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1.
HLA ; 91(2): 80-87, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29220104

RESUMEN

The reliability of a scientific work depends on the accuracy of the analysis. Scientific publications in the field of kidney transplantation still contain methodical errors that may lead to wrong conclusions and result in severe consequences for the patients. Using the data from the Collaborative Transplant Study, we are presenting in this study six examples of the erroneous usage of statistical methods and show how these mistakes can be avoided.


Asunto(s)
Supervivencia de Injerto , Factores de Edad , Humanos , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Factores de Riesgo
2.
HLA ; 90(2): 102-105, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28470865

RESUMEN

FoxP3 and Vav1 are known to be involved in the development of regulatory T cells. Two polymorphic sites in the FoxP3 promoter (rs3761548 and a (GT) n -dinucleotide repeat) and 2 single nucleotide polymorphisms in intron 1 of the Vav1 gene (rs2546133 and rs2617822) have been shown to correlate with gene expression levels. We investigated a potential impact of FoxP3 and Vav1 genetic variants on kidney allograft failure using samples and data of the Collaborative Transplant Study. A cohort of 384 kidney transplant patients was tested. We found no significant association of FoxP3 promoter rs3761548 or (GT) n repeat length with presumed immunological graft failure. The genotype frequencies of Vav1 intron polymorphisms did not significantly differ between patients with graft failure and matched controls.


Asunto(s)
Factores de Transcripción Forkhead/genética , Genotipo , Supervivencia de Injerto/genética , Trasplante de Riñón , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-vav/genética , Adulto , Aloinjertos , Femenino , Factores de Transcripción Forkhead/inmunología , Supervivencia de Injerto/inmunología , Humanos , Intrones , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-vav/inmunología
3.
HLA ; 87(2): 89-99, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26840927

RESUMEN

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.


Asunto(s)
Rechazo de Injerto/sangre , Isoanticuerpos/sangre , Antígeno Ki-1/sangre , Trasplante de Riñón , Activación de Linfocitos , Periodo Preoperatorio , Linfocitos T/metabolismo , Adulto , Anciano , Complemento C1/inmunología , Complemento C1/metabolismo , Femenino , Rechazo de Injerto/inmunología , Humanos , Isoanticuerpos/inmunología , Antígeno Ki-1/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Linfocitos T/inmunología
4.
Tissue Antigens ; 85(2): 104-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25582053

RESUMEN

Complement-mediated humoral rejection has become the main focus of research in organ transplantation. The aim of this study was to investigate the possible association of the complement C5aR gene 450 C/T polymorphism in antibody-mediated renal allograft rejection. This polymorphism was investigated in 290 first deceased donor kidney graft recipients with well functioning grafts and no rejection treatment during the first transplant year (WFG), 265 recipients with graft failure within the first transplant year (F), and 187 healthy controls. Frequency of the 450 CT genotype was lower in the total population of 555 kidney recipients (4.7%) than in 187 healthy controls (8.6%), but the difference was not statistically significant (P = 0.065). A significantly higher frequency of CT genotype was found in F patients (CT: 6.8%) when compared to WFG patients (CT: 2.8%, P = 0.027). The CT genotype was also significantly lower in WFG patients than in healthy controls (P = 0.009). Low frequency of the C5aR 450 CT genotype, which apparently is a feature of certain kidney diseases, appears to be associated with good graft outcome in kidney transplantation and might be helpful for identifying recipients who are at low risk for graft rejection.


Asunto(s)
Trasplante de Riñón , Polimorfismo de Nucleótido Simple/genética , Receptor de Anafilatoxina C5a/genética , Receptores de Trasplantes , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
5.
Am J Transplant ; 13(8): 2096-105, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23750878

RESUMEN

Death with a functioning graft remains a major challenge following kidney transplantation. Steroid dosing may be a modifiable risk factor. Collaborative Transplant Study (CTS) data were analyzed to assess the relationship between long-term steroid dose and death with function during years 2-5 posttransplant in 41 953 adult recipients of a deceased-donor kidney transplant during 1995-2010. Steroid dose at year 1 correlated significantly with death with function overall, and with death due to cardiovascular disease or infection (all p < 0.001). In patients with optimal graft function (serum creatinine <130 µmol/L) and no anti-rejection treatment during (a) year 1 (b) years 1 and 2, these significant associations remained (all p < 0.001). The center-specific incidence of steroid withdrawal during year 2 showed a significant inverse association with death due to cardiovascular disease (p < 0.001) or infection (p < 0.001) overall, and within the subpopulation with good graft function and no rejection during year 1 (p = 0.002 and p < 0.001, respectively). Maintenance steroid dose shows a highly significant association with death with a functioning graft caused by cardiovascular disease or infection during years 2-5 after kidney transplantation, even in patients with good graft outcomes in whom steroid treatment would appear to be unnecessary.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Rechazo de Injerto/mortalidad , Supervivencia de Injerto/efectos de los fármacos , Infecciones/mortalidad , Fallo Renal Crónico/terapia , Trasplante de Riñón/mortalidad , Prednisona/efectos adversos , Adolescente , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Enfermedades Cardiovasculares/etiología , Femenino , Rechazo de Injerto/etiología , Humanos , Inmunosupresores/uso terapéutico , Infecciones/etiología , Agencias Internacionales , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
6.
Am J Transplant ; 13(4): 1063-1068, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23398855

RESUMEN

Natural killer (NK) cell function can be modulated by the killer cell immunoglobulin-like receptors (KIR) which interact with human leukocyte antigen (HLA) class I molecules on target cells. KIR-ligand mismatching has recently been shown by van Bergen et al. (American Journal of Transplantation 2011; 11(9): 1959-1964) to be a significant risk factor for long-term graft loss in HLA-A, -B and -DR compatible kidney transplants. To verify this potentially important finding, we performed genotyping of 608 deceased-donor kidney graft recipients and their HLA-A, -B and -DR compatible donors for KIR and HLA, using samples and clinical data provided by the Collaborative Transplant Study. Graft survival of KIR-ligand-matched and -mismatched transplants was compared. We found no impact of KIR-ligand mismatching on 10-year graft survival in HLA-A, -B, -DR compatible kidney transplants. Further analysis did not reveal a significant effect of recipient activating/inhibitory KIR or KIR genotypes on graft survival. Our data do not support the concept that KIR-HLA matching might serve as a tool to improve long-term renal allograft survival.


Asunto(s)
Antígenos de Histocompatibilidad Clase I/genética , Trasplante de Riñón/métodos , Receptores KIR/metabolismo , Insuficiencia Renal/inmunología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Genotipo , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Ligandos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Insuficiencia Renal/cirugía , Factores de Riesgo , Factores de Tiempo , Adulto Joven
7.
Tissue Antigens ; 82(4): 235-42, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24461002

RESUMEN

Inclusion of human leukocyte antigen (HLA) matching in donor kidney allocation schemes has been based solely on its association with graft survival. Other long-term effects associated with HLA incompatibility are largely unexplored. Data from deceased donor kidney transplants reported to the Collaborative Transplant Study have been analyzed to assess the relation between HLA mismatching and clinical events to 3 years post-transplant, and an overview of these analyses is presented. A significant correlation was observed between the number of mismatches and the need for anti-rejection therapy during the first year post-transplant, which was maintained for HLA-DR and HLA-A + B mismatching separately and at years 2 and 3 post-transplant. The number of HLA-DR mismatches and the number of HLA-A + B mismatches as well as rejection treatment showed significant associations with the dose of maintenance steroids. The cumulative incidences of death with a functioning graft from infection or cardiovascular causes, but not from cancer, were also significantly associated with HLA mismatching. The number of HLA-DR mismatches showed a significant association with the incidence of non-Hodgkin lymphoma and hip fractures. These findings show that the adverse consequences of HLA mismatching on kidney transplants extend beyond an effect on graft survival, and include an increased risk of death with a functioning graft, non-Hodgkin lymphoma and hip fracture.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Antígenos HLA/inmunología , Fracturas de Cadera/mortalidad , Trasplante de Riñón/mortalidad , Linfoma no Hodgkin/mortalidad , Adolescente , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/inmunología , Supervivencia de Injerto , Fracturas de Cadera/etiología , Fracturas de Cadera/inmunología , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Riñón/inmunología , Trasplante de Riñón/efectos adversos , Linfoma no Hodgkin/etiología , Linfoma no Hodgkin/inmunología , Esteroides/uso terapéutico , Análisis de Supervivencia , Donantes de Tejidos
8.
Am J Transplant ; 12(11): 3031-8, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22900931

RESUMEN

HLA mismatches may correlate with risk of death with a functioning graft (DWFG) because of requirement for higher immunosuppression doses and more antirejection therapy. Deceased-donor kidney transplants (n = 177 584) performed 1990-2009 and reported to the Collaborative Transplant Study were analyzed. The incidence of DWFG was found to be 4.8% during year 1 posttransplant and 7.7% during years 2-5 (Kaplan-Meier estimates). Most frequent causes of DWFG were infection, cardiovascular disease and malignancy (32.2%, 30.9% and 3.6% in year 1; 16.4%, 29.6% and 15.9% in years 2-5). HLA-A + B + DR mismatches were significantly associated with DWFG during year 1 (p < 0.001), a correlation that diminished but persisted during years 2-5 (p < 0.001). HLA mismatch was associated with DWFG because of infection (p < 0.001 during year 1, p = 0.043 during years 2-5) or cardiovascular disease (p < 0.001 during year 1, p = 0.030 during years 2-5) but not malignancy. There was also a significant association between HLA mismatch and hospitalization for viral (p < 0.001) or bacterial (p = 0.002) infection. Multivariable analysis showed that mismatches for HLA class II were more strongly associated with both hospitalization and DWFG than mismatches for HLA class I.


Asunto(s)
Infecciones Bacterianas/mortalidad , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Trasplante de Riñón/inmunología , Adolescente , Adulto , Infecciones Bacterianas/etiología , Infecciones Bacterianas/fisiopatología , Cadáver , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Intervalos de Confianza , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Alemania , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Adulto Joven
9.
Am J Transplant ; 11(11): 2483-9, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21929646

RESUMEN

Whether treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) increases the risk of cancer is controversial. Collaborative transplant study data were analyzed according to whether kidney transplant recipients were treated with ACEi/ARB at year 1. Twenty-four thousand and ninety patients were studied of whom 9079 (38%) patients received ACEi/ARB. There were 872 nonskin malignancies during years 2-8 posttransplant, including 107 respiratory/intrathoracic tumors. The standardized incidence ratio (SIR) for all nonskin malignancies was similar between the ACEi/ARB (1.91) and no ACEi/ARB (1.81) groups (p = 0.42). For respiratory/intrathoracic tumors, however, SIR was significantly higher with ACEi/ARB (1.65 vs. 1.09 for no ACEi/ARB, p = 0.033). Multivariate Cox regression analysis showed that ACEi/ARB treatment was not associated with an increased risk of respiratory/intrathoracic tumors in nonsmokers. In patients with a history of smoking, however, the risk of respiratory/intrathoracic tumors was 2.77 (95% CI 1.19-6.43, p = 0.018) in patients without ACEi/ARB treatment as compared to 7.10 (95% CI 3.27-15.4, p < 0.001) in patients treated with ACEi/ARB. Our data indicate that in kidney transplant recipients, ACEi/ARB treatment is associated with a significant increase in the rate of respiratory/intrathoracic tumors in the subpopulation of patients with a history of smoking.


Asunto(s)
Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Trasplante de Riñón/efectos adversos , Neoplasias del Sistema Respiratorio/inducido químicamente , Fumar/efectos adversos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/inducido químicamente , Modelos de Riesgos Proporcionales
10.
Infection ; 38(6): 491-6, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20981468

RESUMEN

Here, we report on a male infant with low serum IgG, IgA and IgM levels who suffered from Pneumocystis jirovecii and cytomegalovirus (CMV) pneumonia. The patient was tested to be HIV-negative. Absolute and relative numbers of lymphocyte subsets were normal, excluding the diagnosis of an X-linked agammaglobulinaemia (Bruton's disease). Despite the decreased serum IgM level, an X-linked hyper-IgM syndrome (X-HIGM) was considered. X-HIGM is a rare immunodeficiency usually characterised by recurrent severe opportunistic infections, low serum IgG and IgA, but normal or increased serum IgM. The syndrome is caused by mutations of the CD40 ligand (CD40L) gene. In our patient, CD40L mutation analysis proved a novel mutation at codon 257 associated with non-detectable expression of CD40L on the surface of activated T cells. A literature search revealed that approximately 6.4% of X-HIGM patients had been found to have low serum IgM levels. Our statistical analysis of the IgM levels as reported by different studies arouses suspicion that many patients with low IgM levels may not have undergone diagnostic procedures for X-HIGM. In summary, in this report and critical review of the literature, we described a new mutation of CD40L and highlighted the pitfalls of the diagnosis of X-HIGM.


Asunto(s)
Ligando de CD40/genética , Síndrome de Inmunodeficiencia con Hiper-IgM/sangre , Síndrome de Inmunodeficiencia con Hiper-IgM/genética , Inmunoglobulina M/sangre , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Mutación , Adulto Joven
11.
Am J Transplant ; 9(7): 1674-8, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19392983

RESUMEN

HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that are expressed on natural killer (NK) cells. Based on their KIR specificity, HLA-C alleles can be divided into two groups, termed HLA-C1 and HLA-C2. Donor HLA-C group has recently been identified by Hanvesakul et al. (Am J Transplant 2008) as a critical determinant of clinical outcome following liver transplantation: Possession of at least one HLA-C group 2 allele by the donor was associated with significantly improved long-term graft and patient survival, presumably due to an inhibition of host NK cell function. To verify this study, we performed genotyping of 913 deceased liver donors for the relevant KIR epitopes of HLA-C and correlated the presence or absence of donor HLA-C2 genotype with graft and patient survival. In our study, donor HLA-C2 genotype had no impact on 10-year graft or patient survival. We cannot confirm a major role of donor HLA-C2 genotype on long-term allograft survival after liver transplantation.


Asunto(s)
Supervivencia de Injerto/genética , Supervivencia de Injerto/inmunología , Antígenos HLA-C/genética , Trasplante de Hígado/inmunología , Donantes de Tejidos , Adulto , Alelos , Estudios de Cohortes , Femenino , Genotipo , Alemania , Heterocigoto , Homocigoto , Humanos , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Receptores KIR/metabolismo , Análisis de Supervivencia , Factores de Tiempo , Adulto Joven
14.
Transplantation ; 72(7): 1267-73, 2001 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-11602854

RESUMEN

BACKGROUND: Previous analysis of kidney transplant data from the Collaborative Transplant Study database showed that patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 7 years posttransplantation. Longer-term and additional analyses have now been performed. METHODS: Data from cadaver kidney transplants performed between 1985 and 1998 were analyzed retrospectively. Patients were included if they had a functioning graft 1 year posttransplantation, and the daily cyclosporine dose administered 1 year posttransplantation was reported. Data on cyclosporine dose, serum creatinine concentration, and systolic blood pressure were recorded 1 and 5 years after transplantation; information on graft survival was documented at yearly intervals. RESULTS: Patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 10 years posttransplantation. Cyclosporine <2 mg/kg/day was least beneficial overall and in subanalyses based on age, risk level, and 1-year serum creatinine concentration. The microemulsion cyclosporine formulation (Neoral) was associated with a significantly higher 4-year graft survival rate than the conventional formulation (Sandimmune; P=0.0001). Median systolic blood pressure 5 years posttransplantation was similar in each 1-year cyclosporine dose category (range of medians 139.0-140.0 mmHg). The percentages of patients with serum creatinine concentrations of <130, 130-260, 260-400, or >400 micromol/L 1 and 5 years posttransplantation were similar across 1-year cyclosporine dose categories, with the exception of >6 mg/kg/day, where there was a shift toward a less favorable serum creatinine concentration over time. CONCLUSIONS: The 1-year cyclosporine dose was significantly associated with long-term graft survival, with evidence of underimmunosuppression at doses <3 mg/kg/day and overimmunosuppression at doses >6 mg/kg/day, but had little influence on systolic blood pressure or serum creatinine concentration at doses up to 6 mg/kg/day.


Asunto(s)
Ciclosporina/uso terapéutico , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Química Farmacéutica , Niño , Preescolar , Creatinina/sangre , Ciclosporina/administración & dosificación , Ciclosporina/química , Relación Dosis-Respuesta a Droga , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/química , Lactante , Recién Nacido , Estudios Longitudinales , Persona de Mediana Edad , Estudios Retrospectivos
15.
Transplantation ; 69(7): 1337-40, 2000 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-10798750

RESUMEN

BACKGROUND: Preliminary studies showed an excellent success rate of kidney grafts in patients with high pretransplantation serum levels of IgA autoantibodies directed against the Fab region of the human IgG molecule. METHODS: With the collaboration of 30 centers from around the world, we attempted to verify the role of IgA-anti-Fab autoantibodies in kidney transplantation in an entirely new series of 4316 cadaveric kidney transplants, with special consideration of presensitized and poorly HLA-matched recipients. RESULTS: In agreement with previously published preliminary findings, 147 recipients with a high pretransplantation IgA-anti-Fab of >1000 had a 2-year kidney graft survival rate of 88+/-3% (+/- SE), compared with an 80+/-1% rate in 851 recipients with a low IgA-anti-Fab of <60 (P = 0.02). Even in patients at an increased risk of graft rejection, high pretransplantation IgA-anti-Fab autoantibody activity was associated with superior graft survival. Among 815 presensitized patients, 31 had a high pretransplantation IgA-anti-Fab activity of >1000 and their 2-year graft survival rate was 94+/-4%, in contrast to a 71+/-4% rate in 165 presensitized recipients with a low IgA-anti-Fab of <60 (P = 0.02). Of 2294 recipients who received a kidney with > or =3 HLA-A+B+DR mismatches, 79 recipients had a high pretransplantation IgA-anti-Fab of >1000 and a 2-year graft survival rate of 90+/-4%, as compared with a 79+/-2% rate in 459 patients with a low IgA-anti-Fab of <60 (P = 0.04). CONCLUSIONS: The present study confirms that kidney graft recipients with high pretransplantation IgA-anti-Fab activity have excellent graft survival, and it extends this observation to presensitized recipients and poor HLA matches.


Asunto(s)
Autoanticuerpos/análisis , Supervivencia de Injerto/fisiología , Inmunoglobulina A/análisis , Fragmentos Fab de Inmunoglobulinas/inmunología , Adulto , Femenino , Rechazo de Injerto/etiología , Humanos , Inmunización , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Factores de Riesgo
16.
Transplantation ; 69(5): 818-21, 2000 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-10755533

RESUMEN

BACKGROUND: There are conflicting reports in the literature concerning the efficacy of maintenance immunosuppression in renal transplantation with a regimen of azathioprine and steroids. METHODS: The daily dosage (mg/kg) of azathioprine administered 1 year after transplantation was analyzed in relation to subsequent long-term graft outcome. Transplants performed from 1985 to 1996 and reported to the Collaborative Transplant Study were analyzed. RESULTS: In patients on maintenance immunosuppression without cyclosporine, the daily dosage of azathioprine had a highly significant influence on long-term graft outcome. Patients who received > 1.5 mg/kg/ day of azathioprine had a 69% graft survival rate at 7 years, compared with a 55% rate in patients receiving 1.01-1.5 mg/kg/day (P<0.0001) and a 45% rate in patients receiving < or = 1.00 mg/kg/day (P<0.0001). This observation was valid for patients who were taken off cyclosporine during the first year as well as for patients who were treated with azathioprine and steroids (without cyclosporine) from the beginning. CONCLUSION: Maintenance immunosuppression with azathioprine and steroids results in good long-term kidney graft survival, provided azathioprine is administered at a daily dose of >1.5 mg/kg.


Asunto(s)
Azatioprina/administración & dosificación , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Azatioprina/uso terapéutico , Estudios de Cohortes , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Umbral Diferencial , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Humanos , Inmunosupresores/uso terapéutico , Esteroides/uso terapéutico , Factores de Tiempo
18.
Rev Immunogenet ; 1(3): 334-42, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-11256424

RESUMEN

The influence of HLA compatibility on organ transplant survival was analyzed in more than 150,000 recipients transplanted from 1987 to 1997 at transplant centers participating in the Collaborative Transplant Study. A statistically highly significant effect of HLA matching on graft and patient survival rates was found in the analysis of kidney transplants (P < 0.0001). Ten years after transplantation, the graft survival rate of first cadaver kidney transplants with a complete mismatch (6 HLA-A+B+DR mismatches) was 17% lower than that of grafts with no mismatch. During the first post-transplant year, the class II HLA-DR locus had a stronger impact than the class I HLA-A and HLA-B loci. During subsequent years, however, the influence on graft survival of the three loci was found to be equivalent and additive. For optimal graft outcome, compatibility at all three HLA loci is, therefore, desirable. The excellent correlation of HLA matching observed in recipients of cadaver kidneys with very short ischemic preservation (0-6 hours) or recipients of kidneys from living unrelated donors contradicts reports that short ischemia can eliminate the influence of matching. Although HLA has a significant effect on graft outcome regardless of the state of presensitization, the matching effect is potentiated in patients with highly reactive preformed lymphocytotoxic antibodies. Among first cadaver transplant recipients with an antibody reactivity against > 50% of the test panel, the difference in graft survival at 5 years between patients with 0 or 6 mismatches reached 30%. A collaborative project, in which molecular DNA typing methods were employed, showed that the correction of serological HLA typing errors by more accurate DNA typing results in a significantly improved HLA matching effect. Moreover, matching for the class II locus HLA-DP, a locus that can be typed reliably only by DNA methods, showed a significant effect in cadaver kidney retransplants, especially in the presence of preformed lymphocytotoxic antibodies. The analysis of heart transplants showed a highly significant impact of HLA compatibility on graft outcome (P < 0.0001). This result is of particular interest because donor hearts are not allocated according to the HLA match. A biasing influence of donor organ allocation (i.e. a preferential allocation of good matches to good risk recipients) can, therefore, be excluded. In liver transplantation, neither matching for HLA class I nor HLA class II could be shown to influence transplant outcome.


Asunto(s)
Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Órganos , Prueba de Histocompatibilidad , Humanos , Trasplante Homólogo
19.
Z Gesamte Hyg ; 36(11): 599-601, 1990 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-2085039

RESUMEN

The calculations of the spinal column loading of miners are based on working time studies in operations with predominantly physical heavy work and elevated mechanical load. An elaborated model for the mining of ores, the applicability to underground workers and the comparability of loading quantities, based on the dosage measurement, are described.


Asunto(s)
Minería , Esfuerzo Físico/fisiología , Postura/fisiología , Columna Vertebral/fisiología , Fenómenos Biomecánicos , Metabolismo Energético/fisiología , Frecuencia Cardíaca/fisiología , Humanos
20.
Beitr Orthop Traumatol ; 37(3): 165-9, 1990 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-2375740

RESUMEN

Suppositions concerning the technique of tools were performed for recording the so-called mechanogram, which is intended for wide objective estimation of function of the handgrip-musculature. Based on an explorative study in 44 probands the first results and experiences may be reported.


Asunto(s)
Brazo/fisiología , Mano/fisiología , Contracción Muscular , Frecuencia Cardíaca , Humanos , Medicina del Trabajo , Resistencia Física , Pulso Arterial
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