Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection in heart transplantation.

BACKGROUND: The indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular enzyme with immunosuppressive effects mainly on lymphocyte populations. It has been postulated that indirect determination of IDO serum activity may be a marker of renal graft rejection, but its potential usefulness in heart transplantation (HT) is unknown. METHODS: This longitudinal study included 98 HT patients (83% males) who survived ≥1 year. Mean age was 54.14 ± 11.57 years. Serum IDO activity was analyzed one month after HT by means of high performance liquid chromatography and correlated with the cumulative incidence of acute rejection (AR) during one-year follow-up. AR was defined as biopsy-proven ≥ ISHLT grade 2R rejection or empirically treated non-biopsy-proven rejection. The study sample was divided into two groups: AR group (n = 51), including patients who experienced at least one AR episode during the first year after HT; No-AR group (N = 47), including the remaining patients. RESULTS: Mean serum IDO activity one month after HT was significantly higher (P = .021) in the AR group (3.32 ± 1.56) than in the no-AR group (2.62 ± 1.35). No significant association between serum IDO activity and gender (male: 3.1 ± 1.56, women: 2.43 ± 0.99, P = .092), recipient age (r = -.07, P = .943) or donor age (r = 0.108, P = 0.293) was observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%: 1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no significant modification upon forced adjustment for age and sex. Mean glomerular filtration rate 1 month after HT was 67.01 ± 28.51 mL/min/m(2). No significant correlation between this parameter and serum IDO activity was observed (r = .160, P = .117). CONCLUSIONS: Our study suggests that serum IDO activity one month after HT might be associated with a higher risk of AR during one-year follow-up. This association seems to be independent of recipient gender, age or renal function.

Cumulative incidence of cytomegalovirus infection and disease after heart transplantation in the last decade: effect of preemptive therapy.

INTRODUCTION: Infection by cytomegalovirus (CMV) is a major concern in solid organ transplant (SOT). It increases morbidity and mortality. The prevalence of CMV asymptomatic infection and disease is variable among centers, partially related to immunosuppressive protocols and therapeutic strategies to treat CMV. Induction therapy with basiliximab is associated with fewer CMV infections than therapy with OKT3. In our center, universal prophylaxis is used in the first month post-heart transplant (HT) and preemptive therapy (PET) is used later, according to viral load monitoring. OBJECTIVE: To analyze the short- and long-term incidence of CMV infection and disease post-HT according to CMV status of recipient (R)/donor (D) in a cohort of patients who received induction therapy with basiliximab. MATERIALS AND METHODS: Retrospective analysis of 201 consecutive patients over 18 years of age who underwent HT between February 2001 (when induction therapy with basiliximab was initiated) and June 2011. Patients were divided in two risk subgroups of developing CMV disease: high-risk (D+/R- or D-/R- who received blood transfusions or R-, or donor with unknown serostatus) and low-risk (any other combination). RESULTS: Of 201 patients (mean age 53.81 ± 11.61 years, 81.1% men). 165 patients were classified in the low-risk and 36 in the high-risk group. The cumulative incidence of asymptomatic CMV infection during the first year post-HT was 47%: 46% in the low-risk and 50% in the high-risk group (P = .668). The incidence of CMV disease during the first year post-HT was 7.5%: 3.6% in the low-risk versus 25% in the high-risk group (P < .001). CONCLUSIONS: In our series, asymptomatic CMV infection after HT is frequent, affecting almost 50% of patients. However, the incidence of CMV disease is very low (7.5%), which confirms the effectiveness of PET. The higher incidence of disease in the high-risk group recommends closer monitoring of viral load in these patients or performing more prolonged universal prophylaxis.

Conversion of heart transplant patients from standard to sustained-release tacrolimus requires a dosage increase.

INTRODUCTION: It has been suggested that for adequate maintenance of tacrolimus levels, the total daily dosage should be increased when switching from the conventional twice-daily regimen tacrolimus (CT) to once-daily sustained-release tacrolimus (SR-T). OBJECTIVE: To evaluate the safety and efficacy of a 25% increase in daily dosage when switching heart transplant (HT) patients from CT to SR-T. METHODS: We switched 75 HT patients including 72% males and an overall mean age of 55.6 years from CT to SR-T using a 25% increase in daily dosage. We screened for adverse events by measurements of lipids, creatinine, glycemia, and tacrolimus in blood samples taken at 1, 3, 7, and 12 weeks after the conversion, as well as by repeated echocardiography and routine clinical examinations. RESULTS: Just two patients (2.7%) were returned to CT because of failure of SR-T to attain therapeutic levels. In the remainder of subjects, tacrolimus levels remained stable, with trough values of 8.7±3.2, 8.7±2.9, 8.3±2.6, and 7.5±2.0 mg/dL, respectively. Twenty-three patients (31%) required no dosage change in the first 3 months, but 44 (33%) required one or two changes. No departure from therapeutic levels was associated with rejection; there was no case of severe intercurrent infection. We did not observe significant changes in glycemia, creatinine, lipid profile, or blood pressure. CONCLUSIONS: Administration of SR-T at a dosage 25% higher than the daily dosage of CT was safe. It ensured adequate tacrolimus levels in one-third of patients. Nevertheless, strict analytical surveillance is necessary during the initial months to allow dosage adjustments and to detect the minority of patients for whom SR-T does not achieve therapeutic tacrolimus levels.

Efficacy and tolerance of different types of prophylaxis for prevention of early aspergillosis after heart transplantation.

BACKGROUND: The incidence of aspergillosis (ASP) after heart transplantation (HTx) is low (<4%-5%), but the mortality is high (>78%). AIM: To determine the incidence of ASP in the first 3 months post-HTx according to the type of prophylaxis and assess the tolerance to these regimens. METHODS: This retrospective study of 571 adult HTx patients engrafted from 1991 to December 2009 included 83% males with an overall group age of 54.9±11 years. Three types of prophylaxis were compared: group A was no prophylaxis (n=99; 1991-1994); group B, itraconazole for 3 months (n=352; 1995-November 2004); and group C, inhaled amphotericin for 3 months (n=120; December 2004-2009). The dependent variables were the presence and severity or tracheobronchitis and invasive/disseminated disease as well as, prognosis of Aspergillus infection and tolerance to the regimen. RESULTS: The incidences of aspergillosis were 5% in group A (n=5); 1.4% in group B (n=5); and 0% in group C. Significant differences were observed between groups A versus B (P=.030) and between groups A versus C (P=.013), but there were no differences between groups B versus C. In terms of severity, there were no significant differences among the five cases of tracheobronchitis (20% group A/80% group B), five of invasive/disseminated disease (80% group A/20% group B). There were two deaths (20%) from invasive/disseminated ASP at 0.67 months after diagnosis. The mean time from HTx to ASP was 0.98±0.40 months. There were no adverse effects associated with itraconazole, but they occurred in 3/120 patients (2.5%) treated with inhaled amphotericin, all of whom were on mechanical ventilation, developing respiratory failure requiring amphotericin withdrawal. CONCLUSIONS: Prophylaxis with itraconazole or inhaled amphotericin was effective for the prevention and severity of pulmonary ASP in the first 3 months post-HTx. Although the incidence of early ASP was low in our series, the 20% mortality rate justified the use of preventive measures. Tolerance to both prophylactic treatments was good.