22 results on '"Manuel Anibal A. Ferreira"'
Search Results
2. MO520: Prevalence of Anemia in Patients With Stage 3 or 4 Chronic Kidney Disease in Portugal–The Nefropor Study
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Manuel Anibal A. Ferreira, Inês Aires, Maria Do Mar Menezes, Sara Cardoso Fernandes, Ana Cortesão Costa, Sara Fernandes, Ana Farinha, Teresa Furtado, Nídia Marques, Francisco Gonçalves, Marisa Roldão, Anabela Malho Guedes, Roberto Calças Marques, Ana Galvão, Ana Gaspar, Nicole Pestana, Ana Carlota Vida, Noélia Lopez, and José António Lopes
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Transplantation ,Nephrology - Abstract
BACKGROUND AND AIMS Anemia is a highly prevalent and modifiable comorbidity in patients with chronic kidney disease (CKD), which tends to aggravate as the disease progresses. The economic burden of anemia in CKD is high, and quality of life issues (e.g. fatigue, reduced productivity) is common in these patients. Data on the prevalence and treatment of anemia in CKD stages 3 and 4 (based on the estimated glomerular filtration rate according to KDIGO classification) in Portugal are lacking. The NEFROPOR study aimed to estimate the prevalence of anemia in patients with CKD stage 3 or 4 admitted to a Nephrology consultation between 1 January and 31 March 2017 and characterize anemia treatment in this patient population. METHODS NEFROPOR was a retrospective, multicentric study carried out in 10 Portuguese centers. All patients aged ≥18 years with stage 3 or 4 CKD admitted to a Nephrology consultation in one of those centers between 1 January and 31 March 2017 were invited to participate, and data for up to 24 months after admission were collected from patients’ clinical files. Retrieved data included age, body mass index (BMI), anemia status according to the World Health Organization (WHO) diagnostic criteria, and anemia treatment type and duration. Three assessments of the prevalence anemia were performed: at the time of the first Nephrology visit (presentation), at the first analytical results and the overall prevalence in the study cohort. Statistical analysis was performed in SPSS Statistics (v26) and a 0.05 significance level was adopted. RESULTS A total of 176 patients were included in this study, mostly (61.9%) male, with a median age of 76 years (range, 26–97) and a mean BMI indicative of pre-obesity (28.2; standard deviation, 4.2). CKD stage 3b was predominant (43.2%), followed by stage 4 (32.4%) and stage 3a (24.4%). The most frequent CKD etiologies in this cohort were diabetes (39.8%), followed by arterial hypertension (27.8%) and unknown cause (25.6%). Arterial hypertension was largely the most frequent comorbidity, present in 90.3% of patients, followed by diabetes (54.0%). Although less prevalent, coronary artery disease (18.2%) and congestive heart failure (14.8%) were also identified in this patient population. A total of 44.9% of patients [95% confidence interval (CI), 37.7%–52.3%] had anemia at presentation, which was significantly associated with CKD stage, diabetes, peripheral vascular disease and myocardial infarction comorbidities, and diabetes and unknown CKD etiology. The overall prevalence of anemia in the study cohort was 61.9% (95% CI 54.6%–68.9%), and it was significantly associated with diabetes and peripheral vascular disease comorbidities and with diabetes and primary glomerulonephritis as CKD etiologies. The prevalence of anemia at the first analytical results was 49.4% (95% CI 42.1%–56.8%), and it was significantly associated with CKD stage, diabetes, non-skin cancer, peripheral vascular disease and myocardial infarction comorbidities, and diabetes as CKD etiology. Figure 1 shows the evolution of anemia treatment in this cohort over 24 + months. CONCLUSION The three estimates of the prevalence of anemia in this study were consistent with each other, particularly those for the first visit and first analytical results. The latter were also consistent with evidence in the literature reporting a prevalence of anemia in the population of patients with CKD stages 3 and 4 between 40% and 60%. The overall prevalence of anemia in this study was 12%–15% higher than first visit and first analytical results estimates, in agreement with the fact that this refers to a cumulative prevalence. These data support the need for optimized and individualized treatment strategies for patients with CKD stages 3 and 4, maximizing the efficiency of health-care resource use.
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- 2022
3. MO607: Intradialytic Exercise: A Large-Scale Nationwide Implementation Study
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Pedro Martins, Diogo Vaz Leal, Manuel Anibal A Ferreira, Kenneth Wilund, and João Viana
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Transplantation ,Nephrology - Abstract
BACKGROUND AND AIMS Intradialytic exercise (IDE) is recommended for HD patients. However, this recommendation is mostly based on research conducted under optimal instead of real-world conditions, limiting generalizability and its implementation into routine clinical care. This study aims to analyze implementation outcomes of IDE in real-world conditions at a large-scale, nationwide level. METHOD After a pilot experience in a single unit, all NephroCare Portugal dialysis clinics were invited to initiate an IDE program. A national coordinator was nominated, and a nurse and a doctor were selected in each unit as local coordinators. A simple exercise protocol was designed to be easily applied by current dialysis staff (though some units benefited from exercise science student internships). The IDE protocol includes a bout of aerobic exercise (cycle ergometer) and lower limb resistance exercises (ankle weights). The RE-AIM (reach, effectiveness, adoption, implementation and maintenance) framework was used to study clinical implementation over the first year. For each RE-AIM dimension, specific implementation outcomes were adapted to IDE. Effectiveness measures included safety (incidence of intradialytic adverse events over 1 year) and physical function at baseline and at 1 year (sit to stand 30, 8-foot up & go, handgrip strength, sit to stand 5 and single leg stance). For safety measures, IDE group was compared to a group of patients that refused IDE. Physical function measures were only applied to IDE patients, and so comparisons were made between low- and high-frequency exercise groups. RESULTS Adoption: 21 dialysis units (58.3%). Reach: 1270 eligible patients (55.8%). Main reasons for noneligibility were physical/cognitive incapacity (50.8%) and cardiovascular risk (34.9%). Eligible patients were younger (P CONCLUSION Large-scale implementation of IDE is a realistic and safe way to promote physical activity in HD patients with benefits on physical function. Yet, to optimize its generalizability, strategies to increase patients´ acceptability and long-term adherence are needed.
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- 2022
4. MO538: Lower Serum Levels of Magnesium are Associated With Higher Risk of Fractures in Haemodialysis Patients
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Gonçalo Ávila, Patricia Matias, Ivo Laranjinha, Tiago Amaral, Célia Gil, and Manuel Anibal A. Ferreira
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Transplantation ,Nephrology - Abstract
BACKGROUND AND AIMS Magnesium (Mg) deficiency is associated with altered bone metabolism, However, the relationship between Mg and the risk of fragility fractures haemodialysis (HD) patients is still unclear. The aim of this study was to evaluate the association between pre-dialysis Mg serum levels and the risk of incident bone fractures in a cohort of prevalent HD patients. METHOD We performed a prospective study of 206 prevalent HD patients followed from 2009 until 2021. Demographic, clinical and biochemical parameters were evaluated. RESULTS A total of 37 episodes of fragility fractures were identified with a median HD vintage of 42 months, which corresponds to an incidence rate of 29/1000 person-years. The mean age of the studied population was 68.3 ± 13.1 years, 121 (59%) were male and the median follow-up time on HD was 58 months. Patients with incident fractures showed significantly lower Mg levels compared with those without fractures (2.3 ± 0.3 versus 2.8 ± 0.4 mg/dL, P Patients with a Mg serum level CONCLUSION This study shows that the incidence of bone fragility fractures in HD patients is high and significantly associated with lower pre-dialysis Mg levels. Management of fracture risk in HD patients and assessment of its risk factors requires further study.
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- 2022
5. MO600: Effects of Intradialytic Progressive Resistance and Aerobic Exercise Training on Physical Function
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Daniela Cardoso, Diogo Vaz Leal, Pedro Martins, Manuel Anibal A Ferreira, Luke Baker, Alice Smith, and João Viana
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Transplantation ,Nephrology - Abstract
BACKGROUND AND AIMS Haemodialysis (HD) patients frequently experience reduced physical function, which is exacerbated throughout dialysis vintage, therefore compromising their quality of life. Despite recent studies highlighting improvements in physical function regardless of exercise modality, well-designed randomized controlled trials with progressive resistance exercise training protocols are scarce. Thus, this study investigated the effects of 12 weeks of intradialytic progressive resistance exercise (RE) and aerobic exercise (AE) training on physical function in HD patients. METHOD Fifty-six adult HD patients from three NephroCare Portugal SA clinics were included in this study. Following a 6-week run-in control period, participants were randomly allocated into either a supervised intradialytic AE [(n = 29, male: 66%, age: 66 ± 16 years)] or RE [(n = 27, male: 67%, age: 63 ± 14 years)] training protocol, 3 sessions per week for 12 weeks. Intradialytic RE training consisted of 2 sets of 12 repetitions of 8 different exercises for upper and lower body using free-weight dumbbells and a newly designed weight machine, while intradialytic AE training was performed on a cycle ergometer at 50–70 rpm for 30 min at a rating of perceived exertion (RPE) 12–14 (Borg scale). Physical function was assessed by completing the Sit to Stand 60 (STS-60) test, the Short Physical Performance Battery (SPPB), the Incremental Shuttle Walk Test (ISWT), the Timed Up and Go (TUG) test and isometric handgrip strength (HGS) on three occasions: before and after the 6-week run-in control, and after the 12-week exercise periods. The 6-week control period data were analyzed by paired sample t-tests or Wilcoxon rank test as this is prior to randomization. Training effects were examined using an ANOVA with mixed design (within- and between-subjects) for data with normal distribution or if data still with non-normal distribution after log transformation, Wilcoxon rank test (within subjects) and Mann–Whitney test (between subjects) were used with a significance value of P RESULTS There was no change in any variable when comparing before and after the 6-week control period (P > 0.05). AE and RE training significantly increased the number of repetitions performed on the STS-60 test compared to before the 12-week intervention, but had no effect on the SPPB scores. Additionally, despite no changes in the distance covered in ISWT in the AE group, AE training reduced the TUG time and an increase in HGS was observed. On the other hand, patients that performed RE training increased their walking distance in ISWT. However, no change in HGS was observed. Yet, and despite not impactful, a 0.1 s significant increase in the median time performed on the TUG test was also observed. Nevertheless, no changes between groups were observed after the 12-week exercise intervention (Table 1). CONCLUSION We conclude that 12 weeks of AE training seem to improve HGS, STS-60 and TUG test performance in HD patients, whereas progressive RE training only had an effect on the STS-60 and ISWT performance in these patients. This may suggest that HD patients can benefit from different exercise interventions which can improve their overall physical function. FUNDING Portuguese Foundation of Science and Technology (SFRH/BD/138 940/2018 and UID/04 045/2020). ACKNOWLEDGEMENTS We would like to acknowledge the support of NephroCare Portugal, the University of Maia staff, MSc students and all study participants for their collaboration.
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- 2022
6. MO904: Potassium Intake Does Not Predict High Serum Potassium Levels in Haemodialysis Dash Diet Consumers
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Cristina Garagarza, Ana Valente, Cristina Caetano, Inês Ramos, Joana Sebastião, Mariana Pinto, Telma Oliveira, Manuel Anibal A. Ferreira, and Catarina Sousa Guerreiro
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Transplantation ,Nephrology - Abstract
BACKGROUND AND AIMS As high serum potassium levels can lead to adverse outcomes in haemodialysis (HD) patients, dietary potassium is frequently restricted in these patients. However, recent studies have questioned whether dietary potassium really affects serum potassium levels. Dietary approaches to stop hypertension (DASH) emphasizes the consumption of potassium rich foods, specially from plant sources, such as: fruits, vegetables, whole grains, nuts and seeds. The aim of this study was to analyze the association between the DASH dietary pattern and serum potassium levels. METHOD This was an observational cross-sectional multicentre study with 582 HD patients from 37 dialysis centers. Clinical and biochemical data were registered. Dietary intake was obtained using the Food Frequency Questionnaire. Adherence to DASH dietary pattern was obtained from Fung´s DASH index (8–40 points). For the statistical analysis, Fung´s DASH index was categorized into terciles and mean differences were analyzed with one-way ANOVA. Linear regression was used to analyze the relationship between serum potassium and adherence to the Dash dietary pattern. The multivariate model was adjusted to age, gender, presence of diabetes mellitus, energy intake, dietary potassium intake, residual diuresis, dialysis adequacy (Kt/V), dialysis vintage and intake of potassium binders. All statistical tests were performed using SPSS 26.0 software. A P-value lower than 0.05, was considered statistically significant. RESULTS Patients’ mean age was 67.8 ± 17.7 years and median HD vintage was 65 (43–104) months. Mean serum potassium was 5.3 ± 0.67 mEq/L, dietary potassium intake was 2465 ± 1005 mg/day and mean Fung´s Dash Index was 23.9 ± 3.9. Of the whole sample, 36.4% of the patients presented low adherence to the DASH dietary pattern (0–22 points), 39.0% presented a moderate adherence (23–26 points) whereas 24.6% a high adherence (≥27 points). Comparing to the lower adherence, patients with a higher adherence to the DASH dietary pattern were older (P CONCLUSION Most of the patients presented a moderate adherence to the DASH dietary pattern. Following this dietary pattern, which is rich in potassium, is not associated with increased serum potassium levels in HD patients. What is more, a higher adherence to the DASH dietary pattern predicts lower serum potassium levels. Therefore, tight dietary potassium restrictions may not be adequate, at least for those with a DASH diet plan as a more flexible diet, especially regarding plant-based foods rich in potassium, may promote other health benefits and reduce patient´s dietary plan limitations.
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- 2022
7. MO572BONE BIOPSY AND MINERAL METABOLISM, CARDIOVASCULAR DISEASE AND PATIENT SURVIVAL IN END-STAGE RENAL PATIENTS
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Inês Aires, Rute Salvador, Cecília Silva, Guadalupe Cabral, Ana Carina Ferreira, Patrícia Cotovio, Marco Mendes, Manuel Anibal A Ferreira, Fernando Nolasco, David Navarro, Fernando Caeiro, and Bruna Correia
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Transplantation ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Patient survival ,Roentgen rays ,Disease ,medicine.disease ,Gastroenterology ,Nephrology ,Calcitonin ,Internal medicine ,Biopsy ,Medicine ,Mineral metabolism ,Stage (cooking) ,business ,Hypophosphatemia - Abstract
Background and Aims Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequent in end-stage renal disease (ESRD) patients, increasing morbid-mortality. The aim of this study was to determine the prevalence and phenotype of bone disease before transplantation; and to correlate FGF23, klotho and sclerostin serum levels with bone histomorphometric parameters and CV disease. The secondary aim was to correlate bone biopsies data with other bone related parameters, as PTH, bone alkaline phosphatase, 25-hidroxivitamin D3, calcitonin, calcium, phosphorus, and magnesium. Method We performed a prospective cohort study of a sample of ESRD patients listed for renal transplant. All patients were submitted to renal transplant and were followed for 12 months. Patient and graft survival were recorded. At inclusion, demographic and clinical data were collected, laboratorial evaluation; bone biopsy and X-ray of the pelvis and hands (Adragão score) were performed. Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank sum test, Fisher and Kruskal Wallis test. Multivariate analysis was performed using logistic regression. STATA software was used and p < 0.05 was considered statistically significant. Results We included 84 patients. Median age 53.5 (IQ range: 40.5 – 61.5) years, 59 men (70.2%), 65 caucasian (77.4%). The median left ventricular mass index was 108.5 (92 – 129) g/m2, with 32 patients presenting left ventricular hypertrophy and 19 valve calcifications. Median Adragão score was 1 (0 – 2). We diagnosed adynamic bone disease in 15 patients; hyperparathyroid bone disease in 19 patients; osteomalacia in 1 patient and mixed renal osteodystrophy in 3 patients. At the end of 12 months, 4 patients died, 5 had graft failure (non-primary function) and 4 had a cardiovascular event. Sclerostin was found to be a risk factor for low bone volume; whereas low phosphorus, low FGF23 and high bAP risk factors for abnormal mineralization. High turnover was mainly present in patients with high bAP and phosphorus and low sclerostin levels. The presence of valve calcifications was associated with low volume and with low or high turnover disorder. FGF23 appears as an important independent factor for vascular calcifications [as well age (p=0.009), BMI (p=0.02), presence of diabetes (p=0.01)], and for cardiovascular events. Sclerostin emerged as a risk factor for vascular calcifications and lower levels of sclerostin were associated with patient survival at the end of 12 months. Conclusion From the bone-derived hormones, sclerostin and FGF23 seem to act as risk factors for vascular calcifications and worse outcomes.
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- 2021
8. MO574MINERAL AND BONE DISORDERS CHANGES IN RENAL TRANSPLANTED PATIENTS
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Manuel Anibal A Ferreira, Bruna Correia, Guadalupe Cabral, Inês Aires, Rute Salvador, Fernando Caeiro, Cecília Silva, Marco Mendes, Fernando Nolasco, David Navarro, Ruben Ramos, Ana Carina Ferreira, and Patrícia Cotovio
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Fibroblast growth factor 23 ,Transplantation ,Kidney ,medicine.medical_specialty ,medicine.anatomical_structure ,McNemar's test ,Nephrology ,business.industry ,Vitamin D and neurology ,medicine ,Urology ,Agatston score ,business - Abstract
Background and Aims Successful renal transplant restores many physiologic abnormalities, including improvement of chronic kidney disease- mineral and bone disorder (CKD-MBD) syndrome. The primary aims of this study were: analyse the changes and evolution of the 3 components of CKD-MBD pre and 1 year post renal transplantation: the mineral abnormalities, the bone disorders and the vascular calcifications; and to correlate fibroblast grow factor 23 (FGF23), klotho and sclerostin serum levels with bone histomorphometric parameters and CV disease. The secondary aims were to study the evolution of other bone related parameters and correlate those with bone biopsies data, as well as to validate Adragão vascular calcification score in a population of renal transplant patients. Method We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (for Adragão score) and echocardiographic findings were recorded. All patients were submitted to a bone biopsy and laboratorial evaluation at baseline (time 0 – T0). Patients were followed for 12 months (time 1 – T1), after which performed laboratorial evaluation, a 2nd bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry and non-contrast cardiac CT (Agatston score). Continuous variables are presented as medians and categorical variables as frequencies. Differences between T0 and T1 were accessed by Wilcoxon matched-pairs test and paired McNemar test. Correlations between bone histomorphometric findings and severity of vascular calcifications with demographic and laboratorial parameters were obtained with Wilcoxon rank-sum test or Kruskall Wallis test. STATA software was used and p < 0.05 was considered statistically significant. Results We recruited 84 patients in a 28 month-period. At the end of 12 months, 69 patients performed a 2nd evaluation. Median age 53 years, 48 men, 53 caucasian, median dialysis vintage 55 months. We observe a significant reduction on phosphorus, magnesium, PTH, calcitonin, sclerostin, bone alkaline phosphatase and FGF23. Both calcium and alpha-klotho serum levels increase, with no significant changes in vitamin D levels. 68% of the patients presented renal osteodystrophy at the 2nd bone biopsy, and we observed a significant increase in the development of low turnover bone disorder, with no major changes in volume or mineralization. Changes in alpha-klotho, bAP and sclerostin (from T0 to T1) were important determinants of changes in turnover, mineralization and volume, respectively. Despite not being statistically significant, we were able to observe an improvement in the cortical bone porosity. Vascular calcifications and echocardiographic findings weren’t different comparing to the baseline (Median Adragão score was 1 in both evaluations, and valve calcifications were present in 22% and 23% of patients, with no changes in LVMI). The median Agatston score was 48.5, being the median adjusted percentile of 82%. FGF23 and sclerostin were found to be independent risk factors for extra-osseous calcifications, as well as low bone volume, cortical porosity and osteoid volume. Adragão score and valve calcifications correlated well with the increased severity of coronary calcifications determined by Agatston score (absolute and percentile). Conclusion In conclusion, renal transplantation improves two of the three components of CKD-MBD (biochemical and bone disorders), slowing the progression of vascular calcifications. FGF23, sclerostin and bAP seemed to be key parameters in understanding the bone changes observed in post transplant period, and these hormones also interfere with extra osseous calcification severity. Adragão score seems to be a good tool to access vascular calcifications in renal transplanted patients.
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- 2021
9. FC 122BONE DENSITOMETRY IN RENAL TRANSPLANTED PATIENTS
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Fernando Caeiro, Ana Carina Ferreira, David Navarro, Patrícia Cotovio, Fernando Nolasco, Guadalupe Cabral, Cecília Silva, Rute Salvador, Bruna Correia, Inês Aires, Manuel Anibal A Ferreira, and Marco Mendes
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Transplantation ,Pathology ,medicine.medical_specialty ,Nephrology ,business.industry ,Medicine ,Histology ,Densitometry ,business ,Diagnostic radiologic examination - Abstract
Background and Aims Renal transplant and associated immunosuppression can influence bone volume. The aim of this study was to analyze the relations between bone biopsy data and levels of bone-related molecules [phosphorus (Pi), Calcium (Ca), Magnesium (Mg), parathyroid hormone (PTH), bone alkaline phosphatase (bAP), calcitonin, vitamin D (vitD), alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin], obtained 1-year after transplantation with bone densitometry findings in the same time point in renal transplanted patients. Method We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (Adragão score) and echocardiographic findings were recorded. All patients were submitted to a laboratorial evaluation and a bone biopsy at baseline. Patients were followed for 12 months, after which performed laboratorial evaluation, 2nd bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry (DXA) and non-contrast cardiac CT. For this report we use the information of the 2nd analysis: laboratorial information, bone histology information, as well the densitometry evaluation. Continuous variables were presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank-sum test, Fisher exact test, Kruskal Wallis rank test or Spearman correlation test. Multivariate analysis was performed using linear regression models. STATA software was used and p < 0.05 was considered statistically significant. Results We recruited 84 patients and, at the end of 12 months, we performed a 2nd evaluation in 69 patients. Median age 53 years, 48 men, 53 caucasian (78.8%), median BMI 24.6, median dialysis vintage 55 months. Patients had a median cumulative steroid dose of 5692.5 mg. Analyzing bone biopsies, we found that 28 patients had adynamic bone disease; 6 had hyperparathyroid bone disease; 2 had osteomalacia and 3 other abnormal mineralization; 8 patients presented only with osteoporosis. There was no significant difference between bone volume / total volume pre transplant (18%) and 1 year after transplantation (19%). Using DXA technique, 14 patients were classified has having osteoporosis, and all those had low volume at the bone biopsy. Nevertheless, in 4 patients low bone turnover was also present. The positive predictive value dropped from 100% to 57%, if we add the other abnormalities of bone, in addiction to the volume. DXA exam wasn’t a good tool to detect a normal bone volume, as the negative predicted value dropped from 78% (normal volume, irrespective of turnover and mineralization) to 37% (normal bone biopsy). Nevertheless, overall bone volume assessed by a bone biopsy correlated well with densitometry findings. Conclusion DXA exam isn’t a good tool to identify the bone quality. Nevertheless, once osteoporosis is detected the probability of the patient having low bone volume is high, but we still need a bone biopsy in order to exclude mineralization or turnover deviations.
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- 2021
10. FC 079HIGH SERUM PHOSPHATE, A NOVEL POTENTIAL RISK FACTOR FOR BONE FRAGILITY FRACTURES IN THE COSMOS STUDY
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Jürgen Floege, Enrique Rodríguez Rubio, Minerva Rodríguez García, Francesco Locatelli, José Luis Fernandez-Martin, Carmine Zoccali, Miguel Ángel Suárez Hevia, Martine Cohen-Solal, Jose Luis Gorriz Teruel, Carlos Gómez-Alonso, Gérard M. London, Jesús María Fernández Gómez, Jorge B. Cannata-Andía, Manuel Anibal A Ferreira, Pedro Barrera Baena, Beatriz Martín-Carro, Cristina Alonso-Montes, Markus Ketteler, Lucía González Llorente, and Alberto Ortiz
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Transplantation ,medicine.medical_specialty ,Endocrinology ,Nephrology ,business.industry ,Potential risk ,Internal medicine ,Medicine ,Serum phosphate ,Bone fragility ,business - Abstract
Background and Aims Bone fragility fractures (bone fractures) are extremely frequent in haemodialysis (HD) patients. Serum phosphate (P) has been suggested as a risk factor for bone fracture, nonetheless, evidence is poor. The aim of this study was to assess the association between incidence of bone fractures and serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) in patients from the COSMOS study. Method COSMOS is an observational, prospective, open cohort study with 3 years of follow-up including 6797 haemodialysis patients from 227 centres randomly selected from 20 European countries. At baseline, demographics, comorbidities, treatments, serum biochemical parameters of the previous six months and bone fractures of the previous 12 months were collected. Every 6 months, all these variables, outcomes, and incident bone fractures, were collected. Patients who had at least one bone fracture during follow-up were compared with those who had not. Multivariate binary logistic regression and Poisson regression were used to assess the association between incidence of bone fractures and serum P, Ca and PTH. Time to fracture (and possible re-fracture) was also evaluated using Cox regression and Cox regression for recurrent events. All the results were adjusted by 23 variables including Ca, P, PTH, albumin and haemoglobin (full adjusted model). Results Analysis included 6274 patients who had follow-up data and non-missing information regarding bone fractures at baseline and during follow-up; 252 patients (4.0%), suffered at least one incident bone fracture. The fractured patients were older (68.1±12.9 vs. 63.8±14.5 years, p Multivariate binary logistic regression showed that “well known risk factors for bone fracture”, such as a previous bone fracture (OR: 7.78[95%CI:4.83-12.55], p 800 pg/mL (OR: 1.60[95%CI: 1.01-2.55], p=0.047), were associated with a higher incidence of follow-up bone fractures. In addition to the “well known bone risk factors for fracture”, serum P > 6.1 mg/dL (OR: 1.50[95% CI: 1.07-2.11], p=0.02) and serum Ca > 9.7 mg/dL (OR: 1.42[95%CI: 1.01-2.03], p=0.043), were also associated with a higher incidence of bone fractures in the full-adjusted model. These findings were partly consistent with Poisson regression for serum P >6.1 mg/dL (IRR: 1.46[95% CI: 1.00-2.13], p=0.0085) and serum Ca > 9.7 mg/dL (IRR: 1.49[95%CI: 1.06-2.08], p=0.0047), but not for PTH. In addition, Cox regression analysis showed association between bone fractures and serum P >6.1 mg/dl (HR: 1.61 [95%CI: 1.16-2.24], p=0.0049) and 1.60 [95%CI: 1.14-2.24] (p=0.0066) for simple and recurrent events respectively, but no association was found with serum Ca and PTH in the 2 full-adjusted models for the Cox regression analyses. Conclusion In COSMOS, a large haemodialysis patient’s cohort with 3 years follow up, serum P was the only biochemical parameter that remained as a significant risk factor for bone fractures after 4 statistic approaches. Thus, for the first time, in a large scale well controlled study, high serum P has been identified as a new independent potential risk factor for incident bone fractures in haemodialysis patients.
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- 2021
11. P1675BONE DENSITOMETRY IN RENAL TRANSPLANTED PATIENTS
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Guadalupe Cabral, Inês Aires, Cecília Silva, Fernando Nolasco, Manuel Anibal A Ferreira, Ana Carina Ferreira, Marco Mendes, Rute Salvador, Patrícia Cotovio, Bruna Correia, Fernando Correia Caeiro Pereira, and David Navarro
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Transplantation ,Kidney ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Urology ,medicine.disease ,Interval data ,Osteopenia ,medicine.anatomical_structure ,Nephrology ,medicine ,Hemodialysis ,Densitometry ,business ,Vascular calcification ,Diagnostic radiologic examination - Abstract
Background and Aims Renal transplant and associated immunosuppression can influence bone volume. Presently, the data is conflicting with older studies showing bone loss after transplant, while recent ones didn’t conclude the same. The aim of this study was to analyse the relations between bone-related molecules [phosphorus (Pi), Calcium (Ca), Magnesium (Mg), parathyroid hormone (PTH), bone alkaline phosphatase (bAP), calcitonin, vitamin D (vitD), alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin] and bone densitometry findings in renal transplanted patients. Method We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (Adragão score) and echocardiographic findings were recorded. All patients were submitted to a laboratorial evaluation and a bone biopsy at baseline (time 0). Patients were followed for 12 months, after which performed laboratorial evaluation, 2nd bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry (DXA) and non-contrast cardiac CT for Agatston score (time 1). Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon matched-pairs test and Spearman correlation test. STATA software was used and p < 0.05 was considered statistically significant. Results We recruited 85 patients from 1st October 2015 to 1st March 2018. At the end of 12 months, 6 patients refuse to perform the 2nd evaluation, 5 had primary non-function of the kidney graft, 1 had no 1st bone biopsy sample in time 0 and 4 patients died. We performed a 2nd evaluation in 69 patients and included those in this study. Mean age 50.2±12.4 years, 48 men, 53 caucasian (78.8%), median BMI 24.5 (22.7 – 27.8), median dialysis vintage 55 months (42 – 84). Patients had a median cumulative steroid dose of 5692.5 (5260 – 7250) mg. At 12 months, the median FRAX value for osteoporotic fracture was 3.5 (2.2 – 6.2) and for femoral neck fracture was 0.8 (0.2 – 2.7). The DXA findings are shown in Table 1. We found a negative correlation between vascular calcifications (Agatston Score and respective calcium percentile) and T and Z score of femoral neck (p=0.04), but not with the other DXA variables. Total femur variables (DMO, T-score, Z-score) were correlated with sclerostin values in time 1 (p Conclusion We found an inverse correlation between T and Z scores of femoral neck and coronary vascular calcifications. Regarding bone-derived hormones, Spine T and Z scores and FRAX values negatively correlated with alfa-klotho. Sclerostin seems to be associated with high mineral density.
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- 2020
12. P1418BONE-DERIVED HORMONES, MINERAL METABOLISM, CARDIOVASCULAR DISEASE AND PATIENT OUTCOME IN END-STAGE RENAL PATIENTS
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Marco Mendes, Guadalupe Cabral, Bruna Correia, Rute Salvador, Fernando Correia Caeiro Pereira, David Navarro, Inês Aires, Ana Carina Ferreira, Patrícia Cotovio, Manuel Anibal A Ferreira, Fernando Nolasco, and Cecília Silva
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Fibroblast growth factor 23 ,Transplantation ,medicine.medical_specialty ,Kidney ,business.industry ,medicine.medical_treatment ,Disease ,medicine.disease ,Gastroenterology ,medicine.anatomical_structure ,Nephrology ,Chronic kidney disease-mineral and bone disorder ,Internal medicine ,medicine ,Vitamin D and neurology ,Hemodialysis ,business ,Prospective cohort study ,Hormone - Abstract
Background and Aims Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequent in end-stage renal disease ESRD (ESRD) patients, increasing morbid-mortality. The aim of this study was to analyse the associations between the new CKD-MBD players [alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin] and the usual markers of the disease [parathyroid hormone (PTH), bone alkaline phosphatase (bAP), vitamin D (vitD), phosphorus (Pi), Calcium (Ca) and Magnesium (Mg)], as well echocardiographic findings [left ventricular mass index (LVMI) measured by Devereux formula, valvular calcifications], vascular calcifications and patients outcomes. Method We performed a prospective cohort study of a sample of ESRD patients listed for renal transplant. All patients were submitted to renal transplant and were followed for 12 months. Patient and graft survival were recorded. At inclusion, demographic and clinical data were collected, laboratorial evaluation, bone biopsy and X-ray of the pelvis and hands (Adragão score) were performed. Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank sum test and Spearman correlation test. STATA software was used and p < 0.05 was considered statistically significant. Results We included 85 patients. Mean age 50.1±12.7 years, 59 men (69.4%), 66 caucasian (77.6%). The median LVMI was 108.5 (92 – 129) g/m2, with 32 patients presenting LVH and 19 valvular calcifications. Median Adragão score was 1 (0 – 2). At the end of 12 months, 4 patients died and 5 had graft failure (non-primary function). Alpha-klotho correlated with bAP (p=0.0006) and marginally with PTH and absence of valvular calcifications (p=0.05). FGF23 correlated with Pi (p Sclerostin correlated negatively with bAP (p=0.007) and PTH (p=0.04). The 3rd sclerostin tertile was associated with high scores of vascular calcifications (p=0.02). Lower levels of sclerostin were associated with patient survival at the end of 12 months (p=0.02). Conclusion From these 3 new bone-derived hormones, sclerostin, a bone formation inhibitor, seems to act as a risk factor for vascular calcifications and worse outcomes.
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- 2020
13. P0928PHYSICALLY ACTIVE PATIENTS IN HEMODIALYSIS: DO THEY HAVE A DIFFERENT EATING PATTERN AND BODY COMPOSITION?
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Catarina Sousa Guerreiro, Mariana Pinto, Cristina Garagarza, Telma Oliveira, Cristina Caetano, Manuel Anibal A Ferreira, Ana Valente, and Inês Ramos
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Transplantation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Body water ,Physical activity ,Nutritional status ,medicine.disease ,Comorbidity ,Nephrology ,Diabetes mellitus ,Internal medicine ,medicine ,Hemodialysis ,medicine.symptom ,business ,Weight gain - Abstract
Background and Aims Body composition influences outcomes in hemodialysis (HD) patients. These patients need to follow specific nutritional recommendations and physical activity has been highly encouraged. The aim of this study was to evaluate if there are differences in body composition and in dietary patterns between physically active and no physically active HD patients. Method This was a multicenter observational cross-sectional study where 582 HD patients from 38 dialysis centers were enrolled. Clinical parameters were recorded and body composition analysis was performed with the Body Composition Monitor®. Dietary intake and physical activity were obtained respectively from the Food Frequency Questionnaire and from the International Physical Activity Questionnaire, both validated for the Portuguese population. For the analysis, patients were divided in 2 groups: physically active (PA), if they follow the World Health Organization recommendations, and no physically active (NPA). T-student and non-parametric tests were performed to compare means and medians respectively. A p Results Mean age was 67.8 ±17.7 years, 41.4% were female, 31.6 % had diabetes mellitus and median HD vintage was 65 (Interquartil range:43-104) months. PA patients were younger (p Conclusion These data shows that, after comparing PA patients with NPA, differences were observed in body composition and clinical parameters related to a better nutritional status. Moreover, the PA patients` dietary intake was more approximated to the existing recommendations for this population, namely for energy and protein daily intake.
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- 2020
14. P1680MINERAL METABOLISM CHANGES AFTER RENAL TRANSPLANTATION
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Guadalupe Cabral, Inês Aires, Ana Carina Ferreira, Cecília Silva, Fernando Nolasco, Bruna Correia, Fernando Correia Caeiro Pereira, Marco Mendes, Manuel Anibal A Ferreira, Rute Salvador, David Navarro, and Patrícia Cotovio
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Transplantation ,Nephrology ,business.industry ,Medicine ,Physiology ,Metabolism ,business - Abstract
Background and Aims Successful renal transplant restores many physiologic abnormalities, including improvement of chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome, and modifications of bone-related molecules in disease and health can help to understand pathophysiology of this syndrome. The aim of this study was to analyse the evolution of some of the new CKD-MBD players [alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin] pre and post transplantation and the associations between those and the usual markers of the CKD-MBD disease [parathyroid hormone (PTH), bone alkaline phosphatase (bAP), calcitonin, vitamin D (vitD), phosphorus (Pi), Calcium (Ca) and Magnesium (Mg)] pre and post transplant. We also looked at the differences between values in the two time-points (delta). Method We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (for Adragão score) and echocardiographic findings were recorded. All patients were submitted to a bone biopsy and laboratorial evaluation at baseline (time 0). Patients were followed for 12 months (time 1), after which performed laboratorial evaluation, a second bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry and non-contrast cardiac CT (Agatston score). Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon matched-pairs test and Spearman correlation test. STATA software was used and p < 0.05 was considered statistically significant. Results We recruited 85 patients from 1st October 2015 to 1st March 2018. At the end of 12 months, 6 patients refuse to perform the 2nd evaluation, 5 had primary non-function of the kidney graft, 1 had no sample on bone biopsy in time 0 and 4 patients died. We performed a 2nd evaluation in 69 patients and included those in this study. Mean age 50.2±12.4 years, 48 men, 53 caucasian (78.8%), median BMI 24.5 (22.7 – 27.8), median dialysis vintage 55 (42 – 84). We observe a significant reduction on phosphorus (delta: -1.1 mg/dl), magnesium (delta: -0.5 mg/dl), PTH (delta: -297.7 pg/ml), Calcitonin (delta: -0.9 ng/L), sclerostin (delta: -1.1 ng/ml), bone alkaline phosphatase (delta: -11.5 U/L) and FGF23 (delta: -1656.5 RU/ml). Both calcium (delta: 0.7 mg/dl) and alpha-klotho (delta: 265.7 pg/ml) serum levels increase, with no significant changes in vitamin D levels. With restoring renal health (time 1) and comparing with time 0, PTH maintain the negative correlation with sclerostin (p=0.02) and the positive correlation with FGF23 (p=0.0002) as in time 0; modify the correlation with Pi, becoming a negative correlation instead of positive (p=0.001) and gain new correlations with Ca (p=0.001) and vitamin D levels (p=0.03). Also, PTH correlated with the delta FGF23 (rho=-0.4, p=0.003) and sclerostin correlated with delta PTH (p=0.01). FGF23 didn’t associate with delta PTH, neither PTH associated with delta sclerostin. FGF23 didn’t reveal statistical association with Pi or Ca levels after transplant, contrasting with positive associations in pre transplant (p=0.002, p Conclusion In conclusion, it seems that sclerostin influences PTH levels and that PTH is the stimulus for the increase or decrease of FGF23 serum levels (as we found a positive association between those two molecules in both time-points and a negative association between PTH and the difference of FGF23 pre and post transplant). Levels of Ca and Pi seemed to be directly influenced by the level of PTH in post transplant, and those minerals seemed to be key factors for sclerostin secretion.
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- 2020
15. P1628ASSESSING CORONARY HEART DISEASE IN SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION - IS THERE SPACE FOR A RISK SCORE MODEL?
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Luísa Pereira, Joana Marques, Nuno Moreira Fonseca, Manuel Anibal A Ferreira, Ana Messias, Fernando Nolasco, Patrícia Cotovio, and Francisco Remédio
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Transplantation ,medicine.medical_specialty ,Framingham Risk Score ,Nephrology ,business.industry ,Internal medicine ,Simultaneous pancreas kidney transplantation ,Cardiology ,Medicine ,business ,Coronary heart disease - Abstract
Background and Aims Type 1 diabetes mellitus (DM1) is associated with an increased risk of coronary heart disease (CHD), which is generally more aggressive and frequently asymptomatic. This risk substantially increases for those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation (SPKT) is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols for silent CHD in this population are still debatable. As so, Gowdak recently developed a simple clinical risk score to determine the pre-test probability of significant CHD in single kidney transplant candidates. Our aim was to identify potential risk factors associated with the presence of significant lesions on pre-SPKT coronary angiography (CA) and test the utility of Gowdak score in SPKT candidates. Method 77 patients submitted to SPKT between 2011 and 2018 were retrospectively included in this study. All subjects underwent CA as screening method for CHD during the eligibility evaluation. Demographic, clinical, laboratory, therapeutic and imaging characteristics were studied. Continuous variables are presented as means or medians; categorical variables as frequencies. Univariate analysis (Qui2 or Fisher test) and multivariate analysis (logistic regression) were performed. Comparison between groups of patients with and without CA injury was performed using SPSS statistics version 23 and a p Results In the past 8 years, 99 SPKT were performed; 78% of these patients (N=77) were submitted to preoperative CA; mean age was 36±5.9 years and 64% were male. The mean duration of DM1 was 25 years and 97% had retinopathy, 43% neuropathy, 31% dysautonomia, 19% peripheral arterial disease and 7% cerebrovascular disease. We excluded 1 due to missing data. A minority of SPKT (3%, N=2) was preemptive. The mean time on dialysis was 37 months. Only one patient had angor, wh0 was excluded of Gowdak risk score assessment. Most patients (87%, N=67) were hypertensive; 56% (N=43) were on statin; 48% (N=37) had smoking habits, and 5% (N=4) had a BMI>30 kg/m2. CA identified at least one lesion in 48% (N = 37) of the patients, of which 30% (N=11; 14% of all CA) underwent intervention; none had complaints of angor. Based on Gowdak risk score, mean probability for CHD was 30.8% and 19 patients had a risk >40% - the recommended cut off to pursuit CA as screening method - but only 2 required intervention. In a univariate analysis, we found that the only distinguishing feature between the group of patients with and without CA lesions was smoking (p=0.005). DM1 with 20 or more years of evolution was found to have a significant association with coronary artery disease development (identifiable by any diagnostic test) (p=0.048). In our population of SPKT recipients Gowdak risk score did not predicted those with significant CHD. Conclusion In our study, CA was positive for lesion in almost half of the patients, all of them asymptomatic. Despite the fact that Gowdak probability score failed to identify those with significant CHD before CA (probably because all of our patients were diabetic), in our population for every seven patients submitted to CA, one needed coronary intervention. We highlight that asymptomatic patients with long-term DM and smokers should be carefully evaluated. The task of correctly ascertaining the presence of CAD can be more overwhelming when we take into account that there is a high prevalence of asymptomatic patients with extensive CAD. Facing the importance of an unmissed diagnosis we encourage the use of CA as an initial screening method, even if it is invasive. Further studies should be encouraged to create screening algorithm for SPKT candidates. Finally, medium- and long-term follow-up studies are needed to evaluate the effects of preoperative selection on posttransplant cardiac events and survival rates.
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- 2020
16. P1696VASCULAR CALCIFICATION IN RENAL TRANSPLANTED PATIENTS
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Manuel Anibal A Ferreira, Cecília Silva, Inês Aires, Patrícia Cotovio, Fernando Nolasco, Fernando Correia Caeiro Pereira, Ruben Ramos, Marco Mendes, Ana Carina Ferreira, Rute Salvador, David Navarro, Bruna Correia, and Guadalupe Cabral
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Transplantation ,Pathology ,medicine.medical_specialty ,Nephrology ,business.industry ,medicine ,business ,medicine.disease ,Calcification - Abstract
Background and Aims Chronic kidney disease – mineral and bone disorder (CKD-MBD) is a well-known syndrome in end stage renal disease. Vascular calcifications are one of its components. Renal transplantation seemed to halt the progression of vascular calcifications. The aim of this study was to analyse the progression of vascular calcifications in a cohort of renal transplanted patients, and the associations of those with the old and new bone-derived hormones. Method We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. All patients were submitted to a bone biopsy and laboratorial evaluation at baseline (time 0) including measurements of calcium (Ca), phosphorus (Pi), magnesium (Mg), vitamin D (vitD), calcitonin, parathyroid hormone (PTH), bone alkaline phosphatase (bAP) and total alkaline phosphatase (tAP), alpha-klotho, fibroblast grow-factor 23 (FGF23) and sclerostin. Patients were followed for 12 months, after which performed a second bone biopsy and laboratorial evaluation (time 1). At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (Adragão score) and echocardiographic findings were recorded. At the end of the study, echocardiogram, X-ray of pelvis and hands, bone densitometry and non-contrast cardiac CT (Agatston score) were performed. Immunosuppression included induction therapy followed by tacrolimus, mycophenolate mofetil and prednisolone. Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank sum test and Spearman correlation test. STATA software was used and p < 0.05 was considered statistically significant. Results We recruited 85 patients from 1st October 2015 to 1st March 2018. Mean age 50.1±12.7 years, 59 men (69.4%), 66 caucasian (77.6%), median BMI 25.1±3.4. At the end of 12 months, 6 patients refuse to perform the 2nd evaluation, 5 had primary non-function of the kidney graft, 1 had no sample on bone biopsy in time 0 and 4 patients died. We performed a 2nd evaluation in 69 patients and included those in this study. The median baseline and 12 months Adragão score had no differences [1 (0 – 2)]. The median coronary artery calcium score was 48.5 (0 – 535) and median percentile was 80 (0 – 92.5). Valvular calcifications were present in 15 and 16 patients at baseline and after 1 year respectively, with no statistical difference between the two time points. Coronary artery calcium scores were correlated with age (p Conclusion In conclusion, vascular calcifications stabilize after renal transplant. Adragão score, that is a less expensive exam than cardiac CT, can assess vascular calcifications in renal transplanted patients. Only calcium and sclerostin correlated with both Agatston scores and coronary calcium percentiles.
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- 2020
17. P1394ASSOCIATION BETWEEN PARATHYROID HORMONE AND MORTALITY IN HAEMODIALYSIS: THE DIABETES MAKES THE DIFFERENCE
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Jesús María Fernández Gómez, Cristina Alonso-Montes, Francesco Locatelli, J. Emilio Sánchez-Álvarez, Markus Ketteler, Miguel Ángel Suárez Hevia, Beatriz Martín-Carro, Gérard M. London, Jürgen Floege, Manuel Anibal A Ferreira, José Luis Fernandez-Martin, José Luis Górriz, Carmine Zoccali, and Jorge B. Cannata-Andía
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Transplantation ,medicine.medical_specialty ,Endocrinology ,Nephrology ,business.industry ,Internal medicine ,Diabetes mellitus ,medicine ,Parathyroid hormone ,medicine.disease ,business - Abstract
Background and Aims Diabetes is the most common cause of chronic kidney disease (CKD) stage 5 and a relevant risk factor for mortality. The available CKD-MBD guidelines do not make differences between diabetics and non-diabetics regarding the optimal targets of the serum bone and mineral biochemical parameters. Thus, the objective of this analysis of COSMOS was to compare the association between the main serum bone and mineral biochemical parameters (calcium-Ca, phosphorus-P and parathyroid hormone-PTH) and mortality in diabetic and non-diabetic patients in haemodialysis. Method COSMOS is a 3-year, observational, prospective, open-cohort study that includes 6797 patients from 227 dialysis centres that were randomly selected from 20 European countries. Cox proportional hazard regression models with penalized splines smoothing were used to analyse the association between relative risk of mortality vs. Ca, P or PTH. Hazard ratios were adjusted by demographics, comorbidities, treatments and biochemical parameters. Interaction analysis was used to analyse if diabetes can influence the association between relative risk of mortality and Ca, P and PTH. Results The present analysis includes 6306 patients with follow-up data and accurate information on diabetes status. The mortality rate in COSMOS was 13.3 deaths per 100 patient-years (17.8 in diabetics and 11.4 in non-diabetics). At baseline, diabetic patients were older (66.7 ± 11.7 vs. 62.8 ± 15.3 years, p Conclusion These results suggest for the first time a differential effect of diabetes on the association between relative risk of mortality and serum PTH. High serum PTH predicts death only in diabetics. These findings could have relevant implications for the diagnosis and treatment of CKD-MBD in diabetic and non-diabetic patients in haemodialysis.
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- 2020
18. Institutional factors and subnational location choice for multinationals’ R&D subsidiaries
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Manuel Anibal Portugal Ferreira and Christian Christian Falaster
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Institutional environmen ,media_common.quotation_subject ,05 social sciences ,Subsidiary ,IInstitutional environment ,Location choice ,International business ,Multinational corporation ,0502 economics and business ,ddc:650 ,Institution ,Regional differences ,Economic geography ,Business ,Institutional environment ,050207 economics ,Innovation ,050203 business & management ,media_common - Abstract
Purpose Using an institution-based view, this study aims to conceptualize how sub-national institutional characteristics are likely to explain location choice of multinationals’ research and development (R&D) subsidiaries. Design/methodology/approach In a conceptual paper, this study explores specific institutional facets of the regional environments within a country that are capable of explaining, at least in part, the location choices of multinational corporations’ R&D subsidiaries. Findings This study thus explores the more nuanced influences of the institutional environments at a subnational level and develops propositions to explain location choices based on the differences of the institutional environments. Originality/value This study contributes to international business theory by incorporating a location-specific analysis that contrasts to the usual country-level observation on the determinants of firms’ location decisions.
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- 2020
19. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial
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Hiddo J L Heerspink, Hans-Henrik Parving, Dennis L Andress, George Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John J V McMurray, Joel Z Melnick, Michael G Miller, Pablo E Pergola, Vlado Perkovic, Sheldon Tobe, Tingting Yi, Melissa Wigderson, Dick de Zeeuw, Alicia Elbert, Augusto Vallejos, Andres Alvarisqueta, Laura Maffei, Luis Juncos, Javier de Arteaga, Gustavo Greloni, Eduardo Farias, Alfredo Zucchini, Daniel Vogel, Ana Cusumano, Juan Santos, Margaret Fraenkel, Martin Gallagher, Tim Davis, Shamasunder Acharya, Duncan Cooke, Michael Suranyi, Simon Roger, Nigel Toussaint, Carol Pollock, Doris Chan, Stephen Stranks, Richard MacIsaac, Zoltan Endre, Alice Schmidt, Rudolf Prager, Gert Mayer, Xavier Warling, Michel Jadoul, Jean Hougardy, Chris Vercammen, Bruno Van Vlem, Pieter Gillard, Adriana Costa e Forti, Joao Lindolfo Borges, Luis Santos Canani, Freddy Eliaschewitz, Silmara Leite, Fadlo Fraige Filho, Raphael Paschoalin, Jose Andrade Moura Neto, Luciane Deboni, Irene de Lourdes Noronha, Cintia Cercato, Carlos Alberto Prompt, Maria Zanella, Nelson Rassi, Domingos D'Avila, Rosangela Milagres, Joao Felicio, Roberto Pecoits Filho, Miguel Carlos Riella, Joao Salles, Elizete Keitel, Sergio Draibe, Celso Amodeo, Joseph Youmbissi, Louise Roy, Serge Cournoyer, Shivinder Jolly, Vincent Pichette, Gihad Nesrallah, Harpreet Singh Bajaj, Hasnain Khandwala, Ronnie Aronson, Richard Goluch, Paul Tam, Christian Rabbat, Gordon Bailey, Stephen Chow, Alvaro Castillo, Alfredo Danin Vargas, Fernando Gonzalez, Rodrigo Munoz, Vicente Gutierrez, Gonzalo Godoy, Hongwen Zhao, Zhangsuo Liu, Minghui Zhao, Xiaohui Guo, Benli Su, Shuxia Fu, Yan Xu, Jinkui Yang, Bingyin Shi, Guanqing Xiao, Wei Shi, Chuanming Hao, Changying Xing, Fanfan Hou, Qun Luo, Yuxiu Li, Linong Ji, Li Zuo, Song Wang, Zhaohui Ni, Guohua Ding, Nan Chen, Jiajun Zhao, Weiping Jia, Shengqiang Yu, Jian Weng, Gang Xu, Ping Fu, Shiren Sun, Bicheng Liu, Xiaoqiang Ding, Ivan Rychlik, Alexandra Oplustilova, Dagmar Bartaskova, Vaclava Honova, Hana Chmelickova, Martin Petr, Petr Bucek, Vladimir Tesar, Emil Zahumensky, Johan Povlsen, Kenneth Egstrup, Anna Oczachowska-Kulik, Peter Rossing, Jorma Lahtela, Jorma Strand, Ilkka Kantola, Catherine Petit, Christian Combe, Philippe Zaoui, Vincent Esnault, Pablo Urena Torres, Jean-Michel Halimi, Bertrand Dussol, Tasso Bieler, Klemens Budde, Frank Dellanna, Thomas Segiet, Christine Kosch, Hans Schmidt-Guertler, Isabelle Schenkenberger, Volker Vielhauer, Frank Pistrosch, Mark Alscher, Christoph Hasslacher, Christian Hugo, Anja Muehlfeld, Christoph Wanner, Ploumis Passadakis, Theofanis Apostolou, Nikolaos Tentolouris, Ioannis Stefanidis, Konstantinos Mavromatidis, Vasilios Liakopoulos, Dimitrios Goumenos, Konstantinos Siamopoulos, Vincent Yeung, Risa Ozaki, Samuel Fung, Kathryn Tan, Sydney Tang, Sing Leung Lui, Siu Fai Cheung, Seamus Sreenan, Joseph Eustace, Donal O'Shea, Peter Lavin, Austin Stack, Yoram Yagil, Julio Wainstein, Hilla Knobler, Josef Cohen, Irina Kenis, Deeb Daoud, Yosefa Bar-Dayan, Victor Frajewicki, Faiad Adawi, Loreto Gesualdo, Domenico Santoro, Francesco Marino, Andrea Galfre, Chiara Brunati, Piero Ruggenenti, Giuseppe Rombola, Giuseppe Pugliese, Maura Ravera, Fabio Malberti, Giuseppe Pontoriero, Teresa Rampino, Salvatore De Cosmo, Ciro Esposito, Felice Nappi, Cataldo Abaterusso, Giuseppe Conte, Vincenzo Panichi, Davide Lauro, Giovambattista Capasso, Domenico Russo, Jiichi Anzai, Motoji Naka, Keita Ato, Tetsuro Tsujimoto, Toshinori Nimura, Eitaro Nakashima, Tetsuro Takeda, Shinya Fujii, Kunihisa Kobayashi, Hideaki Iwaoka, Koji Nagayama, Hiroyuki Harada, Hajime Maeda, Rui Kishimoto, Tadashi Iitsuka, Naoki Itabashi, Ryuichi Furuya, Yoshitaka Maeda, Daishiro Yamada, Nobuhiro Sasaki, Hiromitsu Sasaki, Shinichiro Ueda, Naoki Kashihara, Shuichi Watanabe, Takehiro Nakamura, Hidetoshi Kanai, Yuichiro Makita, Keiko Ono, Noriyuki Iehara, Daisuke Goto, Keiichiro Kosuge, Kenichi Tsuchida, Toshiaki Sato, Takashi Sekikawa, Hideki Okamoto, Tsuyoshi Tanaka, Naoko Ikeda, Takenobu Tadika, Koji Mukasa, Takeshi Osonoi, Fuminori Hirano, Motonobu Nishimura, Yuko Yambe, Yukio Tanaka, Makoto Ujihara, Takashi Sakai, Mitsuo Imura, Yutaka Umayahara, Shinya Makino, Jun Nakazawa, Yukinari Yamaguchi, Susumu Kashine, Hiroaki Miyaoka, Katsunori Suzuki, Toshihiko Inoue, Sou Nagai, Nobuyuki Sato, Masahiro Yamamoto, Noriyasu Taya, Akira Fujita, Akira Matsutani, Yugo Shibagaki, Yuichi Sato, Akira Yamauchi, Masahiro Tsutsui, Tamayo Ishiko, Shizuka Kaneko, Nobuyuki Azuma, Hirofumi Matsuda, Yasuhiro Hashiguchi, Yukiko Onishi, Mikiya Tokui, Munehide Matsuhisa, Arihiro Kiyosue, Junji Shinoda, Kazuo Ishikawa, Ghazali Ahmad, Shalini Vijayasingham, Nor Azizah Aziz, Zanariah Hussein, Yin Khet Fung, Wan Hasnul Halimi Wan Hassan, Hin Seng Wong, Bak Leong Goh, Norhaliza Mohd Ali, Nor Shaffinaz Yusuf Azmi Merican, Indralingam Vaithilingam, Nik Nur Fatnoon Nik Ahmad, Noor Adam, Norlela Sukor, V Paranthaman P Vengadasalam, Khalid Abdul Kadir, Mafauzy Mohamed, Karina Renoirte Lopez, Aniceto Leguizamo-Dimas, Alfredo Chew Wong, Jose Chevaile-Ramos, Jose Gonzalez Gonzalez, Raul Rico Hernandez, Jose Nino-Cruz, Leobardo Sauque Reyna, Guillermo Gonzalez-Galvez, Magdalena Madero Rovalo, Tomasso Bochicchio-Ricardelli, Jorge Aldrete, Jaime Carranza-Madrigal, Liffert Vogt, Peter Smak Gregoor, JNM Barendregt, Peter Luik, Ronald Gansevoort, Gozewijn Laverman, Helen Pilmore, Helen Lunt, John Baker, Steven Miller, Kannaiyan Rabindranath, Luis Zapata-Rincon, Rolando Vargas-Gonzales, Jorge Calderon Ticona, Augusto Dextre Espinoza, Jose Burga Nunez, Carlos Antonio Zea-Nunez, Benjamin Herrada Orue, Boris Medina-Santander, Cesar Delgado-Butron, Julio Farfan-Aspilcueta, Stanislaw Mazur, Miroslaw Necki, Michal Wruk, Katarzyna Klodawska, Grazyna Popenda, Ewa Skokowska, Malgorzata Arciszewska, Andrzej Wiecek, Kazimierz Ciechanowski, Michal Nowicki, Rita Birne, Antonio Cabrita, Aura Ramos, Manuel Anibal Antunes Ferreira, Evelyn Matta Fontanet, Altagracia Aurora Alcantara-Gonzalez, Angel Comulada-Rivera, Eugenia Galindo Ramos, Jose Cangiano, Luis Quesada-Suarez, Ricardo Calderon Ortiz, Jose Vazquez-Tanus, Rafael Burgos-Calderon, Carlos Rosado, Nicolae Hancu, Ella Pintilei, Cristina Mistodie, Gabriel Bako, Lavinia Ionutiu, Ligia Petrica, Romulus Timar, Liliana Tuta, Livia Duma, Adriana Tutescu, Svetlana Ivanova, Ashot Essaian, Konstantin Zrazhevskiy, Natalia Tomilina, Elena Smolyarchuk, Anatoly Kuzin, Olga Lantseva, Irina Karpova, Minara Shamkhalova, Natalia Liberanskaya, Andrey Yavdosyuk, Yuri Shvarts, Tatiana Bardymova, Olga Blagoveshchenskaya, Oleg Solovev, Elena Rechkova, Natalia Pikalova, Maria Pavlova, Elena Kolmakova, Rustam Sayfutdinov, Svetlana Villevalde, Natalya Koziolova, Vladimir Martynenko, Vyacheslav Marasaev, Adelya Maksudova, Olga Sigitova, Viktor Mordovin, Vadim Klimontov, Yulia Samoylova, Tatiana Karonova, Lee Ying Yeoh, Boon Wee Teo, Marjorie Wai Yin Foo, Adrian Liew, Ivan Tkac, Aniko Oroszova, Jozef Fekete, Jaroslav Rosenberger, Ida Obetkova, Alla Fulopova, Eva Kolesarova, Katarina Raslova, Peter Smolko, Adrian Oksa, Larry Distiller, Julien Trokis, Luthando Adams, Hemant Makan, Padaruth Ramlachan, Essack Mitha, Kathleen Coetzee, Zelda Punt, Qasim Bhorat, Puvenesvari Naiker, Graham Ellis, Louis Van Zyl, Kwan Woo Lee, Min Seon Kim, Soon-Jib Yoo, Kun Ho Yoon, Yong-Wook Cho, Tae-Sun Park, Sang Yong Kim, Moon-Gi Choi, Tae Keun Oh, Kang-Wook Lee, Ho Sang Shon, Sung Hwan Suh, Byung-Joon Kim, Kim Doo-Man, Joo Hark Yi, Sang Ah Lee, Ho Chan Cho, Sin-Gon Kim, Dae-Ryong Cha, Ji A Seo, Kyung Mook Choi, Jeong-Taek Woo, Kyu Jeung Ahn, Jae Hyuk Lee, In-Joo Kim, Moon-Kyu Lee, Hak Chul Jang, Kyong-Soo Park, Beom Seok Kim, Ji Oh Mok, Mijung Shin, Sun Ae Yoon, Il-Seong Nam-Goong, Choon Hee Chung, Tae Yang Yu, Hyoung Woo Lee, Alfonso Soto Gonzalez, Jaume Almirall, Jesus Egido, Francesca Calero Gonzalez, Gema Fernandez Fresnedo, Ildefonso Valera Cortes, Manuel Praga Terente, Isabel Garcia Mendez, Juan Navarro Gonzalez, Jose Herrero Calvo, Secundino Cigarran Guldris, Mario Prieto Velasco, Jose Ignacio Minguela Pesquera, Antonio Galan, Julio Pascual, Maria Marques Vidas, Judith Martins Munoz, Jose Rodriguez-Perez, Cristina Castro-Alonso, Josep Bonet Sol, Daniel Seron, Elvira Fernandez Giraldez, Javier Arrieta Lezama, Nuria Montero, Julio Hernandez-Jaras, Rafael Santamaria Olmo, Jose Ramon Molas Coten, Olof Hellberg, Bengt Fellstrom, Andreas Bock, Dee Pei, Ching-Ling Lin, Kai-Jen Tien, Ching-Chu Chen, Chien-Ning Huang, Ju-Ying Jiang, Du-An Wu, Chih-Hsun Chu, Shih-Ting Tseng, Jung-Fu Chen, Cho-Tsan Bau, Wayne Sheu, Mai-Szu Wu, Ramazan Sari, Siren Sezer, Alaattin Yildiz, Ilhan Satman, Betul Kalender, Borys Mankovskyy, Ivan Fushtey, Mykola Stanislavchuk, Mykola Kolenyk, Iryna Dudar, Viktoriia Zolotaikina, Orest Abrahamovych, Tetyana Kostynenko, Olena Petrosyan, Petro Kuskalo, Olga Galushchak, Oleg Legun, Ivan Topchii, Liliya Martynyuk, Vasyl Stryzhak, Svitlana Panina, Sergii Tkach, Vadym Korpachev, Peter Maxwell, Luigi Gnudi, Sui Phin Kon, Hilary Tindall, Phillip Kalra, Patrick Mark, Dipesh Patel, Mohamed El-Shahawy, Liqun Bai, Romanita Nica, Yeong-Hau Lien, Judson Menefee, Robert Busch, Alan Miller, Azazuddin Ahmed, Ahmed Arif, Joseph Lee, Sachin Desai, Shweta Bansal, Marie Bentsianov, Mario Belledonne, Charles Jere, Raul Gaona, Gregory Greenwood, Osvaldo Brusco, Mark Boiskin, Diogo Belo, Raffi Minasian, Naveen Atray, Mary Lawrence, John Taliercio, Pablo Pergola, David Scott, German Alvarez, Bradley Marder, Thomas Powell, Wa'el Bakdash, George Stoica, Christopher McFadden, Marc Rendell, Jonathan Wise, Audrey Jones, Michael Jardula, Ivy-Joan Madu, Freemu Varghese, Brian Tulloch, Ziauddin Ahmed, Melanie Hames, Imran Nazeer, Newman Shahid, Rekha John, Manuel Montero, David Fitz-Patrick, Lawrence Phillips, Antonio Guasch, Elena Christofides, Aijaz Gundroo, Mohammad Amin, Cynthia Bowman-Stroud, Michael Link, Laura Mulloy, Michael Nammour, Tarik Lalwani, Lenita Hanson, Adam Whaley-Connell, Lee Herman, Rupi Chatha, Sayed Osama, Kenneth Liss, Zeid Kayali, Anuj Bhargava, Ezra Israel, Alfredo Peguero-Rivera, Michael Fang, Judith Slover, Elena Barengolts, Jose Flores, Rosemary Muoneke, Virginia Savin, Stella Awua-Larbi, Andrew Levine, George Newman, Laden Golestaneh, Guillermo Bohm, Efrain Reisin, Lucita Cruz, Robert Weiss, Franklin Zieve, Edward Horwitz, Peale Chuang, James Mersey, John Manley, Ronald Graf, Fadi Bedros, Sudhir Joshi, Juan Frias, Ali Assefi, Andrew O'Shaughnessy, Roman Brantley, Todd Minga, David Tietjen, Samuel Kantor, Aamir Jamal, Ramon Guadiz, Kenneth Hershon, Peter Bressler, Nelson Kopyt, Harold Cathcart, Scott Bloom, Ronald Reichel, Samer Nakhle, Emily Dulude, Joshua Tarkan, Penelope Baker, Steven Zeig, Jaynier Moya Hechevarria, Armando Ropero-Cartier, Gilda De la Calle, Ankur Doshi, Fadi Saba, Teresa Sligh, Sylvia Shaw, Jayant Kumar, Harold Szerlip, George Bayliss, Alan Perlman, Lakhi Sakhrani, Steven Gouge, Georges Argoud, Idalia Acosta, John Elder, Sucharit Joshi, John Sensenbrenner, Steven Vicks, Roberto Mangoo-Karim, Claude Galphin, Carlos Leon-Forero, John Gilbert, Eric Brown, Adeel Ijaz, Salman Butt, Mariana Markell, Carlos Arauz-Pacheco, Lance Sloan, Odilon Alvarado, Serge Jabbour, Eric Simon, Anjay Rastogi, Sam James, Karen Hall, John Melish, Brad Dixon, Allen Adolphe, Csaba Kovesdy, Srinivasan Beddhu, Richard Solomon, Ronald Fernando, Ellis Levin, Charuhas Thakar, Brooks Robey, David Goldfarb, Linda Fried, Geetha Maddukuri, Stephen Thomson, Andrew Annand, Saeed Kronfli, Paramjit Kalirao, Rebecca Schmidt, Neera Dahl, Samuel Blumenthal, Debra Weinstein, Ove Ostergaard, Talia Weinstein, Yasuhiro Ono, Murat Yalcin, Shahana Karim, APH - Health Behaviors & Chronic Diseases, Nephrology, ACS - Amsterdam Cardiovascular Sciences, ACS - Microcirculation, Biomedical Signals and Systems, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Heerspink, H. J. L., Parving, H. -H., Andress, D. L., Bakris, G., Correa-Rotter, R., Hou, F. -F., Kitzman, D. W., Kohan, D., Makino, H., Mcmurray, J. J. V., Melnick, J. Z., Miller, M. G., Pergola, P. E., Perkovic, V., Tobe, S., Yi, T., Wigderson, M., de Zeeuw, D., Elbert, A., Vallejos, A., Alvarisqueta, A., Maffei, L., Juncos, L., de Arteaga, J., Greloni, G., Farias, E., Zucchini, A., Vogel, D., Cusumano, A., Santos, J., Fraenkel, M., Gallagher, M., Davis, T., Acharya, S., Cooke, D., Suranyi, M., Roger, S., Toussaint, N., Pollock, C., Chan, D., Stranks, S., Macisaac, R., Endre, Z., Schmidt, A., Prager, R., Mayer, G., Warling, X., Jadoul, M., Hougardy, J., Vercammen, C., Van Vlem, B., Gillard, P., Costa e Forti, A., Borges, J. L., Santos Canani, L., Eliaschewitz, F., Leite, S., Fraige Filho, F., Paschoalin, R., Moura Neto, J. A., Deboni, L., de Lourdes Noronha, I., Cercato, C., Prompt, C. A., Zanella, M., Rassi, N., D'Avila, D., Milagres, R., Felicio, J., Pecoits Filho, R., Riella, M. C., Salles, J., Keitel, E., Draibe, S., Amodeo, C., Youmbissi, J., Roy, L., Cournoyer, S., Jolly, S., Pichette, V., Nesrallah, G., Bajaj, H. S., Khandwala, H., Aronson, R., Goluch, R., Tam, P., Rabbat, C., Bailey, G., Chow, S., Castillo, A., Danin Vargas, A., Gonzalez, F., Munoz, R., Gutierrez, V., Godoy, G., Zhao, H., Liu, Z., Zhao, M., Guo, X., Su, B., Fu, S., Xu, Y., Yang, J., Shi, B., Xiao, G., Shi, W., Hao, C., Xing, C., Hou, F., Luo, Q., Li, Y., Ji, L., Zuo, L., Wang, S., Ni, Z., Ding, G., Chen, N., Zhao, J., Jia, W., Yu, S., Weng, J., Xu, G., Fu, P., Sun, S., Liu, B., Ding, X., Rychlik, I., Oplustilova, A., Bartaskova, D., Honova, V., Chmelickova, H., Petr, M., Bucek, P., Tesar, V., Zahumensky, E., Povlsen, J., Egstrup, K., Oczachowska-Kulik, A., Rossing, P., Lahtela, J., Strand, J., Kantola, I., Petit, C., Combe, C., Zaoui, P., Esnault, V., Urena Torres, P., Halimi, J. -M., Dussol, B., Bieler, T., Budde, K., Dellanna, F., Segiet, T., Kosch, C., Schmidt-Guertler, H., Schenkenberger, I., Vielhauer, V., Pistrosch, F., Alscher, M., Hasslacher, C., Hugo, C., Muehlfeld, A., Wanner, C., Passadakis, P., Apostolou, T., Tentolouris, N., Stefanidis, I., Mavromatidis, K., Liakopoulos, V., Goumenos, D., Siamopoulos, K., Yeung, V., Ozaki, R., Fung, S., Tan, K., Tang, S., Lui, S. L., Cheung, S. F., Sreenan, S., Eustace, J., O'Shea, D., Lavin, P., Stack, A., Yagil, Y., Wainstein, J., Knobler, H., Cohen, J., Kenis, I., Daoud, D., Bar-Dayan, Y., Frajewicki, V., Adawi, F., Gesualdo, L., Santoro, D., Marino, F., Galfre, A., Brunati, C., Ruggenenti, P., Rombola, G., Pugliese, G., Ravera, M., Malberti, F., Pontoriero, G., Rampino, T., De Cosmo, S., Esposito, C., Nappi, F., Abaterusso, C., Conte, G., Panichi, V., Lauro, D., Capasso, G., Russo, D., Anzai, J., Naka, M., Ato, K., Tsujimoto, T., Nimura, T., Nakashima, E., Takeda, T., Fujii, S., Kobayashi, K., Iwaoka, H., Nagayama, K., Harada, H., Maeda, H., Kishimoto, R., Iitsuka, T., Itabashi, N., Furuya, R., Maeda, Y., Yamada, D., Sasaki, N., Sasaki, H., Ueda, S., Kashihara, N., Watanabe, S., Nakamura, T., Kanai, H., Makita, Y., Ono, K., Iehara, N., Goto, D., Kosuge, K., Tsuchida, K., Sato, T., Sekikawa, T., Okamoto, H., Tanaka, T., Ikeda, N., Tadika, T., Mukasa, K., Osonoi, T., Hirano, F., Nishimura, M., Yambe, Y., Tanaka, Y., Ujihara, M., Sakai, T., Imura, M., Umayahara, Y., Makino, S., Nakazawa, J., Yamaguchi, Y., Kashine, S., Miyaoka, H., Suzuki, K., Inoue, T., Nagai, S., Sato, N., Yamamoto, M., Taya, N., Fujita, A., Matsutani, A., Shibagaki, Y., Sato, Y., Yamauchi, A., Tsutsui, M., Ishiko, T., Kaneko, S., Azuma, N., Matsuda, H., Hashiguchi, Y., Onishi, Y., Tokui, M., Matsuhisa, M., Kiyosue, A., Shinoda, J., Ishikawa, K., Ahmad, G., Vijayasingham, S., Aziz, N. A., Hussein, Z., Fung, Y. K., Hassan, W. H. H. W., Wong, H. S., Goh, B. L., Ali, N. M., Merican, N. S. Y. A., Vaithilingam, I., Nik Ahmad, N. N. F., Adam, N., Sukor, N., Vengadasalam, V. P. P., Abdul Kadir, K., Mohamed, M., Renoirte Lopez, K., Leguizamo-Dimas, A., Chew Wong, A., Chevaile-Ramos, J., Gonzalez Gonzalez, J., Rico Hernandez, R., Nino-Cruz, J., Sauque Reyna, L., Gonzalez-Galvez, G., Madero Rovalo, M., Bochicchio-Ricardelli, T., Aldrete, J., Carranza-Madrigal, J., Vogt, L., Smak Gregoor, P., Barendregt, J. N. M., Luik, P., Gansevoort, R., Laverman, G., Pilmore, H., Lunt, H., Baker, J., Miller, S., Rabindranath, K., Zapata-Rincon, L., Vargas-Gonzales, R., Calderon Ticona, J., Dextre Espinoza, A., Burga Nunez, J., Zea-Nunez, C. A., Herrada Orue, B., Medina-Santander, B., Delgado-Butron, C., Farfan-Aspilcueta, J., Mazur, S., Necki, M., Wruk, M., Klodawska, K., Popenda, G., Skokowska, E., Arciszewska, M., Wiecek, A., Ciechanowski, K., Nowicki, M., Birne, R., Cabrita, A., Ramos, A., Antunes Ferreira, M. A., Matta Fontanet, E., Alcantara-Gonzalez, A. A., Comulada-Rivera, A., Galindo Ramos, E., Cangiano, J., Quesada-Suarez, L., Calderon Ortiz, R., Vazquez-Tanus, J., Burgos-Calderon, R., Rosado, C., Hancu, N., Pintilei, E., Mistodie, C., Bako, G., Ionutiu, L., Petrica, L., Timar, R., Tuta, L., Duma, L., Tutescu, A., Ivanova, S., Essaian, A., Zrazhevskiy, K., Tomilina, N., Smolyarchuk, E., Kuzin, A., Lantseva, O., Karpova, I., Shamkhalova, M., Liberanskaya, N., Yavdosyuk, A., Shvarts, Y., Bardymova, T., Blagoveshchenskaya, O., Solovev, O., Rechkova, E., Pikalova, N., Pavlova, M., Kolmakova, E., Sayfutdinov, R., Villevalde, S., Koziolova, N., Martynenko, V., Marasaev, V., Maksudova, A., Sigitova, O., Mordovin, V., Klimontov, V., Samoylova, Y., Karonova, T., Yeoh, L. Y., Teo, B. W., Foo, M. W. Y., Liew, A., Tkac, I., Oroszova, A., Fekete, J., Rosenberger, J., Obetkova, I., Fulopova, A., Kolesarova, E., Raslova, K., Smolko, P., Oksa, A., Distiller, L., Trokis, J., Adams, L., Makan, H., Ramlachan, P., Mitha, E., Coetzee, K., Punt, Z., Bhorat, Q., Naiker, P., Ellis, G., Van Zyl, L., Lee, K. W., Kim, M. S., Yoo, S. -J., Yoon, K. H., Cho, Y. -W., Park, T. -S., Kim, S. Y., Choi, M. -G., Oh, T. K., Lee, K. -W., Shon, H. S., Suh, S. H., Kim, B. -J., Doo-Man, K., Yi, J. H., Lee, S. A., Cho, H. C., Kim, S. -G., Cha, D. -R., Seo, J. A., Choi, K. M., Woo, J. -T., Ahn, K. J., Lee, J. H., Kim, I. -J., Lee, M. -K., Jang, H. C., Park, K. -S., Kim, B. S., Mok, J. O., Shin, M., Yoon, S. A., Nam-Goong, I. -S., Chung, C. H., Yu, T. Y., Lee, H. W., Soto Gonzalez, A., Almirall, J., Egido, J., Calero Gonzalez, F., Fernandez Fresnedo, G., Valera Cortes, I., Praga Terente, M., Garcia Mendez, I., Navarro Gonzalez, J., Herrero Calvo, J., Cigarran Guldris, S., Prieto Velasco, M., Minguela Pesquera, J. I., Galan, A., Pascual, J., Marques Vidas, M., Martins Munoz, J., Rodriguez-Perez, J., Castro-Alonso, C., Bonet Sol, J., Seron, D., Fernandez Giraldez, E., Arrieta Lezama, J., Montero, N., Hernandez-Jaras, J., Santamaria Olmo, R., Molas Coten, J. R., Hellberg, O., Fellstrom, B., Bock, A., Pei, D., Lin, C. -L., Tien, K. -J., Chen, C. -C., Huang, C. -N., Jiang, J. -Y., Wu, D. -A., Chu, C. -H., Tseng, S. -T., Chen, J. -F., Bau, C. -T., Sheu, W., Wu, M. -S., Sari, R., Sezer, S., Yildiz, A., Satman, I., Kalender, B., Mankovskyy, B., Fushtey, I., Stanislavchuk, M., Kolenyk, M., Dudar, I., Zolotaikina, V., Abrahamovych, O., Kostynenko, T., Petrosyan, O., Kuskalo, P., Galushchak, O., Legun, O., Topchii, I., Martynyuk, L., Stryzhak, V., Panina, S., Tkach, S., Korpachev, V., Maxwell, P., Gnudi, L., Kon, S. P., Tindall, H., Kalra, P., Mark, P., Patel, D., El-Shahawy, M., Bai, L., Nica, R., Lien, Y. -H., Menefee, J., Busch, R., Miller, A., Ahmed, A., Arif, A., Lee, J., Desai, S., Bansal, S., Bentsianov, M., Belledonne, M., Jere, C., Gaona, R., Greenwood, G., Brusco, O., Boiskin, M., Belo, D., Minasian, R., Atray, N., Lawrence, M., Taliercio, J., Pergola, P., Scott, D., Alvarez, G., Marder, B., Powell, T., Bakdash, W., Stoica, G., Mcfadden, C., Rendell, M., Wise, J., Jones, A., Jardula, M., Madu, I. -J., Varghese, F., Tulloch, B., Ahmed, Z., Hames, M., Nazeer, I., Shahid, N., John, R., Montero, M., Fitz-Patrick, D., Phillips, L., Guasch, A., Christofides, E., Gundroo, A., Amin, M., Bowman-Stroud, C., Link, M., Mulloy, L., Nammour, M., Lalwani, T., Hanson, L., Whaley-Connell, A., Herman, L., Chatha, R., Osama, S., Liss, K., Kayali, Z., Bhargava, A., Israel, E., Peguero-Rivera, A., Fang, M., Slover, J., Barengolts, E., Flores, J., Muoneke, R., Savin, V., Awua-Larbi, S., Levine, A., Newman, G., Golestaneh, L., Bohm, G., Reisin, E., Cruz, L., Weiss, R., Zieve, F., Horwitz, E., Chuang, P., Mersey, J., Manley, J., Graf, R., Bedros, F., Joshi, S., Frias, J., Assefi, A., O'Shaughnessy, A., Brantley, R., Minga, T., Tietjen, D., Kantor, S., Jamal, A., Guadiz, R., Hershon, K., Bressler, P., Kopyt, N., Cathcart, H., Bloom, S., Reichel, R., Nakhle, S., Dulude, E., Tarkan, J., Baker, P., Zeig, S., Moya Hechevarria, J., Ropero-Cartier, A., De la Calle, G., Doshi, A., Saba, F., Sligh, T., Shaw, S., Kumar, J., Szerlip, H., Bayliss, G., Perlman, A., Sakhrani, L., Gouge, S., Argoud, G., Acosta, I., Elder, J., Sensenbrenner, J., Vicks, S., Mangoo-Karim, R., Galphin, C., Leon-Forero, C., Gilbert, J., Brown, E., Ijaz, A., Butt, S., Markell, M., Arauz-Pacheco, C., Sloan, L., Alvarado, O., Jabbour, S., Simon, E., Rastogi, A., James, S., Hall, K., Melish, J., Dixon, B., Adolphe, A., Kovesdy, C., Beddhu, S., Solomon, R., Fernando, R., Levin, E., Thakar, C., Robey, B., Goldfarb, D., Fried, L., Maddukuri, G., Thomson, S., Annand, A., Kronfli, S., Kalirao, P., Schmidt, R., Dahl, N., Blumenthal, S., Weinstein, D., Ostergaard, O., Weinstein, T., Ono, Y., Yalcin, M., Karim, S., Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic
- Subjects
Male ,endothelin ,albuminuria ,nephropathy ,inhibition ,Diabetes Mellitus, Type 2/drug therapy ,Endocrinology, Diabetes and Metabolism ,Placebo-controlled study ,Administration, Oral ,030204 cardiovascular system & hematology ,Settore MED/13 - Endocrinologia ,chemistry.chemical_compound ,0302 clinical medicine ,ENDOTHELIN ,80 and over ,Diabetic Nephropathies ,030212 general & internal medicine ,Renal Insufficiency ,Chronic ,Aged, 80 and over ,Diabetic Nephropathies/blood ,General Medicine ,Middle Aged ,Atrasentan/administration & dosage ,Editorial Commentary ,Treatment Outcome ,Nephrology ,Creatinine ,Administration ,young adult ,Female ,medicine.symptom ,Glomerular filtration rate ,Type 2 ,Endothelin A Receptor Antagonists/administration & dosage ,medicine.drug ,Glomerular Filtration Rate ,Human ,Oral ,Adult ,medicine.medical_specialty ,ALBUMINURIA ,Endothelin A Receptor Antagonists ,NEPHROPATHY ,Urology ,INHIBITION ,Renal function ,Serum Albumin, Human ,Placebo ,Nephropathy ,03 medical and health sciences ,Young Adult ,Double-Blind Method ,Atresentan ,diabetes, chronic kidney disease ,medicine ,Diabetes Mellitus ,Aged ,Atrasentan ,Diabetes Mellitus, Type 2 ,Humans ,Renal Insufficiency, Chronic ,Serum Albumin ,business.industry ,Creatinine/blood ,medicine.disease ,Serum Albumin, Human/urine ,n/a OA procedure ,chemistry ,Albuminuria ,Renal Insufficiency, Chronic/blood ,business ,aged, 80 and over ,Kidney disease - Abstract
Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
- Published
- 2019
20. How Generalized and Arbitrary Institutional Inefficiencies Shape Equity in Acquisitions
- Author
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Manuel Anibal Portugal Ferreira and Christian Falaster
- Subjects
Equity (finance) ,General Medicine ,Monetary economics ,Business - Abstract
Institutional inefficiencies are likely to lead firms to approach ownership in cross-border acquisitions more carefully, possibly undertaking only a partial equity stake on the target firms. Howeve...
- Published
- 2018
21. Diagnosis of renal osteodystrophy: when and how to use biochemical markers and non-invasive methods; when bone biopsy is needed
- Author
-
Manuel Anibal A Ferreira
- Subjects
Pathology ,medicine.medical_specialty ,Biopsy ,Bone and Bones ,Diagnosis, Differential ,medicine ,Humans ,Renal osteodystrophy ,Bone Resorption ,Biochemical markers ,Chronic Kidney Disease-Mineral and Bone Disorder ,Transplantation ,medicine.diagnostic_test ,business.industry ,Non invasive ,medicine.disease ,Nephrology ,Parathyroid Hormone ,Kidney Failure, Chronic ,business ,Complication ,beta 2-Microglobulin ,Bone biopsy ,Biomarkers ,Kidney disease - Published
- 2000
22. Ozone action onStreptococcus mutansandLactobacillus fermentum: A pilot study
- Author
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Manuel Anibal A Ferreira, Anabela Paula, Eunice Carrilho, Joana Marques, and Teresa Gonçalves
- Subjects
Lactobacillus fermentum ,Biology ,biology.organism_classification ,Streptococcus mutans ,Microbiology - Published
- 2013
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