Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study.

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.

Return to work after renal transplantation: a study of the Brazilian Public Social Security System.

BACKGROUND: Return to work is an objective parameter used worldwide to evaluate the success of organ transplantation and is especially feasible after renal transplantation. This study sought to describe the frequency of return to work after renal transplantation and related characteristics. METHODS: Retrospective cohort of 511 isolated kidney transplant recipients was recruited from a Brazilian referral center from January 2005 to December 2009; all were matched to the public social security database to determine inclusion and benefit awards, as well as the rate of resumption of contributions to the public social security system, a surrogate marker of work rehabilitation. Characteristics associated with work return were analyzed. RESULTS: No social security records were found for 28 subjects. The remaining 483 subjects had a mean age of 45±13 years; 62% were male; 401 (83%) received some public social security benefit; 298 were paying dues and could, therefore, receive temporary or permanent disability benefits. Of these, 78 subjects made social security payments after transplantation, resulting in a work return rate of 26% (95% confidence interval, 21-32). Younger age, living donor graft, and chronic glomerulonephritis were significantly associated with return to work. CONCLUSION: In Brazil, most renal transplant recipients are on social security benefits, but only a small proportion return to work after surgery. Clinical characteristics may help define work resumption trends.

Liver transplantation in Latin America: the state-of-the-art and future trends.

We reviewed the current status of liver transplantation in Latin America. We used data from the Latin American and Caribbean Transplant Society and national organizations and societies, as well as information obtained from local transplant leaders. Latin America has a population of 589 million (8.5% of world population) and more than 2,500 liver transplantations are performed yearly (17% of world activity), resulting in 4.4 liver transplants per million people (pmp) per year. The number of liver transplantations grows at 6% per year in the region, particularly in Brazil. The top liver transplant rates were found in Argentina (10.4 pmp), Brazil (8.4 pmp), and Uruguay (5.5 pmp). The state of liver transplantation in some countries rivals those in developed countries. Model for End-Stage Liver Disease-based allocation, split, domino, and living-donor adult and pediatric transplantations are now routinely performed with outcomes comparable to those in advanced economies. In contrast, liver transplantation is not performed in 35% of Latin American countries and lags adequate resources in many others. The lack of adequate financial coverage, education, and organization is still the main limiting factor in the development of liver transplantation in Latin America. The liver transplant community in the region should push health care leaders and authorities to comply with the Madrid and Istambul resolutions on organ donation and transplantation. It must pursue fiercely the development of registries to advance the science and quality control of liver transplant activities in Latin America.

Randomized trial of early corticosteroid reduction vs. regular-dose corticosteroid maintenance in combination with tacrolimus and mycophenolate mofetil in living donor kidney transplant recipients: the Brazilian CORRETA trial.

This multicenter, randomized trial aimed to compare the safety and efficacy of an early reduction in corticosteroid dose vs. long-term maintenance in Brazilian patients on an immunosuppressive regimen based on tacrolimus and mycophenolate mofetil (MMF). In the control arm, prednisone was progressively reduced from days 8 to 90 and then kept for 12 months. In the experimental arm, prednisone was given for 12 months at the dose of 5 mg every other day. Endpoints were the composite occurrence of death, graft loss, or Banff III acute rejection, and safety. A total of 83 patients were enrolled, and 77 were analyzed for efficacy safety. One death occurred in each group. There were no cases of graft loss and one case of grade 3 acute rejection in the early reduction arm. There was no difference in the rate of the composite primary endpoint between both arms (p=0.215), and there were no significant differences between both arms in terms of adverse events. Except for higher incidence of hypertriglyceridemia levels among patients in the regular-dose arm, there were no significant differences between both arms in terms of adverse events. The results of this trial suggest that early reduction of corticosteroid can be feasible and safe within a timeframe of 12 months in patients receiving tacrolimus and MMF.

Transfusäo sanguíneo e transplante renal / Blood transfusion and renal transplant

O efeito benéfico das transfusöes sangüíneas na melhoria dos resultados dos transplantes renais encontrado pela maioria dos centros de transplantes tem sido questionado nos últimos três anos. Resultados recentes revelam uma sobrevida do enxerto semelhante no paciente que receberam transfusöes sangüíneas específicas ou inespecíficas, quando comparados com aqueles que näo houve transfusäo antes do transplante. As transfusöes sangüíneas näo säo inócuas, pois, além dos riscos de anticorpos linfotóxicos, dificultando a obtençäo de órgäos, estäo associadas a aumento da susceptibilidade a infecçäo e podem transmitir doenças infecciosas, principalmente hepatite e AIDS. Entäo, a perda do benefício das transfusöes associada com os riscos decorrentes, tende a tornar desnecessária a política de transfusäo pré-transplante