In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.
Summary To determine short‐ and long‐term patient and graft survival in obese [body mass index (BMI) ≥ 30 kg/m2] and nonobese (BMI < 30 kg/m2) renal transplant patients we retrospectively analyzed our national‐database. Patients 18 years or older receiving a primary transplant after 1993 were included. A total of 1871 patients were included in the nonobese group and 196 in the obese group. In the obese group there were significantly more females (52% vs. 38.6%, P < 0.01) and patients were significantly older [52 years (43–59) vs. 48 years (37–58); P < 0.05]. Patient survival and graft survival were significantly decreased in obese renal transplant recipients (1 and 5 year patient survival were respectively 94% vs. 97% and 81% vs. 89%, P < 0.01; 1 and 5 year graft survival were respectively 86% vs. 92% and 71% vs. 80%, P < 0.01). Initial BMI was an independent predictor for patient death and graft failure. This large retrospective study shows that both graft and patient survival are significantly lower in obese renal transplant recipients.
Summary Large‐scale clinical trials using C2 monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard‐exposure or low‐exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C2 monitoring significantly reduces the severity and incidence of acute rejection compared with C0 monitoring, without adverse consequences in terms of renal function or tolerability. Different C2 targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1–2 weeks post‐transplant, and this should be taken into account to avoid overshooting C2 target range. A patient with a low C2 value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C2 monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C2 monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single‐center trials have evaluated Neoral C2 monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.
HLAMatchmaker determines HLA compatibility at the level of polymorphic amino acid triplets in antibody-accessible sequence positions. Recent studies have shown that among HLA-DR-matched kidney transplants, the HLA-A,B antigen mismatches which are compatible at the triplet level have almost identical graft survival rates as the zero-HLA-A,B antigen mismatches. This finding provides the basis of a new strategy to identify HLA-mismatched organs that have similar success rates as the zero-HLA-antigen mismatches. This report describes how in conjunction with the Acceptable Mismatch program in Eurotransplant, HLAMatchmaker can expand the pool of potential donors for highly sensitized patients, for whom it is very difficult to find a compatible transplant. Sera from 35 highly sensitized kidney transplant candidates with an average PRA of 96% were screened by lymphocytotoxicity with HLAtyped panels that included cells that were selectively mismatched for one or two HLA antigens for each patient. Acceptable and unacceptable HLA-A,B antigen mismatches were determined from the serum reactivity with the cell panel. HLAMatchmaker analysis was applied to identify additional HLA class I antigens that were matched at the triplet level. For each patient, we calculated the probability of finding a donor (PFD) in the different match categories from HLA gene frequencies in the kidney donor population. The median PFD for a zero-antigen mismatch was 0.025%. Matching at the triplet level increased the median PFD to 0.037% (P = 0.008). The median PFD was 0.058% for a 0-1-triplet mismatch and 0.226% for a 0-2-triplet mismatch. Serum screening identified acceptable antigen mismatches for 28 of 35 highly sensitized patients, and the median PFD increased to 0.307% for a zero/ acceptable antigen mismatch. The application of HLAMatchmaker permitted for 33 patients (or 92%) the identification of additional antigens that were acceptable at the triplet level, and the median PFD for a zero/acceptable triplet mismatch went up to 0.425%. Inclusion of one-triplet mismatches increased the median PFD to 1.112%. Validation studies have shown that patient sera reacted with none of the zero-tripletmismatched antigens, 8-13% of the one-triplet mismatches, and 12-19% of the two-triplet mismatches. Although most antigens with one or two mismatched triplets appear acceptable to highly sensitized patients, a serum analysis must ascertain that the patient's antibodies do not recognize such mismatched triplets. HLAMatchmaker offers a useful strategy of identifying more 23 donors with acceptable HLA mismatches and could alleviate the problem of accumulation of highly sensitized patients on the transplant waiting list.
Organ transplant recipients (OTRs) have an increased risk of developing keratinocyte carcinomas (KCs). The aim of this study was to correlate infection with human papillomaviruses (HPVs) belonging to the beta genus (Beta-papillomavirus (Beta-PV)) at transplantation with later development of KCs. In a cohort study, sera collected between 1 year before and 1 year after transplantation of OTRs transplanted between 1990 and 2006 were tested for antibody responses against the L1 capsid antigen of Beta-PV and other HPV genera (Gamma-, Mu-, Nu-, and Alpha-PV) using multiplex serology. The OTRs were followed for a maximum of 22 years. Cox regression models with KC, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) as outcome variables were used. Out of 445 OTRs, 60 had developed KC: 14 developed only SCC, 24 only BCC, and 22 both types of KC. The time-dependent hazard ratio (HR) to develop either or both types of KC, adjusted for age, sex, and transplanted organ, in tested Beta-PV-seropositive OTR around the time of transplantation compared with Beta-PV-seronegative OTR was 2.9 (95% confidence interval (CI) 1.3-6.4). The HR for SCC was 2.9 (95% CI 0.99-8.5) and for BCC it was 3.1 (95% CI 1.2-8.0). There was also an association between Mu-PV seropositivity and KC, but there were no significant associations between other HPV genera tested and KC. A positive seroresponse for Beta-PV around transplantation significantly predicted the development of KC in OTRs up to 22 years later, providing additional evidence that infection with Beta-PV has a role in KC carcinogenesis.
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