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1.
Clin Transplant ; 37(5): e14945, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36807636

RESUMO

INTRODUCTION: Demand for donor kidneys far exceeds the availability of organs from deceased donors. Living donor kidneys are an important part of addressing this shortfall, and laparoscopic nephrectomy is an important strategy to reduce donor morbidity and increase the acceptability of living donation. AIM: To retrospectively review the intraoperative and postoperative safety, technique, and outcomes of patients undergoing donor nephrectomy at a single tertiary hospital in Sydney, Australia. METHOD: Retrospective capture and analysis of clinical, demographic, and operative data for all living donor nephrectomies performed between 2007 and 2022 at a single University Hospital in Sydney, Australia. RESULTS: Four hundred and seventy-two donor nephrectomies were performed: 471 were laparoscopic, two of which were converted from laparoscopic to open and hand-assisted nephrectomy, respectively, and one (.2%) underwent primary open nephrectomy. The mean warm ischemia time was 2.8 min (±1.3 SD, median 3 min, range 2-8 min) and the mean length of stay (LOS) was 4.1 days (±1.0 SD). The mean renal function on discharge was 103 µmol/L (±23.0 SD). Seventy-seven (16%) patients had a complication with no Clavien Dindo IV or V complications seen. Outcomes demonstrated no impact of donor age, gender, kidney side, relationship to the recipient, vascular complexity; or surgeon experience, on complication rate or LOS. CONCLUSION: Laparoscopic donor nephrectomy is a safe and effective procedure with minimal morbidity and no mortality in this series.


Assuntos
Transplante de Rim , Laparoscopia , Doadores Vivos , Nefrectomia , Humanos , Austrália , Rim/fisiologia , Rim/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/métodos
2.
Nephrology (Carlton) ; 28(11): 639-643, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37635271

RESUMO

We present the case of a recent ABO incompatible kidney transplant recipient with persistent SARS-CoV-2 infection and pneumonitis. Serial whole genome sequencing confirmed intra-host viral evolution, which was used as a surrogate to confirm active viral replication and support re-treatment with antivirals, late in the course of infection. A prolonged course of remdesivir combined with immunosuppression modulation resulted in successful clearance of virus and clinical improvement. The diagnostic process undertaken in this case provides a useful guide for other clinicians when approaching similar patients.


Assuntos
COVID-19 , Transplante de Rim , Pneumonia , Humanos , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , COVID-19/diagnóstico , Rejeição de Enxerto , Terapia de Imunossupressão , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , SARS-CoV-2/genética , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Pneumonia/tratamento farmacológico
3.
JAMA ; 330(13): 1266-1277, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37787795

RESUMO

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.


Assuntos
Albuminas , Albuminúria , Creatinina , Cistatina C , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Fibrilação Atrial , Creatinina/análise , Cistatina C/análise , Estudos Retrospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso , Albuminas/análise , Progressão da Doença , Internacionalidade , Comorbidade
4.
Transpl Int ; 35: 10199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185379

RESUMO

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 Tratamento
5.
Nephrol Dial Transplant ; 36(6): 1048-1056, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32170940

RESUMO

BACKGROUND: Quality-of-life is an essential outcome for clinical care. Both chronic kidney disease (CKD) and diabetes have been associated with poorer quality-of-life. The combined impact of having both diseases is less well understood. As diabetes is the most common cause of CKD, it is imperative that we deepen our understanding of their joint impact. METHODS: This was a prospective, longitudinal cohort study of community-based Australians aged ≥25 years who participated in the Australian Diabetes, Obesity and Lifestyle study. Quality-of-life was measured by physical component summary (PCS) and mental component summary sub-scores of the Short Form (36) Health Survey. Univariate and multivariate linear mixed effect regressions were performed. RESULTS: Of the 11 081 participants with quality-of-life measurements at baseline, 1112 had CKD, 1001 had diabetes and of these 271 had both. Of the 1112 with CKD 421 had Stage 1, 314 had Stage 2, 346 had Stage 3 and 31 had Stages 4/5. Adjusted linear mixed effect models showed baseline PCS was lower for those with both CKD and diabetes compared with either disease alone (P < 0.001). Longitudinal analysis demonstrated a more rapid decline in PCS in those with both diseases. CONCLUSIONS: The combination of CKD and diabetes has a powerful adverse impact on quality-of-life, and participants with both diseases had significantly poorer quality-of-life than those with one condition.


Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Austrália/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , Estudos Prospectivos , Qualidade de Vida , Insuficiência Renal Crônica/epidemiologia
6.
Transpl Int ; 34(12): 2431-2441, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34626503

RESUMO

Delayed graft function (DGF) after kidney transplantation is associated with inferior outcomes and higher healthcare costs. DGF is currently defined as the requirement for dialysis within seven days post-transplant; however, this definition is subjective and nonspecific. Novel biomarkers have potential to improve objectivity and enable earlier diagnosis of DGF. We reviewed the literature to describe the range of novel biomarkers previously studied to predict DGF. We identified marked heterogeneity and low reporting quality of published studies. Among the novel biomarkers, serum NGAL had the greatest potential as a biomarker to predict DGF, but requires further assessment and validation through larger scale studies of diagnostic test performance. Given inadequacies in the dialysis-based definition, coupled with the high incidence and impact of DGF, such studies should be pursued.


Assuntos
Testes Diagnósticos de Rotina , Transplante de Rim , Proteínas de Fase Aguda , Biomarcadores , Função Retardada do Enxerto/diagnóstico , Sobrevivência de Enxerto , Humanos , Rim , Lipocalina-2 , Lipocalinas , Proteínas Proto-Oncogênicas
7.
Transpl Int ; 34(8): 1517-1529, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34115918

RESUMO

The COVID-19 pandemic has challenged the delivery of health services. Telehealth allows delivery of care without in-person contacts and minimizes the risk of vial transmission. We aimed to describe the perspectives of kidney transplant recipients on the benefits, challenges, and risks of telehealth. We conducted five online focus groups with 34 kidney transplant recipients who had experienced a telehealth appointment. Transcripts were thematically analyzed. We identified five themes: minimizing burden (convenient and easy, efficiency of appointments, reducing exposure to risk, limiting work disruptions, and alleviating financial burden); attuning to individual context (depending on stability of health, respect patient choice of care, and ensuring a conducive environment); protecting personal connection and trust (requires established rapport with clinicians, hampering honest conversations, diminished attentiveness without incidental interactions, reassurance of follow-up, and missed opportunity to share lived experience); empowerment and readiness (increased responsibility for self-management, confidence in physical assessment, mental preparedness, and forced independence); navigating technical challenges (interrupted communication, new and daunting technologies, and cognizant of patient digital literacy). Telehealth is convenient and minimizes time, financial, and overall treatment burden. Telehealth should ideally be available after the pandemic, be provided by a trusted nephrologist and supported with resources to help patients prepare for appointments.


Assuntos
COVID-19 , Transplante de Rim , Telemedicina , Humanos , Pandemias , SARS-CoV-2
8.
BMC Urol ; 21(1): 87, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098936

RESUMO

BACKGROUND: Kaposi's sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower extremities. Penile involvement has been reported only rarely. Management of cutaneous-limited disease is primarily reduction of immunosuppression and conversion to an mTOR-inhibitor, whereas the treatment of disseminated disease in transplant patients is more variable. CASE PRESENTATION: A 75-year-old male, originally from Somalia, received a deceased-donor kidney transplant for diabetic and hypertensive nephropathy. Seven months post-transplant he presented with lower limb lesions, oedema and bilateral deep vein thromboses. He then developed a fast-growing painful lesion on his penile shaft. A biopsy of this lesion confirmed KS, and a PET scan demonstrated disseminated disease in the lower extremities, penis and thoracic lymph nodes. His tacrolimus was converted to sirolimus, and his other immunosuppression was reduced. He was treated with single agent paclitaxel chemotherapy in view of his rapidly progressing, widespread disease. The penile lesion completely resolved, and the lower extremity lesions regressed significantly. His kidney allograft function remained stable throughout treatment. CONCLUSION: This case illustrates a rare presentation of an uncommon post-transplant complication and highlights the need for a high index of suspicion of KS in transplant patients presenting with atypical cutaneous lesions. It serves to demonstrate that the use of single agent paclitaxel chemotherapy, switch to an mTORi and reduction in immunosuppression where possible produces excellent short-term outcomes, adding to the body of evidence for this management strategy in disseminated Kaposi's sarcoma.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Transplante de Rim , Paclitaxel/uso terapêutico , Neoplasias Penianas/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Idoso , Humanos , Masculino
9.
Ann Intern Med ; 173(6): 426-435, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32658569

RESUMO

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.


Assuntos
Albuminúria/diagnóstico , Creatinina/urina , Programas de Rastreamento/métodos , Proteinúria/diagnóstico , Fitas Reagentes , Insuficiência Renal Crônica/diagnóstico , Urinálise/métodos , Albuminúria/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/urina , Insuficiência Renal Crônica/urina , Sensibilidade e Especificidade , Urinálise/instrumentação
10.
BMC Infect Dis ; 20(1): 613, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811453

RESUMO

BACKGROUND: Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. CASE PRESENTATION: A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1-0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. CONCLUSIONS: This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.


Assuntos
Soropositividade para HIV/fisiopatologia , HIV/imunologia , Transplante de Rim/efeitos adversos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Estrongiloidíase/etiologia , Transplantados , Negro ou Afro-Americano , Animais , Antiparasitários/uso terapêutico , Soropositividade para HIV/virologia , Humanos , Ivermectina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologia , Doadores de Tecidos , Resultado do Tratamento
11.
Intern Med J ; 50(4): 492-494, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32270609

RESUMO

Renal failure is a common feature of multiple myeloma affecting 20-55% of patients at the initial presentation and is being associated with a significant increase in morbidity and mortality. Renal transplantation for patients with multiple myeloma is rarely considered given the incurable nature of the disease, the risk of post-transplant disease progression and perceived high risk of infections. Here we report a 57-year-old man with end-stage renal failure attributed to presumed IgA nephropathy, with pre-existing stable multiple myeloma, who received a kidney transplant from a two haplotype-matched sibling. Transplantation has been successful and with excellent kidney function and stable multiple myeloma 6 years post-transplant. This case highlights the potential benefits of renal transplantation in highly selected patients with multiple myeloma.


Assuntos
Falência Renal Crônica , Transplante de Rim , Mieloma Múltiplo , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Insuficiência Renal
12.
Nephrology (Carlton) ; 25(4): 339-350, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31257667

RESUMO

AIM: We aimed to describe the impact and experience of being deemed ineligible as a living kidney donor. METHODS: Semi-structured interviews were conducted with 27 ineligible donor candidates. Transcripts were analysed thematically. RESULTS: Seven themes were identified: deriving health and relationship benefits in the process (strengthening emotional connection, identifying problematic health conditions); devastating loss and disappointment (harbouring guilt over personal failings, shattering confidence and hope, undermining relationships with extended family and friends, disrupting home dynamics); constrained within a rigid system (denied autonomy, resorting to other avenues); acknowledging as matter of fact (accepting the clinical decision, reassured by preventing a poor outcome); reluctant to relinquish the donor identity (unable to fulfil family duty, having the donor role stolen, holding onto other opportunities to donate); uncertainty in unpredictability, inconsistency and ambiguities (frustrated by inefficiencies, questioning clinician motivation, suspended donor status, unfairness in changeable eligibility criteria, unresolved concerns and questions of own health); and abandoned in despair (lacking practical support to meet eligibility criteria, ill prepared for rejection, dismissed and discarded by the system). CONCLUSION: Being deemed unsuitable for donation took an emotional toll on ineligible donor candidates who felt immense guilt for 'failing' the potential recipient. Ineligible donor candidates were frustrated and angry with the perceived lack of support from clinicians and rigidity of the evaluation process. Informing potential donors of available services, including psychological support, communicating the decision sensitively and with sufficient time, and full disclosure of their health status, may contribute to improved adjustment following the ineligibility decision.


Assuntos
Emoções/fisiologia , Nível de Saúde , Transplante de Rim/psicologia , Doadores Vivos/psicologia , Motivação , Pesquisa Qualitativa , Coleta de Tecidos e Órgãos/métodos , Adulto , Idoso , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade
13.
BMC Nephrol ; 21(1): 47, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050922

RESUMO

BACKGROUND: Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required. CASE PRESENTATION: Two patients underwent SLKT and received our centre's standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant. CONCLUSIONS: These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.


Assuntos
Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim , Transplante de Fígado , Fígado/imunologia , Aloenxertos/imunologia , Feminino , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Imunologia de Transplantes
14.
Kidney Int ; 96(1): 27-30, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31229045

RESUMO

ATHENA, published in this edition of Kidney International, is the third contemporary, multicenter, randomized, controlled trial to compare de novo use of everolimus, calcineurin inhibitor, and steroids to our current standard of care, mycophenolate, tacrolimus, and steroids, in kidney transplant recipients. This commentary highlights the strengths and significant weaknesses of ATHENA. It then seeks to distill the key messages from the 3 trials, ATHENA, TRANSFORM, and US92, and considers the role of everolimus in kidney transplantation today. Ultimately, the 3 trials demonstrate that everolimus with reduced-concentration tacrolimus and steroids provide a viable alternative to our current standard of care.


Assuntos
Transplante de Rim , Tacrolimo , Ciclosporina , Everolimo , Rejeição de Enxerto , Humanos , Imunossupressores , Serina-Treonina Quinases TOR
15.
Am J Transplant ; 19(12): 3367-3376, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31132214

RESUMO

Preemptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants during 1998-2017. Patients were transplanted preemptively (n = 1435) or after receiving up to 6 months of dialysis (n = 712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated predialysis) using left-truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9 mL/min per 1.73 m2 in the non-pre-emptive, and 9.6 mL/min per 1.73 m2 in the preemptive group. In the matched cohort (n = 1398), preemptive transplantation was not associated with a survival advantage hazard ratio (HR) for preemptive vs non-pre-emptive 1.12 (95% confidence interval [CI] 0.79-1.61). Accounting for lead time moved the point estimates toward a survival disadvantage for preemptive transplantation (eg, HR assuming 4 mL/min per 1.73 m2 /year eGFR decline, 1.21 [0.85, 1.73]), but in all cases the 95% CIs crossed 1. The optimal timing of preemptive living donor kidney transplantation requires further study.


Assuntos
Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Doadores Vivos/provisão & distribuição , Diálise Renal/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
16.
Am J Transplant ; 19(10): 2865-2875, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31012541

RESUMO

The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Isoanticorpos/efeitos adversos , Falência Renal Crônica/mortalidade , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos/provisão & distribuição , Adulto Jovem
17.
Am J Transplant ; 19(11): 3018-3034, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31152476

RESUMO

TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = -0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m2 ) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R- high-risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Everolimo/uso terapêutico , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
18.
Nephrol Dial Transplant ; 34(12): 2127-2131, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31157885

RESUMO

BACKGROUND: The US Kidney Donor Risk Index (KDRI) and the UK KDRI were developed to estimate the risk of graft failure following kidney transplantation. Neither score has been validated in the Australian and New Zealand (ANZ) population. METHODS: Using data from the Australia and New Zealand Organ Donor (ANZOD) and Dialysis and Transplant (ANZDATA) Registries, we included all adult deceased donor kidney-only transplants performed in ANZ from 2005 to 2016 (n = 6405). The KDRI was calculated using both the US donor-only and UK formulae. Three Cox models were constructed (Model 1: KDRI only; Model 2: Model 1 + transplant characteristics; Model 3: Model 2 + recipient characteristics) and compared using Harrell's C-statistics for the outcomes of death-censored graft survival and overall graft survival. RESULTS: Both scores were strongly associated with death-censored and overall graft survival (P < 0.0001 in all models). In the KDRI-only models, discrimination of death-censored graft survival was moderately good with C-statistics of 0.63 and 0.59 for the US and UK scores, respectively. Adjusting for transplant characteristics resulted in marginal improvements of the US KDRI to 0.65 and the UK KDRI to 0.63. The addition of recipient characteristics again resulted in marginal improvements of the US KDRI to 0.70 and the UK KDRI to 0.68. Similar trends were seen for the discrimination of overall graft survival. CONCLUSIONS: The US and UK KDRI scores were moderately good at discriminating death-censored and overall graft survival in the ANZ population, with the US score performing slightly better in all models.


Assuntos
Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Medição de Risco/métodos , Doadores de Tecidos/provisão & distribuição , Adulto , Austrália/epidemiologia , Cadáver , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Humanos , Incidência , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
19.
Qual Life Res ; 28(8): 2081-2090, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937731

RESUMO

PURPOSE: Quality-of-life is poor in end-stage kidney disease; however, the relationships between earlier stages of chronic kidney disease (CKD) and are poorly understood. This study explored longitudinal quality-of-life changes in a community-based CKD cohort and assessed associations between CKD and quality-of-life over time, and between baseline quality-of-life and CKD outcomes. METHODS: We used the Australian diabetes, obesity and lifestyle study-a nationally representative, prospective cohort with data collected at baseline, year 5 and year 12-to examine the relationships between CKD stage, quality-of-life and outcomes. Linear mixed regression, cox proportional hazards, Kaplan-Meier and competing risks analyses were used. RESULTS: Of 1112 participants with CKD and baseline quality-of-life data, the physical component summary (PCS) score was significantly lower than for the general population (p = 0.01 age and sex adjusted), while the mental component summary (MCS) score was no different (p = 0.9 age and sex adjusted). In our unadjusted mixed effects model, more advanced kidney disease was associated with lower PCS and higher MCS at baseline (p < 0.001 and p < 0.01, respectively); however, this effect was no longer significant after adjustment for demographic and clinical variables. The rate of decline in PCS over the period of follow-up was greatest for those with more advanced kidney disease (p < 0.001 in unadjusted model, p = 0.007 in adjusted model). There was no association between change in MCS over the period of follow-up and severity of kidney disease in either the unadjusted or adjusted model (p = 0.7 and p = 0.1, respectively). Lower PCS, but not MCS, was associated with increased cardiovascular and increased all-cause mortality even after adjustment for key demographic and clinical variables (p < 0.001). CONCLUSIONS: Physical, but not mental, quality-of-life is significantly impaired in CKD, and continues to decline with disease progression.


Assuntos
Nível de Saúde , Falência Renal Crônica/psicologia , Qualidade de Vida/psicologia , Insuficiência Renal Crônica/psicologia , Adulto , Idoso , Austrália , Estudos de Coortes , Diabetes Mellitus/patologia , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/terapia
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