Deoxythymidine kinase, a possible marker for monitoring activity of cytomegalovirus infection after renal transplantation

Measurement of deoxythymidine kinase activity (S-TK) in serum is used as a marker for cytomegalovirus (CMV) infection following transplant surgery. A case is presented where a kidney transplant patient suffered a fatal CMV infection. The new antiviral drug Foscarnet was used to treat the infection. Retrospective analysis of S-TK showed a good correlation with the course of the disease, its treatment, recurrence and final outcome.     

Identification of patients at risk of symptomatic cytomegalovirus infection after open-heart surgery

In a prospective study, 58 consecutive patients submitted to open-heart surgery were followed from the preoperative period up to 3 months postoperatively with regard to clinical status, cytomegalovirus (CMV) antibodies and signs of enzymatic liver damage. Forty-eight patients (83%) were seropositive prior to operation. Of the ten (17%) preoperatively seronegative patients, five became CMV-seropositive during follow-up. Of the 48 initially seropositive patients, nine showed heightened CMV-antibody titers after the operation. Significant symptomatic CMV illness with protracted fever developed in four patients, all from the group of five with seroconversion. All five of these patients had enzymatic liver damage. The incidence of symptomatic CMV infection after open-heart surgery in CMV-negative patients probably is higher than previously assumed, while CMV-positive patients seem to have complete protection against CMV morbidity.     

Monitoring antigenemia is useful in guiding treatment of severe cytomegalovirus disease after organ transplantation

We investigated the value of monitoring CMV antigenemia during and after antiviral therapy for CMV disease. During the study period, 10 out of 214 renal transplant recipients were treated for CMV disease, receiving a total of 14 courses of treatment. Antigenemia decreased within 7 days after onset of treatment in eight of nine courses associated with a rapid clinical recovery. In three courses with a slow or absent response, antigenemia levels initially increased. Monitoring antigenemia was helpful in differentiating persisting CMV disease from other opportunistic infections and rejection. Relapses of CMV disease were preceded by rises in antigenemia. Viral isolation became negative within 3 days after initiation of ganciclovir, irrespective of the clinical response. Antigenemia is a marker of the effect of ganciclovir on CMV replication in vivo, and its monitoring may be valuable in the management of patients with severe CMV disease.     

Ganciclovir therapy of symptomatic cytomegalovirus infection in renal transplant recipients

We used ganciclovir to treat 11 renal transplant recipients with symptomatic cytomegalovirus infection (seven primary), including one severe, five mild and five moderate cases. Two patients exhibited a non-mechanically ventilated pneumonitis and two others a gastrointestinal involvement. Ganciclovir was used intravenously according to a schedule which took into account renal function, for a median time of 14 days. All patients survived. Cytomegalovirus infection was cured in all patients but two: in the first an early clinical relapse required a second successful ganciclovir course; in the other graftectomy was needed to control infection. Graft was lost in an additional cured patient. Ganciclovir was well tolerated, especially with regard to haematological status. At the current follow-up of at least one month after the end of ganciclovir therapy, no further clinical relapse was observed; however, in one clinically cured patient cytomegalovirus was isolated from blood one week after ganciclovir cessation. These encouraging preliminary data suggest that ganciclovir therapy should be started as soon as cytomegalovirus infection is suspected, especially in cytomegalovirus seronegative recipients receiving a seropositive graft.     

Comparison of quantitative PCR and antigenemia in cytomegalovirus infection in renal transplant recipients

Cytomegalovirus infection is a common complication of renal transplantation. Antigen pp65 levels serve as indicators of viral load, although the technique is difficult to perform and interpret. We sought to determine whether quantitative PCR had a higher sensitivity and predictive value in CMV infection. METHODS: The study included 100 renal transplant recipients who were screened for IgM and IgG at the time of admission. On days 7, 15, 30, 45, 60, 75, 90, 120, 180, and 360, antigenemia tests were performed on blood (pp65) and urine, and a quantitative PCR on blood. Among 59 patients recruited between November 2003 and August 2004 the mean age was 54.5 +/- 12.9 years. Two patients did not reach 90 days follow-up (3%); four patients have not surpassed 90 days (7%); 22, 120 days (37%); and 31, 180 days (53%). Ninety-three percent of patients showed anti-IgG CMV-positive titers with all being IgM CMV-negative at baseline. The patients at risk for infection were given valgancyclovir as prophylaxis throughout the study. RESULTS: At 474 visits, 8 samples (2.4%) were positive with urine; 5 (1.4%) with pp65, and 15 (4.7%) with PCR. Among the 15 positive samples, two (>100,000 and 3250 copies) revealed agreement of positive IgM and shellvial test on urine; two (15,100 and 5670 copies), antigen pp65 1+; one (17,400 copies) with pp65 2+ and shellvial urine; two (99,400 and 28,300 copies) with pp65 1+ and shellvial urine; and eight remaining determinations, 749, 2250, 686, 928, 2250, 26600, 777, and 2790 copies. The rest of the tests were negative. CONCLUSION: The preliminary results of this study demonstrated that quantitative PCR was a useful rapid tool for diagnosing and monitoring CMV infections.     

Cytomegalovirus infection: a quantitative prospective study of three hundred twenty consecutive renal transplants

The quantitative effects of cytomegalovirus (CMV) infection on morbidity and mortality rates were examined in 320 renal transplant cases. With the use of virus cultures and CMV antibody measurements, all patients were studied, regardless of symptoms, from a time before transplantation to at least 1 year, 11 months after transplantation for a maximum of 5 years, 9 months. The posttransplant risk factors of CMV infection--patient age, type of donor (living-related or cadaver), antigen match between donor and recipient, presence of diabetes, and the presence of pretransplant CMV antibody--were evaluated for their relative effects on patient survival, graft survival, fever, and leukopenia. CMV infection was a significant risk factor for these four events. CMV infection occurred in 181 patients after transplantation and accounted for 25% of the deaths, 20% of the graft failures, 30% of the occurrences of fever, and 35% of the occurrences of leukopenia. Unexpectedly, female recipients were at higher risk than men for the adverse effects of CMV infection. Young patients and those receiving their second transplant were at higher risk of graft loss if they had associated CMV infection. CMV infection was most reliably predicted by the presence of pretransplant antibody, indicating that reactivation of endogenous virus was responsible for most infections. The presence of pretransplant antibody offered a small amount of protection against fever, but no protection against death, graft failure, or leukopenia. Simultaneous episodes of CMV infection and transplant rejection, both common posttransplant events, most often occurred by chance.     

Congenital cytomegalovirus infection after recurrent infection in a mother with a renal transplant

A woman with a renal transplant developed a systemic cytomegalovirus infection. She recovered and 3 years later she became pregnant. She had 3 days of fever in the first trimester. She delivered an infant severely affected with congenital cytomegalovirus infection. The incidence of symptomatic congenital cytomegalovirus infection in infants born to immunosuppressed mothers who develop reactivated cytomegalovirus during their pregnancy seems high. Received April 22, 1996; received in revised form September 3, 1996; accepted October 22, 1996     

Idiopathic thrombocytopenia after cytomegalovirus infection in a renal transplant recipient

Infection with cytomegalovirus (CMV) is a frequent complication of organ transplantation and presents a spectrum of disease ranging from asymptomatic viremia to life-threatening tissue-invasive disease. CMV is also lymphotrophic, with the potential to induce autoimmune disease, although immunosuppressive therapy may prevent or attenuate the clinical course in transplant patients. We report a case of idiopathic thrombocytopenic purpura occurring in a renal transplant recipient after primary CMV infection and discuss the possible mechanisms involved.     

Cytomegalovirus infection in peptic ulcer in renal transplant recipient: a case report

Gastroduodenal ulcers in renal transplant recipients are usually originated from excessive acid secretion or infection of Helicobacter pyroli. Herein, we report a case of cytomegalovirus (CMV)--induced gastric ulcer following cadaveric renal transplantation. The patient was a 48-year-old man with chronic renal failure and received cadaveric renal transplantation. A month later, he had epigastralgia without CMV-positive antigenemia and received gastrointestinal fiberscopy. Endoscopically, gastric ulcer was identified. Histological findings revealed conspicious nuclear enlargement of the non-epithelial cells in the ulcer bed, which indicated CMV infection. The patient was treated with ganciclovir for 2 weeks and the symptom was relieved. He discharged with a good renal function on day 75 posttransplant. CMV infection plays an important role in gastric ulcer after renal transplantation. Antigenemia assay dose not seem feasible for the detection of CMV-induced gastric ulcer.     

Comparison between antigenemia and a quantitative-competitive polymerase chain reaction for the diagnosis of cytomegalovirus infection after heart transplantation

BACKGROUND: Antigenemia and quantitative polymerase chain reaction (PCR) are widely used for cytomegalovirus (CMV) diagnosis after heart transplantation due to their enhanced predictive values for disease detection when specific cut-off values are used. The purpose of this study was to compare, in the same patient setting, the predictive values of quantitative PCR and antigenemia for CMV disease detection, using specific cut-off values. METHODS: Thirty heart transplant receptors were ch prospectively monitored for active CMV infection and disease detection, using quantitative PCR and anti- po genemia. Positive and negative predictive values for pr CMV disease detection were calculated using cut-off pr values for both antigenemia (5 and 10 positive cells/300,000 neutrophils) and quantitative-PCR (50,000 and 100,000 copies/10(6) leukocytes). RESULTS: Active CMV infection was diagnosed in 93.3% of patients and CMV disease in 23.3%. The positive and negative predictive (%) values for CMV disease detection were 35/100 and 46.7/100, respectively, for quantitative PCR and antigenemia. Using 5 and 10 positive cells/300,000 neutrophils as cut-off values for antigenemia, the positive and negative predictive values (%) for disease detection were respectively 63.6/100 and 70/100. For quantitative PCR, the positive and th negative predictive values (%) for cut-off values of to 50,000 and 100,000 copies/10(6) leukocytes were 53.8/100 and 60/94.1, respectively. CONCLUSION: In our series, antigenemia and quantitative-PCR had enhanced and similar predictive values for CMV disease detection when specific cut-off values were used. The choice between these two methods for disease detection may rely less on their efficiency and more on the experience and familiarity with them.     

巨细胞病毒DNA动态监测在预防肾移植术后巨细胞病毒性肺炎中的应用价值

目的 探讨荧光定量PCR动态监测在预防肾移植术后人巨细胞病毒(HCMV)肺炎中的临床应用价值.方法 同种异体肾移植患者242例.男144例,女98例,平均年龄42(17～71)岁.随机分为2组:实验组127例,对照组115例.实验组患者移植术后采用荧光定量PCR方法动态检测患者血、尿标本HCMV-DNA,其中任何一项HCMV-DNA拷贝数>1×103拷贝/ml者,连续静脉滴注更昔洛韦4周,按照肌酐清除率计算剂量(肾功能正常者剂量为5 mg/kg 2次/d;肾功能减退者,肌酐清除率50～69 ml/min时2.5 mg/kg,2次/d;肌酐清除率25～49 ml/min时2.5 mg/kg,2次/d;肌酐清除率10～24 ml/min时1.25 mg/kg,1次/d;肌酐清除率<10 ml/min时每周3次每次1.25 mg/kg,于血液透析后给予).对照组不进行定期检测及更昔洛韦预防用药,比较2组患者HC-MV肺炎发病、治疗情况及移植肾1年存活率. 结果实验组术后HCMV肺炎发生率6.3%(8/127);肺炎发生中位时间84(46～167)d;住院治疗中位时间36(30～57)d;病死率12.5%(1/8);呼吸机使用率12.5%(1/8),合并其他病原体感染率25.0%(2/8);移植肾1年存活率98.4%(125/127),其中1例为移植肾带功能死亡,1例为移植肾急性排斥失功.对照组术后HCMV肺炎发生率14.8%(17/115);肺炎发生中位时间51(34～138)d;住院中位时间40(21～67)d;病死率23.5%(4/17);呼吸机使用率29.4%(5/17),合并其他病原体感染率41.2%(7/17);移植肾1年存活率93.0%(107/115),死亡4例中3例为移植肾带功能,1例移植肾功能未恢复;4例为移植肾急性排斥失功.2组间比较住院治疗时间差异无统计学意义(P>0.05),其余各项(HCMV肺炎发生率、发生时间、病死率、呼吸机使用率、合并其他病原体感染率、移植肾1年存活率)差异均有统计学意义(P<0.05).结论 荧光定量PCR动态监测肾移植术后患者血、尿标本HCMV-DNA载量,预防术后HCMV肺炎效果好,移植肾1年存活率提高.     

Cytomegalovirus viremia after kidney transplantation in Thailand: predictors of symptomatic infection and outcome

Background

While prevention of cytomegalovirus (CMV) infection after kidney transplantation (KT) has become a standard practice in Western countries, this approach is not always feasible in Thailand. In order to argue for the need for CMV prevention, the knowledge on the incidence and impact of the CMV infection following KT is highly desirable.

Methods

We retrospectively reviewed medical records of adult patients who underwent KT at our transplant center between January 2006 and December 2010. Patients who developed CMV viremia within 1 year after transplantation were studied for the incidence, risk factors, and outcome of symptomatic infection. The threshold value of blood CMV DNA load indicating symptomatic infection was also analyzed.

Results

Symptomatic CMV infection occurred in 18 (4.6%) patients within a median time of 12.1 (range, 3-30) weeks after KT. At initial presentation, coexisting opportunistic infection was common (44%) and gastrointestinal tract was the major type of organ involvement (44%). Between groups of patients with symptomatic and asymptomatic CMV infection, the mean (±standard deviation) level of blood viral load were significantly higher in the first group [4.2 (±0.5) vs 3.3 (±0.4) log copies/mL]. From multivariate analysis, associated factors of symptomatic infection included acute rejection [odds ratio (OR) 7.32, P = 0.001], and acute tubular necrosis (OR 3.44, P = .019). Death (13%) and graft failure (13%) were significantly higher among the symptomatic infection group than those in the no-infection group (P = .005 and .03, respectively).

Conclusion

Despite a low incidence rate, symptomatic CMV infection clearly resulted in significant morbidity following KT. In Thailand, the prevention of CMV infection should be prioritized among high-risk KT populations.     

Case report of a symptomatic giant renal oncocytoma

Renal oncocytomas are benign tumours, often asymptomatic, and picked incidentally on radiological imaging. We present a case report of a symptomatic giant renal oncocytoma in a 61-year old man having lower back/right flank pain. A large right renal mass was identified on abdominal CT scan. Radiological features were not sufficient to differentiate this lesion from renal cancer. Right radical nephrectomy was performed. Typical features of oncocytoma, without evidence of malignancy, were seen on histological examination of the specimen. In this report, we discuss literature review of radiological, genetic, and pathological characteristics of renal oncocytoma.