Browsing by Author "Mendes, Miguel"
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- Applying virtual crossmatch approach in portuguese kidney transplantsPublication . Lima, Bruno A.; Mendes, Miguel; Alves, HelenaPresence of donor specific antibodies anti-human leukocyte antigen (HLA) is generally a contra-indication for transplantation and nowadays the identification of these antibodies are part of most pre-transplantation evaluations. In Portugal, the implemented protocol for the registration and maintenance of the active list for kidney transplant includes a complement-dependent cytotoxity (CDC) panel-reactive antibody (PRA) screening method, and Luminex technology for detecting and characterizing HLA alloantibodies. Under the current Portuguese kidney allocation system from deceased donors, implemented in August 2007, deceased donor kidneys are primarily allocated via ABO identical and time on dialysis with extra points to hyperimmunized patients, namely PRA CDC>50%. Additional risk for the candidate or transplant organ can be represented by a proposed calculated PRA (cPRA) based upon unacceptable HLA antigens detected by Luminex to which the patient has been sensitized. These unacceptable HLA antigens used to generate cPRA represents a ‘virtual’ crossmatch (XM). Sensitized patients are less likely to be matched with a suitable donor organ. Even after clearing the hurdle of procuring a living donor, it is still possible that this is not sufficient due to the likelihood of having a XM-positive. In these cases and in the presence of incompatible blood type between recipients and their intended living donors, kidney paired donation (KPD) can provide an answer by facilitating exchanges between willing donors’ kidneys. A national Portuguese KPD program, when realized, may prevent the current loss of a significant number of suitable living donors and reduce waiting list time for a deceased donor. An upgrade of a suggested point system in a Portuguese KPD program will be the use of cPRA instead of the values of PRA CDC. In Portugal, the virtual XM approach simply represents the optimization of an existing technique.
- Interleukine-6 promoter polymorphism -174g/C association with chronic nephropathy of the graft: a meta-analysisPublication . Lima, Bruno; Mendes, Miguel; Alves, HelenaDespite being the subject of several independent studies, the relationship between Interleukine-6 (IL-6) polymorphisms and kidney graft outcome continue to be plagued by contradictory conclusions. In this meta-analysis we collect all the relevant studies to further clarify the association of IL-6 genotypes and Chronic Nephropathy of the Graft (CNG). Relevant published data was retrieved through Medline with references to kidney transplant outcome and IL-6 polymorphisms. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the association. Z test was used to determine the significance of the pooled OR. Statistical heterogeneity was measured using the Q statistic. A total of 6 studies, including 474 transplanted patients with CNG and 731 transplanted patients as control group with stable graft function, were collected. The distribution of IL-6 polymorphims was evaluated and no heterogeneity was observed among individual estimates. Original data was combined using the fixed-effects model. For the total population, we found that G/G and G/C IL-6 genotypes were less common in the CNG group than in the control group with an OR of 0.61, (95 % CI=0.42–0.87), and p=0.006, which shows a protective association of IL-6 high producers genotypes in the CNG group. IL-6 is both a major proinflammatory cytokine and an important anti-inflammatory mediator, these complex actions would yield variable effects on atherosclerosis and cardiovascular risk profile in kidney transplant recipients. Our comprehensive meta-analysis indicated that there is sufficient evidence to demonstrate an association between the IL-6 polymorphisms and CNG after kidney transplantation.
- Interleukine-6 promoter polymorphism -174G/C is not associated with acute rejection episodes after kidney transplantation: a meta-analysisPublication . Lima, Bruno; Mendes, Miguel; Alves, HelenaProinflammatory and anti-inflammatory cytokines play key roles in immunologic phenomena leading to Acute Rejection Episodes (ARE) after kidney transplantation which are responsible for kidney graft loss. In particular, interleukin-6 (IL-6), regulates the immune response by acting on various cells including differentiation and maturation of B and T cells or macrophages. This investigation seek to summarize current knowledge on the clinical impact on ARE of IL-6 -174G/C polymorphisms. Relevant published data was retrieved through Medline pertaining to kidney transplant outcome and IL-6 polymorphisms. Odds ratios (OR) with 95 % confidence intervals (CI) were used to assess the strength of the association. Z test was used to determine the significance of the pooled OR. Statistical heterogeneity was measured using the Q statistic. The effect of heterogeneity was quantified using the I2-statistic. A total of 16 studies, including 672 ARE transplanted cases and 1290 transplanted controls without rejection episodes, were collected in this meta-analysis. For high vs. low IL-6 genotypes, no heterogeneity (Q =12.07, p=0.67, I2 =0.0%) was observed among individual estimates, and original data was combined using the fixed-effects model. For the total population, we found no association between G/G and G/C IL-6 genotypes with ARE, we obtained an effect summary OR=1.14, with a 95 % CI=0.84-1.55, and p=0.4. In conclusion, in recipients with a high producer (G/G and G/C) genotype of IL-6, the -174G/C polymorphism is not associated with acute rejection of renal allograft.
- Kidney Transplant allocation in PortugalPublication . A Lima, Bruno; Mendes, Miguel; Alves, Helena[ENG] Factors such as: patient age, place of residence, socioeconomic status, cause of kidney failure, prognosis, duration of dialysis and co-morbidities influence transplantation outcome. Also the quality of available donors must be taken into account when looking for the balance between utility and justice. In the USA, UK and Portugal deceased donor kidney allocation rules are based on systems of points assigned to each possible receptor. However, the key factor in organ allocation is time on dialysis (first come, first served basis). The discussion about access to kidney transplantation with deceased donors never comes to a close and must be done clearly and systematically in order to enable the best decisions at any given moment.
- Measuring access to Kidney transplantationPublication . Lima, Bruno A.; Mendes, Miguel; Alves, HelenaKidney allocation from cadaveric donors must balance two main principles: medical utility and justice. The principle of medical benefit is gauged by maximizing efficiency in the use of organs, and the principle of justice by its effectiveness ensuring that all patients have a reasonable opportunity to be transplanted. The survival benefit of transplant patients when compared with dialyzed values is well described even after adjusting for age, comorbidities, albumin and Body Mass Index (BMI). This benefit is also observed in patients over the age of 60 years. Several factors are related to transplant efficiency: maximization of HLA matching for patients that are more relevant (children and youth), preference for children; minimization of ischemia time, and the relation of life expectancy of the graft with life expectancy of the receptor. The factors related to justice are: reduction of waiting times, and greater equity of access for patients regardless of their race, blood group, HLA homozygosity and geographic location. There are socio-demographic and immunological factors associated with longer waiting time for kidney transplantation, such as: age, blood group or sensitization against HLA antibodies.Knowing the prevalence and incidence (per year, per million inhabitants) of kidney transplant candidates’ demographic factors such as: sex, age groups, socioeconomic status, clinical and immunological characteristics: blood group, PRA values, BMI, type of dialysis, cause of renal failure, and comorbidities; allows for an objective comparison of allocation programs. The waiting time for transplantation should be measured as the median time between the start of dialysis and transplantation of wait listed patients each year. By using the Cox regression analysis, with time on dialysis to transplantation as a dependent variable and clinical and socio-demographic factors as independent variables, will shed light on which characteristics most affect the access to transplantation. Only by defining and applying standardized metrics to kidney transplant candidates over time, is it possible to make informed decisions when debating organ allocation rules. “What gets measured gets improved”.
- Measuring kidney transplantation activityPublication . Lima, Bruno A.; Mendes, Miguel; Alves, Helena[ENG] Kidney allocation from cadaveric donors must balance two main principles: medical utility and justice. The principle of medical benefit is gauged by maximizing efficiency in the use of organs and the principle of justice by its effectiveness, ensuring that all patients have a reasonable opportunity of transplantation. In this paper we present some metrics that, when applied to candidates for kidney transplantation, will help in the best judgment defining kidney allocation systems. Knowing the prevalence and incidence (per year, per million inhabitants) of kidney transplant, candidates demographic factors, such as: sex, age groups, and socioeconomic status; as well as clinical and immunological characteristics: blood group, Panel Reactive Antibody values, Body Mass Index, type of dialysis, cause of renal failure, and comorbidities; allows for an objective comparison of allocation programmes. The waiting time for transplantation should be measured as the median time between the start of dialysis and transplantation of wait -listed patients each year. By using the Cox regression analysis, with time on dialysis for transplantation as a dependent variable and clinical, socio -demographic factors as independent variables, we will shed light on which characteristics affect the access to transplantation.
- A proposal for a new kidney allocation systemPublication . Lima, Bruno A.; Mendes, Miguel; Alves, HelenaIn light of the fact that deceased donor organs are a scarce resource, their distribution must be balanced in order to maximize utility and justice. It should take into account the relationship between supply and demand, hence seeking a balance between the higher net benefit of survival that can be provided by a particular organ and the transplant candidates’ waiting time (as well as the probability of being transplanted). We propose a colour system classification for kidney allocation that will allow clinicians to know the position of a particular patient in the access to kidney transplantation from a deceased donor at all times. This colour system would prioritize candidates by colour ranging from red to green. Red will be attributed to all clinically urgent candidates. Orange would be allocated to candidates with values of calculated PRA (cPRA) >85% or their time on dialyses being higher than the third quartile of wait listed patients’ time on dialysis to transplantation (i.e., how long it takes for 75% of wait-listed candidates to receive a transplant). Yellow would be given to candidates with cPRA >50% or time on dialysis being higher than the median of wait listed patients’ time on dialysis to transplantation (i.e., how long it takes for 50% of wait-listed candidates to receive a transplant). Green will be for all of the remaining candidates. Within each colour group, the candidates’ order will be determined taking into account the number of HLA compatibilities with the donor and, if a tie still persists, the decision is made by the time on dialysis. This proposition for a new allocation system of kidney transplantation would be more transparent than existing point systems and advantageous for both doctor and patient; with it, clinicians can explain to the patient in a more intuitive manner how far they are from being transplanted. Also the realization that patients classified as green will likely wait too long for an organ, can easily sway them toward the solution of transplantation with a living donor. The discussion about access to kidney transplantation with deceased donors never comes to a close and is always in need of improvements; therefore, it must be done clearly and systematically in order to enable the best decisions at any given moment.
- Seeking transparency on allocation of kidneys from deceased donorsPublication . Lima, Bruno; Mendes, Miguel; Alves, HelenaKidney transplantation is the preferred treatment for many end stage renal disease patients; however, the small number of organs for transplantation does not allow all patients to have access to this scarce resource. An allocation system for deceased donor kidneys should be anchored to transparent policies and rules. It should take into account the relationship between supply and demand, hence seeking a balance between the higher net benefit of survival that can be provided by a particular organ and the transplant candidates’ waiting time (as well as the probability of being transplanted).