI 4.75-13.08) (P < 0.001). Asymptomatic CMV infection and CMV disease were not independent risk factors for death censored graft loss, but they significantly reduced graft survival uncensored for death, (log rank P= 0.001, respectively). CONCLUSION: Asymptomatic CMV infection and overt CMV disease during the first 100 days increase the risk of recipient mortality beyond 100 days. This raises the question whether CMV prophylaxis should be given routinely after kidney transplantation.     

A polymorphism of matrix Gla protein gene is associated with kidney stones

PURPOSE: Matrix Gla protein, a potent calcification inhibitor in arterial vessels, is also expressed in the kidney and is up-regulated following the administration of ethylene glycol, a precursor of oxalate. Considering the analogous characteristics between arterial calcification and kidney stones, we identified variants of the human matrix Gla protein gene and investigated whether there is an association between MGP genetic polymorphisms and kidney stones. MATERIALS AND METHODS: We studied single nucleotide polymorphisms in matrix Gla protein in 122 kidney stone cases and 125 controls. We resequenced the human genomic MGP gene, including the 1,000 bp promoter 5'-untranslated region, 4 exons and 3'-untranslated regions, and we performed systematic genetic analysis. A single nucleotide polymorphism was genotyped using a fluorescent 5'endonuclease assay and its association with kidney stones was analyzed. RESULTS: We observed 19 polymorphisms. A single nucleotide polymorphism was associated with kidney stones (OR 0.51, 95% CI 0.30-0.87; p = 0.012). The G allele carrier had a 2-fold decreased kidney stone risk compared with A allele carriers in single nucleotide polymorphism 11 (OR 0.55, 95% CI 0.31-1.00, p = 0.047). We found no association between the polymorphism and kidney stone clinical characteristics. CONCLUSIONS: Our findings show that an MGP gene polymorphism is associated with kidney stones and influences genetic susceptibility to kidney stones. In the future functional assays of the polymorphism should permit better understanding of the role of matrix Gla protein genetic variants and kidney stones.     

Association between mannose-binding lectin deficiency and cytomegalovirus infection after kidney transplantation

Mannose-binding lectin (MBL) deficiency has been suggested as a risk factor for certain viral infections. However, there is no data about the possible association between MBL deficiency and cytomegalovirus (CMV) infection, especially after organ transplantation. We measured plasma MBL levels in 16 kidney transplant recipients with high-risk CMV serostatus (donor-positive/recipient-negative). MBL deficiency was diagnosed if MBL levels were <500 ng/mL. Of these 16 patients, seven developed CMV disease, four developed asymptomatic CMV infection, and in five patients CMV replication was not detected. Overall, 9 of 16 patients (56%) had MBL deficiency: five of seven (71%) patients with CMV disease, four of four (100%) patients with asymptomatic CMV infection, and zero of five (0%) patients without CMV infection (P=0.005; CMV infection/disease versus no infection). MBL deficiency may be a significant risk factor for the development of CMV infection in kidney transplant recipients, suggesting a role for innate immunity in the control of CMV infection after organ transplantation.     

CMV-hyperimmune globulin for preventing cytomegalovirus infection and disease in solid organ transplant recipients: a meta-analysis

Abstract. Objective: The goal of this meta-analysis was to investigate the impact of cytomegalovirus hyperimmune globulin (CMVIG) on cytomegalovirus (CMV) infection, CMV disease, and mid-term survival in solid organ transplant recipients. Methods: Medline, EMBASE, and the Cochrane databases were searched since their inceptions until 2006. Inclusion criteria comprised: prospective randomized trials, in solid organ transplantation which received CMV prophylaxis including CMVIG on one of the treatment arms. Random effects models were used to calculate pooled risk ratios (RR) and meta-regression was employed to explain study heterogeneity. Stratified analyses were conducted and Funnel plot was used to assess publication bias. Results: Literature searches identified 11 randomized trials (698 patients; median follow-up: 12 months, range: 3–22 months) including six randomized trials (302 patients) after kidney transplantation. The analysis demonstrated a beneficial effect of the prophylactic use of CMVIG on total survival [RR (95% confidence interval; CI): 0.67 (0.47–0.95)] and prevention of CMV-associated death [RR (95% CI): 0.45 (0.24–0.84)] in solid organ transplant recipients but not kidney transplant recipients [RR (95% CI): 0.35 (0.12–1.04)]. CMV disease was significantly reduced in all recipients receiving prophylactic CMVIG [RR (95% CI): 0.697 (0.57–0.85)]. CMVIG had no impact on CMV-infections and clinically relevant rejections. Conclusions: Prophylactic administration of CMVIG after solid organ transplantation is associated with improved total survival, reduced CMV disease, and CMV-associated deaths.     

Persistent cytomegalovirus infection in kidney allografts is associated with inferior graft function and survival

The long-term effects of cytomegalovirus (CMV) infections on kidney allografts are unknown. We examined the impact of persistent intragraft CMV infection on long-term kidney allograft function and survival. CMV was diagnosed in 82/172 renal transplant recipients by antigenemia test and viral cultures. Biopsies from 48 of 82 patients taken after CMV infection and from 15 patients with no previous CMV infection detected were available for the immunohistochemical demonstration of CMV antigens and DNA hybridization in situ. Five-year follow-up data from these 63 patients were analysed. In 17 patients, CMV antigens and/or DNA persisted in the biopsy >2 months after the last positive finding in blood or urine. Patients with persistent intragraft CMV had reduced graft survival (P = 0.041) and Cox regression analysis showed persistent CMV as a risk factor for reduced graft survival (RR: 3.5). Recipients with persistent intragraft CMV had reduced creatinine clearance 1 and 2 years after transplantation (P = 0.007) and in multivariate logistic regression analyses including several potential pre- and posttransplant risk factors, persistent CMV was an independent risk factor for lower clearance at 1 and 2 years (OR: 4.4 and 4.9). Our novel findings show that persistent intragraft CMV infection was associated with reduced kidney allograft function and survival.     

Cytomegalovirus prophylaxis with ganciclovir in kidney transplant recipients receiving induction antilymphocyte antibodies

BACKGROUND: Cytomegalovirus (CMV) is one of the serious viral infections after organ transplantation, especially in patients receiving anti-lymphocyte antibodies. Prevention of the infection using antiviral chemotherapy (ganciclovir) has gained interest in the transplant community due to the availability of quantitative methods for viral detection and monitoring. METHODS: Forty-six CMV seropositive kidney transplant recipients were assigned to receive induction immunosuppression with anti-thymocyte globulin (ATG, Fresenius). Prophylactic intravenous ganciclovir was administered for 2 weeks at a dose of 5 mg/kg/d (adjusted to kidney function) starting from the day of surgery. Patients were monitored regularly for CMV infection or disease over 1 year posttransplant. The time to CMV manifestation, the number of antigenemia assay-positive cells, the clinical severity of infection, the incidence of acute rejection, the graft function, and the duration of hospital stay were evaluated. This group was compared to a historical matched control cohort (n = 37) transplanted earlier who did not receive prophylactic ganciclovir. RESULT: The incidence of CMV disease was significantly less among the prophylaxis than the control group (6/46 patients [13%] vs 16/37 patients [43.2%], P = <.004). The time to develop CMV manifestations was much longer in the prophylaxis group than in the control group (median 92 vs 32 days, P 相似文献   

The influence of innate immunity gene receptors polymorphisms in renal transplant infections

BACKGROUND: Genetically defined deficiencies in key components of the innate immune system have been associated with a greater risk of infection. The aim of this study was to assess the influence of genetic variability of innate immune receptors (mannose-binding lectin [MBL], mannose-associated serine-protease-2 [MASP-2], and Toll-like receptors [TLR4]) in the risk of infections after a kidney transplantation. METHODS: All patients undergoing a kidney or kidney-pancreas transplantation during a 3-year period were included. Functionally relevant mutations in MBL2, MASP2, and TLR4 genes were determined by DNA sequencing. The incidence of major bacterial infections, asymptomatic cytomegalovirus (CMV) infection, and CMV disease were compared among groups. RESULTS: There were no differences regarding major transplant characteristics among groups. Older age, requirements for posttransplant hemodialysis, and pretransplant diabetes, but not gene polymorphisms, were associated with a greater number of bacterial infections. In univariate analysis, low-MBL genotypes were associated with CMV disease in pretransplant CMV seropositive patients (P=0.015), whereas the TLR4 mutation was associated with higher risk of CMV primary infection (P=0.024). TLR4 mutation was an independent factor associated with CMV disease (odds ratio 5.84, 95% confidence interval 1.35-25.20, P=0.018). CONCLUSION: Polymorphisms of innate immunity receptors, especially TLR4 mutation, were associated with higher risk of CMV disease, while susceptibility to other infectious disorders was not observed.     

Primary CMV Infections Are Common in Kidney Transplant Recipients After 6 Months Valganciclovir Prophylaxis

Prolonging cytomegalovirus (CMV) prophylaxis in CMV seronegative recipients of a kidney from CMV seropositive donor (D+/R–) may reduce the incidence of late infections. We analyzed late‐onset primary CMV infections after 6 months valganciclovir prophylaxis. Data from all CMV D+/R– kidney transplant recipients between January 2004 and December 2008 at our center were analyzed. Patients with a functioning graft at 6 months after transplantation who received 6 months of valganciclovir prophylaxis 900 mg once daily were included (N = 127). CMV was diagnosed with quantitative PCR. Prophylaxis was completed in 119 patients. Prophylaxis was stopped at 3–5 months due to leukopenia or gastrointestinal side effects in eight patients. Late‐onset primary CMV infection developed in 47/127 (37%) patients median 244 days after transplantation (range 150–655) and median 67 days after the cessation of prophylaxis (range 1–475). Four infections were asymptomatic. In others, symptoms included fever (N = 28), gastrointestinal symptoms (nausea, vomiting, diarrhea) (N = 24), respiratory tract symptoms (N = 12), and hepatopathy (N = 6). Median peak viral load was 13500 copies/mL (range 400–2 831 000). Recurrent CMV infection developed in 9/47 (19%) patients. No significant risk factors for CMV infection were identified. Symptomatic primary CMV infections were commonly detected also after prolonged valganciclovir prophylaxis.     

Risk factors and impact of cytomegalovirus disease in simultaneous pancreas-kidney transplantation.

BACKGROUND: The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis. METHODS: This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R-) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R-) SPK transplant recipients was also evaluated. RESULTS: The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D-/R+: 0%; D-/R-: 2.8%; D+/R+: 25.6%; and D+/R-: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P=0.0052). In the high-risk (D+/R-) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival. CONCLUSIONS: Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed.     

Long-term outcome of cytomegalovirus infection in simultaneous pancreas–kidney transplant recipients without ganciclovir prophylaxis

As cytomegalovirus (CMV) infection frequently occurs in simultaneous pancreas kidney transplantation (SPKT), most centers use general ganciclovir prophylaxis. The aim of the study was to analyze the impact of CMV in a patient cohort with preemptive therapy only. Incidence, course and risk factors of CMV infection were retrospectively analyzed in 94 adult SPK recipients without prophylaxis. Patients with asymptomatic pp65-antigenemia were treated preemptively with intravenous ganciclovir for 14 days. Survival rates after 1, 3, and 5 years were 98%, 97%, and 94% for patients, 96%, 94%, and 88% for renal grafts and 88%, 85%, and 82% for pancreas grafts. CMV infections occurred in 51% of patients and CMV syndrome in 16%. No tissue-invasive disease was observed. Thirty-eight per cent of patients with CMV infection developed a recurrence. Risk factors for CMV in multivariate analysis were the D+/R- constellation, acute rejections, anti-rejection therapy and coronary heart disease. CMV had no impact on patient or graft survival, occurrence of acute or chronic rejection and bacterial infections. Preemptive therapy seems to be safe and effective in SPK recipients, but as the present study was retrospective, prospective randomized studies are needed to confirm our results.     

Cytomegalovirus infections following renal transplantation – effects of antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study

Post-transplant cytomegalovirus (CMV) infections are a source of significant morbidity. However, the extent of the problem and the benefits of various antiviral prophylactic therapies remain incompletely understood. The North American Pediatric Renal Transplant Cooperative Study registry was screened to identify patients hospitalized for CMV infections during the 1st post-renal transplant year between 1987 and 1993. Using a control group of transplant recipients, we performed a retrospective analysis of risk factors for CMV disease among these hospitalized patients and studied the effects of various viral prophylactic strategies on CMV risk, clinical manifestations, and outcome. We identified 142 patients hospitalized with CMV infections, the majority of which included major organ involvement. A CMV-positive kidney donor was the most significant risk factor for hospitalization [odds ratio (OR) = 5.2, P<0.0001] irrespective of recipient age or CMV immune status. As opposed to antiviral agents (acyclovir, ganciclovir) or pooled IgG, prophylaxis with enriched anti-CMV IgG significantly reduced the risk of CMV hospitalization (OR = 0.31, P = 0.03). The prophylactic use of antiviral agents was associated with a decreased risk of major organ involvement during the CMV infection (OR = 0.34, P<0.005). Among the patients with CMV, the 3-year graft survival was significantly better for those who received any form of prophylaxis compared with those who received none (88% vs. 52%, P<0.001). Our findings suggest a role for combined CMV-enriched IgG and antiviral agent prophylaxis for post-transplant CMV disease. Such an approach could diminish the incidence and severity of CMV infection and appears to have an independent favorable effect on graft outcome. Received November 14, 1996; received in revised form March 21, 1997; accepted April 11, 1997     

Cytomegalovirus prophylaxis using oral ganciclovir or valganciclovir in kidney and pancreas-kidney transplantation under antibody preconditioning

We investigated retrospectively the risk factors for cytomegalovirus (CMV) infection under ganciclovir or valganciclovir prophylaxis (oral ganciclovir 1 g tid, valganciclovir 450 mg/d) in our kidney and simultaneous pancreas-kidney (SPK) transplant patients undergoing transplantation between July 1, 2001 and February 28, 2003. Two hundred eleven patients receiving prophylactic oral ganciclovir or valganciclovir were included in the study. All patients were given antibody preconditioning (thymoglobulin 178, alemtuzumab 33). Duration of prophylactic treatment was between 3 and 8 months. Fifteen (7.1%) patients developed a positive CMV antigenemia in the first 6 months after transplantation, and 18 of 176 (10.2%) patients developed a positive CMV antigenemia during the first year. No patient developed tissue invasive CMV disease. At 6 months after transplantation, valganciclovir was slightly more effective than ganciclovir prophylaxis (P=.052). Positive donor CMV serology significantly increased the risk of CMV infection compared to CMV-negative donors (P=.014 and P=.003 at 6 and 12 months, respectively). Duration of CMV prophylaxis for more than 3 months decreased the risk of CMV infection (P=.04 and P=.009 at 6 and 12 months, respectively). Either valganciclovir prophylaxis (450 mg/d) or high-dose oral ganciclovir (1 g tid) is effective in preventing tissue-invasive CMV disease, and results in a low incidence of CMV antigenemia in patients undergoing kidney and SPK transplantation.     

Impact of Cytomegalovirus Disease in D+/R– Kidney Transplant Patients Receiving 6 Months Low‐Dose Valganciclovir Prophylaxis

Late‐onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R–) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6‐month low‐dose valganciclovir (VGCV) prophylaxis, risk factors for late‐onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R– kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow‐up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late‐onset CMV disease (AHR 2.91, 95% CI 1.18–7.20, p = 0.021 and AHR 1.03, 95% CI 1.01–1.06, p = 0.016, respectively). Late‐onset CMV disease was associated with increased risk for death‐uncensored graft loss (AHR 2.95, 95% CI 1.15–7.61, p = 0.025). In conclusion, late‐onset CMV disease continues to negatively impact kidney transplant outcome despite 6‐month low‐dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.     

肾移植受者术后BK病毒激活危险因素的荟萃分析

目的对国内外报道的肾移植术后BK病毒(BKV)激活的危险因素进行荟萃分析，为临床BKV肾病的防治提供参考。 方法通过系统检索PubMed数据库、中国知网、万方数据库以及中国生物医学数据库从建库至2019年7月公开发表的关于肾移植术后BKV激活危险因素的相关研究论文，并通过其参考文献进行手工补充搜索。采用纽卡斯尔－渥太华量表对纳入文献进行质量评价，运用RevMan 5.3软件进行荟萃分析。 结果最终纳入22篇文献，其中英文15篇、中文7篇。结果显示血液中检测到BKV的危险因素为排斥反应(OR＝1.91，95%CI：1.30～2.80)、移植肾功能延迟恢复(OR＝1.51，95%CI：0.99～2.31)、服用他克莫司(OR＝1.50，95%CI：1.22～1.84)、使用抗胸腺细胞球蛋白(ATG)诱导(OR＝1.75，95%CI：1.02～2.98)、使用输尿管支架(OR＝1.98，95%CI：1.19～3.30)和合并CMV感染(OR＝2.23，95%CI：1.61～3.09)；而尿液中检测到BKV的危险因素为持续服用糖皮质激素(OR＝1.49，95%CI：1.09～2.04)。 结论肾移植术后服用他克莫司、合并CMV感染、使用输尿管支架和ATG诱导的受者发生BKV血症的风险更高，长期服用糖皮质激素的肾移植受者发生BKV尿症的风险更高。     

Viral load,CMV‐specific T‐cell immune response and cytomegalovirus disease in solid organ transplant recipients at higher risk for cytomegalovirus infection during preemptive therapy

Despite advances in prevention, cytomegalovirus (CMV) recurrence is an important challenge in high‐risk organ recipients. The present study prospectively evaluates the impact of CMV‐specific T‐cell immune response and secondary prophylaxis on the risk of recurrence in a cohort of CMV high‐risk organ recipients and whether it is possible to determine a safe standardized viral load value below which CMV disease is unlikely. Thirty‐nine recipients were included. Thirty‐six had primary infections, and 88.9% recurred. Rate and duration of recurrent CMV infection was similar in patients with and without secondary prophylaxis: 57.9% vs. 53.6%, P = 0.770 and 16 vs. 15 days, P = 0.786, respectively. The only factor independently associated with no episodes of CMV recurrence was the acquisition of CMV‐specific T‐cell immune response (OR: 0.151, 95% CI: 0.028–0.815; P = 0.028). Cytomegalovirus diseases (N = 5) occurred in patients with CMV viral load above 1500 IU/ml who did not follow the planned monitorization schedule. Our observations suggest that episodes of recurrent CMV infection are common after preemptive therapy despite secondary prophylaxis and that CMV‐specific T‐cell immune response is associated with a decreased risk of recurrent infections. Preemptive therapy may be safe in patients at high risk for CMV infection with strict close monitoring of the CMV viral load.     

Cytomegalovirus infection in simultaneous pancreas-kidney transplantation

INTRODUCTION: In this open-label multicenter study, 205 simultaneous pancreas-kidney (SPK) transplant recipients between 1998 and 2000 were randomly assigned to tacrolimus or cyclosporine-microemulsion (ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil and short-term corticosteroids. We report the 3-year data related to the occurrence, severity and effect of cytomegalovirus (CMV) infections. The type of CMV prophylaxis and treatment was at the discretion of the investigator. RESULTS: The overall incidence of CMV infection was 34% with no difference in incidence between the tacrolimus and cyclosporine-ME treatment arms. Statistically significant fewer CMV infections occurred among patients who received ganciclovir (22%) than those who did not receive prophylaxis (42%; P = .0075) or were treated with acyclovir (43%; P = .0066). The CMV infection rate according to donor recipient CMV serological status was: D-/R- group 11%, which was lower than the D-/R+ group at 40% (P = .0035), the D+/R+ group at 37% (P = .0024), or the D+/R- group at 52% (P = .00001). Among the last three groups, the infection rate was lower in patients on ganciclovir than those with no prophylaxis or on acyclovir (22% vs 64%; P = .00001). The incidence of acute rejection episodes was higher among patients without ganciclovir prophylaxis. No difference was observed in actuarial patient, kidney, or pancreas survival rates between patients with versus without infection. CONCLUSIONS: Ganciclovir prophylaxis effectively prevented CMV infection in SPK transplant recipients, especially in higher risk groups. An effect of CMV prophylaxis on the incidence of rejection is possible.     

Valacyclovir prevention of cytomegalovirus reactivation after heart transplantation: a randomized trial.

BACKGROUND: Cytomegalovirus (CMV) is a major cause of serious morbidity following solid organ transplantation via both direct and indirect mechanisms. The aim of this study was to investigate the efficacy and safety of valacyclovir prophylaxis in heart transplant recipients. METHODS:Twenty-seven CMV seropositive adults due to receive a heart transplant were included in a single-center, randomized, double-blind study. Patients were randomized to receive either oral valacyclovir 2000 mg or oral acyclovir 200 mg four times daily starting within 3 days of heart transplant and continuing for 90 days. The primary outcome measure was time to development of CMV antigenemia assessed for 6 months after surgery. Other measures were time to asymptomatic CMV infection, symptomatic CMV infections, and end-organ CMV disease. Patients were monitored for other herpes infections, other opportunistic infections, and acute graft rejection. Safety was assessed by evaluating changes in hematology and clinical chemistry parameters and by the occurrence of adverse events. RESULTS: The median time to CMV antigenemia was 19 days for the acyclovir group compared with 119 days for the valacyclovir group (hazard ratio 0.42; 95% CI, 0.18-0.99; p = 0.049). Similar delays of approximately 100 days were found for CMV infection, symptomatic CMV infection, and CMV disease. There was also a trend for delayed acute rejection, and fewer opportunistic or other herpesvirus infections occurred in the valacyclovir group. Valacyclovir was well tolerated in the study population. CONCLUSION: Oral valacyclovir is a safe and effective mode of prophylaxis of CMV after heart transplantation.