RESUMO
BACKGROUND: Disparities in aspects of chronic kidney disease progression and management exist for patients from culturally and linguistically diverse (CALD) backgrounds, including with treatment and outcomes for kidney transplantation. OBJECTIVE: This study aimed to explore factors that impact kidney transplant outcomes from the perspective of kidney transplant recipients (KTRs) from CALD backgrounds and their family caregivers. METHODS: A descriptive qualitative design was utilised. Participants were recruited from two tertiary hospitals in Victoria, Australia. Semi-structured interviews were conducted with KTRs who were born overseas in countries where English is not the primary language. Interviews were also conducted with family caregivers. Analysis was guided by the Framework Method, and emergent subcategories were mapped into the categories identified in Andersen's Health Service Utilisation Model. RESULTS: Data from 21 KTRs and five caregivers were grouped under the categories of Population Characteristics, Environment, Health Behaviour and Outcomes. KTRs believed that neither culture nor religious beliefs impacted how they managed their transplant or healthcare utilisation. KTRs expressed satisfaction with their care, felt no inequity with how they were treated by health professionals and expressed gratitude for the Australian healthcare system. Language did not necessarily impact transplant outcomes, but there was a reliance on interpreters for non-English-speaking patients as most written information was in English. Caregivers were instrumental in providing support but discussed the challenges involved. CONCLUSION: This study explored factors influencing kidney transplantation for KTRs from a CALD background. The study provided insight into how to deliver quality healthcare to these patients, highlighting the importance of health services providing information that is written in the patient's own language and respectively asking KTRs about their health beliefs or customs. Caregivers were instrumental in supporting KTRs, but there is a need to better prepare them for this role. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement was integrated into the design and delivery of the study. KTRs from CALD backgrounds assisted with framing the research questions and offering advice on the recruitment and data collection process.
Assuntos
Transplante de Rim , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Vitória , Cuidadores/psicologia , Entrevistas como Assunto , Idioma , Idoso , Diversidade CulturalRESUMO
Patients with diabetes are at an increased risk for acute kidney injury (AKI) after renal ischemia/reperfusion injury (IRI). However, there is a lack preclinical models of IRI in established diabetes. The current study characterized renal IRI in mice with established diabetes and investigated potential therapies. Diabetes was induced in C57BL/6J mice by low-dose streptozotocin injection. After 7 weeks of sustained diabetes, mice underwent 13 minutes of bilateral renal ischemia and were euthanized after 24 hours of reperfusion. Age-matched, nondiabetic controls underwent the same surgical procedure. Renal IRI induced two- and sevenfold increases in plasma creatinine level in nondiabetic and diabetic mice, respectively (P < 0.001). Kidney damage, as indicated by histologic damage, tubular cell death, tubular damage markers, and inflammation, was more severe in the diabetic IRI group. The diabetic IRI group showed greater accumulation of spleen tyrosine kinase (Syk)-expressing cells, and increased c-Jun N-terminal kinase (Jnk) signaling in tubules compared to nondiabetic IRI. Prophylactic treatment with a Jnk or Syk inhibitor substantially reduced the severity of AKI in the diabetic IRI model, with differential effects on neutrophil infiltration and Jnk activation. In conclusion, established diabetes predisposed mice to renal IRI-induced AKI. Two distinct proinflammatory pathways, JNK and SYK, were identified as potential therapeutic targets for anticipated AKI in patients with diabetes.
Assuntos
Injúria Renal Aguda , Diabetes Mellitus Experimental , Traumatismo por Reperfusão , Injúria Renal Aguda/etiologia , Animais , Diabetes Mellitus Experimental/metabolismo , Feminino , Humanos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/patologia , Transdução de Sinais/fisiologia , Quinase Syk/metabolismoRESUMO
Activation of the JUN amino-terminal kinase (JNK) pathway is prominent in most forms of acute and progressive tubulointerstitial damage, including acute renal ischemia/reperfusion injury (IRI). Two forms of JNK, JNK1 and JNK2, are expressed in the kidney. Systemic administration of pan-JNK inhibitors suppresses renal IRI; however, the contribution of JNK1 versus JNK2, and the specific role of JNK activation in the proximal tubule in IRI, remains unknown. These questions were addressed in rat and mouse models of acute bilateral renal IRI. Administration of the JNK inhibitor, CC-930, substantially reduced the severity of renal failure, tubular damage, and inflammation at 24 hours in a rat IRI model. Additionally, Jnk1-/- mice, but not Jnk2-/- mice, were shown to be significantly protected against acute renal failure, tubular damage, and inflammation in the IRI model. Furthermore, mice with conditional Jnk1 deletion in the proximal tubule also showed considerable protection from IRI-induced renal failure, tubular damage, and inflammation. Finally, primary cultures of Jnk1-/-, but not Jnk2-/-, tubular epithelial cells were protected from oxidant-induced cell death, in association with preventing phosphorylation of proteins (receptor interacting serine/threonine kinase 3 and mixed lineage kinase domain-like pseudokinase) in the necroptosis pathway. In conclusion, JNK1, but not JNK2, plays a specific role in IRI-induced cell death in the proximal tubule, leading to acute renal failure.
Assuntos
Injúria Renal Aguda/patologia , Inflamação/patologia , Sistema de Sinalização das MAP Quinases , Traumatismo por Reperfusão/patologia , Animais , Morte Celular , Modelos Animais de Doenças , Células Epiteliais/patologia , Rim/patologia , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Ratos , Ratos Sprague-DawleyRESUMO
Reduced estimated glomerular filtration rate (eGFR) at 12-months after kidney transplantation is associated with increased risk of allograft loss, but it is uncertain whether donor age and types modify this relationship. Using Australia and New Zealand registry data, multivariable Cox proportional modelling was used to examine the interactive effects between donor age, types and 12-month eGFR on overall allograft loss. We included 11,095 recipients (4,423 received live-donors). Recipients with lowest 12-month eGFR (<30 ml/min/1.73 m2) experienced the greatest risk of allograft loss, with adjusted HR [95% CI) of 2.65 [2.38-2.95] compared to eGFR of 30-60 ml/min/1.73 m2; whereas the adjusted HR for highest eGFR (>60 ml/min/1.73 m2) was 0.67 [0.62-0.74]. The association of 12-month eGFR and allograft loss was modified by donor age (but not donor types) where a higher risk of allograft loss in recipients with lower compared with higher 12-month eGFR being most pronounced in the younger donor age groups (p < 0.01). Recipients with eGFR <30 ml/min/1.73 m2 12-months after transplantation experienced ≥2.5-fold increased risk of overall allograft loss compared to those with eGFR of >60 ml/min/1.73 m2, and the magnitude of the increased risk is most marked among recipients with younger donors. Careful deliberation of other factors including donor age when considering eGFR as a surrogate for clinical endpoints is warranted.
Assuntos
Transplante de Rim , Aloenxertos , Criança , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To identify barriers and enablers to COVID-19 vaccination in renal transplant recipients who are undecided about vaccination. METHODS: An online survey was distributed to 876 adult kidney transplant recipients at a tertiary referral service, who had not been vaccinated against COVID-19. The survey assessed willingness to be vaccinated, attitudes toward COVID-19 vaccines, and barriers and enablers to proceeding with vaccination. RESULTS: The survey response rate was 54% (473/876). Three hundred and forty-six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p < .001) and more concerned about (93.3% vs. 25.1%, p < .001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testing in transplant recipients. Undecided recipients had received less vaccine-specific information from medical specialists than the yes group. Most undecided participants (95.1%) were willing to proceed with vaccination with appropriate supports. The most desired supports were information and a recommendation to proceed with vaccination from their treating transplant specialist and team. CONCLUSION(S): Concerns about vaccine safety (including harm to transplant), poor vaccine efficacy, and lack of rigorous testing were barriers to vaccine uptake. Most undecided recipients would proceed with vaccination with specific recommendations and vaccine information provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.
Assuntos
COVID-19 , Transplante de Rim , Vacinas , Adulto , Atitude , Vacinas contra COVID-19 , Humanos , Transplante de Rim/efeitos adversos , SARS-CoV-2 , Transplantados , VacinaçãoRESUMO
The aim of this study was to determine if natural killer cell number (CD3- /CD16± /CD56± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.
Assuntos
Infecções por Citomegalovirus/complicações , Transplante de Rim/efeitos adversos , Células Matadoras Naturais/citologia , Transplantados , Área Sob a Curva , Citomegalovirus , Infecções por Citomegalovirus/sangue , Feminino , Humanos , Imunossupressores/farmacologia , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Curva ROC , Análise de Regressão , RiscoRESUMO
Antibody-mediated rejection, whereby transplant recipient B cells and/or plasma cells produce alloreactive anti-human leukocyte antigen (HLA) antibodies, negatively influences transplant outcomes and is a major contributor to graft loss. An early humoral immune response is suggested by the production of anti-HLA donor-specific antibodies (DSA) that can be measured using solid phase assays. We report the early posttransplant coexistence of a shared anti-HLA antibody profile in 5 solid organ transplant recipients who received organs from the same donor. Retrospective analysis of the donor's serum confirmed the presence of the same anti-HLA profile, suggesting the transfer of donor-derived anti-HLA antibodies, or the cells that produce them, to multiple solid organ transplant recipients. The time frame and extent of transfer suggest a novel variant of the passenger lymphocyte syndrome. These findings have important implications for the consideration of all posttransplant antibody measurements, particularly the interpretation of non-DSAs in the sera of transplant recipients.
Assuntos
Antígenos HLA/imunologia , Imunidade Humoral/imunologia , Isoanticorpos/imunologia , Transplante de Pulmão/métodos , Linfócitos/imunologia , Complicações Pós-Operatórias/imunologia , Doadores de Tecidos/provisão & distribuição , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Prognóstico , Estudos Retrospectivos , SíndromeRESUMO
BACKGROUND: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. METHODS: We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. RESULTS: Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). CONCLUSION: Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.
Assuntos
Infecções/diagnóstico , Transplante de Rim/efeitos adversos , Transplantados , Biomarcadores/análise , Linfócitos T CD4-Positivos/imunologia , Feminino , Humanos , Imunoglobulinas/análise , Terapia de Imunossupressão , Transplante de Rim/estatística & dados numéricos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de RiscoRESUMO
The demand for kidney transplantation continues to exceed the availability of deceased donor kidneys. Balancing the overarching principles of the optimal use of (utility) and equal access to (equity) this scarce resource requires a sophisticated allocation system. This review will examine how various factors are addressed in allocation systems around the world to strike a balance between utility and equity.
Assuntos
Técnicas de Apoio para a Decisão , Seleção do Doador , Equidade em Saúde , Disparidades em Assistência à Saúde , Transplante de Rim/métodos , Obtenção de Tecidos e Órgãos/métodos , Fatores Etários , Sobrevivência de Enxerto , Alocação de Recursos para a Atenção à Saúde , Necessidades e Demandas de Serviços de Saúde , Histocompatibilidade , Humanos , Transplante de Rim/efeitos adversos , Avaliação das Necessidades , Fatores de Risco , Fatores de Tempo , Listas de EsperaRESUMO
Tissue typing is the process by which an individual's human leukocyte antigens (HLA) are determined. In transplantation, this vital process allows the immunologic or rejection risk of a donor-recipient pairing to be assessed through reviewing their HLA matching and whether any anti-HLA antibodies present in recipient serum are donor specific. Tissue typing has increased in sophistication over time which has allowed a deeper appreciation of the antigenically important parts of HLA and increased the complexity of determining immunologic risk.
Assuntos
Rejeição de Enxerto , Teste de Histocompatibilidade/métodos , Transplante de Rim/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunologia de TransplantesRESUMO
AIM: Our aim was threefold: first, to determine the incidence of active TB in our cohort, second to investigate the risk factors for active TB and third, to understand current screening practices. The ultimate goal was to use our findings to inform development of local and national guidelines. METHODS: The records of all adult patients who underwent renal transplantation at our centre from 2005 to 2014 were retrospectively reviewed to assess current screening practices, the risks for and burden of active TB. RESULTS: A total of 660 individuals underwent renal transplantation during this period, totalling 3647 person years of follow up. Two patients were diagnosed with active TB after renal transplant, resulting in an incidence of 55 per 100 000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in high TB incidence countries and 89 (13.5%) had an interferon gamma release assay (IGRA) at any point. Individuals born in high TB risk countries had a much higher incidence of active TB (353 per 100 000 person-years). Ten individuals had positive IGRA tests, of whom two were treated for active TB, two received chemoprophylaxis and six were not treated. CONCLUSIONS: In the absence of formal guidelines, IGRA-based screening for LTBI was infrequently performed. Our data suggest that screening and treatment of renal transplant recipients born in high incidence countries is an important preventive measure.
Assuntos
Transplante de Rim/efeitos adversos , Tuberculose Latente/microbiologia , Mycobacterium tuberculosis/patogenicidade , Infecções Oportunistas/microbiologia , Adulto , Emigrantes e Imigrantes , Emigração e Imigração , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Incidência , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Vitória/epidemiologiaRESUMO
Cytomegalovirus (CMV) infection represents a major cause of morbidity and mortality in immunocompromised hosts. Skin ulceration is a rare manifestation of tissue-invasive disease, with the anogenital region being the most typical site of involvement. We present a case of CMV ulceration on the right leg occurring 16 years following renal transplantation and 1 year after adjuvant radiotherapy for a Marjolin ulcer at this site. We suggest radiotherapy may provide a mechanism for local reactivation of the virus in the skin of seropositive patients.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Infecções por Citomegalovirus/diagnóstico , Úlcera da Perna/virologia , Neoplasias Cutâneas/radioterapia , Transplantados , Idoso , Anticorpos Antivirais/sangue , Carcinoma de Células Escamosas/cirurgia , Cicatriz/patologia , Citomegalovirus/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Transplante de Rim , Masculino , Radioterapia Adjuvante , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Conjugated pneumococcal vaccine is recommended for kidney transplant recipients, however, their immunogenicity and potential to trigger allograft rejection though generation of de novo anti-human leukocyte antigen antibodies has not been well studied. METHODS: Clinically stable kidney transplant recipients participated in a prospective cohort study and received a single dose of 13-valent conjugate pneumococcal vaccine. Anti-pneumococcal IgG was measured for the 13 vaccine serotypes pre and post vaccination and functional anti-pneumococcal IgG for 4 serotypes post vaccination. Anti-human leukocyte antigen antibodies antibodies were measured before and after vaccination. Kidney transplant recipients were followed clinically for 12 months for episodes of allograft rejection or invasive pneumococcal disease. RESULTS: Forty-five kidney transplant recipients participated. Median days between pre and post vaccination serology was 27 (range 21-59). Post vaccination, there was a median 1.1 to 1.7-fold increase in anti-pneumococcal IgG antibody concentrations for all 13 serotypes. Kidney transplant recipients displayed a functional antibody titer ≥1:8 for a median of 3 of the 4 serotypes. Post vaccination, there were no de novo anti-human leukocyte antigen antibodies, no episodes of biopsy proven rejection or invasive pneumococcal disease. CONCLUSION: A single dose of 13-valent conjugate pneumococcal vaccine elicits increased titers and breadth of functional anti-pneumococcal antibodies in kidney transplant recipients without stimulating rejection or donor-specific antibodies.
Assuntos
Transplante de Rim , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/farmacologia , Anticorpos Antibacterianos/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , VacinaçãoRESUMO
AIM: Matrix metalloproteinase-12 (MMP-12; macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP-12 is highly up-regulated in experimental anti-glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP-12 is required for glomerular macrophage infiltration and crescent formation in anti-GBM glomerulonephritis. METHODS: Accelerated anti-GBM disease was induced in groups of MMP-12 gene deficient mice (MMP-12-/-) and wild-type C57BL/6J controls, which were killed 12 days after injection of anti-GBM serum. RESULTS: Wild-type and MMP-12-/- mice developed glomerular damage and glomerular tuft adhesions to Bowman's capsule. Both groups developed severe proteinuria. Wild-type mice also developed significant loss of renal function and crescents in 22% of glomeruli, which were associated with macrophage infiltration and Bowman's capsule rupture. In contrast, MMP-12-/- mice were partially protected from renal function decline, crescent formation and Bowman's capsule rupture. This was associated with reduced macrophage infiltration in both glomeruli and the interstitium, and with reduced expression of CCL2, TNF-α and iNOS mRNA in MMP-12-/- kidneys. In addition, KIM-1 mRNA levels were reduced in MMP-12-/- mice indicating less tubular damage. CONCLUSION: These data demonstrate that endogenous MMP-12 facilitates macrophage accumulation and activation in anti-GBM glomerulonephritis which is required for glomerular crescent formation, Bowman's capsule rupture, tubular damage and renal function decline.
Assuntos
Doença Antimembrana Basal Glomerular/prevenção & controle , Glomérulos Renais/enzimologia , Macrófagos/enzimologia , Metaloproteinase 12 da Matriz/deficiência , Animais , Doença Antimembrana Basal Glomerular/enzimologia , Doença Antimembrana Basal Glomerular/genética , Doença Antimembrana Basal Glomerular/patologia , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Receptor Celular 1 do Vírus da Hepatite A/genética , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Mediadores da Inflamação/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Macrófagos/patologia , Metaloproteinase 12 da Matriz/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fenótipo , Proteinúria/enzimologia , Proteinúria/genética , Proteinúria/prevenção & controle , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders.1 Low serum phosphorus levels occur post-transplantation; however, its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre. METHODS: A retrospective cross-sectional analysis of 146 patients (75 M, 71 F) who had been referred for dual energy X-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression. RESULTS: The mean age of patients was 54 years and mean time post-transplantation 6.7 years. A total of 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining femoral neck (FN) T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, estimated glomerular filtration rate and pre-transplant history of fracture (P=.011 and P=.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use. CONCLUSION: Fracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.
Assuntos
Fraturas Ósseas/etiologia , Transplante de Rim/efeitos adversos , Fósforo/sangue , Adulto , Idoso , Estudos Transversais , Feminino , Colo do Fêmur/patologia , Traumatismos do Pé , Humanos , Masculino , Menopausa , Pessoa de Meia-Idade , Fraturas por Osteoporose , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Clinical guidelines recommend double-dose hepatitis B vaccination for patients requiring dialysis, due to an increased risk of hepatitis B infection and reduced vaccine responsiveness. There are no recommendations for patients with chronic kidney disease (CKD) prior to dialysis. Methods: We performed a systematic review and meta-analysis of randomized and quasi-randomized trials comparing efficacy (seroresponses) and harms of double-dose compared with standard-dose hepatitis B vaccination in patients with CKD, including those requiring dialysis. A systematic literature search (CENTRAL, MEDLINE and EMBASE) was performed using a predetermined search strategy. Relative risks were calculated from pooled data using a random-effects model with subgroup analysis by dialysis requirement and vaccine type. Results: Seven studies (501 patients) fulfilled review criteria: four in patients receiving dialysis and three in patients not receiving dialysis. The incidence of seroconversion was not increased with double-dose vaccination overall [risk ratio (RR) 1.17, 95% confidence interval (CI) 0.98-1.39], by dialysis requirement or vaccine type. The incidence of seroprotection (reported by only four studies) was increased with double-dose vaccination overall (RR 1.53, 95% CI 1.17-2.00) but not by dialysis requirement. Adverse events were not reported by treatment arm, precluding comparison. The overall quality of included studies was moderate to low. Conclusions: The current data do not support clinical guideline recommendations for administering double-dose vaccination for patients with CKD as seroconversion was not improved and seroprotection was inadequately assessed. Large high-quality studies are required to overcome the current evidence gap regarding vaccine dosing in CKD.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Insuficiência Renal Crônica/imunologia , Vacinação/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Chronic antibody-mediated rejection (cAMR) is the major cause of premature renal allograft loss and is resistant to therapy with 12-month graft failure of up to 50% reported. We examined the duration of graft survival and associates of graft failure in patients with donor-specific antibody-positive cAMR and treatment-resistant peritubular capillaritis between June 2007 and October 2010. Those with advanced interstitial fibrosis (n=5) were excluded. Included patients (n=24) received treatment with high-dose intravenous immunoglobulin and fixed-dose rituximab (500 mg). Compared with previous reports, the study group experienced prolonged graft survival (median 82.1 months). Graft loss was predicted by eGFR and degree of proteinuria at diagnosis but not by donor-specific HLA antibody class or intensity, nor individual or summed Banff scores. Allograft biopsies were further examined for infiltrating leukocyte subtypes and location with high numbers of glomerular leukocytes, particularly macrophages, independently associated with an increased risk of graft failure. This study suggests that patients with cAMR and persistent microcirculatory inflammation, excluding those with advanced histological damage, can expect prolonged graft survival when treated with IVIg and rituximab. Trial level evidence is required to validate this observation. Further examination of the role of macrophages in cAMR is warranted.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Rituximab/uso terapêutico , Vasculite/tratamento farmacológico , Adulto , Capilares/imunologia , Doença Crônica , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/imunologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Resultado do Tratamento , Vasculite/imunologiaRESUMO
BACKGROUND: Owing to limited availability of donor organs, previous solid organ transplant (SOT) recipients are increasingly considered as potential organ donors. We report donor-derived transmission of herpes simplex virus type-2 (HSV-2) to two clusters of SOT recipients with transmission from the original donor and an HSV-2-infected recipient who subsequently became a donor. METHODS: We reviewed medical records of the donors and recipients in both clusters. Pre-transplant serology and virological features of HSV-2 were characterized. Genotyping of HSV-2 isolates to determine potential for donor transmission of HSV-2 through transplantation of organs from prior organ recipients was performed. RESULTS: A kidney-pancreas recipient died day 9 post transplant. Following confirmation of brain death, the lungs and recently transplanted kidney were donated to two further recipients. The liver was not retrieved, but biopsy confirmed HSV-2 infection. Testing on the original donor showed negative HSV-2 polymerase chain reaction and HSV immunoglobulin (Ig)M, but positive HSV-2 IgG. The liver recipient from the original donor developed HSV-2 hepatitis and cutaneous infection that responded to treatment with intravenous acyclovir. In the second cluster, lung and kidney recipients both developed HSV-2 viremia that was successfully treated with antiviral therapy. Genotyping of all HSV-2-positive samples showed 100% sequence homology for three recipients. CONCLUSIONS: Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis.
Assuntos
Herpes Simples/transmissão , Herpesvirus Humano 2 , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Adulto , Antivirais/uso terapêutico , Feminino , Herpes Simples/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Thrombotic microangiopathy (TMA) is a well-recognised complication following transplantation, often due to an underlying genetic predisposition, medications or rejection. The use of eculizumab in these settings has been previously described, but its role still remains to be clarified. A 45-year-old man, with a history of type 1 diabetes mellitus and subsequent end-stage kidney failure, presented for a simultaneous pancreas-kidney transplant. Immunologically, he was well matched with the donor, and he received standard induction immunosuppression including tacrolimus. His early transplant course was complicated by Haemophilus parainfluenzae paronychia and a Pseudomonas aeruginosa catheter-associated urinary tract infection. Within 1 week, he developed thrombotic microangiopathy with significant renal dysfunction and eventual dialysis dependence, without evidence of transplant rejection on biopsy. He was also noted to have antiphospholipid antibodies in moderate titres. The TMA did not resolve despite cessation of tacrolimus, and he was subsequently commenced on eculizumab. The patient achieved a partial remission from TMA, with ongoing biochemical evidence of haemolysis, although now with stable graft function, despite significant damage. His transplanted pancreas remained seemingly unaffected by TMA, and continues to function well. This case describes an unusual presentation of TMA post-transplantation and is the only described case of eculizumab use following pancreas-kidney transplant. It remains unclear in this case what the likely precipitant for TMA was, although it seems to be, at least in part, controlled by ongoing use of eculizumab, presumably by terminal complement inhibition.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Microangiopatias Trombóticas/tratamento farmacológico , Microangiopatias Trombóticas/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/cirurgia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Microangiopatias Trombóticas/diagnósticoRESUMO
BACKGROUND: Pharmacologic stress testing is utilized in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation in potential renal transplant recipients due to the perceived lower feasibility of ESE for achieving adequate workload and target heart rate (THR) in this population. METHODS: Consecutive patients referred for cardiac risk evaluation prior to potential kidney transplantation were evaluated. All patients attempted ESE before pharmacologic testing was considered. Treadmill ESE utilized BRUCE protocol to maximum capacity. THR was defined as >85% of the maximum predicted heart rate (220-age). Functional capacity was assessed by metabolic equivalents (METs) and the rate pressure product (RPP). RESULTS: Of 535 patients (349 male, age 56±11), 372(70%) reached THR. Mean METs were 10±3 with 531(99%) achieving ≥4 METs and 87% ≥7 METs. Mean RPP was 25 821±5820 bpm×mm Hg (83% achieving >20 000 bpm×mm Hg). On multivariate analysis, independent predictors of failure to reach THR were rate-control medication and diabetes; failure to reach 7 METs: females, diabetics, age≥65, and previous cardiac disease; failure to reach RPP>20 000: rate-control medication. There were 97% of ESE completed to physiologic endpoints. CONCLUSION: In unselected potential renal transplant candidates, cardiac assessment by ESE is well tolerated, with 9-in-10 exercising to satisfactory functional capacity. ESE should be considered a feasible alternative to pharmacologic testing in this population.