Aníbal Ferreira

Use of phosphate-binding agents is associated with a lower risk of mortality

Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study

BACKGROUND Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated. METHODS COSMOS is a 3-year, multicentre, open-cohort, prospective study carried out in 6797 adult chronic haemodialysis patients randomly selected from 20 European countries. RESULTS Using Cox proportional hazard regression models and penalized splines analysis, it was found that both high and low serum phosphorus, calcium and PTH were associated with a higher risk of mortality. The serum values associated with the minimum relative risk of mortality were 4.4 mg/dL for serum phosphorus, 8.8 mg/dL for serum calcium and 398 pg/mL for serum PTH. The lowest mortality risk ranges obtained using as base the previous values were 3.6-5.2 mg/dL for serum phosphorus, 7.9-9.5 mg/dL for serum calcium and 168-674 pg/mL for serum PTH. Decreases in serum phosphorus and calcium and increases in serum PTH in patients with baseline values of >5.2 mg/dL (phosphorus), >9.5 mg/dL (calcium) and <168 pg/mL (PTH), respectively, were associated with improved survival. CONCLUSIONS COSMOS provides evidence of the association of serum phosphorus, calcium and PTH and mortality, and suggests survival benefits of controlling chronic kidney disease-mineral and bone disorder biochemical parameters in CKD5D patients.

COSMOS: the dialysis scenario of CKD–MBD in Europe

BACKGROUND Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. METHODS COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. RESULTS The haemodialysis population in Europe is an aged population (mean age 64.8±14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3±14.3 versus 66.0±13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. CONCLUSIONS The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

Influence of Body Mass Index on the Association of Weight Changes with Mortality in Hemodialysis Patients

BACKGROUND AND OBJECTIVES A high body mass index (BMI) is associated with lower mortality in patients undergoing hemodialysis. Short-term weight gains and losses are also related to lower and higher mortality risk, respectively. The implications of weight gain or loss may, however, differ between obese individuals and their nonobese counterparts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Current Management of Secondary Hyperparathyroidism: A Multicenter Observational Study (COSMOS) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007, with prospective data collection every 6 months for 3 years. Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality. Analyses were performed after patient stratification according to their starting BMI. RESULTS Among 6296 patients with complete data, 1643 died. At study entry, 42% of patients had a normal weight (BMI, 20-25 kg/m(2)), 11% were underweight, 31% were overweight, and 16% were obese (BMI ≥ 30 kg/m(2)). Weight loss or gain (<1% or >1% of body weight) was strongly associated with higher rates of mortality or survival, respectively. After stratification by BMI categories, this was true in nonobese categories and especially in underweight patients. In obese patients, however, the association between weight loss and mortality was attenuated (hazard ratio, 1.28 [95% confidence interval (CI), 0.74 to 2.14]), and no survival benefit of gaining weight was seen (hazard ratio, 0.98 [95% CI, 0.59 to 1.62]). CONCLUSIONS Assuming that these weight changes were unintentional, our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients. In addition, a patients BMI modifies the strength of the association between weight changes with mortality.

Bone biopsy practice patterns across Europe: the European renal osteodystrophy initiative - a position paper

Renal osteodystrophy (ROD) is a heterogeneous group of metabolic bone diseases complicating progressive chronic kidney disease (CKD). Bone biomarkers and bone imaging techniques may help to assess bone health and predict fractures in CKD but do have important inherent limitations. By informing on bone turnover and mineralization, a bone biopsy may help to guide prevention and treatment of ROD and its consequences. According to a recent survey conducted among European nephrologists, bone biopsies are performed rather exceptionally, both for clinical and research purposes. Obviously, clinical research in the field of ROD is threatened by vanishing clinical and pathological expertise, small patient cohorts and scientific isolation. In March 2016, the European Renal Osteodystrophy (EU-ROD) initiative was created under the umbrella of the ERA-EDTA CKD-mineral and bone disorder (MBD) Working Group to revitalize bone biopsy as a clinically useful tool in the diagnostic workup of CKD-MBD and to foster research on the epidemiology, implications and reversibility of ROD. As such, the EU-ROD initiative aims to increase the understanding of ROD and ultimately to improve outcomes in CKD patients.

Risk of hospitalization associated with body mass index and weight changes among prevalent haemodialysis patients

The impact of body mass index (BMI) and body weight on hospitalization rates in haemodialysis patients is unknown. This study hypothesizes that being either underweight or obese is associated with a higher hospitalization rate. Observational study of 6296 European haemodialysis patients with prospective data collection and follow-up every six months for three years (COSMOS study). The risk of being hospitalized was estimated by a time-dependent Cox regression model and the annual risk (incidence rate ratios, IRR) by Poisson regression. We considered weight loss, weight gain and stable weight. Weight change analyses were also performed after patient stratification according to their baseline BMI. A total of 3096 patients were hospitalized at least once with 9731 hospitalizations in total. The hospitalization incidence (fully adjusted IRR 1.28, 95% CI [1.18-1.39]) was higher among underweight patients (BMI <20kg/m2) than patients of normal weight (BMI 20-25kg/m2), while the incidence of overweight (0.88 [0.83-0.93]) and obese patients (≥30kg/m2, 0.85 [0.79-0.92]) was lower. Weight gain was associated with a reduced risk of hospitalization. Conversely, weight loss was associated with a higher hospitalization rate, particularly in underweight patients (IRR 2.85 [2.33-3.47]). Underweight haemodialysis patients were at increased risk of hospitalization, while overweight and obese patients were less likely to be hospitalized. Short-term weight loss in underweight individuals was associated with a strikingly high hospitalization rate.

The European Certificate in Nephrology: towards harmonization and excellence in training

Abstract Nephrology is a young medical specialty that has evolved and expanded during the last 4 decades of the past century, becoming recognized as one of the most innovative and challenging medical specialties. The training of nephrology takes place mainly in public hospitals, and there are important variations in the duration and assessment of training among the European countries. The Union of European Medical Specialties (UEMS) Renal Section and the European Renal Association–European Dialysis and Transplant Association have been working jointly since 2010 to harmonize European nephrology training and more recently to establish the European Certificate in Nephrology (ECN). The first two editions of the ECN were held in early 2017 and 2018. In total, 122 candidates from 26 countries have sat for the exam, with a success rate of 59% (72/122). To date, Switzerland has adopted the exam as their national training assessment and we expect that other countries will join Switzerland in the near future. Fostering the development and importance of the ECN requires that member states work to increase the academic and professional profile of the ECN within their countries. The ECN should be considered a ‘quality mark’ and a sign of high achievement in nephrology training in Europe. If holding the ECN becomes advantageous for employment or improving scientific careers, the number of candidates will increase and the sustainability of the ECN will be guaranteed. A recent, positive development is the pre-agreement between the UEMS Renal Section, UK Renal Association and Royal Colleges of the UK to adopt a unique pan-European exam beginning in 2020. However, any decision to commence the pan-European exam will depend, in part, on strong candidate enrolment for the ECN 2019 edition. Thus support of the national societies is crucial for the sustainability and growth of a European exam, because of their capacities to influence strategic policies in hospitals, universities and medical associations, with a longer-term aim to increase the professional recognition of the European exam.