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1.
Artigo em Inglês | MEDLINE | ID: mdl-38383906

RESUMO

BACKGROUND AND HYPOTHESIS: The population with kidney failure is at increased risk of cancer and associated mortality. Relative survival can provide insight into the excess mortality, directly or indirectly, attributed to cancer in the population with kidney failure. METHODS: We estimated relative survival for people all ages receiving dialysis (n = 4089) and kidney transplant recipients (n = 3253) with de novo cancer, and for the general population with cancer in Australia and New Zealand (n = 3 043 166) over the years 1980-2019. The entire general population was the reference group for background mortality, adjusted for sex, age, calendar year and country. We used Poisson regression to quantify excess mortality ratios. RESULTS: Five-year relative survival for all-site cancer was markedly lower than the general population for people receiving dialysis (0.25, 95%CI:0.23-0.26) and kidney transplant recipients (0.55, 95%CI:0.53-0.57). In dialysis, excess mortality was more than double (2.16, 95%CI:2.08-2.25) that of the general population with cancer and for kidney transplant recipients 1.34 higher (95%CI:1.27-2.41). There was no difference in excess mortality from lung cancer between people with kidney failure and the general population with cancer. Comparatively, there was a significant survival deficit for people with kidney failure, compared to the general population with cancer, for melanoma, breast cancer and prostate cancers. CONCLUSION: Decreased cancer survival in kidney failure may reflect differences in multi-morbidity burden, reduced access to treatment, or greater harm from or reduced efficacy of treatments. Our findings support research aimed at investigating these hypotheses.

2.
J Clin Med ; 12(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36769579

RESUMO

The aim was to identify patient- and disease-related characteristics predicting moderate-to-high disease activity in recent-onset psoriatic arthritis (PsA). We performed a multicenter observational prospective study (2-year follow-up, regular annual visits) in patients aged ≥18 years who fulfilled the CASPAR criteria and had less than 2 years since the onset of symptoms. The moderate-to-high activity of PsA was defined as DAPSA > 14. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. The sample comprised 158 patients. At the first follow-up visit, 20.8% of the patients who attended the clinic had a moderate-to-severe disease. This percentage rose to 21.2% on the second visit. The variables predicting moderate-high activity were the PsAID score, tender joint count, level of physical activity, and sex. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (98%; 95% CI: 86.89-100.00). PsAID was the most important variable in the prediction algorithms, reinforcing the convenience of its inclusion in daily clinical practice. Strategies that focus on the needs of women with PsA should be considered.

3.
Nephrol Dial Transplant ; 38(6): 1552-1559, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36323457

RESUMO

BACKGROUND: Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation. METHODS: We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis. RESULTS: During a follow-up of 12 years (interquartile range 8-14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03-8.27], adjusting for smoking (OR 4.020, 95% CI 1.34-12.02) and other covariates. PTDM was not associated with other types of cancer. CONCLUSIONS: Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance.


Assuntos
Carcinoma de Células Renais , Diabetes Mellitus , Neoplasias Renais , Transplante de Rim , Masculino , Humanos , Transplante de Rim/efeitos adversos , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/complicações , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/diagnóstico , Fatores de Risco , Neoplasias Renais/epidemiologia , Neoplasias Renais/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
4.
Kidney Med ; 3(4): 665-668, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34401733

RESUMO

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a newer and effective therapeutic option approved for patients with relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Acute kidney injury is a complication of CAR T-cell therapy that can result in kidney failure. In most cases, it is thought to be related to hemodynamic changes due to cytokine release syndrome. Kidney biopsy in this clinical scenario is usually not performed. We report on a kidney transplant recipient in his 40s who developed a posttransplant lymphoproliferative disorder of B-cell origin refractory to conventional treatments and received anti-CD19 CAR T-cell therapy as compassionate treatment. Beginning on day 12 after CAR T-cell infusion, in the absence of clinical symptoms, a progressive decline in estimated glomerular filtration rate of the kidney graft occurred. A subsequent allograft biopsy showed mild tubulointerstitial lymphocyte infiltrates, falling into a Banff borderline-changes category and resembling an acute immunoallergic tubulointerstitial nephritis. Neither CAR T cells nor lymphomatous B cells were detected within the graft cellular infiltrates, suggesting an indirect mechanism of kidney injury. Although kidney graft function partially recovered after steroid therapy, the posttransplant lymphoproliferative disorder progressed and the patient died 7 months later.

5.
Nephron ; 145(6): 614-623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33975320

RESUMO

BACKGROUND: Data from the WHO show an increasing rate of overweight and obesity in general population in the last decades. This increase in obesity also affects population with end-stage renal disease (ESRD) and kidney transplant (KT) candidates. SUMMARY: In this review, we focused on how obesity impacts on KT stages: access to KT and outcomes of KT candidates; how to reduce weight and its consequences; short and long-term outcomes in obese recipients and the impact of weight variations; and the implications of obesity in living donor KT. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials until November 30, 2020. We selected systematic reviews and meta-analyses and randomized clinical trials. When no such reports were found for a topic, observational studies were included in the assessment. Key Messages: Although obesity is a risk factor to present worst outcomes after KT, several studies have demonstrated a survival benefit compared to patients who continue on dialysis. There is a need for a public health campaign to raise awareness in KT candidates and to highlight the importance of self-care, increasing exercise, healthy diet, and weight loss.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Obesidade/complicações , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Humanos , Falência Renal Crônica/complicações , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Doadores de Tecidos , Resultado do Tratamento , Redução de Peso
6.
Clin Transplant ; 35(5): e14278, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33682207

RESUMO

BACKGROUND: Low adherence to chronic immunosuppression is associated with suboptimal transplantation outcomes. Mobile-health technology is a promising tool to monitor medication adherence, but data on patient engagement to these tools are lacking. METHODS: Prospective, observational, multicenter, 2-phase trial in kidney and liver transplant recipients, investigating the degree of engagement to TrackYourMed® (TYM), a novel m-Health technology with a QR code-scan app to track immunosuppression adherence and its association with drug monitoring. RESULTS: Out of 204 consecutive transplant patients, 90 patients were eligible to participate. 61 (68%) used TYM regularly, 21 (23%) never or barely used it, 5 (5.5%) were irregular users, and 3 (3.3%) were lost to follow-up. 6-month total correct intakes (CIN) ranged between 69%-76%, 12%-19% intakes were out-of-time (OUT), and 9%-12% were missed (MIS). Notably, a rate of intakes out of the scheduled time higher than 20% in the 6 days prior to blood immunosuppressant trough levels was associated with a higher intra-patient variability (17 IQR 13-21% vs. 29 IQR 23%-36%, p = .001), and with a higher dose-adjustment (p < .001). At 1 year, 53(59%) patients were still active users of TYM. CONCLUSIONS: Implementing m-Health technologies promoting immunosuppression adherence may be useful for a relevant number of transplant patients and help transplant physicians identifying erratic immunosuppression adherence.


Assuntos
Transplante de Rim , Aplicativos Móveis , Transplante de Órgãos , Telemedicina , Tecnologia Biomédica , Humanos , Terapia de Imunossupressão , Imunossupressores , Adesão à Medicação , Projetos Piloto , Estudos Prospectivos , Tecnologia
7.
Transplantation ; 103(10): 2031-2056, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31343574

RESUMO

BACKGROUND: The current standard of care immunosuppressive regimen in kidney transplantation (KT) includes a combination of mycophenolates (MMF/MPA) with a calcineurin inhibitor (CNI). METHODS: We designed a systematic review including all randomized clinical trials (RCTs) assessing the outcomes in KT recipients receiving mTORi + CNI compared with regimens containing MMF/MPA or azathioprine with CNI. RESULTS: A total of 24 studies with 7356 participants were included. The comparison between mTORi-CNI and MMF/MPA-CNI did not show differences in acute rejection, mortality, or graft loss rates. Better graft function was observed using MMF/MPA-CNI than using mTORi + CNI, but this difference was not evident when the mTORi was associated with reduced dose CNI in more recent studies with everolimus. Dyslipidemia, lymphoceles, and impaired wound healing were more frequent with mTORi-CNI and diarrhea and leukopenia were more frequent with MMF/MPA-CNI. Viral infections at any time and malignant neoplasia beyond 2 years were less frequent with mTORi-CNI. Rates of discontinuation because of adverse effects in the mTORi groups varied between 17% and 46% compared to 0%-26.6% in MMF/MPA groups. The current use of lower mTORi dosage has decreased the discontinuation rates. CONCLUSIONS: Efficacy is similar with mTORi + CNI and MMF/MPA-CNI. The safety profile is the predominant difference between the 2 regimens.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Inibidores de Calcineurina/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/normas , Imunossupressores/efeitos adversos , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrão de Cuidado , Serina-Treonina Quinases TOR/imunologia , Resultado do Tratamento
8.
Int J Pharm ; 554: 337-351, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30439492

RESUMO

In this study, a new alternative of ionic crosslinked nanoparticles (NPs) based on chitosan (C) and bovine serum albumin (A; BSA) was evaluated as drug delivery system for antitumour compounds (doxorubicin hydrochloride as a model). The different responses to the pH of the medium were determined by the electrostatic interactions induced by each polymeric combination (C50/A50; C80/A20; C20/A80). NPs revealed a nanoscale size (167-392 nm) and a positive net charge (12-26 mV), modulated by doxorubicin (DOX) loading. Drug loading capacity was higher than 5.2 ±â€¯1.8 µgDOX/mgNP (Encapsulation efficiency = 34%), and an initial burst release was followed by a sustained delivery. Cellular uptake assays confirmed the entry of NPs in three human tumor cells (MCF7, T47D and Hela), triggering antioxidant responses (superoxide dismutase, catalase, glutathione reductase and total glutathione content) in those cells. This was also consistent with the decreased in IC50 values observed after the incubation of these cells with C20/A80-DOX and C50/A50-DOX NPs (1.90-3.48 µg/mL) compared with free DOX (2.36-6.025 µg/mL). In vivo results suggested that the selected proportions of chitosan-BSA created nonhemolytic and biocompatible stable NPs at the selected dose of 20 mg/kg. Despite the different formulations, this study demonstrated that these NPs could serve as safe drug carriers in further in vivo investigations.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Administração Intravenosa , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Quitosana/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Feminino , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Ratos , Ratos Wistar , Soroalbumina Bovina/química
9.
Clin Kidney J ; 11(6): 777-785, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30524711

RESUMO

Renal injury is a common complication in multiple myeloma (MM). In fact, as many as 10% of patients with MM develop dialysis-dependent acute kidney injury related to increased free light chain (FLC) production by a plasma cell clone. Myeloma cast nephropathy (MCN) is the most prevalent pathologic diagnosis associated with renal injury, followed by light chain deposition disease and light chain amyloidosis. Several FLC removal techniques have been explored to improve kidney disease in MM but their impact on renal clinical outcomes remains unclear. According to the evidence, high cut-off haemodialysis should be restricted to MM patients on chemotherapy with histological diagnosis of MCN and haemodialysis requirements. From our perspective, more efforts are needed to improve kidney outcomes in patients with MM and renal failure.

10.
PLoS One ; 13(7): e0200696, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30059561

RESUMO

Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT) and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after kidney transplantation. Adding IL15 to the PRT assay (PRT+IL15) may uncover the presence of pathogenic alloreactive CD28-Tmem. Face-to-face comparisons of these assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT assays (±IL15, against six B-cell lines) in 168 consecutive kidney transplant recipients and evaluated the multivariable-adjusted associations with biopsy-proven acute rejection (BPAR), de novo donor-specific antibodies (DSA), and eGFR decline over a 48-month follow-up period. D-sp ELISPOT was positive in 81 (48%) subjects, while 71 (42%) and 81 (48%) subjects displayed positive PRT and PRT+IL15, respectively. Their median [interquartile range] numerical test result was 23 [6-65], 18 [8-37], and 26 [10-45] spots/3x105 PBMCs, respectively. The number of PRT spots were weakly correlated with those of d-sp ELISPOT, but highly correlated with PRT+IL15 (rho = 0.96, P<0.001). d-sp ELISPOT, but not PRT (±IL15) was independently associated with BPAR (adjusted Odds Ratio of BPAR associated with d-sp ELISPOT positivity: 4.20 [95%CI: 1.06 to 21.73; P = 0.041]). Unlike d-sp ELISPOT, median PRT and PRT+IL15 were independently associated with higher Δ3-48month eGFR decline post-transplantation (for both assays, about -3mL/min/1.73m2 per one standard deviation unit increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays identifies kidney transplant candidates at high risk of BPAR and worse kidney allograft progression.


Assuntos
ELISPOT/métodos , Rejeição de Enxerto/imunologia , Transplante de Rim/efeitos adversos , Monitorização Imunológica/métodos , Linfócitos T/imunologia , Adulto , Idoso , Aloenxertos/imunologia , Aloenxertos/patologia , Linfócitos B/imunologia , Biópsia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Humanos , Memória Imunológica/imunologia , Interferon gama/análise , Interferon gama/imunologia , Interleucina-15/análise , Interleucina-15/imunologia , Isoanticorpos/imunologia , Rim/imunologia , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Doadores de Tecidos
11.
Cochrane Database Syst Rev ; 5: CD011403, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29734473

RESUMO

BACKGROUND: Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with rheumatoid factor activity generated by an expansion of B-cells. The immune complexes formed precipitate mainly in the skin, joints, kidneys or peripheral nerve fibres. Current therapeutic approaches are aimed at elimination of HCV infection, removal of cryoglobulins and also of the B-cell clonal expansions. The optimal treatment for it has not been established. OBJECTIVES: This review aims to look at the benefits and harms of the currently available treatment options to treat the HCV-associated mixed cryoglobulinaemia with active manifestations of vasculitis (cutaneous or glomerulonephritis). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 30 November 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at interventions directed at treatment of HCV-associated cryoglobulinaemic vasculitis (immunosuppressive medications and plasma exchange therapy) have been included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the retrieved titles and abstracts. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). The planned primary outcomes were kidney disease, skin vasculitis, musculoskeletal symptoms, peripheral joint arthralgia, peripheral neuropathies, liver involvement, interstitial lung involvement, widespread vasculitis and death. Other planned outcomes were: therapy duration, laboratory findings, adverse effects, antiviral therapy failure, B-cell lymphoma, endocrine disorders and costs of treatment. MAIN RESULTS: Ten studies were included in the review (394 participants). None of them evaluated direct-acting antivirals. Seven studies were single-centre studies and three were multicentre. The duration of the studies varied from six to 36 months. The risk of bias was generally unclear or low. Three different interventions were examined: use of rituximab (3 studies, 118 participants); interferon (IFN) (IFN compared to other strategies (5 studies, 223 participants); six IFN months versus one year (1 study, 36 participants), and immunoadsorption apheresis versus only immunosuppressive therapy (1 study, 17 participants).The use of rituximab may slightly improve skin vasculitis (2 studies, 78 participants: RR 0.57, 95% CI 0.28 to 1.16; moderate certainty evidence) and made little of no difference to kidney disease (moderate certainty evidence). In terms of laboratory data, the effect of rituximab was uncertain for cryocrit (MD -2.01%, 95% CI -10.29% to 6.27%, low certainty evidence) and HCV replication. Rituximab may slightly increase infusion reactions compared to immunosuppressive medication (3 studies, 118 participants: RR 4.33, 95%CI 0.76 to 24.75, moderate certainty evidence) however discontinuations of the treatment due to adverse reactions were similar (3 studies, 118 participants: RR 0.97, 95% CI 0.22 to 4.36, moderate certainty evidence).Effects of lFN on clinical symptoms were evaluated only in narrative results. When laboratory parameters were assessed, IFN made little or no difference in levels of alanine transaminase (ALT) at six months (2 studies, 39 participants: MD -5.89 UI/L, 95%CI -55.77 to 43.99); rheumatoid factor activity at six months (1 study, 13 participants: MD 97.00 UI/mL, 95%CI -187.37 to 381.37), or C4 levels at 18 months (2 studies, 49 participants: MD -0.04 mg/dL, 95%CI -2.74 to 2.67). On the other hand, at 18 months IFN may probably decrease ALT (2 studies, 39 participants: MD -28.28 UI/L, 95%CI -48.03 to -8.54) and Ig M (-595.75 mg/dL, 95%CI -877.2 to -314.3), but all with low certainty evidence. One study reported infusion reactions may be higher in IFN group compared to immunosuppressive therapy (RR 27.82, 95%CI 1.72 to 449.18), and IFN may lead to higher discontinuations of the treatment due to adverse reactions (4 studies, 148 participants: RR 2.32, 95%CI 0.91 to 5.90) with low certainty evidence. Interferon therapy probably improved skin vasculitis (3 studies, 95 participants: RR 0.60, 95% CI 0.36 to 1.00) and proteinuria (2 studies, 49 participants: MD -1.98 g/24 h, 95% CI -2.89 to -1.07), without changing serum creatinine at 18 months (2 studies, 49 participants: MD -30.32 µmol/L, 95%CI -80.59 to 19.95).Six months versus one year treatment with IFN resulted in differences terms of the maintenance of the response, 89% of patients in the six months group presented a relapse and only 11% maintained a long-term response at one year, while in the one year group only 78% relapsed and long-term response was observed in 22%. The one-year therapy was linked to a higher number of side-effects (severe enough to cause the discontinuation of treatment in two cases) than the six-month schedule.One study reported immunoadsorption apheresis had uncertain effects on skin vasculitis (RR 0.44, 95% CI 0.05 to 4.02), peripheral neuropathies (RR 2.70, 95%CI 0.13 to 58.24), and peripheral joint arthralgia (RR 2.70, 95%CI 0.13 to 58.24), cryocrit (MD 0.01%, 95%CI -1.86 to 1.88) at six months, and no infusion reactions were reported. However when clinical scores were evaluated, they reported changes were more favourable in immunoadsorption apheresis with higher remission of severe clinical complications (80% versus 33%, P = 0.05) compared to immunosuppressive treatment alone.In terms of death, it was not possible to present a pooled intervention effect estimate because most of the studies reported no deaths, or did not report death as an outcome. AUTHORS' CONCLUSIONS: To treat HCV-associated mixed cryoglobulinaemia, it may be beneficial to eliminate HCV infection by using antiviral treatment and to stop the immune response by using rituximab. For skin vasculitis and for some laboratory findings, it may be appropriate to combine antiviral treatment with deletion of B-cell clonal expansions by using of rituximab. The applicability of evidence reviewed here is limited by the absence of any studies with direct-acting antivirals, which are urgently needed to guide therapy.


Assuntos
Antivirais/uso terapêutico , Crioglobulinemia/terapia , Hepatite C/tratamento farmacológico , Dermatopatias/terapia , Vasculite/terapia , Remoção de Componentes Sanguíneos/métodos , Crioglobulinemia/virologia , Hepacivirus , Hepatite C/complicações , Humanos , Fatores Imunológicos/uso terapêutico , Técnicas de Imunoadsorção , Imunossupressores/uso terapêutico , Interferons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Dermatopatias/virologia , Vasculite/etiologia
12.
Transplantation ; 101(4): 727-745, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28072755

RESUMO

The old-for-old allocation policy used for kidney transplantation (KT) has confirmed the survival benefit compared to remaining listed on dialysis. Shortage of standard donors has stimulated the development of strategies aimed to expand acceptance criteria, particularly of kidneys from elderly donors. We have systematically reviewed the literature on those different strategies. In addition to the review of outcomes of expanded criteria donor or advanced age kidneys, we assessed the value of the Kidney Donor Profile Index policy, preimplantation biopsy, dual KT, machine perfusion and special immunosuppressive protocols. Survival and functional outcomes achieved with expanded criteria donor, high Kidney Donor Profile Index or advanced age kidneys are poorer than those with standard ones. Outcomes using advanced age brain-dead or cardiac-dead donor kidneys are similar. Preimplantation biopsies and related scores have been useful to predict function, but their applicability to transplant or refuse a kidney graft has probably been overestimated. Machine perfusion techniques have decreased delayed graft function and could improve graft survival. Investing 2 kidneys in 1 recipient does not make sense when a single KT would be enough, particularly in elderly recipients. Tailored immunosuppression when transplanting an old kidney may be useful, but no formal trials are available.Old donors constitute an enormous source of useful kidneys, but their retrieval in many countries is infrequent. The assumption of limited but precious functional expectancy for an old kidney and substantial reduction of discard rates should be generalized to mitigate these limitations.


Assuntos
Seleção do Doador , Transplante de Rim/métodos , Doadores de Tecidos/provisão & distribuição , Fatores Etários , Idoso , Causas de Morte , Distribuição de Qui-Quadrado , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Razão de Chances , Perfusão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Transplant Rev (Orlando) ; 30(3): 144-53, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27279024

RESUMO

BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2 receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin-inhibitor-minimization is not recommended. CONCLUSIONS: There is very limited evidence for the benefits and harms of different immunosuppression strategies in the elderly. Most of the published literature are observational studies, and randomized controlled trials are urgently needed.


Assuntos
Rejeição de Enxerto , Terapia de Imunossupressão , Transplante de Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Inibidores de Calcineurina , Humanos , Imunossupressores/uso terapêutico
14.
Colloids Surf B Biointerfaces ; 136: 222-31, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26402420

RESUMO

Nanotoxicology has emerged as an important subdiscipline of nanotechnology due to the new healthy risks associated with the use of nanosystems for therapy and diagnostic. The biocompatibility of four stimuli-responsive nanohydrogel (NG) formulations based on different proportions of N-isopropylacrylamide (NIPA), N-hydroxyethyl acrylamide (HEAA) and 2-acrylamidoethyl carbamate (2AAECM), and cross-linked with N,N-cystaminebisacrylamide (CBA) or N-methylenebisacrylamide (NMBA) has been evaluated after intravenous injection in Wistar rats. All nanohydrogels were pH-sensitive, and those with CBA were also glutathione-responsive. Haematological and coagulation parameters revealed most nanogel formulations did not cause modification, only the NHA 80/15/5-CBA formulation induced a transitory light increase in platelets. Prothrombin time was in the reference normal range, there were no modifications of fibrinogen concentration and an increase in antithrombin III was observed on the last day of the study. Blood biochemical parameters such as AST, ALT, ALP, BUN, and creatinine were in the standard range for rats. The activity of enzyme antioxidant defences (SOD, CAT and GSSG-R) and total glutathione were evaluated in liver, kidney and spleen samples. Nanohydrogels cross-linked with the disulphide reducible CBA-cross-linker caused a decrease in GSSG/GSH content and an increase in GSSG-R activity in the spleen. The antioxidant response is also reflected by modifications of SOD activity in liver and kidney of NHA 80/15/5-CBA and NHA 80/10/10-NMBA groups. Histology showed no tissue damage, inflammation or morphological change in liver, kidney and spleen. Overall, the results demonstrated modifications of antioxidant defences; however, no acute or very significant changes in biomarkers of liver or kidney damage were observed.


Assuntos
Materiais Biocompatíveis , Glutationa/química , Hidrogéis , Nanoestruturas , Animais , Testes de Coagulação Sanguínea , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Concentração de Íons de Hidrogênio , Injeções Intravenosas , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
15.
Exp Clin Transplant ; 12(2): 101-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24702140

RESUMO

OBJECTIVES: Fungal infections represent 5% of infections in renal transplant recipients. Candidiasis is the most frequent, followed by aspergillosis and cryptococcosis. Invasive aspergillosis is severe and has a poor prognosis, but recent series focused on outcomes are scarce in the literature. We analyzed invasive aspergillosis cases in a cohort of kidney transplant recipients and suggest that prognosis is improved with early diagnosis and treatment. PATIENTS AND METHODS: A retrospective study was performed in all kidney transplant undertaken in our hospital from January 1979 to December 2012. The incidence and characteristics of invasive aspergillosis were collected from kidney transplant prospective registry and microbiology laboratory. RESULTS: We found 7 invasive aspergillosis cases (6 probable invasive aspergillosis and 1 possible invasive aspergillosis, according to EORTC/IFICG criteria); cumulative incidence 0.78% (7/891). The median posttransplant time until the disease onset was 3.03 months (interquartile range, 2.4-3.2 months), with a mean age of 56 years at the time of diagnosis. Six patients were male. Four patients had previous pulmonary disease. Six patients had received induction therapy (5 anti-IL2R antibodies, 1 with antilymphocytic antibodies). Two patients had received extra immunosuppression (1 with thymoglobulin to treat an acute rejection and the other 1 had a lymphoproliferative disorder and was on chemotherapy). Six patients were on calcineurin inhibitors at the time of diagnosis. Aspergillus fumigatus was the specimen most commonly isolated (6 cases). Six patients had a bacterial coinfection and 1 had a cytomegalovirus coinfection. All patients were treated with antifungal agents; 3 of which received voriconazole. Four patients satisfactorily resolved the episode and 3 died. CONCLUSIONS: Invasive aspergillosis incidence is low in kidney transplant although potentially lethal. We observed an acceptable survival of patients analyzed, better than usually reported. A high index of suspicion is essential to get an early diagnosis and start treatment.


Assuntos
Aspergillus/patogenicidade , Aspergilose Pulmonar Invasiva/microbiologia , Transplante de Rim/efeitos adversos , Antifúngicos/uso terapêutico , Aspergillus/classificação , Aspergillus/efeitos dos fármacos , Diagnóstico Precoce , Feminino , Humanos , Imunossupressores/efeitos adversos , Incidência , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/imunologia , Aspergilose Pulmonar Invasiva/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento
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