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BACKGROUND: Quality of life (QoL) is a measure to evaluate kidney transplant (KT) results. AIM: To describe the QoL profile in a larger sample of Brazilian patients who underwent KT according to age, sex, and access to KT. METHODS: We conducted a secondary data analysis of the ADHERE BRAZIL multicenter cross-sectional study including 1105 patients from 20 centers, considering KT access region and transplant activity. QoL was assessed by the WHOQOL-BREF. Data was compared using Generalized Estimating Equations. RESULTS: Overall, 58.5 % of the patients were men, mean age of 47.6 ± 12.6 years. The general QoL score was 81 ± 15.1, 58.6 ± 11.6 for physical, 65.5 ± 11.4 for psychological, 68.3 ± 17.1 for social relationships, and 64.2 ± 13.3 for environmental domain. Higher QoL scores were observed in men compared to women in three WHOQOL-BREF domains: psychological (OR:2.62; CI, 1.29 ̶ 3.95, p < 0.0001), social relationships (OR:3.21; CI, 1.2 ̶ 5.23, p = 0.002) and environmental (OR:3.79; CI:2.23 ̶ 5.35, p < 0.0001). Younger patients (18-44 years) had higher scores in the psychological (OR:-2.69; CI, -4.13 ̶ -1.25; p < 0.001; OR:-3.52; CI, -5.39 ̶ -1.66; p < 0.001) and social (OR:-3.46; CI, -5.64 ̶ -1.27; p = 0.002; OR:-7.17; CI, -10 ̶ -4.35; p < 0.0001) domains than older ones (45-59 and > 60 years, respectively). Patients from higher KT access region had higher scores in environmental domain (OR:3.53; CI, 0.28 ̶ 6.78; p = 0.033). CONCLUSIONS: Featuring the results of KT under patient view, the physical and social relationships domains were the most and least affected, respectively. Lower QoL subgroups (females and age > 45 years) should be targeted in future multi-professional interventions.
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Transplante de Rim , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Masculino , Feminino , Transplante de Rim/psicologia , Estudos Transversais , Brasil , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Idoso , Adulto JovemRESUMO
During an epidemiological survey, a potential novel species within the basidiomycetous yeast genus Trichosporon was observed. The clinical strain was obtained from a urine sample taken from a Brazilian kidney transplant recipient. The strain was molecularly identified using the intergenic spacer (IGS1) ribosomal DNA locus and a subsequent phylogenetic analysis showed that multiple strains that were previously reported by other studies shared an identical IGS1-genotype most closely related to that of Trichosporon inkin. However, none of these studies provided an in-depth characterization of the involved strains to describe it as a new taxon. Here, we present the novel clinically relevant yeast for which we propose the name Trichosporon austroamericanum sp. nov. (holotype CBS H-24937). T. austroamericanum can be distinguished from other siblings in the genus Trichosporon using morphological, physiological, and phylogenetic characters.
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DNA Fúngico , DNA Espaçador Ribossômico , Filogenia , Análise de Sequência de DNA , Transplantados , Trichosporon , Tricosporonose , Trichosporon/classificação , Trichosporon/genética , Trichosporon/isolamento & purificação , DNA Espaçador Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Fúngico/genética , Humanos , Brasil , Tricosporonose/microbiologia , Análise por Conglomerados , Técnicas de Tipagem Micológica , Transplante de Rim , Microscopia , GenótipoRESUMO
Background and Objectives: Overweight/obesity puts individuals at greater risk for COVID-19 progression and mortality. We aimed to evaluate the impact of overweight/obesity on oxygen (O2) requirement outcomes of male and female kidney transplant recipients (KTRs) during the COVID-19 pandemic. Materials and Methods: We conducted a retrospective analysis of a cohort of KTRs diagnosed with COVID-19. Participants were stratified based on BMI categories, and data on the need for O2 therapy outcome were collected and analyzed separately for male and female KTRs. Results: In total, 284 KTRs (97 males and 187 females) were included in the study. Overweight/obesity was observed in 60.6% of male KTRs and 71% of female KTRs. Strikingly, overweight/obese women had a significantly higher requirement for supplemental O2 (63.3% vs. 41.7%, OR = 2.45, p = 0.03), particularly among older individuals (OR = 1.05, p = 0.04), smokers (OR = 4.55, p = 0.03), those with elevated lactate dehydrogenase (LDH) levels (OR = 1.01, p = 0.006), and those with lower admission and basal estimated glomerular filtration rate (eGFR) levels. Within this cohort, the necessity for O2 supplementation was correlated with more unfavorable outcomes. These included heightened mortality rates, transfers to the intensive care unit, employment of invasive mechanical ventilation, and the emergence of acute kidney injury requiring hemodialysis. On the other hand, although overweight/obese male KTRs had a higher prevalence of hypertension and higher fasting blood glucose levels, no significant association was found with COVID-19-related outcomes when compared to lean male KTRs. Conclusions: Overweight/obesity is highly prevalent in KTRs, and overweight/obese women demonstrated a higher need for supplemental O2. Therefore, the early identification of factors that predict a worse outcome in overweight/obese female KTRs affected by COVID-19 contributes to risk stratification and guides therapeutic decisions.
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COVID-19 , Transplante de Rim , Feminino , Masculino , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Caracteres Sexuais , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , OxigênioRESUMO
INTRODUCTION: Obesity is one of the components of the cardiometabolic syndrome that contributes to COVID-19 progression and mortality. Immunosuppressed individuals are at greater risk of the COVID-19 burden. Therefore, we sought to investigate the impact of the combination of overweight/obesity and kidney transplant on oxygen (O2) requirements in the COVID-19 setting. METHODS: Retrospective analysis of 284 kidney transplant recipients (KTRs) from March/2020 to August/2020 in a single center. We investigated the risk factors associated with O2 requirements in overweight/obese KTRs. RESULTS: Overall, 65.1% had a BMI (body mass index) ≥ 25 kg/m2, 52.4% were male, the mean age was 53.3 ± 11 years old, 78.4% had hypertension, and 41.1% had diabetes mellitus. BMI was an independent risk factor for O2 requirements (OR = 1.07, p = 0.02) alongside age, lymphopenia, and hyponatremia. When overweight/obese KTRs were older, smokers, they presented higher levels of lactate dehydrogenase (LDH), and lower levels of estimated glomerular filtration rate (eGFR), lymphocytes, and sodium at admission, and they needed O2 more often. CONCLUSION: Being overweight/obese is associated with greater O2 requirements in KTRs, in particular in older people and smokers, with worse kidney allograft functions, more inflammation, and lower sodium levels. Therefore, the early identification of factors that predict a worse outcome in overweight/obese KTRs affected by COVID-19 contributes to risk stratification and therapeutic decisions.
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The study aimed to investigate the impact of HLA-DPB1 allelic and molecular mismatches on the occurrence of acute rejection (AR) and low 5-year graft function (5Y-GF) in first kidney transplant (KT) recipients. This is a single center retrospective study of 130 deceased donor KT recipients transplanted between 2014 and 2016. HLA-DPB1 allelic MM and the following molecular MM (mMM) were analyzed: expression MM with the high expression G allele in the donor; T cell epitope MM (TCE MM); epitope MM (EMM), considering all six hypervariable regions (EMM-ABCDEF HVR), or only ABEF regions (EMM-ABEF HVR); eplet MM (EpMM); antibody-verified eplet MM (AbVer EpMM); and solvent accessible amino acid MM (SAMM). There was no association of allelic MM with AR or 5Y-GF. The variables independently associated (Cox regression analyses) with AR were high donor final creatinine, nonpermissive TCE MM, ABCDEF EMM load ≥6, EpMM load ≥6; SAMM load ≥5, and AbVer EpMM load ≥3. No association between any HLA-DPB1 mMM and 5Y-GF was observed when all 130 transplant recipients were considered. However, when transplants from expanded criteria donors were excluded, independent associations were detected (logistic regression analyses) with AbVerEpMM load ≥2, SAMM load ≥7, cerebro-vascular death, donor age, and AR. To our knowledge, this is the first study that shows that some HLA-DPB1 mMM are associated with AR and low 5Y-GF in a population of exclusively first kidney transplant recipients.
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Transplante de Rim , Humanos , Estudos Retrospectivos , Teste de Histocompatibilidade , Alelos , Fatores de Risco , Epitopos de Linfócito T , Rejeição de Enxerto/genéticaRESUMO
BACKGROUND: COVID-19 severity is determined by cardiometabolic risk factors, which can be further aggravated by chronic immunosuppression in kidney transplant recipients (KTRs). We aimed to verify the main risk factors related to hypertension (HTN) that contribute to COVID-19 progression and mortality in that population. METHODS: Retrospective analysis of 300 KTRs from March 2020 to August 2020 in a single center. We compared the main outcomes between HTN (n = 225) and non-HTN (n = 75), including admission to the intensive care unit (ICU), development of acute kidney injury (AKI), need for invasive mechanical ventilation or oxygen, and mortality. RESULTS: Of the patients in the study, 57.3% were male, 61.3% were white, the mean age was 52.5 years, and 75% had HTN. Pre-existing HTN was independently associated with higher rates of mortality (32.9%, OR = 1.96, p = 0.036), transfer to the ICU (50.7%, OR = 1.94, p = 0.017), and AKI with hemodialysis (HD) requirement (40.4%, OR = 2.15, p = 0.011). In the hypertensive group, age, diabetes mellitus, heart disease, smoking, glycemic control before admission, C-reactive protein, lactate dehydrogenase, lymphocytes, and D-dimer were significantly associated with COVID-19 progression and mortality. Both lower basal and previous estimated glomerular filtration rates posed KTRs with HTN at greater risk for HD requirement. CONCLUSIONS: Therefore, the early identification of factors that predict COVID-19 progression and mortality in KTRs affected by COVID-19 contributes to therapeutic decisions, patient flow management, and allocation of resources.
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Injúria Renal Aguda , COVID-19 , Hipertensão , Transplante de Rim , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Transplantados , Hipertensão/epidemiologia , Hipertensão/etiologia , Fatores de Risco , Estudos de CoortesRESUMO
Kidney transplant recipients present higher rates of pre-existing comorbidities, in particular diabetes mellitus (DM), hypertension, and cardiac disease. We aimed to verify the main risk factors related to DM that contribute to COVID-19 progression and mortality in a kidney transplant setting. From March to August 2020, we evaluated 300 kidney transplant recipients affected by COVID-19. We used propensity score matching (PSM) to estimate the impact of DM on COVID-19. After matching, all baseline characteristics were well balanced between those with and without DM (n = 100 in each group). Case fatality rate, the requirement of invasive mechanical ventilation (IMV), and acute kidney injury (AKI) were associated with previous fasting blood glucose, and C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels on admission. These findings were similar in kidney transplant patients with and without DM. Glycemia on admission and estimated glomerular filtration rate (eGFR) either on admission or basal correlated to the need of IMV and development of AKI, respectively. Poor glycaemic control, eGFR, markers of inflammation (CRP) and tissue damage (LDH) were indicative of COVID-19 burden in kidney transplant recipients and may be useful tools for risk-stratifying this population, independently of the DM status, during the pandemic.
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Injúria Renal Aguda , COVID-19 , Diabetes Mellitus , Transplante de Rim , Injúria Renal Aguda/etiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Humanos , Transplante de Rim/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , TransplantadosRESUMO
HLA-DQB2 is a gene of limited polymorphism, with unknown function that presents at least two transcript variants: v1, which encodes the full-length beta-chain, and v2, which lacks exon 4 and could give rise to a soluble protein. We previously showed a strong correlation between high v2 expression in preimplantation biopsies (PIB) of kidneys from young (18- to 49-year olds) but not from old, deceased donors and 1-year posttransplant low (estimated glomerular filtration rate < 45 ml/min/1.73 m2 ) graft function (GF). In this study, we aimed to investigate the impact of posttransplant soluble HLA-DQB2 (sDQB2) serum levels, v1 expression in PIB, and recipient HLA-DQB2 rs7453920 A/G polymorphism on GF. sDQB2 was evaluated by enzyme-linked immunosorbent assay in sera from 114 recipients, collected at least 1 year (median 2.1 years) after transplantation. Higher sDQB2 levels were observed in recipients of kidneys from young, but not from old, donors that had a ≥30% decline in GF within 1 year after blood collection for sDQB2 determination. Among the 15 recipients of kidneys from young donors with sDQB2 ≥ 1.52 ng/ml, 40% presented a ≥30% decline in GF, whereas this occurred in none of the 43 recipients with lower sDQB2 levels (p = 0.007; OR: 36.5). Expression of HLA-DQB2 variant 1, measured by reverse transcription-polymerase chain reaction (RT-PCR) in 92 PIB from young or old donors, did not significantly differ between transplants with high or low 4-year GF. HLA-DQB2 rs7453920 single nucleotide polymorphism (SNP) frequencies did not significantly differ between recipients with low or high 4-year GF. We conclude that HLA-DQB2 variant 1 expression in PIB and recipient rs7453920 SNP polymorphism are not associated with graft outcome. On the other hand, the association, in transplants of kidneys from young donors, between high posttransplant serum sDQB2 levels and decline in GF is a very interesting finding that deserves a validation study in a larger cohort.
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Sobrevivência de Enxerto , Transplante de Rim , Estudos de Coortes , Rejeição de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Doadores de TecidosRESUMO
The purpose of this single center retrospective study was to investigate the relationship between HLA and ABO polymorphisms and COVID-19 susceptibility and severity in kidney transplant recipients. It included 720 recipients who had COVID-19 and 1680 controls composed by recipients in follow-up who did not contact the transplantation center for COVID-19 symptoms, up to the moment of their inclusion in the study. HLA-A, -B, and -DRB1 allele groups and ABO frequencies were compared between recipients with COVID-19 (all cases, or separately mild/moderate and severe disease) and controls. The HLA association study was conducted in two case-control series and only associations that showed a p-value <0.05 in both series were considered. No HLA association regarding COVID-19 occurrence or severity met this criterion. Homozygosity at HLA-A locus was associated with COVID-19 susceptibility (odds ratio 1.4) but not severity. Blood groups A and O were associated with susceptibility and resistance to COVID-19, respectively. COVID-19 severity was associated only with older age and cardiac disease, in a multivariate analysis. We conclude that an influence of HLA on COVID-19 susceptibility is supported by the association with homozygosity at HLA-A locus but that there is no evidence for a role of any particular HLA-A, -B, or -DRB1 polymorphism. Thus, we suggest that what matters is the overall capability of an individual's HLA molecules to present SARS-CoV-2 peptides to T cells, a factor that might have a great influence on the breadth of the immune response.
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COVID-19 , Idoso , Alelos , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-A/genética , Cadeias HLA-DRB1/genética , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-ß. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.
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Criptococose/etiologia , Criptococose/mortalidade , Transplante de Rim/efeitos adversos , Criptococose/diagnóstico , Criptococose/epidemiologia , Cryptococcus , Cryptococcus neoformans/imunologia , Suscetibilidade a Doenças/imunologia , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim/métodos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismoRESUMO
BACKGROUND: The safety of immunosuppressive regimens is influenced by the induction agent, maintenance drug combination, and prophylactic strategy for cytomegalovirus (CMV) infection. Herein, this safety analysis compares rabbit antithymocyte globulin (r-ATG) or basiliximab (BAS) combined with everolimus (EVR) versus BAS combined with mycophenolate sodium (MPS) in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy. METHODS: In this single-center, prospective, randomized study, adverse events (AEs), serious AEs (SAEs), viral infections, laboratory abnormalities, dose reductions, and temporary or permanent discontinuation of the immunosuppressant were compared among patients receiving r-ATG/EVR (n = 85), BAS/EVR (n = 102), and BAS/MPS (n = 101). RESULTS: A total of 2741 AEs and 344 SAEs were observed. There were no differences in the proportion of patients with at least one AE (96% versus 98% versus 96%, respectively; P > 0.05). The proportion of patients with at least one SAE was highest in the BAS/MPS group (33% versus 48% versus 69%, respectively; P < 0.05). This difference was due primarily to a high incidence of CMV infection in the BAS/MPS group (4.7% versus 10.8% versus 37.6%, respectively). The incidence of mild/moderate abnormalities in creatinine, cholesterol, and triglyceride levels was higher in both EVR groups. The cumulative freedom from dose reduction or treatment discontinuation due to an AE was higher in both EVR groups than in the BAS/MPS group (89.2% versus 92.8% versus 76.3%, respectively, P = 0.003). There was no difference in the incidence of biopsy-confirmed acute rejection (9.4% versus 18.6 versus 15.8%, respectively; P = 0.403). CONCLUSIONS: This analysis suggests that r-ATG induction combined with EVR is associated with a comparable incidence of acute rejection, lower incidence of CMV infection, and fewer changes in initial immunosuppressive regimen due to AEs in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy.
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Everolimo , Imunossupressores , Transplante de Rim , Tacrolimo , Soro Antilinfocitário/uso terapêutico , Basiliximab/uso terapêutico , Everolimo/efeitos adversos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Tacrolimo/efeitos adversosRESUMO
As the availability of kidneys for transplantation continues to be outpaced by its growing demand, there has been an increasing utilization of older deceased donors in the last decades. Considering that definition of factors that influence deceased donor kidney transplant outcomes is important for allocation policies, as well as for individualization of post-transplant care, the purpose of this study was determine the risks for death censored graft survival and for patient survival conferred by older age of the donor in the context of the age of the recipient and of risk factors for graft and/or patient survival. The investigation was conducted in a single-center cohort of 5,359 consecutive first kidney transplants with adult deceased donors performed on non-prioritized adult recipients from January 1, 2002, to December 31, 2017. Death censored graft survival and patient survival were lower in older donors, whereas graft survival was higher and patient survival was lower in old recipients. The analyses of combinations of donor and recipient ages showed that death censored graft survival was lower in younger recipients in transplants from 18 to 59-year old donors, with standard or extended criteria, but no difference in graft survival was observed between younger and older recipients when the donor was ≥ 60-year old. Patient survival was higher in younger recipients in transplants with younger or older donors. Two to six HLA-A,B,DR mismatches, when compared to 0-1 MM, conferred risk for death-censored graft survival only in transplants from younger donors to younger recipients. Pre-transplant diabetes conferred risk for patient survival only in 50-59-year old recipients, irrespectively, of the age of the donor. Time on dialysis ≥ 10 years was a risk factor for patient survival in transplants with all donor-recipient age combinations, except in recipients with ≥ 60 years that received a kidney from an 18-49-year old donor. In conclusion, the results obtained in this study underline the importance of analyzing the impact of the age of the donor taking into consideration different scenarios.
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Seleção do Doador , Sobrevivência de Enxerto , Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Transplantados , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
We describe cases of donor-derived transmission of Cryptococcus deuterogattii in 2 kidney transplant recipients in Brazil and published information on other cases. Prompt reduction of immunosuppression and initiation of antifungal therapy was required to successfully control the fungal infections and preserve engraftment.
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Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Transplante de Rim , Antifúngicos/uso terapêutico , Brasil , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus gattii/genética , Humanos , Transplante de Rim/efeitos adversos , TransplantadosRESUMO
Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2 ± 1.3vs. 40.7 ± 0.6 years old, OR 1.04; P = 0.001) and pretransplant hyperglycaemia and BMI ≥ 25 kg/m2 (32.8% vs. 21.6%, OR 0.54; P = 0.032 and 57.4% vs. 27.7%, OR 3.5; P < 0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03; P = 0.0001), acute rejection (P = 0.021), calcium channel blockers (P = 0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol) ratio ≥ 3.5 at 1 year (P = 0.01) and at 3 years (P = 0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P = 0.035), pretransplant BMI ≥ 25 kg/m2 (P = 0.0001), posttransplant transient hyperglycaemia (P = 0.0001), and TG/HDL ratio ≥ 3.5 at 3-year posttransplant (P = 0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.
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Diabetes Mellitus/etiologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Complicações Pós-Operatórias/etiologia , Prednisona/uso terapêutico , Fatores de Risco , Tacrolimo/uso terapêuticoRESUMO
BACKGROUND: Pancreas transplant is an effective treatment for insulin-dependent diabetic individuals with end-stage renal disease, yet immunosuppression-associated adverse events may adversely affect patient and graft survival. The aim of the study was to document whether mammalian target of rapamycin inhibitors (mTORi) are safe and effective as a second-line drug after pancreas transplant. METHODOLOGY: An observational single-center study was performed in a cohort of 490 simultaneous pancreas-kidney transplant and 45 pancreas-after-kidney transplant individuals after conversion to mTORi (n = 13) owing to adverse events of either tacrolimus or mycophenolate. RESULTS: mTORi conversion was performed 11.5 ± 10.1 (range, 1-28) months after pancreas transplant, mainly owing to cytomegalovirus infection and gastrointestinal intolerance. We frequently observed clinical complications after mTORi conversion, yet creatinine, eGFR, proteinuria, fasting plasma glucose, HbA1c, and C-peptide remained stable throughout the study (mean follow-up 8.2 ± 5, range 1-17) years, as did the lipid profile (P > .05). However, graft loss occurred in almost 20% of patients owing to chronic alterations. LIMITATIONS: The small number of patients and a single-center cohort were limitations of the study. CONCLUSIONS: Late mTORi conversion is a safe and effective approach when tacrolimus or mycophenolate-mediated adverse events occur after pancreas transplant.
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Everolimo/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Pâncreas/métodos , Sirolimo/uso terapêutico , Adulto , Substituição de Medicamentos/métodos , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Terapia de Imunossupressão/métodos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Hialoifomicose/microbiologia , Transplante de Rim/efeitos adversos , Infecções Oportunistas/microbiologia , Transplante de Pâncreas/efeitos adversos , Sinusite/microbiologia , Diagnóstico Diferencial , Humanos , Hialoifomicose/diagnóstico , Hialoifomicose/imunologia , Hialoifomicose/terapia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/terapia , Valor Preditivo dos Testes , Sinusite/diagnóstico , Sinusite/imunologia , Sinusite/terapia , Resultado do TratamentoRESUMO
BACKGROUND: The prevalence and clinical epidemiological profile of hepatitis C virus (HCV) infection have changed over time. AIM: This study aimed to evaluate these changes in renal transplant recipients (RTx) comparing two different decades. MATERIALS AND METHODS: RTx with HCV referred to RTx from 1993 to 2003 (A) and from 2004 to 2014 (B) were studied retrospectively. The demographic and clinical characteristics and different outcomes were compared between groups A and B. Variables that were statistically different were tested for inclusion in a multivariate Cox proportional hazard model predicting patient survival within the group. RESULTS: Among 11 715 RTx, the prevalence of HCV was 7% in A and 4.9% in B. In the more recent period (B), the mean age was older (46.2 vs. 39.5 years), with more males (72 vs. 60.7%), larger number of deceased donors (74 vs. 55%), higher percentage of previous RTx (27 vs. 13.7%), less frequent history of blood transfusion (81 vs. 89.4%), lower prevalence of hepatitis B virus coinfection (4.7 vs. 21.4%), and higher percentage of cirrhotic patients (13 vs. 5%). Patients of group B more frequently underwent treatment of HCV (29 vs. 9%), less frequently used azathioprine (38.6 vs. 60.7%) and cyclosporine (11.8 vs. 74.7%), and more frequently used tacrolimus (91 vs. 27.3%). In the outcomes, graft loss showed no difference between periods; however, decompensation was more frequent (P = 0.007) and patients' survival was lower in the more recent period (P = 0.032) compared with the earlier one. CONCLUSION: The profile of RTx with HCV has changed over the last 20 years. Despite a decrease in the prevalence of HCV, new clinical challenges have emerged, such as more advanced age and a higher prevalence of cirrhosis.
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Hepatite C Crônica/epidemiologia , Hepatite C Crônica/terapia , Transplante de Rim , Adulto , Brasil , Feminino , Hepatite C Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Background Kidney transplant recipients (KTR) receive fixed daily doses of mycophenolate sodium as part of the immunosuppressive regimen. Dose reductions occur primarily due to adverse events and may be associated with an increased risk of acute rejection and graft loss. Objectives To evaluate the tolerability of mycophenolate in kidney transplant recipients receiving tacrolimus and prednisone. Setting The study was performed at Hospital do Rim, Federal University of São Paulo in Brazil. Method This was a retrospective cohort study including 506 patients. Tolerability of mycophenolate sodium was classified into the following groups: Temporary reduction (TR), definitive reduction (DR), temporary interruption (TI), permanent discontinuation (PD) and without modification (WM). Main outcome measure The cause of mycophenolate dose change and its influence on rejection-free survival during the first 3 years after transplantation. Results The cumulative incidence of dose change was 51.2% (11%TR, 44%DR, 24%TI, and 21%PD). Gastrointestinal (45.3%), infection (31.9%) and hematological (14.9%) systems accounted for most of the dose changes. The adverse events with higher incidence were diarrhea, cytomegalovirus (CMV) infection and leukopenia. Changes in dose of mycophenole were associated with reduced acute rejection-free survival compared with patients WM group (71.4%TR, 58.9%DR, 56.7%TI, 53.7%PD vs. 74.2%WM, p = 0.020). Only patients with PD showed inferior patient (59.3% vs. 94.4%, p = 0.001) and death-censored graft (83.3% vs. 92.5%, p = 0.074) survivals compared to patients WM. Conclusion In this cohort, changes in the dose of mycophenolate were associated with increased risk of acute rejection and permanent discontinuation was associated with inferior patient and graft survival.
Assuntos
Imunossupressores/efeitos adversos , Transplante de Rim , Ácido Micofenólico/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: The risk of death after kidney transplant is associated with the age of the recipient, presence of comorbidities, socioeconomic status, local environmental characteristics and access to health care. OBJECTIVE: To investigate the causes and risk factors associated with death during the first 5 years after kidney transplantation. METHODS: This was a single-center, retrospective, matched case-control study. RESULTS: Using a consecutive cohort of 1,873 kidney transplant recipients from January 1st 2007 to December 31st 2009, there were 162 deaths (case group), corresponding to 5-year patient survival of 91.4%. Of these deaths, 25% occurred during the first 3 months after transplant. The most prevalent cause of death was infectious (53%) followed by cardiovascular (24%). Risk factors associated with death were history of diabetes, dialysis type and time, unemployment, delayed graft function, number of visits to center, number of hospitalizations, and duration of hospital stay. After multivariate analysis, only time on dialysis, number of visits to center, and days in hospital were still associated with death. Patients who died had a non-significant higher number of treated acute rejection episodes (38% vs. 29%, p = 0.078), higher mean number of adverse events per patient (5.1 ± 3.8 vs. 3.8 ± 2.9, p = 0.194), and lower mean eGFR at 3 months (50.8 ± 25.1 vs. 56.7 ± 20.7, p = 0.137) and 48 months (45.9 ± 23.8 vs. 58.5 ± 20.2, p = 0.368). CONCLUSION: This analysis confirmed that in this population, infection is the leading cause of mortality over the first 5 years after kidney transplantation. Several demographic and socioeconomic risk factors were associated with death, most of which are not readily modifiable.