Browsing by Author "Pratas, J"
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- Cadaveric donor factor variations during a 12-year period: influence on kidney transplant outcomesPublication . Nunes, P; Parada, B; Pratas, J; Roseiro, A; Figueiredo, A; Macário, F; Rolo, F; Mota, AOur purpose was to evaluate changes in cadaveric donor factors between 1993 and 2004 and their impact on the short- and long-term outcomes of renal transplants in a single center. PATIENTS AND METHODS: Cadaveric renal transplants performed in our unit between 1993 and 2004 were divided in two groups of identical length: A (n = 455; 1993-1998) and B (n = 465; 1999-2004). Major differences related to donor, graft, and recipient factors were analyzed between groups and correlated with main outcome parameters. Recipient age, gender, weight, etiology of end-stage renal disease, average length of dialysis, and cold ischemia were not different in the two periods. RESULTS: Grafts harvested in our hospital were more frequent in group A (92.3 vs 78.2%; P < .005). Traumatic causes of death were more frequent before 1999: 90.9 vs 70.9% (P < .001). Mean donor age was higher after 1999: 31.37 vs 35.94 years (P < .005). Female donors were more frequent in the second period: 20.5 vs 26.6% (P < .05). Mean donor weight was also higher: 52.36 vs 67.86 kg (P < .05). All of these differences were unfavourable characteristics regarding graft outcomes. Delayed graft function (A = 13%, B = 24.2%), acute rejection episodes (A = 41.2%, B = 28%), and chronic allograft dysfunction (A = 23.5%, B = 14.4%) were also significantly different between the two cohorts (P < .005). Graft function (serum creatinine at 1 and 2 years), patient and graft survivals, causes of graft loss, and of patient death were similar across time. CONCLUSION: The unfavorable tendency in the quality of cadaveric donors during the last 12 years had no negative impact on graft function and patient outcome.
- Calcineurin inhibitor-free immunosuppression in renal transplantationPublication . Parada, B; Mota, A; Nunes, P; Macário, F; Pratas, J; Bastos, C; Figueiredo, APURPOSE: To describe our initial results using a calcineurin inhibitor-free immunosuppression protocol in renal transplants. PATIENTS AND METHODS: Between October 2001 and June 2003, 56 recipients of a renal allografts were started on an immunosuppression protocol without calcineurin inhibitors, consisting of basiliximab, sirolimus, mycophenolate mofetil, and steroids. We analyzed patient and graft survival, acute rejection episodes, and renal function. RESULTS: The mean follow-up was 19.6 months. Actuarial patient survival at 1 and 2 years was 98.1% and 95.3%, respectively. Actuarial graft survival at 1 and 2 years was 92.9% and 87.6%, respectively. Acute rejection occurred in 27.8% of the patients, usually Banff 1 (73.3%). There was stable renal function with mean serum creatinine of 1.3, 1.4, 1.3, and 1.3 mg/dL at 1, 6, 12, and 24 months after transplant. CONCLUSIONS: The use of immunosuppression free of calcineurin inhibitors is effective and safe. Further follow-up is needed to evaluate the impact on long-term results.
- Fibrogenesis in Kidney Transplant: Dysfunction Progress BiomarkersPublication . Costa, J S; Alves, R; Sousa, V; Marinho, C; Romãozinho, C; Santos, L; Macário, F; Pratas, J; Prado E Castro, L; Campos, M; Figueiredo, AFibrogenesis markers, such as alpha-actin (AA), CD163 (macrophages), and E-cadherin, have been studied as chronic kidney allograft injury (CAI) predictors, a major cause of allograft failure. OBJECTIVE: Investigate the value of these markers in predicting CAI and initiation of dialysis. MATERIALS AND METHODS: Retrospective analysis of 26 kidney allograft biopsies (from 22 patients with CAI) during 2 years, evaluating intensity and percentage of marked cells on glomeruli and tubulointerstitial compartment. At the time of the biopsy, patients were 45.5 ± 15.8 years and 4.2 years after transplant, and they had a mean glomerular filtration rate (GFR) of 25.8 ± 9.9 mL/min. From an average of 8.5 glomeruli per biopsy, there was ≤25% sclerosis in 17 cases, 26% to 50% in 5, and >50% in 4. Interstitial fibrosis or tubular atrophy affected ≤25% of cortical area in 14 cases, 26% to 50% in 8, and >50% in 2. Twelve patients started dialysis 5.8 ± 4.7 years after transplant, with an average GFR 20.9 mL/min at the time of the biopsy. RESULTS: There was a higher intensity and percentage of CD163-marked cells in the tubulointerstitial compartment in advanced interstitial fibrosis. We found an association between intensity of AA in the tubulointerstitial compartment and initiation of dialysis (P = .003) and a negative correlation between intensity of E-cadherin loss and GFR (r = -0.56, P = .012). CONCLUSIONS: In our study, intensity of tubulointerstitial AA was shown to be a predictor of initiation of dialysis, and E-cadherin loss intensity was associated to CAI progression. However, prospective and larger studies are needed to evaluate the predictive value of these markers.
- Genetic basis of Alzheimer's dementia: role of mtDNA mutationsPublication . Grazina, M; Pratas, J; Silva, F; Oliveira, S; Santana, I; Oliveira, CRAlzheimer's disease (AD) is the most common neurodegenerative disorder associated to dementia in late adulthood. Amyloid precursor protein, presenilin 1 and presenilin 2 genes have been identified as causative genes for familial AD, whereas apolipoprotein E epsilon4 allele has been associated to the risk for late onset AD. However, mutations on these genes do not explain the majority of cases. Mitochondrial respiratory chain (MRC) impairment has been detected in brain, muscle, fibroblasts and platelets of Alzheimer's patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the aetiology of the disease. Several reports have identified mtDNA mutations in Alzheimer's patients, suggesting the existence of related causal factors probably of mtDNA origin, thus pointing to the involvement of mtDNA in the risk contributing to dementia, but there is no consensual opinion in finding the cause for impairment. However, mtDNA mutations might modify age of onset, contributing to the neurodegenerative process, probably due to an impairment of MRC and/or translation mechanisms.
- Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiencyPublication . Ribeiro, C; Macário, MC; Viegas, AT; Pratas, J; Santos, MJ; Simões, M; Mendes, C; Bacalhau, M; Garcia, P; Diogo, L; Grazina, MLeigh syndrome (LS) is a rare, progressive neurodegenerative mitochondrial disorder of infancy. It is a genetically heterogeneous disease. The mutations in SURF1 gene are the most frequently known cause. Here two cases of LS likely caused by SURF1 gene variants are reported: a 39-year-old male patient with a novel homozygous deletion (c.-11_13del), and a case of a 6-year-old boy with the same deletion and a nonsense mutation (c.868dupT), both in heterozygosity. Blue native PAGE showed absence of assembled complex IV. This is the first report of a variant that may abolish the SURF1 gene initiation codon in two LS patients.
- Mitochondrial DNA Variants in a Portuguese Population of Patients with Alzheimer’s DiseasePublication . Grazina, M; Silva, F; Santana, I; Pratas, J; Santiago, B; Oliveira, M; Carreira, I; Cunha, L; Oliveira, CRAlzheimer's disease (AD) is the most common neurodegenerative disorder associated with dementia in late adulthood. Mitochondrial respiratory chain impairment has been detected in the brain, muscle, fibroblasts and platelets of AD patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the etiology of the disease. Several reports have identified mtDNA mutations in AD patients, but there is no consensual opinion regarding the cause of the impairment. We have studied mtDNA NADH dehydrogenase subunit 1 nucleotides 3337-3340, searching for mutations. Our study group included 129 AD patients and 125 healthy age-matched controls. We have found alterations in two AD patients: one had two already known mtDNA modifications (3197 T-C and 3338 T-C) and the other a novel transition (3199 T-C) which, to our knowledge, has not been described before.
- Mitochondrial-dependent apoptosis in Huntington's disease human cybridsPublication . Ferreira, IL; Nascimento, MV; Ribeiro, MH; Almeida, S; Cardoso, SM; Grazina, M; Pratas, J; Santos, MJ; Januário, C; Oliveira, CR; Rego, ACWe investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) vs. control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. Furthermore, apoptotic nuclei morphology and a moderate increase in caspase-3 activation, as well as increased levels of superoxide ions and hydroperoxides were observed in HD cybrids upon 3-NP or STS treatment. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death, linked to the loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their moderate susceptibility to mitochondrial-dependent apoptosis
- Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective StudyPublication . Leal, R; Pinto, H; Galvão, A; Santos, L; Romãozinho, C; Macário, F; Alves, R; Pratas, J; Sousa, V; Marinho, C; Prado E Castro, L; Campos, M; Mota, A; Figueiredo, AINTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss.
- Polyomavirus Nephropathy: Ten-Year ExperiencePublication . Costa, JS; Ferreira, E; Leal, R; Bota, N; Romãozinho, C; Sousa, V; Marinho, C; Santos, L; Macário, F; Alves, R; Pratas, J; Campos, M; Figueiredo, ABACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.
- Renal transplantation with expanded criteria donors: the experience of one portuguese centerPublication . Ferrer, F; Mota, A; Alves, R; Bastos, C; Macário, F; Figueiredo, A; Santos, L; Roseiro, A; Parada, B; Pratas, J; Nunes, P; Campos, MBACKGROUND: The shortage of kidneys available for transplantation has led to enlarged criteria donors (ECD): namely, donors older than 60 years or aged between 50 and 59 years with 2 of the following characteristics-hypertension, predonation serum creatinine level higher than 1.5 mg/dL or cerebrovascular disease as the cause of death. The aim of this study was to analyze renal transplants using ECD compared with standard criteria donors (SCD) concerning the incidences of delayed graft function (DGF), acute rejection episodes (ARE), and patient and graft survivals. MATERIALS AND METHODS: This retrospective study of 409 cadaveric renal transplants over the last 4 years identified ECD in contrast with SCD. RESULTS: Of the transplants, 24.4% used ECD. The baseline characteristics of recipients of ECD versus SCD kidneys were similar, except for age and cold ischemia time. Comparing ECD and SCD, we observed an higher incidence of DGF (35% vs 18%), occurrence of ARE (34.4% vs 16.6%), average serum creatinine levels at 6 (1.87 vs 1.4 mg/dL), and 12 months (1.88 vs 1.43 mg/dL) as well as lower graft survival at 1 (82% vs 91%) and 3 years (75% vs 84%) after transplantation. Recipient survival at 1 year was not different. Multivariate analysis identified recipient age, cold ischemia time, ARE, and DGF as risk factors for graft failure. CONCLUSIONS: Renal transplantation with grafts from ECD shows significantly worse outcomes with higher rates of DGF and ARE, worse graft function, and lower graft survival.