Negative pretransplant serostatus for Toxoplasma gondii is associated with impaired survival after heart transplantation

Chronic Toxoplasma gondii infection is known to trigger potentially adverse immunoregulatory changes, but limited data exist on long‐term implications for heart transplant (HTX) recipients. We evaluated the risk of all cause mortality regarding T. gondii serostatus prior to HTX. Pre‐HTX T. gondii serostatus was obtained in 344 recipients and 294 donors. Mean age was 52.1 ± 10.2 years and mean follow‐up time after HTX was 5.7 (±5.5, median 3.5) years. All seronegative patients received prophylaxis with pyrimethamine/sulfomethoxazole or cotrimoxazol for 6 months after transplantation. Multivariate survival analysis adjusted for diabetes mellitus, pre‐HTX renal function, recipient age, type of primary immunosuppression (i.e. HTX before 2001), cytomegalovirus (CMV) high‐risk status, ischemic time, and number of treated rejection episodes was performed. Overall, 190 recipients (55.2% of total) were seronegative and 154 (44.8% of total) were seropositive for T. gondii prior to HTX. One hundred and fifty‐two recipients died during follow‐up (44.2% of total). Negative recipient Toxoplasma serostatus was associated with a significantly higher risk of all‐cause mortality (P = 0.0213). Recipient T. gondii serostatus did not influence the number of cellular or humoral rejection episodes. Analyses of specific causes of death showed a trend toward a higher number of infection‐related deaths in the seronegative subgroup (P = 0.13). No statistically significant effects of T. gondii donor/recipient seropairing, or seroconversion were observed. Negative preoperative serostatus for T. gondii in HTX recipients appears to be an independent risk factor associated with increased all‐cause mortality. The cause of impaired survival in Toxoplasma seronegative recipients is currently unclear; possible explanations include an alteration of immune‐reactivity/‐regulation or adverse effects of prophylactic medication.     

Donor‐Derived Trypanosoma cruzi Infection in Solid Organ Recipients in the United States, 2001–2011

Although Trypanosoma cruzi, the parasite that causes Chagas disease, can be transmitted via organ transplantation, liver and kidney transplantation from infected donors may be feasible. We describe the outcomes of 32 transplant recipients who received organs from 14 T. cruzi seropositive donors in the United States from 2001 to 2011. Transmission was confirmed in 9 recipients from 6 donors, including 3 of 4 (75%) heart transplant recipients, 2 of 10 (20%) liver recipients and 2 of 15 (13%) kidney recipients. Recommended monitoring posttransplant consisted of regular testing by PCR, hemoculture, and serology. Thirteen recipients had no or incomplete monitoring; transmission was confirmed in five of these recipients. Four of the five recipients had symptomatic disease and all four died although death was directly related to Chagas disease in only one. Nineteen recipients had partial or complete monitoring for T. cruzi infection with weekly testing by PCR, hemoculture and serology; transmission was confirmed in 4 of 19 recipients with no cases of symptomatic disease. Our results suggest that liver and kidney transplantation from T. cruzi seropositive donors may be feasible when the recommended monitoring schedule for T. cruzi infection is followed and prompt therapy with benznidazole can be administered.     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Serological and molecular survey of toxoplasmosis in renal transplant recipients and hemodialysis patients in Kashan and Qom regions,central Iran

Toxoplasma gondii is one of the important opportunistic pathogen among solid-organ transplant recipients and hemodialysis patients (HD). This study was aimed to detect toxoplasmosis among 50 renal transplant recipients (RTR), 135?HD and 120 healthy individuals in two cities (Kashan and Qom) that located in the center of Iran, from 2014 to 2015. Serological detection (IgG and IgM antibodies) was performed among all individuals in case and control groups. Molecular detection was performed on all IgM positive individuals or IgG positive with moderate to high (>51?IU/mL) antibody titers in HD (n?=?42) and control groups (n?=?21). In RTR patients, molecular detection was conducted among all seropositive or seronegative individuals (n?=?50). IgG seropositivity was detected in 52% (26/50) of RTR, 63% (85/135) of HD and 33.3% (40/120) of the control group. The rate of anti-T. gondii IgG antibody was significantly elevated in RTR and HD patients than the control group (p?=?0.023 and p?<?0.001, respectively). IgM seropositivity was only detected in one HD patient. T. gondii DNA was detected in 12% (6/50) of RTR and 7.1% (3/42) of HD patients. The results of this study suggested that the screening of toxoplasmosis should be given greater consideration among RTR and hemodialysis patients.     

Toxoplasma gondii primary infection in renal transplant recipients. Two case reports and literature review

Toxoplasmosis after solid organ transplantation is a complication associated with high morbidity and mortality. Universal prophylaxis with trimethoprim–sulfamethoxazole (TMP‐SMX) is effective to prevent post‐transplant toxoplasmosis. We report two cases of renal transplant recipients with negative antibodies against Toxoplasma gondii pretransplant who developed toxoplasmosis after TMP‐SMX discontinuation. We have also performed a review of published cases of primary toxoplasmosis after renal transplantation. Of 20 cases reviewed, 11 were male and the mean age was 37.8 years (SD = 13.8). Donor serology for T. gondii was determined in 15 donors, two of them (13%) with negative immunoglobulin (Ig)G and four (27%) with positive IgG and IgM antibodies. Fever was present in 85% of primary toxoplasmosis and hematologic abnormalities were observed in 69% of the cases. Ten patients died (50%). All patients with fatal outcomes had clinical evidence of toxoplasmosis during the early post‐transplant period (first 90 days), while no patient with late toxoplasmosis died (P = 0.003). Primary toxoplasmosis is associated with high mortality rates and TMP‐SMX prophylaxis can delay the onset of symptoms resulting in an improvement of prognosis.     

Effectiveness of low-dose contrimoxazole prophylaxis against Pneumocystis carinii pneumonia after renal and/or pancreas transplantation

We retrospectively examined the effectiveness of prophylaxis with cotrimoxazole in preventing Pneumocystis carnii pneumonia in recipients of kidney and combined kidney-pancreas transplants between 1985 and 1989. Cotrimoxazole prophylaxis (480 mg daily or 300 mg/m²), when used, was started within 2 months after transplantation and usually continued until 6 months after surgery. Eight (3.7%) of the 214 patients who were not given prophylaxis were infected with Pneumocystis carinii, and there were 4 fatalities (50% mortality). There were no cases among the 161 patients given prophylaxis (P 0.03). No serious adverse effects were noted in the prophylaxis group. It is concluded that prophylaxis against Pneumocystis carinii infection is well tolerated and should be given as soon as possible to all organ transplant recipients for at least 6 months.     

Cytomegalovirus infection accelerates cardiac allograft vasculopathy: correlation between angiographic and endomyocardial biopsy findings in heart transplant patients

In order to determine the impact of cytomegalovirus (CMV) infection on cardiac allograft vasculopathy (CAV), we quantitated angiograms and endomyocardial biopsy (EMB) specimens obtained from 53 heart transplant recipients. CMV infection was particularly associated with the development of discrete stenosis in major branch vessels (P<0.03). Also, the number of diffusely affected vessel segments was significantly higher in CMV patients than in CMV-free recipients after the 2nd post-operative year (P<0.05). The EMB histology correlated well with angiography. Significantly higher levels of arteriolar endothelial cell proliferation and intimal thickness were recorded in biopsies of CMV patients than in those of CMV-free recipients during the 1st postoperative year (P<0.02 and P<0.005, respectively). The CMV-associated vascular changes in EMB histology clearly preceded angiographically detectable CAV findings. Taken together, CMV infection accelerated heart allograft arteriosclerosis. The histological changes appeared prior to changes detected by coronary angiography. The CMV effect was particularly pronounced during the first 2 post-transplant years but leveled off thereafter. Thus, CMV-accelerated allograft arteriosclerosis may be linked in particular with early graft loss of CMV-infected heart transplant recipients.     

Spectrum of Pulmonary Infections in Renal Transplant Recipients in the Tropics: A Single Center Study

Background: Pulmonary infections have been implicated as the most common cause of infection related mortality in renal transplant recipients. An appropriate empirical treatment of post transplant pulmonary infections requires knowledge of the spectrum of the microorganisms involved in causing these infections. Besides this knowledge, an aggressive diagnostic approach including the use of invasive tests is often essential to make an early diagnosis for instituting timely and appropriate therapy. We carried out a prospective cohort study to analyze the spectrum of pulmonary infections in these patients and study the utility of bronchoalveolar lavage (BAL) in the diagnosis of the same. Methods: From September 2001 to December 2002, 428 patients were under follow up with the department. In all, 40 renal transplant recipients reported with 44 episodes of pulmonary infection during this study period. All patients underwent detailed and appropriate investigations including specific laboratory tests, sputum analysis, X-ray chest, CT and BAL. The spectrum of the causative organisms and the utility of BAL as compared to the other methods of diagnosis were studied and compared. Results: Out of the 44 episodes of pulmonary infection evaluated, single causative organism could be found in only 24 (54.5%) episodes and multiple etiologies were found in 15 (34.1%) episodes. No definitive cause could be found in 5 episodes. Out of 57 organisms isolated in the 44 episodes, 20 (45.4 %) were bacteria, 16 (36.3 %) each were M. tuberculosis and fungus, 3 were CMV infection and 2 were nocardia. BAL gave a diagnostic yield of 75.8% (25 out of 33 cases). Nine of forty patients died (mortality rate 22.5%) of which 6 deaths could be attributed directly to pulmonary infection. Out of these 9 patients who died, cause of pulmonary infection was bacterial in 5, fungal in 2 and CMV disease in 1. In one patient, organism could not be isolated. Conclusions: Our study has shown that more than 1/3rd of pulmonary infections in renal transplant recipients can be attributed to multiple organisms. Bacterial infections were the commonest cause of post transplant pulmonary infection. Tuberculosis is common cause of pulmonary infection in these patients in our set up. Because of its high diagnostic yield, BAL should be considered in all patients with suspected pulmonary infections in the post transplant period.     

Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.     

Neosynthesized IgG detected by Western blotting in Toxoplasma-seropositive heart or lung transplant recipients

Toxoplasmosis is a life-threatening disease in heart- or lung transplant recipients that can result either from the reactivation of a latent infection or from an organ-transmitted infection. The diagnosis of acute toxoplasmosis is easy in cases of seroconversion following a mismatch. However, when the recipient is Toxoplasma-seropositive before transplantation, usual serological techniques do not allow the differentiation between endogenous and organ-related reinfection. The aim of this study was to determine whether western blotting could contribute to this differentiation. Sequential sera from two heart- and one liver- and lung transplant patients whose anti-Toxoplasma antibody titers strongly increased after transplantation, were analyzed by western blotting. Neosynthesized IgG were observed on blots incubated with the sera from two patients who had received transplants from Toxoplasma-seropositive donors, whereas no neosynthesized IgG was detected on blots from the patient who had received a transplant from a Toxoplasma-seronegative donor. Our results suggest that the detection of neosynthesized IgG in the recipient may be related to the recognition of a new parasite strain possibly brought by the transplant from a Toxoplasma-seropositive donor. Received: 28 September 1999 Revised: 22 March 2000 Accepted: 11 August 2000     

The use of donor and recipient screening for toxoplasma in the era of universal trimethoprim sulfamethoxazole prophylaxis

BACKGROUND: Toxoplasmosis is a serious complication of solid organ transplantation. The highest risk of infection and disease occurs in heart recipients with primary infection transmitted by a seropositive donor to a seronegative recipient (donor-recipient mismatch). Toxoplasmosis has been reported to occur in noncardiac transplant recipients; however, no large studies examining the frequency of such events or the need for serologic screening exist. METHODS: A retrospective cohort study of 1,006 solid organ transplant recipients transplanted in our center between 1984 and 1997 was performed to examine the incidence of Toxoplasma seroconversion, reactivation, and clinical toxoplasmosis and to evaluate the impact of trimethoprim sulfamethoxazole (TMP/SMX) prophylaxis on these outcomes. RESULTS: Pretransplant Toxoplasma seroprevalence was 13.4% in donors and 17.8% in recipients. The incidence of Toxoplasma donor-recipient mismatch was 9.5% during the 14-year study period, and only 39.1% of mismatched recipients received TMP/SMX prophylaxis. Only four patients seroconverted, of whom two had received prophylaxis. There were no cases of clinical disease; either primary or reactivation. CONCLUSIONS: We therefore conclude that in transplant centers with low Toxoplasma seroprevalence, routine screening for Toxoplasma in solid organ donors and recipients is not necessary, particularly in the era of routine TMP/SMX prophylaxis.     

Graft and patient outcomes of zero‐human leucocyte‐antigen‐mismatched deceased and live donor kidney transplant recipients

Greater compatibility of human leucocyte antigen (HLA) alleles between kidney donors and recipients may lead to improved graft outcomes. This study aimed to compare the incidence of acute rejection and graft failure in zero‐HLA‐mismatched recipients of living‐related (LD) and deceased donor (DD) kidney transplants. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we compared the risk of any acute rejection and biopsy‐proven acute rejection (BPAR) and graft failure in recipients of zero‐HLA‐mismatched kidneys between LD and DD using logistic and Cox regression models. Of the 931 zero‐HLA‐mismatched recipients transplanted between 1990 and 2012, 19 (2.0%) received kidneys from monozygotic/dizygotic twins (twin), 500 (53.7%) from nontwin LD and 412 (44.3%) from DD. Twin kidney transplant recipients did not experience rejection. Compared to DD transplant recipients, the risk of any acute rejection (adjusted odds ratio 0.52, 95%CI 0.34–0.79, P = 0.002) and overall graft failure (adjusted hazard ratio 0.55, 95%CI 0.41–0.73, P < 0.001) was significantly lower in LD recipients independent of initial immunosuppression, but not for BPAR (adjusted odds ratio 0.52, 95%CI 0.16–1.64, P = 0.263). Zero‐HLA‐mismatched DD kidney transplant recipients have a significantly higher risk of any acute rejection episodes and graft loss compared to zero‐HLA‐mismatched LD kidney transplant recipients. A cautious and careful approach in reducing immunosuppression appears to be warranted in this group of transplant recipients.     

False Serologic Evidence for Acute Primary Toxoplasmosis During Liver Transplantation for Fulminant Hepatitis B: A Case Report

Acute primary Toxoplasma gondii infection is usually considered to be a contraindication for solid organ transplantation. Recent reports of acute T. gondii infection have highlighted the need to include T. gondii serology in the pretransplant screening of solid-organ transplant recipients. However such serology might be misleading. We describe the case of a 25-year-old woman who received a liver transplantation for life-threatening liver failure due to hepatitis B virus infection. The presence of high IgM titers against T. gondii, as detected by membrane immunoassay, immunofluorescence, and μ-capture ELISA tests, together with the absence of IgG antibodies in the immediate pretransplant serology screening suggested acute primary T. gondii infection at the time of transplantation. We initiated a preemptive therapy with intravenous clindamycin and cotrimoxazole. However, negative PCR and IgA capture assays, together with the absence of a sustained IgG response finally excluded the initial diagnosis of primary toxoplasmosis, leading to discontinuation of antitoxoplasmosis therapy. This case illustrates the problem that, in the context of fulminant hepatitis B, serologic markers for acute primary toxoplasmosis can be falsely positive. Confirmation by PCR and IgA antibody determinations is required to confirm this diagnosis.     

Bloodstream infection in heart transplant recipients: 12-year experience at a university hospital in Taiwan

Objective: Bloodstream infection (BSI) is a well-recognized problem and it affects 10–50% of solid organ transplant recipients. The purpose of this study was to assess the incidence and prognosis of BSI in heart transplant recipients at our hospital. Methods: The study is a retrospective chart review. Results: We diagnosed 101 episodes of BSI in 73 out of 306 heart transplant patients (24%) during the 12-year study period. BSI occurred at a median of 191 days (range 1–3376) after transplant and 50% occurred within 6 months after transplant. Most BSI episodes were nosocomial (73%), especially those occurring within the first month (94%). As far as pathogen was concerned, Gram-negative bacteria predominated (57%), followed by Gram-positive bacteria (34%), fungus (5%), anaerobics (2%), and cryptococcus (2%). Overall 30-day mortality rate was 30%. Death occurred in 36% (13/36) of the patients with early-onset BSI, 14% (2/14) of the patients with BSI in months 2–6, and 29% (15/51) of the patients with late-onset BSI. Mortality rate was over 50% in those patients with Pseudomonal infection, fungal infection, cryptococcal infection of central nervous system, lung infection, and severe sepsis. Compared to Western series, there was a high incidence of infections caused by Enterobacter species and Acinetobacter baumannii. Conclusions: There was a high incidence of BSI after heart transplantation in Taiwan, especially infections caused by Enterobacter species and A. baumannii. Mortality was high in patients with infection caused by Pseudomonas, Candida, and Cryptococcus and in patients with severe sepsis.     

Definitions of cytomegalovirus disease after heart transplantation: Antigenemia as a marker for antiviral therapy

In this prospective study, cytomegalovirus (CMV) antigenemia was defined as the marker for initiation and episodes of antigenemia as the indicator for the duration of antiviral therapy (CMV hyperimmune globulin and ganciclovir). The CMV antigenemia assay and CMV-specific IgM and IgG antibody tests were used to monitor CMV infection in 22 heart transplant recipients who, between October 1992 and July 1994, were followed up for 6 months. A total of 178 out of 627 antigenemia assays tested positive. The highest number of positive cells was greater after primary infection than after either reactivation (43.3 vs 0.3; P<0.01) or reinfection (43.3 vs 9.3; P=NS). Sixty episodes of antigenemia were observed. More episodes of antigenemia were seen after primary infection than after either reactivation (4.6 vs 0.2; P<0.01) or reinfection (4.6 vs 2.2; P=NS). The detection of antigenemia indicated the initiation of antiviral therapy within 24 h after the blood sample was harvested. Therapy was stopped immediately after a subsequent negative result became available. Our experience indicates that antigenemia directed antiviral therapy prevents CMV disease after primary and secondary infection in heart transplant recipients.     

Infections in human liver recipients: different patterns early and late after transplantation

The first 49 consecutive patients who underwent orthotopic liver transplantation between 1984 and 1989 in our department were studied with regard to symptomatic and asymptomatic post-transplantation infections. The major infections carrying a risk of fatal outcome are presented. During the first 4 weeks, fungal and bacterial infections predominated, the percentages of patients affected being 27% and 35%, respectively. Eight patients (17%) suffered from bacterial septicemia, which in six cases was due to gram-negative micro-organisms. The bacterial septicemia was often associated with severe ischemic damage to the graft, rejection, or cholangitis. In addition, a concomitant invasive fungal infection supervened in seven out of eight septic patients, further aggravating the patients' condition. Seventeen of the 49 patients (35%) died after transplantation within 3.3 years. Infection was the cause of death in nine patients (18%), with bacterial septicemia and/or fungemia in eight of these. Cytomegalovirus (CMV) disease was the dominant cause of illness after the 1st month. While only 5 of the 49 patients developed CMV disease during the 1st month (10%), as many as 16 of the 40 recipients who survived beyond that time suffered from symptomatic CMV viremia (40%). CMV mismatching, i.e., the donation of a CMV-positive organ to a CMV-seronegative recipient, entailed the highest risk for CMV disease. Pneumocystis carinii pneumonia occurred within 4 months in 10% of the patients. The four liver recipients affected were among the 20 patients not receiving trimethoprim-sulfamethoxazole prophylaxis. None of the 28 patients who received this prophylaxis over a 12-month period developed this complication (P<0.05). The time-related panorama of infectious complications observed in this study has immediate clinical implications for the screening, prophylaxis, and therapy of infections following liver transplantation.     

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     

(Val-)Ganciclovir prophylaxis reduces Epstein-Barr virus primary infection in pediatric renal transplantation

Epstein‐Barr virus (EBV) primary infection constitutes a serious risk for pediatric transplant recipients, particularly as regards the development of EBV‐related post‐transplant lymphoproliferative disease (PTLD). Currently, there is no established prophylactic regimen. We investigated the association between chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) and the incidence of EBV viremia in EBV‐naïve pediatric renal transplant recipients (R?) who had received a graft from an EBV‐positive donor (D+) and are therefore at high risk of EBV primary infection. In a prospective, multicenter trial (n = 114), we compared a cohort on chemoprophylaxis (n = 20) with a similar control cohort without chemoprophylaxis (n = 8). Over the 1‐year study period, antiviral prophylaxis with VGCV/GCV was associated with a significantly decreased incidence of EBV primary infection: 9/20 patients (45%) in the prophylaxis group experienced an EBV primary infection compared to 8/8 controls (100%) (P < 0.0001). Chemoprophylaxis was associated with a significantly lower EBV viral load (P < 0.001). Type or intensity of immunosuppressive therapy did not influence the occurrence of EBV primary infection or the level/persistence of EBV viral load. Chemoprophylaxis with VGCV/GCV is associated with a reduced incidence of EBV viremia in high‐risk pediatric kidney allograft recipients in the first year post‐transplant. (ClinicalTrials.gov number: NCT00963248).     

Risk factors for cytomegalovirus infection and disease in renal transplant recipients: HLA-DR7 and triple therapy

In a prospective study, an analysis of risk factors for the development of cytomegalovirus (CMV) infection and disease was performed on 77 renal allograft recipients. Twenty-five out of the 77 recipients (32%) had a CMV infection. Twenty-two of the recipients received triple immunosuppressive therapy (cyclosporin A, prednisolone, and azathioprine) while the remaining 55 received standard therapy (cyclosporin A and prednisolone). In 23 recipients (30%) acute rejection was diagnosed and the first positive parameter of infection occurred 22 days after rejection therapy. Infection occurred in 10 out of 18 HLA-DR7-positive recipients (56%) and in 15 out of 59 HLA-DR7-negative recipients (25%; P< 0.02). In multiple regression analysis, HLA-DR7 was found to be a significant predictor of CMV infection (P< 0.005). CMV disease was diagnosed in only 9 out of 25 recipients with an acute infection. Six recipients (67%) with CMV disease received triple therapy for maintenance immuuosuppression; this was significantly correlated to CMV disease (P< 0.05) as compared to three recipients (33%) with CMV disease maintained with standard therapy. Our data suggest that HLA-DR7-positive recipients are more susceptible to CMV infection and that CMV disease is associated with triple immunosuppressive therapy.     

Longitudinal dose and type of immunosuppression in a national cohort of Australian liver,heart, and lung transplant recipients, 1984–2006

Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population‐based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984–2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p < 0.001), and antibody therapy for rejection more common in liver recipients (p < 0.001). Liver recipients were more likely to receive calcineurin inhibitor monotherapy, with or without corticosteroids, compared to heart and lung recipients (p < 0.001). Liver recipients consistently received lower doses of azathioprine than heart and lung recipients (p < 0.001). These differences in immunosuppression may partly explain variations in immunosuppression‐related morbidity by transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time‐dependent data in observational research.