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1.
BMC Nephrol ; 22(1): 79, 2021 03 05.
Article in English | MEDLINE | ID: mdl-33673808

ABSTRACT

BACKGROUND: Whilst there are a number of publications comparing the relationship between body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study has assessed this for a French patient cohort. METHODS: In this study, cause-specific Cox models were used to study patient and graft survival and several other time-to-event measures. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function. RESULTS: Among the 4691 included patients, 747 patients were considered obese with a BMI level greater than 30 kg/m2. We observed a higher mortality for obese recipients (HR = 1.37, p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24, p = 0.0006) and cardiac complications (HR = 1.45, p < 0.0001). We observed a trend towards death censored graft survival (HR = 1.22, p = 0.0666) and no significant increased risk of early surgical complications. CONCLUSIONS: We showed that obesity increased the risk of death and serious bacterial infections and cardiac complications in obese French kidney transplant recipients. Further epidemiologic studies aiming to compare obese recipients versus obese candidates remaining on dialysis are needed to improve the guidelines for obese patient transplant allocation.


Subject(s)
Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Obesity/complications , Adult , Aged , Cohort Studies , Female , France , Graft Survival , Humans , Male , Middle Aged , Treatment Outcome
2.
BMC Nephrol ; 20(1): 365, 2019 10 11.
Article in English | MEDLINE | ID: mdl-31601177

ABSTRACT

BACKGROUND: Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies. MAIN BODY: Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses. CONCLUSION: EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.


Subject(s)
Biomedical Research/trends , Databases, Factual/trends , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/trends , Translational Research, Biomedical/trends , Biomedical Research/standards , Cohort Studies , Databases, Factual/standards , Europe/epidemiology , Follow-Up Studies , Graft Survival/physiology , Humans , Intersectoral Collaboration , Prospective Studies , Reproducibility of Results , Translational Research, Biomedical/standards
3.
Am J Transplant ; 18(5): 1151-1157, 2018 05.
Article in English | MEDLINE | ID: mdl-29316230

ABSTRACT

From a prospective and multicentric French cohort, we proposed an external validation study for the expanded criteria donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject-specific effect from a multivariable Cox model. We confirmed a 1.75-fold (95% confidence interval [CI] 1.53-2.00, P < .0001) increase in graft failure risk if a given patient received an ECD graft compared to a graft from a donor with standard criteria (standard criteria donor [SCD]). Complementarily, we estimated the population-average effect using propensity scores. We estimated a 1.34-fold (95% CI 1.09-1.64, P = .0049) increase in graft failure risk among ECD patients receiving an ECD graft compared to receiving a SCD graft. With a 10-year follow-up, it corresponded to a decrease of 8 months of the mean time to graft failure due to ECD transplantation (95% CI 2-14 months). The population-average relative risk due to ECD transplantation and the corresponding absolute effect seem finally not so high. Regarding the increase of quality of life in transplantation, our study constitutes an argument to extend the definition of marginality by considering more grafts at high risk and thereby enlarging the pool of kidney grafts.


Subject(s)
Graft Rejection/mortality , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Propensity Score , Tissue Donors/supply & distribution , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/statistics & numerical data , Adult , Aged , Donor Selection , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/pathology , Graft Survival , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Prognosis , Prospective Studies , Quality of Life , Risk Factors , Survival Rate , Time Factors , Tissue and Organ Procurement/standards , Transplant Recipients
4.
Ann Phys Rehabil Med ; 61(1): 12-17, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28716536

ABSTRACT

OBJECTIVE: To describe the disability status of non-selected hospitalized persons. METHODS AND FINDINGS: We conducted a cross-sectional survey to assess activity limitations of every person older than 18 years hospitalized in a regional university hospital covering all medical fields. Evaluators rated, on a scale from 0 to 4, 22 selected items of the International Classification of Functioning (ICF), covering the 6 following domains: learning and applying knowledge, general tasks and demands, communication, mobility, self-care, and interpersonal interactions and relationships. Univariate and multivariate analyses were performed to analyze the prevalence, severity and profile of the handicap in terms of sociodemographic characteristics and care pathways. RESULTS: Among 1572 eligible persons, 1267 (81%) were surveyed (mean age 62.7±20.4years; 655 males [51.7%]). Overall, 82% showed at least one activity limitation. For 52%, disability was severe or total for at least one ICF item. Prevalence of disabilities was higher for mobility (75%) and self-care domains (63%). Disability was strongly related to age: age older than 80years versus 18 to 44years (OR=12.8 95% CI 6.4-27.9]; P<0.01). Disability was associated with hospitalization in rehabilitation units (96%; OR=4.3 [95% CI 2.2-5.3]; P<0.01). Severe disability was associated with hospitalization in critical care units (OR=6.7 [CI 3.2-15.1]; P<0.001) and psychiatry units (OR=5.3 [CI 2.7-11.4]; P<0.001). CONCLUSION: Handicap was common in hospitalized persons, involving all 6 tested ICF activity domains, particularly mobility and self-care. This study alerts care givers, hospital administrators, and in general, people influencing health policies about the need to plan actions to reduce activity limitations of hospitalized persons, whatever the cause of the hospitalization.


Subject(s)
Disability Evaluation , Disabled Persons , Inpatients , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Hospital Departments , Humans , Male , Middle Aged
5.
Am J Transplant ; 17(6): 1490-1501, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27888555

ABSTRACT

Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper (Tfh) cells play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh cells from TOL displayed a modified gene expression profile, failed to produce interleukin-21, and were unable to induce IgG production by naive B cells. This Tfh defect is linked to a low incidence of postgraft de novo donor-specific antibody (dnDSA) immunization, suggesting that the lack of Tfh cells in TOL may induce a protolerogenic environment with reduced risk of developing dnDSA. Finally, we showed that elevated Tfh in STA precedes the occurrence of dnDSA during an alloresponse. These data provide new insights into the mechanisms of antibody response in operational tolerance. Disrupted homeostasis and impaired Tfh function in TOL could lead to a reduced risk of developing dnDSA and suggest a predictive role of blood Tfh cells on the occurrence of dnDSA in transplant recipients.


Subject(s)
B-Lymphocytes/immunology , Graft Rejection/immunology , Immune Tolerance/immunology , Isoantibodies/immunology , Kidney Transplantation , Plasma Cells/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adult , Aged , Antibody Formation/immunology , Cell Differentiation , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Interleukins/metabolism , Kidney Failure, Chronic/surgery , Kidney Function Tests , Lymphocyte Activation , Male , Middle Aged , Prognosis , Risk Factors , T-Lymphocytes, Helper-Inducer/pathology , Transplant Recipients
6.
Am J Transplant ; 16(11): 3255-3261, 2016 11.
Article in English | MEDLINE | ID: mdl-27367750

ABSTRACT

Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyze the benefit-risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients.


Subject(s)
Graft Rejection/drug therapy , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Tacrolimus/administration & dosage , Weaning , Adolescent , Adult , Aged , Aged, 80 and over , Calcineurin Inhibitors/administration & dosage , Double-Blind Method , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Survival/drug effects , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Male , Middle Aged , Postoperative Complications/drug therapy , Prospective Studies , Transplant Recipients , Treatment Failure , Young Adult
7.
Am J Transplant ; 16(3): 999-1006, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26820487

ABSTRACT

The deleterious role of CD8 T cells in kidney graft outcome has regained interest over the years, and memory T cells are considered as one of the main hurdles to achieve transplantation success. Monitoring the CD8 immune response in transplant recipients involved a heterogeneous combination of markers, but the justification of their choice is rarely stated. Whereas the number of parameters is not an issue in phenotypic analysis, functional assays have to accommodate the cell number with the narrowing of the subset. The aim of the study was to investigate the similarities and differences of the subsets identified using three nomenclatures (CD45RA and CCR7/CD27/CD28) in kidney transplant recipients with stable graft function. We found that all three nomenclatures can identify naïve and effector memory (EM) rheumatoid arthritis T cell CD8 with similar features. Whereas CM CD8 could only be documented using CCR7 and CD45RA, the characteristics of EM CD8 will differ according to the nomenclature. We found that the use of the CD45RA and CD28 gives the benefit of examining two EM populations at early and late differentiation states. This systematic comparison provides a cohesive layout of the advantages of using these nomenclature strategies in kidney transplant recipients to guide the choice of their use.


Subject(s)
CD28 Antigens/metabolism , CD8-Positive T-Lymphocytes/immunology , Immunologic Memory/immunology , Kidney Failure, Chronic/immunology , Kidney Transplantation , Leukocyte Common Antigens/metabolism , T-Lymphocyte Subsets/immunology , CD28 Antigens/immunology , CD8-Positive T-Lymphocytes/classification , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/metabolism , Cell Differentiation , Female , Flow Cytometry , Follow-Up Studies , Humans , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/surgery , Leukocyte Common Antigens/immunology , Male , Middle Aged , Prognosis , Prospective Studies , T-Lymphocyte Subsets/metabolism , Transplant Recipients
8.
Lab Anim ; 48(4): 313-20, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24939905

ABSTRACT

Alfaxalone is a neurosteroid with anaesthetic effects and it has been used successfully in several animal species. However, there are no data, to our knowledge, about its efficacy and safety in ferrets (Mustela putorius furo). We evaluated a variety of anaesthetic regimens in ferrets, namely, alfaxalone at 20, 10 and 5 mg/kg (n = 1, 10 and 9, respectively; intravenously); medetomidine at 20 µg/kg (n = 3; intramuscularly); medetomidine (20 µg/kg, intramuscularly) plus alfaxalone (2.5 mg/kg, intravenously; n = 7); and tramadol (5 mg/kg, intramuscularly) plus alfaxalone (5 mg/kg, intravenously; n = 2). Two animals treated with alfaxalone at 10 mg/kg and 20 mg/kg, respectively, died. At 5 mg/kg alfaxalone produced anaesthesia with a similar onset but a shorter duration of anaesthesia and analgesia than alfaxalone at 10 mg/kg. The medetomidine-alfaxalone combination produced anaesthesia and analgesia of a longer duration than alfaxalone administered alone at 5 mg/kg (P < 0.0001 and P < 0.001, respectively). Under this anaesthetic regimen, there was a progressive decrease in pulse rate during the first 30 min before the pulse rate stabilized. Respiratory parameters were maintained at acceptable levels. When tramadol was administered, all the animals exhibited a strong excitation reaction and in no case was the toe-pinch reflex clearly abolished. Thus, alfaxalone plus medetomidine provided safe and effective anaesthesia in ferrets. Alfaxalone, alone or in combination with tramadol, did not produce satisfactory results for use as an anaesthetic for this species.


Subject(s)
Anesthetics, Combined/pharmacology , Ferrets/physiology , Heart Rate/drug effects , Medetomidine/pharmacology , Pregnanediones/pharmacology , Respiration/drug effects , Tramadol/pharmacology , Analgesics/administration & dosage , Analgesics/adverse effects , Analgesics/pharmacology , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Analgesics, Opioid/pharmacology , Anesthetics/administration & dosage , Anesthetics/adverse effects , Anesthetics/pharmacology , Anesthetics, Combined/administration & dosage , Anesthetics, Combined/adverse effects , Animals , Injections, Intramuscular , Injections, Intravenous , Medetomidine/administration & dosage , Medetomidine/adverse effects , Pilot Projects , Pregnanediones/administration & dosage , Pregnanediones/adverse effects , Tramadol/administration & dosage , Tramadol/adverse effects
9.
Am J Transplant ; 14(1): 144-55, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24354874

ABSTRACT

Operationally tolerant patients (TOL) display a higher number of blood B cells and transcriptional B cell signature. As they rarely develop an allo-immune response, they could display an abnormal B cell differentiation. We used an in vitro culture system to explore T-dependent differentiation of B cells into plasma cells. B cell phenotype, apoptosis, proliferation, cytokine, immunoglobulin production and markers of differentiation were followed in blood of these patients. Tolerant recipients show a higher frequency of CD20(+) CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of abnormal B cell differentiation. B cells from TOL proliferate normally but produce more IL-10. In addition, B cells from tolerant recipients exhibit a defective expression of factors of the end step of differentiation into plasma cells and show a higher propensity for cell death apoptosis compared to patients with stable graft function. This in vitro profile is consistent with down-regulation of B cell differentiation genes and anti-apoptotic B cell genes in these patients in vivo. These data suggest that a balance between B cells producing IL-10 and a deficiency in plasma cells may encourage an environment favorable to the tolerance maintenance.


Subject(s)
Apoptosis/immunology , B-Lymphocytes/immunology , Cell Differentiation/immunology , Immune Tolerance/immunology , Kidney Transplantation , Plasma Cells/cytology , Adult , Antigens, CD/immunology , Cells, Cultured , Down-Regulation , Female , Humans , Interleukin-10/biosynthesis , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged
10.
Am J Transplant ; 13(10): 2567-76, 2013 10.
Article in English | MEDLINE | ID: mdl-23919486

ABSTRACT

The angiotensin II type 1 receptor (AT1R) is an emerging target of functional non-HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT1R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti-AT1R antibodies (AT1R-Abs) using a quantitative solid-phase assay. A threshold of AT1R-Ab levels was statistically determined at 10 U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT1R-Abs >10 U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT1R-Abs >10 U had a 2.6-fold higher risk of graft failure from 3 years posttransplantation onwards (p = 0.0005) and a 1.9-fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p = 0.0393). Antibody-mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10 U of pretransplant AT1R-Abs. Pretransplant anti-AT1R-Abs are an independent risk factor for long-term graft loss in association with a higher risk of early AR episodes.


Subject(s)
Autoantibodies/blood , Graft Rejection/immunology , Graft Survival/immunology , Kidney Transplantation , Receptor, Angiotensin, Type 1/immunology , Transplantation Immunology , Acute Disease , Adult , Autoantibodies/immunology , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Graft Rejection/blood , Graft Rejection/diagnosis , HLA Antigens/immunology , Humans , Kidney Diseases/blood , Kidney Diseases/surgery , Male , Middle Aged , Preoperative Care , Prospective Studies , Transplantation, Homologous
11.
Transplant Proc ; 45(4): 1497-502, 2013 May.
Article in English | MEDLINE | ID: mdl-23726605

ABSTRACT

BACKGROUND: Steroid minimization strategies attempt to reduce morbidity in kidney transplantation. Concern still exists regarding long-term outcomes using either steroid withdrawal or steroid avoidance regimens. METHODS: During a 10-year period, 572 primary kidney transplant recipients were treated with basiliximab, calcineurin inhibitors, and mycophenolate mofetil: 417 (72.9%) underwent a steroid-taper regimen over 2-3 months (steroid withdrawal) and 155 (27.1%), complete steroid avoidance (steroid avoidance). RESULTS: Despite no significant difference during the first 3 months (hazard ratio [HR], 1.23; P = .5349), steroid withdrawal recipients showed an increased risk of late acute rejection episodes (HR, 4.06; P = .0585), independent of recipient age >55 years (HR, 1.84; P = .0272). The risk of any adverse event was not different among steroid regimen groups (HR, 0.98; P = .8458), independent of recipient age >55 years (HR, 1.69; P = .0002), delayed graft function (DGF) (HR, 1.54; P = .0001), and positive donor Epstein-Barr virus serology (HR, 0.68; P = .0471). Intention-to-treat analyses revealed a significantly greater risk of graft failure only in diabetic recipients in the steroid withdrawal group (HR, 8.18; P = .0065), independent of confounding risk factors such as recipient age >55 years (HR, 1.99; P = .0244), >4 human leukocyte antigen-A, -B, and -DR incompatibilities (HR, 1.64; P = .0475), and DGF occurrence (HR, 2.63; P < .0001). CONCLUSION: Although both steroid minimization strategies were comparable regarding long-term safety and efficacy, an increased rate of graft failure was observed among diabetics who underwent steroid withdrawal compared with steroid avoidance.


Subject(s)
Graft Rejection , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Steroids/administration & dosage , Adult , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Steroids/adverse effects
12.
Neuropsychiatr Dis Treat ; 9: 211-8, 2013.
Article in English | MEDLINE | ID: mdl-23430373

ABSTRACT

BACKGROUND: The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), as well as to obtain information on current therapy patterns and safety characteristics. METHODS: This multicenter, observational, retrospective, noninterventional study included 730 patients aged 4-65 years with a diagnosis of ADHD. Information was obtained based on a review of medical records for the years 2002-2006 in sequential order. RESULTS: The ADHD predominantly inattentive subtype affected 29.7% of patients, ADHD predominantly hyperactive-impulsive was found in 5.2%, and the combined subtype in 65.1%. Overall, a significant lower Clinical Global Impression (CGI) score and mean number of DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) symptoms by subtype were found after one year of treatment with immediate-release methylphenidate; CGI decreased from 4.51 to 1.69, symptoms of inattention from 7.90 to 4.34, symptoms of hyperactivity from 6.73 to 3.39, and combined subtype symptoms from 14.62 to 7.7. Satisfaction with immediate-release methylphenidate after one year was evaluated as "very satisfied" or "satisfied" by 86.90% of the sample; 25.75% of all patients reported at least one adverse effect. At the end of the study, 41.47% of all the patients treated with immediate-release methylphenidate were still receiving it, with a mean time of 3.80 years on therapy. CONCLUSION: Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.

13.
Transplant Proc ; 44(9): 2845-8, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23146538

ABSTRACT

A unique blood transcriptional profile of 49 genes has been previously highlighted that may be used to distinguish drug-free operationally tolerant kidney recipients (TOL) from other kidney recipients with contrasted clinical situations and healthy volunteers. The aim of this study was to investigate whether the pattern of these 49 genes could be influenced by genetic polymorphisms located in the corresponding genomic sequences and whether some of these single nucleotide polymorphisms (SNPs) could be associated with clinical status of kidney transplant recipients. In this study, 1152 candidate tag SNPs spanning these genes were genotyped using a Golden Gate Illlumina assay in a sample of 164 kidney transplant recipients, including 11 operationally tolerant patients, 134 patients with stable graft function, 19 with proven signs of chronic rejection, and 27 healthy volunteers. The gene expression and clinical status were studied according to the different SNPs. Among the genes demonstrating expression difference between TOL compared with CR&STA patients, PARVG, which is a member of a family of actin-binding proteins associated with focal contacts, stands out with 2 SNPs, (rs139144 and rs5764592) explaining about 20% of the gene expression variability. Linkage disequilibrium analysis of these 2 SNPs showed the rs139144GG genotype was associated with decreased PARVG expression and was numerically more frequent in TOL (60%) than in CR&STA (28%) patients (P = .068). These preliminary results, which should be confirmed in a larger population, open new perspective of regulation pathways and hypothesis in operational tolerance mechanism.


Subject(s)
Actinin/genetics , Graft Rejection/genetics , Graft Survival/genetics , Kidney Transplantation/immunology , Polymorphism, Single Nucleotide , Transplantation Tolerance/genetics , Analysis of Variance , Case-Control Studies , Chi-Square Distribution , Chronic Disease , Gene Frequency , Genetic Predisposition to Disease , Graft Rejection/immunology , Haplotypes , Humans , Linkage Disequilibrium , Phenotype , Risk Factors
14.
Am J Transplant ; 12(12): 3296-307, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22974211

ABSTRACT

We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.


Subject(s)
Graft Rejection/immunology , Graft Survival/immunology , Immune Tolerance/immunology , Immunosuppression Therapy , Isoantibodies/immunology , Kidney Transplantation/immunology , Adult , Case-Control Studies , Cohort Studies , Female , Humans , Immunoenzyme Techniques , Kidney Transplantation/mortality , Living Donors , Male , Middle Aged , Survival Rate
15.
Am J Transplant ; 12(10): 2754-62, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22883025

ABSTRACT

There are lines of evidence that B cells may play a role in transplantation. B cell activating factor, BAFF, is a homotrimer that has been shown to play a role in B cell survival, maturation and activation. To date, little is known of the role of BAFF and its receptors in transplantation. We analyzed the level of BAFF mRNA and its soluble protein, as well as transcripts coding for its receptors, BAFF-R, TACI and BCMA, in the blood of 143 patients with stable kidney transplant function 5 years or more posttransplantation. Three endpoints were analyzed: the time to renal dysfunction, the time to appearance of anti-HLA antibodies and the time to development of donor-specific antibodies. We established threshold values for BAFF and BAFF-R and showed that (1) stable patients with high BAFF-R levels had a higher risk of developing graft dysfunction, (2) patients with lower levels of BAFF transcripts or a higher level of soluble BAFF had a significantly higher risk of developing donor-specific antibodies. These data suggest that BAFF constitutes a risk factor for renal graft dysfunction and development of donor-specific antibodies. They also suggest that agents targeting BAFF-R interactions may offer new therapeutic opportunities in transplantation.


Subject(s)
Antibody Formation , B-Cell Activating Factor/metabolism , B-Cell Activation Factor Receptor/metabolism , Kidney Transplantation , Tissue Donors , Female , Humans , Male , Risk Factors
16.
Nutr Hosp ; 27(2): 391-401, 2012.
Article in Spanish | MEDLINE | ID: mdl-22732960

ABSTRACT

INTRODUCTION: Currently, there is a higher occurrence of biopsychosocial diseases, especially eating disorders, involving different body systems and aspects related to the individual and their social relations. OBJECTIVE: Addressing current and relevant issues about the prevalence, incidence and risk factors for anorexia and bulimia nervosa in adolescence. METHODS: Search the databases: MEDLINE, SciELO and LILACS for studies published on the epidemiology and risk factors for eating disorders in adolescence. RESULTS: The highest incidence of anorexia and bulimia nervosa among girls in the middle and final phase of adolescence. Factors that increase the risk for the onset of eating disorders in adolescents are: genetics, body changes during puberty, the vulnerability of adolescents to the ideals of thinness, social pressures to be thin, body image dissatisfaction, restrictive diet, depression and low self-esteem. However, it is suggested that in different cultures, eating disorders may come from a number of conditions unrelated to compensatory behaviors or weight, but the shape of the body. CONCLUSIONS: Several factors determine the occurrence of anorexia and bulimia nervosa in adolescence, however, there is no consensus how these factors interact in this complex process, which indicates the need for further investigations.


Subject(s)
Adolescent Behavior , Feeding and Eating Disorders/epidemiology , Adolescent , Age Factors , Anorexia/epidemiology , Bulimia/epidemiology , Culture , Feeding and Eating Disorders/genetics , Feeding and Eating Disorders/psychology , Female , Humans , Male , Risk Factors , Sex Factors , Social Environment
17.
Am J Transplant ; 12(6): 1370-7, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22486792

ABSTRACT

Both kidney and particularly liver recipients can occasionally discontinue all immunosuppressive drugs without undergoing rejection. These patients, who maintain stable graft function off immunosuppressive drugs without clinically significant detrimental immune responses and/or immune deficits, are conventionally termed operationally tolerant and offer a unique paradigm of tolerance in humans. The immune characterization of operationally tolerant transplant recipients has recently received substantial attention. Operationally tolerant patients might exhibit a signature of tolerance that could potentially be useful to select recipients amenable to drug minimization or withdrawal. Furthermore, elucidation of the molecular pathways associated with the operational tolerance phenotype could provide novel targets for therapy. Particular emphasis has been placed on the use of blood samples and high-throughput transcriptional profiling techniques. In liver transplantation, natural killer related transcripts seem to be the most robust markers of operational tolerance, whereas enrichment in B cell-related gene expression markers has been consistently found in blood samples from operationally tolerant kidney recipients, suggesting that different mechanisms operate in the two situations. In this minireview, we summarize the main achievements of recently published reports focused on the identification of transcriptional markers of operational tolerance, we highlight their mechanistic and clinical implications and describe their methodological limitations.


Subject(s)
Adaptation, Physiological , Biomarkers , Kidney Transplantation , Liver Transplantation , Humans , Transcription, Genetic
18.
Nutr. hosp ; 27(2): 391-401, mar.-abr. 2012.
Article in Spanish | IBECS | ID: ibc-103417

ABSTRACT

Introducción: En la actualidad, existe la mayor ocurrencia de enfermedades de origen biopsicosocial, en especial los trastornos alimentarios, que involucran diferentes sistemas del cuerpo y los aspectos inherentes a la persona y sus relaciones sociales. Objetivo: Abordar temas actuales y relevantes acerca de la prevalencia, la incidencia y los factores de riesgo de anorexia y bulimia nerviosa en la adolescencia. Métodos: Búsqueda en las bases de datos MEDLINE, SciELO y LILACS de estudios publicados sobre la epidemiología y los factores de riesgo de trastornos alimentarios en la adolescencia. Resultados: La mayor incidencia de la anorexia y bulimia nerviosa se presenta entre las niñas en la fase media y final de la adolescencia. Entre los factores que aumentan el riesgo para la aparición de los trastornos alimentarios en la adolescencia se encuentran: la genética, los cambios corporales en la pubertad, la vulnerabilidad de los adolescentes a los ideales de delgadez, la presión social por ser delgada, la insatisfacción con la imagen corporal, la dieta restrictiva, la depresión y la baja autoestima. Sin embargo, se sugiere que en las diferentes culturas los trastornos del comportamiento alimentario pueden venir de una serie de condiciones no relacionadas con las conductas compensatorias o con el peso, pero con la forma del cuerpo o parte de lo mismo. Conclusiones: Varios factores determinan la aparición de la anorexia y la bulimia en la adolescencia, sin embargo, no hay consenso en cómo interactúan estos factores en este complejo proceso, lo que indica la necesidad de más investigaciones (AU)


Introduction: Currently, there is a higher occurrence of biopsychosocial diseases, especially eating disorders, involving different body systems and aspects related to the individual and their social relations. Objective: Addressing current and relevant issues about the prevalence, incidence and risk factors for anorexia and bulimia nervosa in adolescence. Methods: Search the databases: MEDLINE, SciELO and LILACS for studies published on the epidemiology and risk factors for eating disorders in adolescence. Results: The highest incidence of anorexia and bulimia nervosa among girls in the middle and final phase of adolescence. Factors that increase the risk for the onset of eating disorders in adolescents are: genetics, body changes during puberty, the vulnerability of adolescents to the ideals of thinness, social pressures to be thin, body image dissatisfaction, restrictive diet, depression and low self-esteem. However, it is suggested that in different cultures, eating disorders may come from a number of conditions unrelated to compensatory behaviors or weight, but the shape of the body. Conclusions: Several factors determine the occurrence of anorexia and bulimia nervosa in adolescence, however, there is no consensus how these factors interact in this complex process, which indicates the need for further investigations (AU)


Subject(s)
Humans , Male , Female , Adolescent , Feeding and Eating Disorders/epidemiology , Anorexia Nervosa/epidemiology , Bulimia Nervosa/epidemiology , Risk Factors
20.
Am J Transplant ; 11(9): 1916-26, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21827613

ABSTRACT

A proportion of transplant recipients can spontaneously accept their grafts in the absence of immunosuppression (operational tolerance). Previous studies identified blood transcriptional and cell-phenotypic markers characteristic of either liver or kidney tolerant recipients. However, the small number of patients analyzed and the use of different transcriptional platforms hampered data interpretation. In this study we directly compared samples from kidney and liver tolerant recipients in order to identify potential similarities in immune-related parameters. Liver and kidney tolerant recipients differed in blood expression and B-cell immunophenotypic patterns and no significant overlaps were detectable between them. Whereas some recipients coincided in specific NK-related transcripts, this observation was not reproducible in all cohorts analyzed. Our results reveal that certain immune features, but not others, are consistently present across all cohorts of operationally tolerant recipients. This provides a set of reproducible biomarkers that should be explored in future large-scale immunomonitoring trials.


Subject(s)
Immune Tolerance , Kidney Transplantation , Liver Transplantation , Transcription, Genetic , Adult , Aged , B-Lymphocytes/immunology , Humans , Immunophenotyping , Middle Aged , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction
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