Equity matrix for kidney transplant allocation.

There is a general agreement that the distribution of kidneys for transplantation should balance utility criteria with justice. Moreover, a kidney allocation system must be based on transparent policies and seen as an ongoing process. This study aims to present an allocation system grounded on an equity matrix that balances the criteria of utility and justice. Synthetic data for a waiting list with 2000 transplant candidates and a pool of 280 donors were generated. A color priority system, the Eurotransplant (ET) kidney allocation system, and the proposed Equity Matrix (EQM) allocation system were compared after 1000 iterations of kidney allocations. Distributions of variables like the age difference, Human Leukocyte Antigens (HLA) mismatches (mmHLA), recipients' time on dialysis, cPRA, and a transplant score obtained by different allocation models were compared graphically and with Cohen's d effect size. For the analyzed variables, when we compare only the selected recipients from ET with the selected recipients from the EQM neutral model, we can conclude that the former model selects more hypersensitized recipients, a higher number of 65+ years' old recipients with 65+ years' old donors and higher number of recipients with 0 mmHLA. While recipients from EQM neutral are slightly older, have a lower age difference with their donors, have a lower number of mmHLA, are less likely to have 6 mmHLA with their donors, and have more time on dialysis. The proposed EQM model attempts to provide a simple, transparent, and equitable response to a complex question with results that outperform established practices.

Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case-control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Single- and multi-locus analyses were performed to investigate the predictive potential of specific variants in IPF susceptibility and survival. Multifactor dimensionality reduction (MDR) was employed to uncover predictive multi-locus interactions underlying IPF susceptibility. The MUC5B rs35705950 SNP was significantly associated with IPF: T allele carriers were significantly more frequent among IPF patients (75.0% vs 20.3%, P < 1.0 × 10-6). Genotypic and allelic distributions of TOLLIP, PLAU, and SERPINB1 SNPs did not differ significantly between groups. However, the MUC5B-TOLLIP T-C-T-C haplotype, defined by the rs35705950-rs111521887-rs5743894-rs5743854 block, emerged as an independent protective factor in IPF survival (HR = 0.37, 95% CI 0.17-0.78, P = 0.009, after adjustment for FVC). No significant multi-locus interactions correlating with disease susceptibility were detected. MUC5B rs35705950 was linked to an increased risk for IPF, as reported for other populations, but not to disease survival. A haplotype incorporating SNPs of the MUC5B-TOLLIP locus at 11p15.5 seems to predict better survival and could prove useful for prognostic purposes and IPF patient stratification. KEY MESSAGES : The MUC5B rs35705950 minor allele is associated with IPF risk in the Portuguese. No predictive multi-locus interactions of IPF susceptibility were identified by MDR. A haplotype defined by MUC5B and TOLLIP SNPs is a protective factor in IPF survival. The haplotype may be used as a prognostic tool for IPF patient stratification.

Kidney allocation rules simulator.

The greatest challenge of any kidney transplant program lies in finding enough organ donors (in number and quality) for all waitlisted transplant candidates. Unfortunately, we must resign ourselves to a manifestly insufficient supply of organs for the current demand. Furthermore we must be able to predict kidney transplant success at organ allocation if we want to minimize the number of patients who return to an already overcrowded waiting list for transplantation. Therefore, the definition of deceased donors' kidney allocation rules on transplantation must be supported by simulations that allow foreseeing, as much as possible, the consequences of these rules. Here we present the Kidney Allocation Rules Simulator (KARS) application that enables testing different kidney transplant allocation' systems with different donors and transplant candidates' datasets. In this application, it is possible to simulate allocation rules implemented in Portugal, in the United Kingdom, in countries within Eurtotransplant, and a previously suggested color priority system. As inputs, this application needs three data files: a file with transplant candidates' information, a file with candidates' anti-HLA antibodies, and a file with donors' information. As output, we will have a file with donor-recipient pairs selected according to the kidney allocation system simulated. When seeking waste reduction while ensuring a fair distribution of organs from deceased donors, the definition of rules selecting donor-recipient pairs in renal transplantation must be based on evidence supported by data. On the continuously changing process for a better distribution of an increasingly scarce resource must, we must be able to predict transplant outcomes when defining the best allocation rules.

Portuguese calculated panel reactive antibodies online estimator.

Calculated panel reactive antibodies (CPRA) is a sensitization measure used to classify and prioritize transplant candidates in different kidney transplant allocation systems. CPRA is based on identification of HLA unacceptable on potential organ donors making a transplant candidate ineligible for transplantation. Here, we present a CPRA online estimator based on HLA allelic and haplotypic frequencies from Portuguese donors. We also compare the values we obtained from our CPRA estimator (Portuguese [PT]-CPRA) against CPRA values obtained from: Eurotransplant virtual PRA calculator (ET-CPRA); Canadian CPRA calculator (Canadian [CN]-CPRA) and Organ Procurement and Transplantation Network CPRA calculator (United States [US]-CPRA). When we analyzed correlations between CPRA values obtained from pairs of calculators, we observed that they are significantly and highly correlated. Bland-Altman plots for the comparison between PT-CPRA calculator against the other calculators, show higher differences between PT and CN than between PT and ET and PT and US. Also, the lowest value for Lin's concordance coefficient was obtained for the comparison between PT and CN calculators. CPRA values reliability depend on donors' pool from which it is calculated and it is crucial for classify correctly highly sensitized patients. A CPRA calculator must use donors' HLA frequencies similar from those who would be actual organ donors.

[Bone marrow volunteer donors recruitment in northern Portugal]. / Recrutamento de dadores voluntários de medula óssea no norte de Portugal.

Allogeneic haematopoietic stem cell transplantation (HSCT) has been used to treat a variety of malignant and non-malignant diseases, particularly of the blood and immune system. However, as no more than 30% of patients will have HLA-identical sibling, much effort has been devoted to the establishment of bone marrow registries for HSCT. In 2010, there are more than 15 million bone marrow donors and cord blood units in the in the Bone Marrow Donors Worldwide (BMDW) database. Participants are 64 stem cell donor registries from 44 countries, and 44 cord blood banks from 26 countries. The North Center of Histocompatibility (CHN) is one of the three Histocompatibility Centers which made the Portuguese Registry of bone marrow donors--National Center of Bone Marrow, Stem Cells and Cord Blood Donors (CEDACE). The aim of this paper is to present the first 110000 donors recruited by the CHN to the CEDACE. In 2010, the recruited donors throw the CHN distribution by age are 14.6%, 38.7%, 37.8% and 8.9%, for the age groups [18;25], [25;35], [35;45] and = 45, respectively. The 110000 bone marrow donors recruited in the North of Portugal by the CHN are a contribution to the worldwide effort that is the BMDW. Young, preferably male donors, should be targeted as replacement of the donors who retire because of old age or for other reasons. Also, the quest for donors with the so-called unique phenotypes is a challenge for all registries. Portuguese areas which show particularly high levels of phenotype diversity or those in which alleles of haplotypes underrepresented in the registry are identified can and should be targeted for the optimization of recruitment strategies.