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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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Abatacepte/uso terapêutico , Ciclosporinas/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Adulto , Contagem de Linfócito CD4 , Senescência Celular/efeitos dos fármacos , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Imunofenotipagem , Masculino , México , Linfócitos T Reguladores/imunologia , Tacrolimo/uso terapêutico , Células Th17/imunologiaRESUMO
With the limitations of surgical reconstructive procedures, the growing number of gunshot wounds, burns, and work accidents in Mexico that result in complex facial deformities leaves only 1 option-face transplantation. The National Institute of Medical Sciences and Nutrition "Salvador Zubiran" (INCMNSZ) has performed transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb transplantation in Latin America in 2012. We are willing to continue in this manner toward conducting face transplantation at our institute. To this end, we identified and solved various challenges. The 1st challenge was acceptance and inclusion of vascularized composite allotransplantation (VCA) within general Mexican health law and approval of the face transplantation procedure. Subsequently, the health ministry provided a license to INCMNSZ to perform the procedure. The 2nd challenge concerned who would pay for the procedure. The costs will be paid by the patient (1st-party payer), social security institutions (2nd-party payers), and the health ministry (3rd-party payer). The 3rd challenge was to maintain ongoing surgical training of the team using cadavers. The fourth challenge was to locate donors; toward this end, we developed a campaign for promoting face donation in social media, making a comic book, and training organ and tissue coordinators to further VCA. Thus, INCMNSZ has the legal, administrative, medical, and surgical wherewithal to accomplish face transplantation.
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Face/cirurgia , Traumatismos Faciais/cirurgia , Transplante de Face/métodos , Doadores de Tecidos , Cadáver , Traumatismos Faciais/epidemiologia , Humanos , Incidência , México/epidemiologia , Alotransplante de Tecidos Compostos Vascularizados/métodosRESUMO
Infectious diseases are common causes of morbidity and mortality among kidney transplant recipients. Chagas disease (CD) has been recognized as an emerging infectious complication of transplantation caused by the parasite Trypanosoma cruzi. CD is prevalent in Mexico, particularly in the southern coastal region. The impact on Mexican kidney transplant programs has not been previously studied prospectively. From 2009 through 2010, serum samples from 59 kidney transplant donors and 405 renal transplant recipients were screened for antibodies against T. cruzi. Serum was initially screened using a locally developed ELISA test; positive results were confirmed by an indirect immunofluorescense test, in accordance with Panamerican Health Organization/World Health Organization guidelines. None of the donors were seropositive for T. cruzi, while 8 (1.97%) kidney transplant recipients were confirmed to be seropositive for T. cruzi. None of them have developed clinical manifestations of CD, although specific screening of recipients was not performed. A prospective study is planned to define the epidemiology and outcome of CD among kidney transplant donors and recipients in Mexico more thoroughly.
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Anticorpos Antiprotozoários/sangue , Doença de Chagas/sangue , Doença de Chagas/epidemiologia , Transplante de Rim , Trypanosoma cruzi/imunologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Adulto JovemRESUMO
UNLABELLED: Sensitization to HLA antigens creates an obstacle for the accessibility and success of kidney transplantation (KT). Highly sensitized patients have longer waiting times and some may never receive a KT. AIM: To determine the probability of patients on the deceased donor (DD) waiting list to receive a KT based on the panel reactive antibody percentage (% PRA) in our center. METHODS: The DD waiting list from our institution was analyzed from 01/05 to 08/12 documenting the clinical variables from donor and potential recipients (ABO blood group), lymphocyte cross-match [CxM (CDC-AHG)] results, highest % PRA determination, and time on the waiting list. The patients were classified into 4 groups based on the % PRA: 0%, 1-19%, 20-79% and 80-100%. The data was analyzed using odds ratio and logistic regression (significant p<0.05). RESULTS: 58 DD (F:M 34:24, ABO group O=35, A=13, B=10) and 179 potential recipients were analyzed (F:M 98:81, ABO group O=127, A=33, B=19, participating 4.2 ± 3.8 times with different donors to receive KT). The mean PRA for the whole group was 22 ± 32%, median [md] 0 (0-98). A total of 100 patients received KT (mean waiting time 2.2 ± 1.7 years, 12 days-7 years) and their mean % PRA was 11.6 ± 24, md 0 (0-94) vs. 31.4 ± 37 md 8.5 (0-98) in those who have not received a KT. An association between the % PRA group and KT (p<0.003) was observed. The probability of receiving KT with a 0% PRA vs. >0% was higher (OR 2.12, 1.17-3.84). There was no difference between the 0% vs. 1-19% group (OR 1); differences were observed between 0% vs. 20-79% (OR 2.5, 1.18-5.3) and 0% vs. 80-100% (OR 5, 1.67-14.9). For every percent increase in the PRA above 20%, the risk of not receiving a KT increased by 5% (1-9, p<0.01). CONCLUSIONS: The probability of receiving a DD kidney transplant is inversely related to the % PRA although a higher risk for not receiving a KT becomes evident with a PRA >20%.
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Rejeição de Enxerto/epidemiologia , Transplante de Rim/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Adulto , Cadáver , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Humanos , Masculino , Probabilidade , Listas de EsperaRESUMO
We report two cases of adenoviral infection in kidney transplant recipients that presented with different clinical characteristics under similar demographic and posttransplant conditions. The first case presented with fever, gross haematuria, and acute graft dysfunction 15 days following renal transplantation. A graft biopsy, analyzed with immunohistochemistry, yielded negative results. However, the diagnosis was confirmed with blood and urine real-time PCR for adenovirus 3 days after the initial clinical manifestations. The immunosuppression dose was reduced, and ribavirin treatment was started, for which the patient quickly developed toxicity. Antiviral treatment allowed for transient response; however, a relapse occurred. The viral real-time PCR became negative upon immunosuppression reduction and administration of IVIG; graft function normalized. In the second case, the patient presented with fever and dysuria 1 month after transplantation. The initial imaging studies revealed graft enlargement and areas of hypoperfusion. In this case, the diagnosis was also confirmed with blood and urine real-time PCR for adenovirus 3 days after the initial clinical manifestations. Adenoviral nephritis was confirmed through a graft biopsy analyzed with light microscopy, immunohistochemistry, and PCR in frozen tissue. The immunosuppression dose was reduced, and IVIG was administered obtaining excellent clinical results along with a negative real-time PCR.
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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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Transplante de Rim/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Ética Médica , Feminino , Antígenos HLA/metabolismo , Humanos , Hemorragias Intracranianas/mortalidade , Masculino , México , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Obtenção de Tecidos e Órgãos/normasRESUMO
A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented.
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Transplante de Rim , Vacina Antirrábica/imunologia , Raiva/prevenção & controle , Adulto , Anticorpos Antivirais/sangue , Humanos , Imunização Secundária , Imunoglobulinas/administração & dosagem , Imunoglobulinas/imunologia , Masculino , Vacina Antirrábica/administração & dosagemRESUMO
BACKGROUND: Metabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function in donors. METHODS: Data regarding the presence or absence of MetS and renal function, as assessed by estimated glomerular filtration rate (eGFR) were obtained from 140 kidney donors before nephrectomy (BN) and at follow-up (AF). Donors were divided into those with (group 1; n =28) versus without MetS (group 2; n = 112). RESULTS: Comparing the groups, we observed a significantly greater reduction in eGFR among the group with MetS BN versus AF 27.5% (19.3-33.0) versus 21.4% (9.6-34.1 P = .02) respectively using a Cox regression model, including age, gender, serum uric acid, body mass index (BMI), and basal eGFR, MetS BN (hazard ratio = 2.2; 95% confidence interval [CI], 1.21-4.01; p = .01) was an independent factor associated with a greater risk of a-eGFR <70 mL/min/1.73 m(2) at follow-up (P < .001). Additionally, age (hazard ratio = 1.03%; 95% CI, 1.01-1.06; P < .001), and female gender (hazard ratio = 1.86; 95% CI, 1.03-3.36; P = .03) were associated with a greater decrease in eGFR. Individuals with MetS BN showed a GFR <70 mL/min/1.73 m(2) at significantly shorter follow-up time (5.6 ± 0.8 years) versus persons without MetS (12.8 ± 1.0 years; P = .001) CONCLUSION: Kidney donors with MetS BN experiment a significantly greater decrease in eGFR at follow-up.
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Rim/fisiopatologia , Síndrome Metabólica/fisiopatologia , Doadores de Tecidos , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
Organ transplants are currently an alternative treatment for a growing number of diseases, which were previously considered terminal. Bioethics has played an important role since the advent of this surgical technique, mainly in defining death criteria and the optimum transplantation conditions. This issue continues being a universal focal point, mainly concerning the equity of access to transplantation, criteria for assigning deceased-donor organs, living-donor safety, risk of commercial trade, fair access to high-quality immunosuppressive drugs and organ transplant legislation. These problems are characteristic of Latin America and the Caribbean, and were the driving force behind the First Latin American Bioethics and Transplant Forum, sponsored by the Latin American and Caribbean Transplant Society (STALYC), and all the transplant societies from subsidiary countries. The "Document of Aguascalientes" is a collection of all the ideas and opinions that were proposed during round tables and analyses. The document is divided into four sections: 1) living donor; 2) organ trading and transplant tourism; 3) the state role in legislation, transplant distribution and coverage; and 4) access to and quality of immunosuppression. The Bioethics and Transplant Forum was created to analyse and find solutions for this complex issue. The "Document of Aguascalientes" aims to serve as an instrument of expression and a vehicle for the ideas put forward during the Forum, so that they can act as transplant practice guidelines in Latin America.
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Transplante de Órgãos/ética , Obtenção de Tecidos e Órgãos/ética , Consenso , Humanos , América Latina , MéxicoRESUMO
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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Transplante de Rim , Doadores de Tecidos , Coleta de Dados , Humanos , México , Inquéritos e Questionários , Listas de EsperaRESUMO
One of the main goals in the current care of kidney transplant recipients is to extend long-term graft survival. Efficacious immunosuppressive agents devoid of nephrotoxicity are needed. In human clinical transplantation, sirolimus combined with other immunosuppressive drugs has proven to be a powerful immunosuppressant capable of preventing acute graft rejection, as well as of improving renal function, renal histology, and graft survival when compared with immunosuppressive regimens that include calcineurin inhibitors. The valuable experience gained through many clinical studies allows clinicians to plan sirolimus use. We present a review of the clinical experience and literature review on the use of sirolimus in the first 12 months posttransplantation.
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Imunossupressores/administração & dosagem , Transplante de Rim , Sirolimo/administração & dosagem , Rejeição de Enxerto/prevenção & controle , HumanosRESUMO
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that suppresses T-lymphocyte activity. Costimulation blockade through CTLA4lg increases IDO in antigen-presenting cells. The suppressive effect of IDO is thought to be mediated by Foxp3+CD4+CD25+ regulatory T-cells (Tregs). OBJECTIVE: In this descriptive study, we evaluated the percentage of IDO-expressing peripheral cell subpopulations as well as Tregs in 27 stable kidney transplant recipients receiving either belatacept (LEA29Y), a daughter compound of abatacept (CTLA4lg; n = 19) or cyclosporine (n = 8). METHODS: Blood samples were obtained at 24 ± 2 months (belatacept) and 23 ± 6 months (cyclosporine) of treatment. Intracellular IDO was analyzed by flow cytometry in CD14+, CD11c+, CD16+, CD56+, and CD8+ cell subpopulations. Tregs were assessed by intracellular Foxp3 detection in CD4+CD25+ cells. CD3+, CD4+, CD8+, CD20+, CD68+, IDO+, and Foxp3+ cells were evaluated by immunohistochemistry on graft biopsies obtained preimplantation, at 12 months posttransplant, and in subjects with dysfunction during the first 12 months. RESULTS: Only percentages of CD16+/IDO+-expressing peripheral monocytes were significantly increased among the group receiving belatacept. No differences were observed in peripheral Tregs between the groups. In contrast, higher percentages of Tregs, CD4+, CD8+, and CD68+ cells were noted in dysfunction and at 12 months vs baseline among graft biopsies in subjects receiving belatacept, and also among dysfunction cohorts of belatacept vs Cyclosporine treatment. CONCLUSION: Patients receiving belatacept showed greater amounts of peripheral blood CD16+/IDO+ cells and Tregs on graft biopsies than those under cyclosporine treatment.
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Células Apresentadoras de Antígenos/efeitos dos fármacos , Ciclosporina/administração & dosagem , Imunoconjugados/administração & dosagem , Imunossupressores/administração & dosagem , Indolamina-Pirrol 2,3,-Dioxigenase/sangue , Transplante de Rim , Rim/efeitos dos fármacos , Receptores de IgG/sangue , Linfócitos T Reguladores/efeitos dos fármacos , Abatacepte , Adulto , Células Apresentadoras de Antígenos/enzimologia , Células Apresentadoras de Antígenos/imunologia , Biópsia , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Ligadas por GPI/sangue , Humanos , Imuno-Histoquímica , Rim/imunologia , Rim/patologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The long-term fate of renal transplant recipients has remained relatively unchanged over the last 15 years. The cumulative, chronic effects of immunosuppression contribute, to a great extent, to the higher, premature mortality rates linked to cardiovascular disease and malignancy observed in this patient population. Immunosuppression disrupts both antitumor surveillance and antiviral activities, and oncogenic viruses predispose to specific malignancies. Further, some drugs promote carcinogenesis by mechanisms independent of their immunosuppressive effects. In vitro studies have shown that calcineurin inhibitors (CNIs) promote tumor progression by a transforming growth factor-ß-dependent mechanism. In contrast, in vivo mouse models have demonstrated that mammalian target of rapamycin (mTOR) inhibitors inhibit metastatic tumor growth and angiogenesis. The association between mTOR-inhibitor and reduced malignancy has been demonstrated in several studies. United Network for Organ Sharing registry data demonstrate that an mTOR-inhibitor either with or without a CNI, is associated with a reduced incidence of tumors compared to regimens that do not utilize mTOR-inhibitor Five years after renal transplantation, patients in the Rapamune Maintenance Regimen study who received sirolimus (SRL)-based CNI-free therapy after cyclosporine (CsA) withdrawal at 3 months showed a reduced incidence of malignancy compared with those who continued a regimen including (CsA) In the CONVERT study, patients who converted to SRL displayed a significantly lower malignancy rate (3.8%) at 24 months compared with those who continued CNI based therapy (11%; P < .001). A randomized, prospective study to evaluate the effect of conversion to SRL from a CNI, compared with continued CNI, showed that SRL was associated with a lower rate of nonmelanoma skin cancer (NMSC) and a longer time to first biopsy-confirmed new NMSC. An mTOR-inhibitor CNI-free regimen should be considered for transplant recipients at high risk for cancer development and for those who develop malignancies over the posttransplant course.
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Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Neoplasias/prevenção & controle , Animais , Inibidores de Calcineurina , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/mortalidade , Neoplasias/enzimologia , Neoplasias/etiologia , Neoplasias/mortalidade , Medição de Risco , Fatores de Risco , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Advances in surgical techniques had achieved good outcomes in renal transplantation. There has been controversy with respect to the impact of multiple arteries on the outcome of the renal transplantations. OBJECTIVES: The objectives of this study were to examine the renal function and incidence of complications among grafts with one versus two or more arteries. MATERIALS AND METHODS: We evaluated 86 patients with renal transplantations between January 2006 and January 2008 as a retrospective comparative study. The patients were stratified according to the number of renal graft arteries: group 1 had one artery (n = 66); group 2, two or more arteries (n = 16). RESULTS: The warm ischemia time was shorter among group 1 compared with group 2 (P < .03). There were significant differences between the groups with respect to mean blood pressure at 1 year (P < .04). The kidney biopsies after 1-year follow-up did not show any difference. CONCLUSION: We considered that the presence of anatomic variations was not a contraindication for renal transplantation, but that it is necessary to continue our follow-up to determine the real impact of these variations on graft and patient survivals.
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Transplante de Rim , Artéria Renal/anormalidades , Artéria Renal/cirurgia , Adulto , Cadáver , Contraindicações , Família , Feminino , Variação Genética , Sobrevivência de Enxerto , Humanos , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Doadores de TecidosRESUMO
INTRODUCTION: The interpretation and handling of Banff borderline acute rejection observed in protocol biopsies from patients with stable renal function continues to be controversial. Our objective was to identify the risk factors for borderline acute rejection on 1-year protocol biopsies and to evaluate their effect on renal graft function after 2 years' follow-up. METHODS: We included 82 kidney transplant recipients (KTR), who underwent 1-year protocol biopsies with normal or stable graft function. All KTR had follow-up of at least 2 years posttransplantation. We formed three groups: (1) KTR with a normal biopsy, (2) KTR with borderline changes, and (3) KTR with interstitial fibrosis/tubular atrophy (IF/TA). We searched for risk factors related to borderline injury. The main outcome to evaluate was renal function at 1 month, at protocol biopsy, and 2 years posttransplant. RESULTS: The 82 patients included in this study showed no differences in immunosuppression, gender, etiology of renal failure, or percentage of panel-reactive antibodies. The risk factors associated with borderline lesions were: at least one biopsy due to allograft dysfunction and acute rejection events during the first year posttransplant (P = .011 and P = .021, respectively). Increased serum creatinine and estimated glomerular filtration rate decline were greater among the borderline lesion than the normal group, but similar to patients with IF/TA. CONCLUSION: Renal function decline was greater among borderline and IF/TA groups. However, the sum of insults, and not only the borderline injury itself, produces greater declines in renal function with greater risk for graft loss.
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Atrofia , Rejeição de Enxerto/patologia , Transplante de Rim/patologia , Doença Aguda , Biópsia/métodos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Antígenos HLA/imunologia , Humanos , Incidência , Transplante de Rim/imunologia , Transplante de Rim/fisiologia , Masculino , Fatores de Risco , Fatores de TempoRESUMO
INTRODUCTION: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200-250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction. OBJECTIVE: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year. METHODS: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification. RESULTS: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was -0.94 versus 0.27 +/- 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year. CONCLUSIONS: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.
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Velocidade do Fluxo Sanguíneo , Transplante de Rim/fisiologia , Ultrassonografia Doppler/métodos , Adulto , Biópsia , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Transplante de Rim/patologia , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Urinary tract infections (UTI) have been reported to occur with frequencies ranging from 30% to 60% in kidney transplant recipients during the first year posttransplantation. UTI is the main cause of infectious complications in this period. The objective of this study was to evaluate the incidence of UTI, during the first year posttransplantation and to identify the risk factors associated with its development, as well as its impact on graft function. PATIENTS AND METHODS: This retrospective cohort study had as a primary outcome the development of UTI, defined as the presence of more than 100,000 colony-forming units (CFU) of a pathogenic organism by mL of urine. The univariate analysis was performed with chi-square test for categorical variables and Student t test for continuous ones metrics. We performed multivariate analysis with logistic regression. P < .05 was considered statistically significant. RESULTS: We studied 176 kidney transplant recipients, including 54.5% of male gender and with an overall average age of 37 +/- 12 years. The UTI incidence was of 35.8% (n = 63). The bacterium most frequently found in urine cultures was Escherichia coli (n = 46). In this study, the risk factors that were independently associated with UTI development were age, female gender, days of bladder catheterization, genitourinary anatomic alterations, and UTI during 1 month prior to kidney transplantation. CONCLUSION: This type of study makes it possible to identify risk factors and to formulate strategies focused on particular risk factors.
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Transplante de Rim/efeitos adversos , Infecções Urinárias/epidemiologia , Adulto , Fatores Etários , Antibacterianos/uso terapêutico , Cadáver , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Regressão , Estudos Retrospectivos , Caracteres Sexuais , Fatores de Tempo , Doadores de Tecidos , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/tratamento farmacológicoRESUMO
Enteric-coated tablets containing mycophenolate sodium have been developed to reduce gastric toxicity. The objective of this study was to compare 2 enteric-coated formulations containing 360 mg of mycophenolate sodium: the innovator product, Myfortic, and an agent that recently became available in Mexico, Femulan. For both formulations, mycophenolate sodium content was within the 90% to 110% range of the label claimed dose, and no impurities were present as determined at high-performance liquid chromatography. Mycophenolate sodium release was assayed by applying the US Pharmacopeia apparatus 2 dissolution test at 2 different pH values (1.2 and 6.8) to mimic conditions in the stomach and the small intestine, respectively. At pH 1.2, mycophenolate sodium release was less than 2%, with respect to the label claimed dose, for both formulations. At pH 6.8, mean (range) mycophenolate sodium release with Myfortic was 104.9% (104.0%-105.6%), and with femulan was 62.3% (51.3%-67.7%); the difference between formulations achieved statistical significance (P = .04). Moreover, intratablet variability with the generic formulation was unacceptable. Variation between the highest and lowest drug release was 32.0% for Femulan, and 1.02% for Myfortic. Thus, it is likely that Femulan results in insufficient and irreproducible absorption of mycophenolate sodium in the small intestine, leading to inadequate immunosuppressive efficacy. It is concluded that Femulan and myfortic are not equivalent formulations. Furthermore, Femulan is not a suitable formulation for clinical use in organ transplantation because it does not meet pharmaceutical quality standards.
Assuntos
Imunossupressores/química , Ácido Micofenólico/química , Ácido Micofenólico/farmacocinética , Comprimidos com Revestimento Entérico , Estabilidade de Medicamentos , Medicamentos Genéricos/química , Concentração de Íons de Hidrogênio , México , Ácido Micofenólico/uso terapêutico , Sódio , Solubilidade , SoluçõesRESUMO
UNLABELLED: HLA alloantibodies (Abs) are associated with chronic rejection and poorer graft survival. The current study was designed to document the prevalence of HLA Abs in a group of kidney transplant recipients (KTR) and its impact on graft function. PATIENTS AND METHODS: 283 KTR transplanted between January 1990 and December 2003 who had a functional graft were invited to participate. 198 KTR were enrolled. HLA class I and II Abs were measured by Luminex-One Lambda. Graft function was assessed by DeltaCr and GFR calculated by the Levey formula. RESULTS: Median post-kidney transplant (post-KT) follow-up was 51.4 (4.3 to 176.3) months. Forty-four (22.2%) KTR were found to have class I and/or class II Abs. Eleven had both class I and II Abs, ten were positive only for class I, and 23 for class II. Overall, no significant difference was seen in renal function. The DeltaCr for Ab positive and Ab negative were -0.24+/-0.84 and -0.17+/-0.60 mg/dL (P=0.54), respectively. The GFR for Ab positive and Ab negative were 64.4+/-26 and 60.2+/-20 mL/min (P=0.25), respectively. No statistically significant difference was found between HLA Abs and number of HLA mismatches, gender, blood transfusions, pre-KT pregnancies, DGF, history of acute rejection, and chronic allograft nephropathy. Adjusting analysis by transplant year showed no significant difference. CONCLUSION: The prevalence of HLA antibodies was similar to previous reports. In this cross-sectional study, the presence of HLA antibodies was not related to a negative impact on renal function.
Assuntos
Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim/fisiologia , Estudos Transversais , Seguimentos , Sobrevivência de Enxerto/imunologia , Antígenos HLA-D/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Transplante de Rim/imunologia , Prontuários MédicosRESUMO
UNLABELLED: The aim of this study was to explore differences in the cytokine profile among de novo kidney transplant recipients treated with either Rapamycin (Rapa) + cyclosporine (CsA) + prednisone (P) or CsA + azathioprine (Aza) + P. PATIENTS AND METHODS: Among the 13 adult kidney transplant recipients studied, seven received Rapa + CsA + P while the remaining six received CsA + Aza + P with their living donors serving as controls (n = 13). Spontaneous production of IL-2, IFNgamma, IL-10, and TGF-beta were measured by ELISA in supernatants from 24-hour cultured unstimulated peripheral blood mononuclear cell (PBMC) at time zero (the day before the transplant), and at 3 and 6 months posttransplant. Cytokines were also measured 1 month after CsA withdrawal in the Rapa + CsA + P group. RESULTS: From time zero to the end of the study, IL-2, IFNgamma, and IL-10 were present at low or undetectable levels in all three groups. TGF-beta tended to increase in supernatants from patients under Rapa + CsA + P at 6 months posttransplant and at 1 month after CsA withdrawal without correlation to Rapa blood levels. TGF-beta remained stable throughout the study period for patients included in the CsA + Aza + P group. There was no difference in this cytokine level between these study groups at any given time. CONCLUSIONS: This study showed no differences in the spontaneous cytokine profiles evaluated in patients treated with both therapeutic schemes.