Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Abstract Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i.v. ganciclovir therapy in high-risk patients (i.e., CMV donor +/ recipient -). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver -kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporin A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R -) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV - related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i.v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Comparative study of prophylactic oral ganciclovir and valacyclovir in high-risk kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment. METHODS: In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time. RESULTS: No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative). CONCLUSION: The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.     

Evaluation of a Cytomegalovirus Prophylaxis Protocol in Cytomegalovirus-IgG Positive Renal Transplant Recipients (R+)

BackgroundThe aim of the study was to evaluate the efficacy of a unique cytomegalovirus- (CMV) prophylaxis protocol in terms of CMV infection and disease progression in CMV IgG positive kidney transplant recipients.MethodsAchievement of negative CMV load, using concurrent prophylactic intravenous ganciclovir therapy during induction immunosuppression, combined with a 6-month prophylactic course of acyclovir, would yield a reduced incidence of early CMV infection and disease. CMV DNA was tested for at discharge, at the third, and sixth post-op months, and at the occurrence of any event that could be associated with CMV infection. CMV DNA positive patients received ganciclovir treatment until the viral load became negative. CMV replication was monitored using a quantitative PCR method capable of detecting as few as 42.5 copies/mL. All patients were given a maintenance dose of acyclovir.ResultThe file data of 267 patients who had undergone kidney transplantation between 2007 to 2016 were examined. Thirty-four patients were excluded from the study for various reasons, unrelated to the protocol. Of the remaining 233 patients, 42 (18%) had CMV DNA infection. Three patients had CMV disease (1.3%), 1of whom died of pneumonia. Diabetes mellitus (DM) was a risk factor for CMV DNA positivity (P < .004).ConclusionThe incidence of CMV infection and disease is low in renal transplant recipients whose CMV viral load is eliminated after concurrent ganciclovir administration with induction immunosuppression.     

Delay of CMV infection in high-risk CMV mismatch lung transplant recipients due to prophylaxis with oral ganciclovir

Cytomegalovirus (CMV) is a common opportunistic infection in lung transplant recipients. Despite the use of early post-operative intravenous ganciclovir, most high-risk patients develop CMV infection. We conducted this retrospective study to determine the efficacy of extended CMV prophylaxis with oral ganciclovir in high-risk, donor-positive-recipient-negative, lung recipients. All patients initially received 3 months of intravenous ganciclovir and CMV hyperimmune globulin. Clinical outcomes in all CMV mismatch patients undergoing lung transplant surviving at least 3 months were included (n = 42). Since 1998, 14 patients received no oral ganciclovir prophylaxis (group 1) and 28 patients received indefinite oral ganciclovir after completion of intravenous therapy (group 2). In those patients receiving oral ganciclovir, the prevalence of post-transplant CMV infection was significantly reduced over the first 180 d post-transplant (50% in group 1 vs. 4% in group 2; p < 0.001). Although some CMV events were observed with additional follow-up in group 2, there remained a significantly greater freedom from CMV infection by Kaplan-Meier analysis in group 2 as compared with group 1, with over 30 months follow-up time in each group (log-rank, p = 0.02). A moderate rate of drug discontinuation was observed in group 2, and no severe drug-related events occurred. In high-risk lung transplant recipients, CMV prophylaxis with intravenous ganciclovir, followed by indefinite oral ganciclovir, significantly delays and reduces post-transplant CMV infections. A larger prospective randomized study is needed to confirm the benefits of oral ganciclovir on CMV prevention.     

Following Universal Prophylaxis with Intravenous Ganciclovir and Cytomegalovirus Immune Globulin, Valganciclovir is Safe and Effective for Prevention of CMV Infection Following Lung Transplantation

We prospectively determined the safety and efficacy of valganciclovir for prevention of cytomegalovirus (CMV) in at-risk (donor positive/recipient negative [D+/R-] or R+) lung transplant recipients. We also determined the length of prophylaxis required to significantly decrease both CMV infection and disease. Consecutive lung transplant recipients surviving >30 days (n = 90) received combination prophylaxis with intravenous (i.v.) ganciclovir (GCV) 5 mg/kg/day and cytomegalovirus immune globulin (CMV-IVIG) followed by valganciclovir (450 mg twice-daily) to complete 180, 270 or 365 days of prophylaxis. This group was compared to a historical group (n = 140) who received high-dose oral acyclovir following i.v. GCV and CMV-IVIG. CMV disease was significantly lower in patients receiving valganciclovir compared to acyclovir (2.2% vs. 20%; p < 0.0001). Freedom from CMV infection and disease was significantly greater (p < 0.02) in patients receiving 180, 270 or 365 days of prophylaxis (90%, 95% and 90%, respectively) compared to those receiving 100-179 days (64%) or < 100 days (59%). No patient receiving valganciclovir died during the study. Following prophylaxis with i.v. GCV and CMV-IVIG, valganciclovir is safe and effective for prevention of CMV infection and disease in at-risk lung transplant recipients. The required length of prophylaxis was at least 180 days.     

Clinical manifestation, laboratory findings, and the response of treatment in kidney transplant recipients with CMV infection

OBJECTIVES: To report clinical manifestations, laboratory findings, and treatment outcomes of in kidney transplant recipients who had cytomegalovirus (CMV) infections. METHODS: This retrospective study evaluated the records of kidney transplant recipients followed regularly from 2001 to 2006. In some patients information was also gathered through a telephone call or physical examination. The CMV infection diagnosis was also made by detecting PP.65 antigen per 50,000 peripheral blood leukocytes. RESULTS: Of the 200 kidney transplant recipients, 66 were infected with CMV including 42 men and 24 women. The mean patient age was 40 +/- 13 years (range, 14 to 67 years). Seventy-nine percent of the infected patients were diagnosed during the first 6-months after transplantation. All except 22 patients (33%) had constitutional complaints. Fever was present in 65% of patients, abdominal pain in 21%, diarrhea in 20%, and vomiting in 15%. Likewise, pulmonary complaints including cough and dyspnea were reported by 32% and 23%, respectively. However, 20% of patients were completely asymptomatic. Hematologic laboratory data showed anemia (64%), thrombocytopenia (47%), and leukopenia (21%). Seventy eight percent of patients had a serum creatinine 相似文献   

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.     

Cytomegalovirus infection after renal transplantation: selective prophylaxis and treatment

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n=108) or tacrolimus (n=155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case. Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment. Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance.     

Hyperimmunoglobulin prophylaxis,monitoring and preemptive ganciclovir treatment eliminate the risk of CMV infection to improve patient and renal allograft survival

Abstract This study was designed to investigate whether the introduction of ganciclovir to clinical use for anti‐CMV treatment changes the risk of CMV infection in renal transplant patients. A total of 1545 cases who had received cadaveric renal transplants were divided into two groups: group 1 (n = 721) was made up of patients who received their transplants within 6 years before the introduction (1991) of ganciclovir and group 2 (n = 824), of individuals transplanted thereafter. Patient and graft survival of CMV D+/R‐ patients was uni‐ and multivariately compared with non‐CMV D+/R‐ patients. In CMV D+/R‐ patients in group 1, survival was significantly lower, and their relative risk for graft loss was 1.32‐fold (P = 0.0483) that of non‐CMV D+/R‐ patients. In group 2 patient and graft survival was identical regardless of whether the patients were at risk for CMV infection or not. The risk of CMV infection can be eliminated by hyperimmunoglobulin prophylaxis, CMV monitoring and preemptive ganciclovir treatment in renal transplant patients.     

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.     

Signs and symptoms of cytomegalovirus disease in kidney transplant recipients

Purpose

To investigate the range of clinical presentations of cytomegalovirus (CMV) disease in kidney transplant recipients.

Materials and methods

We retrospectively reviewed the records of hundred kidney recipients who developed CMV disease between 1984 and December 2002 for demographic characteristics, laboratory findings, and presenting signs and symptoms.

Results

The most common presentations were elevated serum creatinine in 74 patients, fever in 71, thrombocytopenia in 43, nausea in 32, vomiting in 25, elevated alkaline phosphatase in 24, leukocytosis in 22, and leukopenia in 21. Tissue involvement was relatively rare, but six patients had pneumonia, two had conjunctivitis, and one had vascular dermatitis. Four percent of the patients had received intravenous ganciclovir prophylaxis, and 7% had received oral ganciclovir prophylaxis. Fever was associated with number of hospitalizations (P = .006), elevated creatinine (P = .006), nausea (P = .017), vomiting (P = .031), and previous posttransplantation infections (P < .001). All the patients with conjunctivitis, pneumonia, pulmonary symptoms, and abnormal heart sounds and most of those with arthralgia, nausea, and vomiting were febrile during their CMV disease course.

Conclusion

Our findings showed that leukocytosis should be considered as much as leukopenia when CMV disease is suspected. CMV-induced pneumonia is not common in renal transplant recipients compared to other organ transplant recipients. CMV invasion to other tissues is also rare. Finally, fever is a common symptom and important in assessing the severity and prognosis of the disease.     

Development of intrapancreatic abscess — a consequence of CMV pancreatitis?

Cytomegalovirus (CMV) pancreatitis was diagnosed in eight out of 124 pancreatic transplant recipients. Five of the eight patients developed intrapancreatic abscesses and four of the grafts were lost, but one is still functioning. In the three additional cases of pancreatitis, antiviral treatment with foscarnet or ganciclovir was given as soon as signs of CMV pancreatitis were detected. No such grafts were lost during the acute phase. CMV infection was diagnosed in cells from pancreatic juice, by virus isolation, detection of CMV antigen in cells from pancreatic juice or by CMV serology. The signs and symptoms of CMV pancreatitis included fever, general malaise, abdominal pain, diarrhoea, localized peritonitis, hyperamylasaemia, leukopenia and hyperglycaemia. It is recommended that rapid diagnostic procedures for CMV should be carried out when early signs of pancreatitis develop in pancreatic graft recipients. Antiviral treatment should be given when CMV pancreatitis is suspected or diagnosed in order to prevent the development of intrapancreatic abscesses and graft loss.     

Long-term outcomes of cytomegalovirus infection and disease after lung or heart–lung transplantation with a delayed ganciclovir regimen

Abstract: Background: Information is limited on long‐term outcomes after preemptive use of ganciclovir to control cytomegalovirus (CMV) infection in lung transplantation. Methods: We studied 78 lung recipients who received antithymocyte globulin induction from 1994 to 2000. All patients received six months of oral acyclovir (800 mg TID). This was interrupted three wk post transplantation for a two‐wk course of IV ganciclovir. Additional courses of ganciclovir were administered based on serial virological monitoring. CMV‐mismatched patients (R?D+) also received four doses of CMV immunoglobulin between weeks 2 and 8. Results: The one yr cumulative risk of CMV disease was 2% (1/61) in CMV seropositive (R+) patients, but was 37% (6/17) in R?D+ patients (p < 0.0001). Over 4.3 yr of follow‐up, patients with CMV infection developed more chronic graft dysfunction caused by bronchiolitis obliterans or bronchiolitis obliterans syndrome than patients without CMV infection (p = 0.012). This effect was also apparent in the subgroup of R+ recipients (p = 0.043). Acute rejection and overall survival were not associated with CMV infection. Conclusions: The use of prophylactic acyclovir and short preemptive courses of ganciclovir effectively controlled CMV disease in R+ patients, but was a relative failure in R?D+ patients. CMV infection was significantly associated with chronic graft dysfunction, even in R+ recipients who had good control of CMV symptoms.     

Development of intrapancreatic abscess - a consequence of CMV pancreatitis?

Abstract. Cytomegalovirus (CMV) pancreatitis was diagnosed in eight out of 124 pancreatic transplant recipients. Five of the eight patients developed intrapancreatic abscesses and four of the grafts were lost, but one is still functioning. In the three additional cases of pancreatitis, antiviral treatment with foscarnet or ganciclovir was given as soon as signs of CMV pancreatitis were detected. No such grafts were lost during the acute phase. CMV infection was diagnosed in cells from pancreatic juice, by virus isolation, detection of CMV antigen in cells from pancreatic juice or by CMV serology. The signs and symptoms of CMV pancreatitis included fever, general malaise, abdominal pain, diarrhoea, localized peritonitis, hyperamylasaemia, leukopenia and hyperglycaemia. It is recommended that rapid diagnostic procedures for CMV should be carried out when early signs of pancreatitis develop in pancreatic graft recipients. Antiviral treatment should be given when CMV pancreatitis is suspected or diagnosed in order to prevent the development of intrapancreatic abscesses and graft loss.     

Ganciclovir prophylaxis delays but does not prevent cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) infection is associated with reduced graft and patient survival among renal transplant recipients. The purpose of this study was to examine the effect of routine prophylaxis with 12 weeks of oral ganciclovir on the incidence of CMV infection in a center that predominantly uses antibody induction together with tacrolimus/mycophenolate mofetil-based maintenance immunosuppressive therapy. The control group consisted of a historical patient cohort transplanted immediately prior to the use of oral ganciclovir prophylaxis. The use of tacrolimus (88% vs 77%, P=.02) and cytolytic therapy (81% vs 46%, P <.0001) was likewise greater among patients who received ganciclovir prophylaxis. CMV infection occurred in 20 (9%) patients in the ganciclovir era and 4 (3%) patients in the preganciclovir era (P=.003). The mean time to CMV infection was longer in patients who received ganciclovir prophylaxis than in patients in the preganciclovir era (23.4 +/- 10.9 weeks vs 9.8 +/- 5.6 weeks, P=.03). We conclude that 12 weeks of ganciclovir prophylaxis delays but does not prevent CMV infection from occurring in renal transplant recipients. These results suggest that with the use of 12 weeks of ganciclovir prophylaxis, vigilance for CMV infection is needed well beyond 24 weeks posttransplant.     

Polyoma virus-associated nephropathy and concurrent cytomegalovirus infection in the kidney transplant recipients

INTRODUCTION: Cytomegalovirus (CMV) and polyoma virus BK (BKV) may both establish latency following primary infection. Frequent reactivation of these viruses can occur in the kidney transplant recipients. BKV may induce CMV gene expression by stimulating cellular regulator proteins or by its own gene regulator proteins. A high rate of concurrent CMV infections has been noted in kidney transplant recipients with polyoma virus-associated nephropathy (PVAN). METHODS: PVAN was identified in 10 of 191 patients who received kidney transplants between October 1998 and September 2003. PVAN was confirmed by allograft kidney biopsy. Four of the 10 patients were complicated by concurrent CMV infection. RESULTS: Two patients had only serological evidence of CMV infection and one patient had CMV gastritis. These three patients were treated with intravenous ganciclovir with good results. Disseminated ganciclovir-resistant CMV disease was demonstrated in the remaining patient. This 34-year-old kidney transplant recipient with PVAN died of multiorgan failure despite antiviral therapy with both ganciclovir and foscarnet. CONCLUSION: PVAN with concurrent CMV infection in kidney transplant recipients showed variable clinical courses including mortality. Further studies are needed to elucidate the influence of PVAN on the pathogenesis of CMV 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.     

Effect of cytomegalovirus prophylaxis with acyclovir on renal transplant survival

It is recognized that cytomegalovirus (CMV) infection in transplant recipients may lead to graft loss. Prophylaxis with acyclovir has therefore gained widespread acceptance, but the debate on whether this intervention improves long term graft survival continues. All patients who received renal grafts at the National Renal Transplant Centre, Dublin, between January 1992 and December 1999 were retrospectively analyzed. During this time period, patients who were CMV positive and/or had received grafts from CMV-positive donors were administered prophylactic oral acyclovir 800 mg thrice daily, adjusted for calculated creatinine clearance, from the first day post-transplantation. This treatment was continued for three months unless the graft failed or the patient developed CMV disease or died. Graft and patient outcomes were compared in recipients who received acyclovir with those who did not. Over the study period, 935 patients received renal transplants in our center, of whom 487 were administered acyclovir. The incidence of CMV disease was 3.3 cases per 100 patients per annum in those who required prophylaxis. Despite prophylaxis, graft outcomes were found to be significantly worse (p value < 0.001) in the group that qualified for acyclovir. We conclude that acyclovir provides incomplete protection from the negative impact of CMV on graft survival.     

巨细胞病毒抗原检测对巨细胞病毒病预防的意义

目的：提高对肾移植术后巨细胞病毒（CMV）病的防治水平,方法：应用免疫组织化学方法（LSAB法）对1997年度肾移植患者进行CMV抗原检测,对检查阳性的患者采用丙氧鸟苷预防性治疗,并与1996年度未预防治疗组进行对照.结果：1997年预防性治疗后,CMV病发病率为3．1％（5／160）,病死率为20．0（1／5）,而1996年未预防治疗组,CMV病发病率为11．7％（16／136）,病死率为43．8％（7／16）,结论：对肾移植术后CMV抗原检测阳性患者预防性应用丙氧鸟式能显著降低CMV病的发生率和病死率。     

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients

Aim

A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease.

Patients and methods

With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 μg/5 μL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored.

Results

Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US $721 while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US $64.

Conclusion

Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.