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Previously, we found a substantial number of regulatory T cells (Tregs ) and fewer senescent and T helper type 17 (Th17) and a decrease in interstitial fibrosis (IF) in 12-month graft biopsies in belatacept versus cyclosporin (CNI)-treated patients [Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT) study]. Seven years after kidney transplantation (KT), mean estimated glomerular filtration rate (eGFR), patient and graft survival were significantly higher with belatacept versus CNI treatment. The aim of this study was to determine whether the immunophenotypes of inflammatory and regulatory cell subsets infiltrating the grafts contribute to the BENEFIT's clinical findings a decade after KT. Twenty-three adult patients with functionally stable KT treated with belatacept and 10 treated with CNI were enrolled. Biopsies were analyzed by histomorphometry and immunohistochemistry for proliferation, senescence, apoptosis, inflammatory and regulatory cell markers in a blinded manner. Significantly lower percentages of inflammatory/fibrogenic cells [interleukin (IL)-22+ /Th17/Th2/M1 macrophages] were observed in patients treated with belatacept than in patients treated with CNI. By contrast, remarkably higher percentages of regulatory cells [Tregs /Bregs / plasmacytoid dendritic regulatory cells (pDCregs )/M2] were found in belatacept-treated patients than in CNI-treated patients. Conspicuously lower percentages of apoptosis and senescence and higher proliferation markers were found in belatacept-treated patients than in CNI-treated patients. Consequently, there was significantly more inflammation in the microvascular compartments as well as increased tubular atrophy and IF in CNI-treated patients. These findings strongly suggest that regulatory mechanisms, along with the absence of deleterious effects of CNI, contribute to the long-term graft histology and function stability in patients treated with belatacept.

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This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101-228 vs days 1-100. Twenty-seven patients (48.2%) had treatment-related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment-related serious AEs were reported for nine patients (16.1%) and six withdrew due to AEs. Viremia was centrally confirmed in 10 patients; there was no confirmed CMV disease. One patient tested positive for a resistance mutation (UL97 L595F). Biopsy-proven acute rejection occurred in six patients (10.7%), but no graft loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograft recipients showed a safety profile consistent with that established in adult transplant patients.

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BACKGROUND: The National Transplant Center in Mexico has ruled that deceased-donor kidney allocation is a function of each hospital's Internal Transplant Committee. The aim of this study was to compare and analyze results for of the traditional method and a point-score system in the allocation of deceased patient's kidneys. METHODS: The 12 major kidney transplant centers in the country having a deceased-donor program were invited to participate. Only 3 of them replied to the invitation during 2010. A point-score system was proposed to them, comprising blood group, waiting list time, HLA type, and donor and recipient ages. Once the final recipient was chosen, an explanation of reasons for the choice was requested. Thirty-eight transplants were presented. Kappa coefficient was used to measure degree of agreement in both allocation systems. Organs donated for transplantation came from patients between 4 and 54 years old, including 52% female, 52% O+ blood type, 31% A+, and 11% B+, 44% cranial-encephalic trauma, and 44% brain hemorrhage. RESULTS: Global agreement was 52.6% (kappa = 0.343), and partial agreement was 76.3% (weighted kappa = 0.204), assigning more intensity to extreme values, but with a lower correlation index. A more intense agreement, without discriminating by hospital, was found for "A" category (blood group), followed by "B" category (waiting list time). DISCUSSION: Taking into consideration the determining factors for long-term graft survival, it is indispensable to include criteria such as donor and recipient ages and HLA typife in the allocation process. This first draft of a point-score system in organ allocation included waiting list time, blood group, urgency related to vascular/peritoneal access for dialysis, clinical condition, donor/recipient age ratio, and HLA antigenic compatibility.

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BACKGROUND: The Mexican Health Law stipulated that the criteria to be taken into account for deceased donor kidney allocation should include the following: "seriousness of recipient's condition, opportunity of transplant, expected benefits, compatibility with recipient, and all other accepted medical criteria." The practical application of these criteria has been perceived by several members of transplantation committees as allowing inequity in kidney allocation. The aims of this study were to learn the opinions of transplantation committees regarding current national allocation policies, and to obtain their opinions about the advantages of a point-score system. METHODS: A prepared questionnaire was validated with the collaboration of a team of transplantation physicians from the Mexican Society of Transplantation (MST). Ninety members of the Society, who represent transplantation groups were invited by mail to participate in the survey. RESULTS: We received 70 answered questionnaires, including 54 that represented the views of their respective internal transplantation committees. In agreement with the legislation and allocation policies currently in force were 50% of responders; however, 60% believed that a point-score system for organ allocation should be mandatory and 75% believed that only patients without a possible live donor should be included on the waiting list to compete for a deceased donor kidney. Also, 84% believed that only patients with a complete pre-transplant protocol, including recent viral serology, as well as clinically relevant pre-transplant evaluations by other specialists such as cardiology, psychiatry/psychology and urology should qualify for allocation of deceased donor organs; 76% believed that patients who compete for a deceased donor organ must have permanent support for immunosuppressive drugs as well as for short-term and long-term medical care. CONCLUSION: The answers gathered through this survey pointed out the necessity for continuous coordinated work between healthcare authorities and members of the MST to achieve the best guidelines for allocation of deceased donor kidneys including a point-score system.

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