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1.
Transpl Immunol ; 27(2-3): 95-100, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22813834

RESUMO

BACKGROUND: Eculizumab, a potent inhibitor of terminal complement activation, appears promising in reducing early antibody-mediated rejection in positive crossmatch kidney transplantation. However, its concomitant use with polyclonal rabbit antithymocyte globulin (rATG) might reduce the efficacy of rATG. This study aimed to evaluate the effect of eculizumab on the efficacy of rATG in vivo and determine the role of complement in rATG-induced lymphocyte cell depletion. PATIENTS AND METHODS: Thirty-six kidney transplant recipients were classified into 3 groups according to induction regime: anti-IL-2 receptor antibody alone induction group (basiliximab, n=8); rATG induction (n=20), and rATG+eculizumab induction group (n=8). Peripheral blood T-cell subsets and NK cells were measured 3-4 days after transplant (after 3 doses of rATG). RESULTS: Compared to anti-IL-2 receptor antibody induction group, both groups treated with rATG demonstrated significant depletion of all T-cell subsets (CD3-positive cells) (P<0.0001 for rATG vs. anti-IL-2 receptor antibody induction group; P<0.001 for rATG+eculizumab vs. anti-IL-2 receptor antibody group). However, while T-cell counts were low in all rATG-treated patients, eculizumab treatment resulted in higher peripheral blood T-cell counts in rATG treated patients (P=0.005). Before induction, median total lymphocyte counts were normal for the three study groups. By 1, 4 months and 1 year, median the total lymphocyte count was normal for the anti-IL-2 receptor antibody group but was below normal range or at the lower edge of normality for rATG and rATG+eculizumab groups. CONCLUSIONS: This small-sample size study suggests that peripheral T cells are depleted by rATG in the presence of terminal complement inhibition. However, eculizumab appears to have a mild inhibitory effect on peripheral blood T-cell depletion by rATG in kidney transplant recipients.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Inativadores do Complemento/administração & dosagem , Rejeição de Enxerto/tratamento farmacológico , Transplante de Rim , Células Matadoras Naturais/efeitos dos fármacos , Complicações Pós-Operatórias/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Adulto , Idoso , Animais , Anticorpos Monoclonais/administração & dosagem , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Soro Antilinfocitário/administração & dosagem , Basiliximab , Ativação do Complemento/efeitos dos fármacos , Interações Medicamentosas/imunologia , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Células Matadoras Naturais/imunologia , Depleção Linfocítica , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/imunologia , Coelhos , Proteínas Recombinantes de Fusão/administração & dosagem , Linfócitos T/imunologia , Transplante Homólogo/imunologia
2.
Acad Radiol ; 19(7): 834-41, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22503893

RESUMO

RATIONALE AND OBJECTIVES: Magnetic resonance elastography (MRE) images the propagation of mechanical shear waves in tissue and uses that information to generate quantitative measures of tissue stiffness. Hepatic MRE has been successfully performed in thousands of patients, with good correlation between histologic grade of fibrosis and tissue stiffness. There has been no prior investigation of the utility of MRE for the assessment of kidney transplants. The aims of this study were to prospectively evaluate the feasibility of MRE in a small group of kidney transplant recipients and to correlate the measured magnetic resonance elastographic stiffness values with biopsy-proven histopathologic fibrosis. MATERIALS AND METHODS: MRE of renal transplants was performed in 11 patients returning for protocol allograft biopsies. Calculated tissue stiffness values were compared to histologic degree of fibrosis in nine of the 11 patients. RESULTS: The mean stiffness of two patients with moderate interstitial fibrosis was higher than the mean of six patients with mild interstitial fibrosis, but not significantly so (90 Hz, P = .12; 120 Hz, P = .17; 150 Hz, P = .26). The mean stiffness of the two patients with moderate interstitial fibrosis was slightly greater than the mean of one patient with no significant interstitial fibrosis at 90 Hz (P = .78) and slightly less at 120 and 150 Hz (P = .88 and P = .76). The mean stiffness of the six patients with mild interstitial fibrosis did not differ significantly from that of the one patient with no interstitial fibrosis (90 Hz, P = .35; 120 Hz, P = .22; 150 Hz, P = .16). CONCLUSIONS: Preliminary results demonstrate feasibility and support known multifactorial influences on renal stiffness.


Assuntos
Biópsia por Agulha , Técnicas de Imagem por Elasticidade , Transplante de Rim , Rim/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Estudos de Viabilidade , Feminino , Fibrose/patologia , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
3.
Transplantation ; 91(5): 536-41, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21283064

RESUMO

BACKGROUND: Donor specific alloantibody producing plasma cells (DSA-PCs) appear resistant to conventional immunosuppressive agents. This study aimed to determine the impact of pretransplant monotherapy with the proteasome inhibitor bortezomib on DSA-PCs in sensitized renal allograft candidates and to assess if DSA-PC depletion would enhance the efficacy of DSA removal using plasma exchange (PE). METHODS: Only patients with DSA levels considered too high to successfully undergo transplantation with PE alone were included in this study: i.e. those with a baseline B flow cytometric crossmatch (BFXM) >450 against a potential living donor.Four sensitized patients received 4 doses (1.3 mg/m/dose) of bortezomib and 4 received 16 doses. The number of DSA-PCs was determined pre and post-treatment using an ELISPOT assay. Five of these patients underwent post-treatment PE and their response was compared to 8 highly-sensitized patients (BFXM >450) who underwent PE alone. RESULTS: When considering all 8 patients as one group, bortezomib treatment decreased DSA-PCs in the marrow (mean±SD=16.7±14.5 DSA-PCs/ml pre-treatment vs. 6.2±3.6 DSA-PCs/ml after treatment, P=0.048). In the time frame of the study, bortezomib alone did not decrease serum DSA levels. However, five bortezomib treated patients underwent PE and showed a greater decease in DSA compared to the historical control group of 8 sensitized patients who underwent PE alone (mean decrease in BFXM channel shift=272.6±92.1 with bortezomib vs 95.4±72.2 in PE alone P=0.008). CONCLUSIONS: Bortezomib depletes DSA-PCs and appears to potentiate DSA removal by PE in sensitized renal transplant recipients.


Assuntos
Ácidos Borônicos/farmacologia , Isoanticorpos/sangue , Transplante de Rim/imunologia , Plasmócitos/efeitos dos fármacos , Plasmócitos/metabolismo , Inibidores de Proteases/farmacologia , Inibidores de Proteassoma , Pirazinas/farmacologia , Adulto , Bortezomib , Relação Dose-Resposta a Droga , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Estudos Prospectivos , Doadores de Tecidos , Resultado do Tratamento
4.
Pediatr Transplant ; 15(6): 557-63, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21199216

RESUMO

Advances in anti-HLA antibody characterization have had a major impact on kidney transplantation. Comprehensive characterization of DSA has improved protocols for allosensitized transplant candidates, increasing access to acceptable donors. Sensitive and specific solid phase antibody detection assays have given important insight into the clinical characteristics of antibody-mediated allograft injury, resulting in the development of a classification system for acute AMR. In addition, important insights into the nature of chronic antibody-mediated allograft rejection have been achieved as a result of improvements in DSA characterization. Finally, assays initially developed as tools to detect DSA in the clinical setting have been employed in innovative research protocols, allowing the investigation of new therapeutic approaches.


Assuntos
Anticorpos/imunologia , Antígenos HLA/imunologia , Transplante de Rim/métodos , Insuficiência Renal/terapia , Anticorpos/química , Criança , Rejeição de Enxerto/imunologia , Antígenos HLA/química , Humanos , Rim/imunologia , Transplante de Rim/efeitos adversos , Pediatria/métodos , Insuficiência Renal/imunologia , Reprodutibilidade dos Testes , Risco , Fatores de Tempo , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Transplante Homólogo/métodos , Resultado do Tratamento
5.
Clin Transplant ; 25(4): 594-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21050272

RESUMO

BACKGROUND: Increasing numbers of patients undergo preemptive renal transplantation. Obtaining cardiac catheterizations prior to transplantation to screen for coronary artery disease is controversial because of the perceived risk of inducing contrast nephropathy and the need for dialysis in patients with marginal renal function. We sought to examine the true impact of cardiac catheterization on time to dialysis in a cohort of preemptive renal transplant candidates. METHODS: From a cohort of 376 transplant candidates evaluated preemptively at our program between 2/2001 and 4/2005, 34 patients had positive dobutamine stress echocardiograms. We reviewed the subsequent need for dialysis in these patients. RESULTS: Among candidates undergoing angiography, 8.7% required dialysis within 14 d of contrast administration and 26% eventually needed dialysis prior to transplantation at 5.3 ± 3.7 months after their pre-transplant evaluation. Among patients who did not undergo angiography, 27% needed dialysis prior to transplantation at 2.4 ± 1.8 months after pre-transplant evaluation. CONCLUSIONS: Our results demonstrate a low risk of hastening the need for dialysis after coronary angiography in preemptive renal transplant candidates. Undergoing angiography had no effect on the ultimate need for or timing of dialysis initiation. These findings support completion of full cardiac evaluation as indicated for high-risk preemptive renal transplant candidates.


Assuntos
Angiografia Coronária , Falência Renal Crônica/diagnóstico por imagem , Transplante de Rim/diagnóstico por imagem , Diálise Renal/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Ecocardiografia sob Estresse , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Curr Opin Organ Transplant ; 15(4): 451-5, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20613525

RESUMO

PURPOSE OF REVIEW: To outline recent advances in our understanding of the role of B cells in transplantation. RECENT FINDINGS: While T-cell-mediated alloimmunity has been largely controlled using immunosuppression, the role of B cells in transplantation is just beginning to be understood. Recent studies have outlined some of the important clinical issues involving antibody including early acute humoral rejection and late transplant glomerulopathy. In addition, recent studies have identified bone-marrow-derived long-lived plasma cells that appear to be a major source of donor-specific alloantibody in sensitized renal transplant recipients. New agents are being tested that deplete these cells in vitro and in vivo. Memory B cells appear to be important in early acute humoral rejection, but few basic studies have been performed. Finally, recent studies involving patients undergoing tolerogenic regimens suggest that T-cell tolerance does not always convey tolerance in naive B cells. SUMMARY: Several B cell types have clear and specific roles in transplant recipients. Although our understanding of B cells in transplantation has improved, important gaps remain.


Assuntos
Linfócitos B/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Transplante de Rim/imunologia , Animais , Rejeição de Enxerto/prevenção & controle , Humanos , Imunidade Humoral , Memória Imunológica , Isoanticorpos/imunologia , Resultado do Tratamento
7.
Transplantation ; 89(9): 1088-94, 2010 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-20216485

RESUMO

BACKGROUND.: Anti-human leukocyte antigen antibodies (a-HLA) cause graft injury identified by C4d in peritubular capillaries. We investigated whether a-HLA relate to episodes of C4d negative acute rejection (AR). METHODS.: We analyzed 878 kidney recipients transplanted from January 2000 to December 2006. Pretransplant, 36% of these crossmatch negative recipients had a-HLA measured by solid phase assays. RESULTS.: AR occurred in 154 patients (18%) and 11 of them (9.4%) were C4d+. Forty-six percent of ARs were diagnosed by protocol biopsy. The risk of C4d-AR was increased in patients with a-HLA class I with donor specificity (DSA-I) (hazard ratio=1.519; confidence interval, 1.02-2.26; P=0.039). DSA-II were not associated with an increased risk of C4d-AR. The relationship between DSA-I and C4d-AR was independent of recipient age, BK nephropathy, and HLA mismatches. Compared with DSA-, in DSA+ recipients C4d-AR were most often histologically "borderline." DSA+ was associated with capillaritis in the biopsy (glomerulitis, 6.1% vs. 32%, P=0.003; peritubular capillaritis: 13% vs. 40%, P=0.0009). Compared with no AR, C4d-AR with capillaritis was associated with reduced graft survival (hazard ratio=4.164; confidence interval, 1.763-9.832; P=0.001), independent of other variables. This association was observed even in the cases of borderline AR. CONCLUSIONS.: DSA-I increases the risk of C4d-AR. The presence of DSA-I or II is associated with capillaritis during AR. Capillaritis is associated with reduced graft survival.


Assuntos
Capilares/patologia , Complemento C4b/análise , Rejeição de Enxerto/imunologia , Transplante de Rim/efeitos adversos , Fragmentos de Peptídeos/análise , Doença Aguda , Adulto , Idoso , Autoanticorpos/sangue , Cadáver , Capilares/imunologia , Feminino , Rejeição de Enxerto/patologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Transplante de Rim/patologia , Doadores Vivos , Masculino , Sobreviventes , Doadores de Tecidos , Transplante Homólogo/imunologia , Transplante Homólogo/patologia
8.
Curr Opin Organ Transplant ; 15(1): 8-10, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19890210

RESUMO

PURPOSE OF REVIEW: To outline recent studies describing the mechanisms of antibody-mediated rejection (AMR) and new clinical protocols aimed at prevention and/or treatment of this difficult clinical entity. RECENT FINDINGS: The natural history of acute AMR after positive cross-match kidney transplantation involves an acute rise in donor-specific alloantibody (DSA) in the first few weeks after transplantation. Whereas the exact cellular mechanisms responsible for AMR are not known, it seems likely that both pre-existing plasma cells and the conversion of memory B cells to new plasma cells play a role in the increased DSA production. One recent study suggested that combination therapy with plasmapheresis, high-dose IVIG and rituximab was more effective treatment for AMR than high-dose intravenous immunoglobulin (IVIG) alone, but the role of anti-CD20 antibody is still unclear. Two new promising approaches to AMR focus on depletion of plasma cells with the proteasome inhibitor, bortezomib, and the inhibition of terminal complement activation with a humanized, anti-C5 antibody, eculizumab. SUMMARY: The pathogenesis of AMR in several different clinical settings is becoming clearer and more effective treatments are being developed. Whether the prevention or successful treatment of AMR will decrease the prevalence of chronic injury and improved long-term graft survival will require longer-term studies.


Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Tolerância ao Transplante , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais Murinos , Rejeição de Enxerto/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Plasmaferese , Rituximab , Transplante Homólogo , Resultado do Tratamento
9.
Nephrol Dial Transplant ; 25(1): 307-10, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19846396

RESUMO

Putative antibody-mediated rejection (AMR) in HLA-identical sibling transplantation has rarely been reported and occurred before routine calcineurin inhibitor use. A 29-year-old male developed allograft dysfunction following an HLA-identical renal transplant from his sibling. A pretransplant panel-reactive antibody (PRA) was elevated, pre-transplant crossmatch was negative and no donor-specific antibody (DSA) was identified. Induction with alemtuzumab was followed by maintenance immunosuppression with corticosteroids, tacrolimus and mycophenolate. A biopsy for allograft dysfunction suggested AMR, but DSA could not be detected. Treatment for rejection was transiently successful. Undetectable minor histocompatibility antibodies may have contributed.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim/imunologia , Irmãos , Adulto , Biópsia , Humanos , Rim/patologia , Masculino , Transplante Homólogo
10.
Transplantation ; 87(8): 1232-9, 2009 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-19384172

RESUMO

BACKGROUND: For a subset of adults and children with primary focal segmental glomerulosclerosis (FSGS), proteinuria and renal dysfunction recur after kidney transplantation (KTx). Predicting recurrence and response to plasmapheresis (PP) or other interventions remains problematic. METHODS: The prevalence, recurrence rate, outcomes, and treatment responses of patients with FSGS were determined among 1573 KTx recipients. Although 5.0% carried some diagnosis of FSGS, only 1.9% (n=30) met strict diagnostic criteria for primary FSGS including biopsy-proven FSGS, lack of secondary factors, negative family history, and progression to end-stage renal disease within 10 years. RESULTS: Of these, 47% had recurrent FSGS compared with 8% of those not meeting strict criteria (P<0.001). Recurrence was more common in children compared with adults (86% vs. 35%, P=0.01). Graft survival was lower for recipients with primary FSGS compared with all others and inferior graft survival was attributable to recurrent FSGS. Fourteen patients received PP preemptively (pre-KTx) or therapeutically (post-KTx) for recurrent disease. Four pediatric patients additionally received anti-CD20 (rituximab) therapy. Of the different treatment approaches, only PP combined with rituximab was associated with prolonged remission of proteinuria. CONCLUSIONS: The results indicate that patients at high risk for FSGS recurrence can be identified and may benefit from carefully planned peritransplant interventions.


Assuntos
Glomerulosclerose Segmentar e Focal/cirurgia , Transplante de Rim/fisiologia , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Criança , Feminino , Glomerulosclerose Segmentar e Focal/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Resultado do Tratamento
11.
Pediatr Blood Cancer ; 52(4): 536-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19061212

RESUMO

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition characterized by small-vessel thrombi and a rapid onset of multiorgan system failure associated with systemic inflammatory response syndrome. Current treatment options include anticoagulants, corticosteroids, plasma exchange, and intravenous immunoglobulin, but these are not always effective. Rituximab, a chimeric anti-CD20 monoclonal antibody, may help eliminate autoreactive B cells and thus limit the rapid inflammatory process involved in CAPS. We describe the use of rituximab in the successful initial management of a probable case of pediatric CAPS.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/fisiopatologia , Adolescente , Anticorpos Monoclonais Murinos , Doença Catastrófica , Feminino , Humanos , Rituximab , Tomografia Computadorizada por Raios X
12.
Transplantation ; 86(5): 681-5, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18791449

RESUMO

BACKGROUND: Transplant glomerulopathy (TG) is a histopathologic entity of kidney allografts related to anti-human leukocyte antigen (HLA) antibodies. The goal of this study was to determine the relationships among antibody characteristics (level and specificity), risk for TG, and graft survival. METHODS: The presence and characteristics of anti-HLA antibody were assessed by single antigen beads assays in stored pretransplant sera from 598 kidney recipients with negative T-cell crossmatch. Transplant glomerulopathy was diagnosed by surveillance and clinical biopsies. RESULTS: Thirty-nine percent of patients presented with anti-HLA antibodies pretransplant. Transplant glomerulopathy was diagnosed in 73 patients (12%) during 54+/-19 months of follow-up. The risk of TG increased with higher anti-HLA-II antibody levels (HR=1.890, 95% CI 1.42-2.52; P<0.0001), donor specificity of the antibodies (3.524 [1.67-7.44]; P=0.001), and in patients with history of antibody-mediated rejection (4.985 [2.77-8.97]; P<0.0001, multivariate Cox). Graft survival during the follow-up period was 95% without TG and 62% with TG (P<0.0001). The presence of C4d in peritubular capillaries was an independent risk factor for graft failure after TG diagnosis. Thus, 25% of TG/C4d and 80% of TG/C4d+ grafts failed (P<0.0001). Of interest, higher anti-HLA-II levels were related to the presence of C4d (3.216 [1.376-7.517]; P=0.007). CONCLUSIONS: In T-cell negative crossmatch patients, higher anti-HLA-II antibody levels are related to the increase in the risk of developing TG. Higher antibody levels are also related to the presence of C4d in peritubular capillaries in TG biopsies. Furthermore, the presence of C4d in TG is related to the reduced graft survival.


Assuntos
Autoanticorpos/sangue , Sobrevivência de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Glomérulos Renais/patologia , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Autoanticorpos/imunologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Glomérulos Renais/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/imunologia
13.
Curr Opin Nephrol Hypertens ; 16(6): 529-34, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18089966

RESUMO

PURPOSE OF REVIEW: Although ABO incompatible kidney transplantation is increasingly recognized as effective, the procedure is still evolving. The purpose of this review is to summarize recent advances in this area. RECENT FINDINGS: Short to intermediate-term outcome appears good, although long-term results are still preliminary. Pretransplant risk stratification based on antidonor antibody titer may be of limited value. Splenectomy, previously reported to be an important component of ABO incompatible transplantation, appears to be avoidable under many circumstances. The wider implementation of A2 blood group incompatible transplantation shortens waiting time for deceased donor transplantation of blood group B recipients without significantly disadvantaging others. The diagnosis of acute humoral rejection has become clearer following the recognition that C4d deposition commonly occurs in well functioning ABO incompatible allografts. The long-term implications of acute humoral rejection appear substantial even following successful acute therapy, with a significant percentage of patients developing chronic humoral rejection manifested as transplant glomerulopathy. Finally, although ABO incompatible transplantation entails increased expense, when compared with maintenance dialysis and taking into account the health related quality of life benefits of a successful transplant, it is clearly cost effective. SUMMARY: ABO incompatible kidney transplantation is an effective therapy, and will become more widely implemented in the future.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Transplante de Rim/métodos , Complemento C4b , Rejeição de Enxerto/economia , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Rim/economia , Fragmentos de Peptídeos
14.
Transplantation ; 84(2): 258-64, 2007 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-17667819

RESUMO

BACKGROUND: We evaluated the effect of antithymocyte globulin (ATG) on anti-human leukocyte antigen (HLA) antibody assays. METHODS: We tested sera from six in vivo ATG-treated kidney transplant patients after measuring serum concentrations, as well as six nonsensitized sera with ATG added in vitro. T- and B-cell complement-dependent cytotoxicity (CDC), flow cytometric (FXM), and solid-phase HLA class I and II assays based on antigen-coated microspheres and enzyme-linked immunosorbent assay (ELISA) were studied. Sera were then retested after treatment to remove ATG. RESULTS: We found that ATG affects test results differently depending on whether sera is obtained from in vivo treated patients or added in vitro. In vitro treated sera produced ATG concentration-dependent positive results for T/B CDC, FXM, and flow bead testing for HLA I/II, while the ELISA-based assay was unaffected. In vivo treated sera from ATG-treated patients produced positive test results for T CDC and T/B FXM, while the B-cell CDC crossmatch remained negative. Solid phase assays were minimally affected using in vivo treated sera. After ATG extraction, all tests became negative. CONCLUSION: We conclude that ATG produces positive results in anti-HLA antibody testing, and treatment to remove ATG abolishes this effect. This treatment allows ATG-treated patients to be monitored for anti-HLA antibodies.


Assuntos
Soro Antilinfocitário/farmacologia , Antígenos HLA/imunologia , Imunossupressores/farmacologia , Isoanticorpos , Transplante de Rim/imunologia , Linfócitos B/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/efeitos dos fármacos , Teste de Histocompatibilidade/métodos , Humanos , Isoanticorpos/análise , Isoanticorpos/efeitos dos fármacos , Isoanticorpos/imunologia , Prognóstico , Linfócitos T/imunologia
15.
Transplantation ; 80(11): 1572-7, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16371928

RESUMO

BACKGROUND: Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. METHODS: We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). RESULTS: Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. CONCLUSIONS: Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.


Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos/cirurgia , Rejeição de Enxerto/imunologia , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Esplenectomia , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Masculino , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento
16.
Am J Transplant ; 5(7): 1660-70, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15943624

RESUMO

Primary systemic amyloidosis (AL) is characterized by multiorgan deposition of monoclonal immunoglobulin light chain. Renal involvement is common and impaired kidney function is associated with reduced median survival. Autologous stem cell transplantation (SCT) for AL achieves superior response rates compared to chemotherapy alone but patients with end-stage renal disease (ESRD) may be excluded from consideration. A treatment approach consisting of living donor kidney transplantation (LDKTx) followed by autologous SCT was developed for AL with ESRD. Eight patients underwent LDKTx with immediate graft function. Two suffered unanticipated complications post-KTx and died 10 and 3 months later. Two cases of subclinical acute cellular rejection (ACR) and one case of clinical ACR occurred--all reversible with corticosteroid. Six patients had successful stem cell harvests performed and five of these underwent SCT with satisfactory trilineage engraftment. Renal function remained stable following SCT in four and was reduced in one due to infectious and bleeding complications. One patient, who has thus far elected not to undergo SCT, has proteinuria and histologic evidence of recurrent renal amyloidosis. This experience supports the feasibility of sequential living donor KTx and autologous SCT for carefully selected patients with ESRD due to AL.


Assuntos
Amiloidose/cirurgia , Nefropatias/cirurgia , Transplante de Rim , Doadores Vivos , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Células-Tronco , Coleta de Tecidos e Órgãos , Transplante Autólogo , Resultado do Tratamento
17.
Am J Transplant ; 5(7): 1689-93, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15943627

RESUMO

Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality.


Assuntos
Calcinose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Transplante de Rim , Prontuários Médicos , Adulto , Calcinose/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Tomografia Computadorizada por Raios X
18.
Am J Transplant ; 5(5): 1130-6, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15816896

RESUMO

Kidney allograft failure is most often caused by chronic allograft nephropathy, a process of interstitial fibrosis (GIF) and tubular atrophy (TA). We assessed the pathology of living donor (LD) grafts compared to deceased donor (DD). Included are 321 recipients (245 LD; 76 DD) with protocol biopsies the first 2 years of transplant. In LD, GIF was present in 7%, 31%, 61% and 71% of grafts at 0, 4, 12 and 24 months. TA progressed in parallel to GIF. Compared to LD, more DD grafts had GIF at time 0 (29%, p = 0.002); thereafter the incidence of GIF was similar. In LD, GIF was associated with lower glomerular filtration rate (GFR)(1 year) (no GIF, 62 +/- 16; GIF, 49 +/- 15 mL/min/m(2) iothalamate clearance, p = 0.001) and reduced graft survival (HR = 2.2, p = 0.009). GIF in LD related to acute rejection (HR = 2.6, p = 0.01), polyoma nephropathy (OR = 4.4, p = 0.02) and lower levels of GFR 3 weeks post-transplant (HR = 0.961; p = 0.03, multivariate). However, GIF also developed in 53% of recipients lacking these covariates. Thus, GIF/TA develops in the majority of LD grafts, it is often mild but is associated with reduced function and survival. GIF frequently develops in the absence of risk factors. Lower GFR post-transplant identify patients at highest risk of GIF.


Assuntos
Transplante de Rim/métodos , Rim/patologia , Adulto , Idoso , Atrofia , Biópsia , Índice de Massa Corporal , Cadáver , Feminino , Fibrose , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Nefropatias/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Kidney Int ; 66(4): 1654-61, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15458463

RESUMO

BACKGROUND: Donor age adversely affects deceased-donor kidney transplant outcomes, but its influence on living-donor transplantation is less well characterized. METHODS: Living-donor kidney transplants at a single center between 1998 and 2000 were reviewed. Data were abstracted for 52 transplants from donors aged > or =50 years and for a matched group of 104 transplants from donors aged <50 years. Survival indices were compared during the first three years' post-transplantation. Functional indices, including serial iothalamate clearances, were compared at 1, 12, and 24 months. RESULTS: Predonation glomerular filtration rate (GFR) was lower among older donors (94 +/- 12 vs. 108 +/- 17 mL/min/SA) but post-transplant compensatory hypertrophy was similar (11.7 +/- 26.3% vs. 7.7 +/- 31.4%). Recipients of older-donor grafts were older (52.8 +/- 16.5 vs. 46.1 +/- 15.1 years) and more frequently unrelated to the donor (54% vs. 39%). Trends toward higher frequency of slow graft function, cytomegalovirus (CMV) infection, and polyomavirus nephropathy were observed for older-donor grafts. Three-year recipient, graft, and death-censored graft survivals were > or =90% for both groups. At 1, 12, and 24 months, serum creatinine was higher and GFR was lower among recipients of older- compared with younger-donor grafts. Other functional indices (urine total protein, serum potassium and uric acid, hemoglobin, and number of antihypertensives) were not different. Donor age correlated with graft GFR at 1, 12, and 24 months for the entire study cohort by linear regression. CONCLUSION: Older donor age does not preclude excellent results from living-donor kidney transplantation but should be appreciated as being associated with relatively lower GFR.


Assuntos
Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Doadores Vivos/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Fatores de Risco
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