Factors associated with health-related quality of life after successful kidney transplantation: a population-based study

Kidney transplantation improves the quality of life of end-stage renal disease patients. The quality of life benefits, however, pertain to patients on average, not to all transplant recipients. The aim of this study was to identify factors associated with health-related quality of life after kidney transplantation. Population-based study with a cross-sectional design was carried out and quality of life was assessed by SF-36 Health Survey Version 1. A multivariate linear regression model was constructed with sociodemographic, clinical and laboratory data as independent variables. Two hundred and seventy-two kidney recipients with a functioning graft were analyzed. Hypertension, diabetes, higher serum creatinine and lower hematocrit were independently and significantly associated with lower scores for the SF-36 oblique physical component summary (PCSc). The final regression model explained 11% of the PCSc variance. The scores of oblique mental component summary (MCSc) were worse for females, patients with a lower income, unemployed and patients with a higher serum creatinine. The regression model explained 9% of the MCSc variance. Among the studied variables, comorbidity and graft function were the main factors associated with the PCSc, and sociodemographic variables and graft function were the main determinants of MCSc. Despite comprehensive, the final regression models explained only a little part of the heath-related quality of life variance. Additional factors, such as personal, environmental and clinical ones might influence quality of life perceived by the patients after kidney transplantation.

Donor bone marrow cells play a role in the prevention of accelerated graft rejection induced by semi-allogeneic spleen cells in transplantation

Spleen or spleen plus bone marrow cells from (BALB/c x C57Bl/6)F1 donors were transferred into BALB/c recipients 21 days before skin or cardiac transplantation. Prolonged graft survival was observed on recipients treated with the mixture of donor-derived cells as compared to those treated with spleen cells alone. We evaluated the expression of CD45RB and CD44 by splenic CD4(+) and CD8(+) T cells 7 and 21 days after donor cell transfer. The populations of CD8(+)CD45RB(low) and CD8(+)CD44(high) cells were significantly decreased in mice pre-treated with donor spleen and bone marrow cells as compared to animals treated with spleen cells only, although these cells expanded in both groups when compared to an earlier time-point. No differences were observed regarding CD4+ T cell population when recipients of donor-derived cells were compared. An enhanced production of IL-10 was observed seven days after transplantation in the supernatants of spleen cell cultures of mice treated with spleen and bone marrow cells. Taken together these data suggest that donor-derived bone marrow cells modulate the sensitization of the recipient by semi-allogeneic spleen cells in part by delaying the generation of activated/memory CD8(+) T cells leading to enhanced graft survival. (c) 2007 Elsevier B.V. All rights reserved.

Vimentin Expression and Myofibroblast Infiltration Are Early Markers of Renal Dysfunction in Kidney Transplantation: An Early Stage of Chronic Allograft Dysfunction?

Introduction. The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up. Methods. Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function. Results. Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 +/- 8.5 months. The mean Cr at biopsy time was 1.44 +/- 0.33 mg/dL, and after the follow-up it was 1.29 +/- 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively. Conclusion. Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.

Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism

Heme oxygenase-1 (HO-1) has a microsatellite polymorphism based on the number of guanosine-thymidine nucleotide repeats (GT) repeats that regulates expression levels and could have an impact on organ survival post-injury. We correlated HO-1 polymorphism with renal graft function. The HO-1 gene was sequenced (N = 181), and the allelic repeats were divided into subclasses: short repeats (S) (< 27 repeats) and long repeats (L) (>= 27 repeats). A total of 47.5% of the donors carried the S allele. The allograft function was statistically improved six months, two and three yr after transplantation in patients receiving kidneys from donors with an S allele. For the recipients carrying the S allele (50.3%), the allograft function was also better throughout the follow-up, but reached statistical significance only three yr after transplantation (p = 0.04). Considering only those patients who had chronic allograft nephropathy (CAN; 74 of 181), allograft function was also better in donors and in recipients carrying the S allele, two and three yr after transplantation (p = 0.03). Recipients of kidney transplantation from donors carrying the S allele presented better function even in the presence of CAN.

Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Purpose Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients and Methods We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). Results Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >= 65 years had 2-year survival rates as follows: 44% (95% Cl, 37% to 52%), 50% (95% Cl, 41% to 59%), 34% (95% Cl, 25% to 43%), and 36% (95% Cl, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% Cl, 35% to 49%), 35% (95% Cl, 27% to 43%), 45% (95% Cl, 36% to 54%), and 38% (95% Cl, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P>.3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. Conclusion With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Autofluorescence spectroscopy in liver transplantation: Preliminary results from a pilot clinical study

The evaluation of graft function at various stages after transplantation is relevant, particularly at the moment of organ harvest, when a decision must be made whether to use the organ. Autofluorescence spectroscopy is noninvasive technique to monitor the metabolic condition of a liver graft throughout its course, from an initial evaluation in the donor, through cold ischemia transportation, to reperfusion and reoxygenation in the recipient. Preliminary results are presented in six liver transplantations spanning the periods from liver harvest to implant. The laser-induced fluorescence spectrum at 532-mn excitation was investigated before cold perfusion (autofluorescence), during cold ischemia, at the back table procedure, as well as 5 and 60 minutes after reperfusion. The results showed that the fluorescence analysis was sensitive to changes during the transplantation procedure. Fluorescence spectroscopy potentially provides a real-time, noninvasive technique to monitor liver graft function. The information could potentially be valuable for surgical decisions and transplant success.

Análise clínica e epidemiológica do transplante de medula óssea no Serviço de Oncologia Pediátrica do Hospital de Clínicas de Porto Alegre

Objetivos: Descrever o perfil e as complicações agudas mais importantes das crianças que receberam transplante de medula óssea (TMO) em nosso Serviço. Casuística e métodos: Análise retrospectiva de 41 pacientes menores de 21 anos transplantados entre Agosto de 1997 até Junho de 2002. Deste total 20 receberam transplante alogênico e 21 receberam transplante autogênico. Resultados: No TMO alogênico a média de idade foi de 8,9 + 5,4 anos, sendo 12 pacientes do sexo masculino. As fontes de células foram: medula óssea (MO) 12, sangue periférico (SP) 5, sangue de cordão umbilical não aparentado (SCU) 3. As doenças tratadas foram leucemia linfóide aguda (LLA) 7 pacientes, leucemia linfóide crônica (LMC) 2; leucemia mielóide aguda (LMA) 4; Síndrome mielodisplásica 2; Linfoma de Burkitt 1, Anemia aplástica grave 1; Anemia de Fanconi 1; Síndrome Chediak Higashi 1; Imunodeficiência congênita combinada grave 1. Um paciente desenvolveu doença do enxerto contra hospedeiro (DECH) aguda grau 2 e três DECH grau 4. Três pacientes desenvolveram DECH crônica. Todos haviam recebido SP como fonte de células. A sobrevida global foi de 70,0 + 10,3%. A principal causa do óbito foi DECH em 3 pacientes e sépse em outros 3. Todos os óbitos ocorreram antes do dia 100. Um dos pacientes que recebeu SCU está vivo em bom estado e sem uso de medicações 3 anos e 6 meses pós TMO. No TMO autogênico, a média de idade foi de 8,7 + 4,3 anos, sendo 11 pacientes do sexo masculino. As fontes de células foram SP 16, MO 3, SP + MO 2. As doenças tratadas foram: tumor de Wilms 5; tumores da família do sarcoma de Ewing 4; neuroblastomas 3; linfomas de Hodgkin 3; rabdomiossarcomas 2, tumor neuroectodérmico primitivo do SNC 2; Linfoma não Hodgkin 1; LMA 1. A sobrevida global está em 59,4 + 11,7 %. Cinco óbitos tiveram como causa a progressão da doença de base, um óbito ocorreu devido à infecção 20 meses pós TMO e dois óbitos foram precoces por sépse. As toxicidades mais comuns em ambos os grupos foram vômitos, mucosite, diarréia e dor abdominal. Infecções foram documentadas em 58,5% dos pacientes e 46,9% tiveram no mínimo um agente isolado na hemocultura. Os tempos de enxertia de neutrófilos e plaquetas correlacionaram-se com o número de células progenitoras infundidas. Conclusão: A sobrevida de nossos pacientes é semelhante à encontrada na literatura de outros serviços nacionais e internacionais. Não encontramos diferença entre os dois tipos de transplante com relação às toxicidades agudas e ás infecções.

Germ Cell Transplantation in Felids: A Potential Approach to Preserving Endangered Species

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Limbal autograft transplantation in a dog with alkali-induced ulceration

Descreve-se um caso de um animal da espécie canina, fêmea, sem raça definida, de três meses de idade, com histórico de apatia, contato prévio com produto alcalino (hidróxido de sódio) e relutância em abrir o olho direito. Ao exame oftálmico, foram observados blefarospasmo, fotofobia, epífora, quemose discreta, hiperemia conjuntival, e edema corneal difuso com comprometimento do limbo. Foram realizados o teste da fluoresceína positivo e o Teste Lacrimal de Schirmer 32mm min-1. Com base nos achados, firmou-se o diagnóstico de úlcera por álcali e realizou-se transplante autógeno do limbo. No pós-operatório, observou-se vascularização corneal a partir do terceiro dia e sua intensificação, em número e calibre, nos dias subseqüentes. Também foram observadas mínimas áreas de transparência corneal. Os resultados obtidos permitem admitir que o transplante autógeno de limbo é procedimento factível para o manejo da terapia de úlceras de córnea por álcali.

Sclerocorneal limbal stem cell autograft transplantation in dogs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação do transplante de medula óssea alogênico por meio do estudo de regiões de repetições seqüenciais no genoma humano (VNTRs e STRs)

Os objetivos deste estudo foram estabelecer um protocolo para a análise de minissatélites ou VNTRs e microssatélites ou STRs em pacientes que se submeteram ao TMO alogênico; verificar a validade da metodologia e dos loci estudados e avaliar o tipo de recuperação do paciente. Foram analisados o DNA do paciente anterior e posterior ao transplante de 14 indivíduos e dos respectivos doadores. Amplificações por PCR de seis loci: D1S80, SE33, HumTH01, 33.6, HumARA e HumTPO foram realizadas. Os produtos amplificados foram separados por eletro­forese vertical em gel de poliacrilamida, e os fragmentos visualizados por coloração pela prata. Esse procedimento mostrou ser válido na verificação da recuperação alogênica, autóloga e provavelmente na quimérica. da somatória dos loci estudados, 63,1% apresentaram resultados possíveis de serem avaliados e, desses, 19,0% mostraram resultado informativo, 13,1% parcialmente informativo e 31,0% não informativo. Os 36,9% restantes não foram possíveis de avaliação. Dos loci avaliados, o que demostrou maior índice de resultado informativo foi o SE33, parcialmente informativo o HumTPO e não informativo o HumTH01, sendo o locus 33.6 o que mais apresentou resultados não possíveis de serem avaliados. Por outro lado, determinou-se a recuperação do paciente posterior ao transplante em 71,4% dos indivíduos, sendo que, desses, 90% apresentaram recuperação alogênica e 10% recuperação autóloga.

Chimerism induction by nonmyeloablactive preconditioning and bone marrow infusion in rat small bowel transplantation

Em estudo recente demonstramos que a infusão de células da medula óssea do doador após o transplante intestinal não aumentou a sobrevida do enxerto quando se utilizou series curtas de drogas imunossupressoras. OBJETIVO: Neste estudo avaliamos se a utilização de diferentes regimes de irradiação em associação com a infusão de medula óssea altera a sobrevida do enxerto e a morbidade sobre receptor. MÉTODOS: Realizou-se o transplante heterotópico de intestino delgado, utilizando-se ratos Lewis como receptores e da como doadores, imunossuprimidos com FK 506 na dose de 1mg/kg/dia por 5 dias e distribuídos em 4 grupos: G1 (n= 4), não irradiado e sem infusão de medula óssea; G2 (n= 6), G3 (n= 9) e G4 (n= 6) foram infundidos com 100 x 10(6) células de medula após o transplante. Grupos 3 e 4 foram irradiados com 250 e 400 rd respectivamente. Os animais foram examinados diariamente para a detecção de rejeição e reação do enxerto versus hospedeiro, tendo sido colhidas amostras semanais de sangue para estudos de quimerismose biopsias quinzenais da estomia. RESULTADOS: Animais nos G1 e G2 apresentaram rejeição mínima no 15º pós-operatório, enquanto a reação do enxerto versus hospedeiro foi caracterizada nos G3 e G4. Os níveis de quimerismo total e de células T foram maiores nos grupos irradiados em comparação aos não irradiados. A causa mortis nos G1 e G2 foi a rejeição enquanto que nos G3 e G4 foi a reação do enxerto versus hospedeiro. CONCLUSÃO: Concluímos que a utilização de baixas doses de irradiações retardam o aparecimento da rejeição, mas não previne a ocorrência da reação do enxerto versus hospedeiro.

Muscle graft as a substitute for peripheral nerve graft in rats

OBJETIVO: Avaliar a aplicabilidade do uso de músculo autógeno, tratado de diversas maneiras, em substituição aos enxertos de nervo. MÉTODOS: Os ratos foram separados em sete grupos que receberam, como tratamento a uma lesão nervosa padronizada, os seguintes tipos de enxertos: músculo fresco, músculo fixado com formol 10%, músculo congelado em freezer, músculo congelado em refrigerador, músculo denervado, nervo periférico e um grupo ficou sem qualquer tratamento. Foi avaliado o aspecto histológico das fibras nervosas no segmento reparado. RESULTADOS: A avaliação do segmento nervoso reparado mostrou que existiam axônios em quase todos os grupos, mas a metodologia empregada não possibilitou caracterizar adequadamente as diferenças entre os grupos. CONCLUSÃO: Este estudo mostrou a migração de axônios por meio de todos os enxertos utilizados.

Effects of pancreas transplantation on oxidative stress in pulmonary tissue from alloxan-induced diabetic rats

Purpose. There is considerable evidence that cellular oxidative stress caused by hyperglycemia plays an important role in the genesis and evolution of chronic diabetic lesions. In this study, we determined the effectiveness of pancreas transplantation (PT) in preventing the imbalance caused by excessive production of reactive oxygen species over antioxidant defenses in lungs of rats rendered diabetic by alloxan injection.Methods. Sixty inbred male Lewis rats, weighing 250-280 g, were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each which were killed after 4 and 12 weeks of follow-up. Plasma glucose, glycosylated hemoglobin, and insulin levels were determined in all rats. Lipid hydroperoxide (LPO) concentrations and enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in the pulmonary tissue of all rats.Results. The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). They also showed significantly increased LPO concentrations in the lungs (P < .01) after 4 and 12 weeks of follow-up. In contrast, SOD, CAT, and GSH-Px antioxidant activities were significantly reduced in these periods (P < .01) 12 weeks after diabetes induction. Successful PT corrected all clinical and metabolic changes in the diabetic rats, with sustained normoglycemia throughout the study. Excessive lung LPO production and low SOD, CAT, and GSH-Px antioxidant activities were already back to normal 4 weeks after PT.Conclusion. PT can control oxidative stress in pulmonary tissue of diabetic rats. It may be the basis for preventing chronic diabetic lesions in lungs.