Planned randomized conversion from tacrolimus to sirolimus-based immunosuppressive regimen in de novo kidney transplant recipients.

Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention-to-treat population there were no differences in eGFR (66.2 ± 25.3 vs. 70.7 ± 25.1, p = 0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-to-creatinine ratio (0.36 ± 0.69 vs. 0.15 ± 0.53, p = 0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p = 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.

Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study.

BACKGROUND: Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. METHODS: A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. RESULTS: Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 ± 13.6 years old (range 11-69); creatinine: 1.46 ± 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 ± 83.9 months (range 3-340); and time from YFV at the time of survey: 45 ± 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). CONCLUSIONS: YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life-threatening side effects may occur.

Comparison of the safety and efficacy of cyclosporine minimization versus cyclosporine elimination in de novo renal allograft patients receiving sirolimus.

The safety and efficacy of concentration-controlled use of sirolimus (SRL) and cyclosporine (CsA) followed by CsA minimization (CsAm) or elimination (CsAe) beginning at week 13 was compared in a phase 4, open-label, randomized (1:1) trial of renal transplant recipients enrolled between March 2004 and November 2005. The primary endpoint was renal function, measured at 12 months using the Nankivell formula, in patients remaining on therapy. Though a total enrollment of 140 patients in each group was planned to provide an 80% power to detect a difference in means, only 207 subjects were enrolled in this study. Demographic characteristics were similar between groups, with 98.1% recipients of first grafts, 69.1% from living donors, and 7.2% diabetics. At 12 months, there were no differences in renal function (61.08 vs 65.24 mL/min, P = .132); incidence of biopsy-confirmed acute rejection (14.3% vs 22.5%, P = .152); and patient (89.5% vs 92.2%, P = .632), graft (87.6% vs 88.2%, P = .999), and death-censored graft (98.1% vs 94.1%, P = .166) survivals between CsAm and CsAe groups, respectively. There were no differences in the overall rate of study-drug discontinuation (32.4% vs 36.3%, P = .562) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group (4.8% vs 14.7%, P = .018). This study was underpowered to demonstrate the superiority of one regimen over the other. In summary, SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy. Both regimens offer potential treatment options for de novo renal allograft recipients.

Frequencies at three polymorphic sites of interleukin-10 gene promoter in Brazilian renal recipients.

We genotyped by PCR-RFLP 141 renal patients (77 men and 64 women with ages between 12 and 58, predominantly Caucasians) for allelic variants of three polymorphic sites of the interleukin-10 gene promoter, previously showed to be associated with different production of IL-10 cytokine: -1082 (G/A), -819 (C/T), and -592 (C/A). These polymorphisms may confer flexibility in the common immune responses and influence the outcome of allo-responses after transplantation. Our aim was to determine the frequencies of three functional polymorphic sites -1082, -819, and -592 of the interleukin-10 gene promoter in renal recipients of Curitiba, Paraná. Paraná State is located in southern Brazil, and its capital is Curitiba with approximately 1.5 million inhabitants. Genotypes were classified as follows: "low" IL-10 producer genotypes (ATA/ATA, ACC/ATA, ACC/ACC), "intermediate" genotypes (GCC/ACC, GCC/ATA), and "high" IL-10 producer genotype (GCC/GCC). In our population we observed linkage disequilibrium between alleles -819C and -592C and this haplotypic combination was more frequent (65%) than -819T and -592A. We found significantly reduced frequency of the genotype and haplotype responsible for high production of interleukin-10, maybe because we have a selected group (only renal patients) or maybe because Brazilian people are very heterogeneous (miscegenational), which may differ from other groups.