Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

Dietary calcium intake in Brazilian preschoolers and schoolchhildren: review of the literature / Ingesta de cálcio dietético em pré-escolares e escolares brasileiros: revisão da literatura

ABSTRACT Objective: The objective of this study was to map and synthesize evidence on the adequacy of dietary calcium intake and dairy products in Brazilian preschoolers and schoolchildren. Data source: Evidence searches were performed in the MEDLINE (via PubMed) and Latin American and Caribbean Health Sciences Literature (LILACS; via BVS) databases, with no restriction on date or language of publication. Experimental or observational studies that evaluated healthy Brazilian children between 2 and 12 incomplete years old were included. Data synthesis: A total of 18 studies were included. Seven of 11 studies of 11 studies (63.6%) identified mean values of dietary calcium intake below the age recommendation, especially in schoolchildren, with the progression of the age group. Among preschoolers, studies with direct weighing of food showed higher mean values of dietary calcium ingested compared to those with dietary recall. Children attending public daycare centers on a part-time basis tended to have inadequate calcium intake. The consumption of milk and dairy products was lower among older children, especially schoolchildren. Conclusions: Inadequate dietary calcium intake seems to be prevalent in Brazil during childhood, especially among schoolchildren. Therefore, the evaluation of milk and dairy products intake must be considered in order to desgn appropriate corrective actions.

RESUMO Objetivo: Mapear e sintetizar as evidências sobre a adequação do consumo de cálcio dietético e laticínios em crianças brasileiras pré-escolares e escolares. Fontes de dados: As buscas pelas evidências foram realizadas nas bases de dados Medical Literature Analysis and Retrieval System Online (Medline, via PubMed) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs, via Biblioteca Virtual em Saúde — BVS), sem restrição de data ou idioma de publicação. Foram incluídos estudos experimentais ou observacionais que avaliaram crianças brasileiras saudáveis com idade entre dois e 12 anos incompletos. Síntese dos dados: Foram incluídos 18 estudos. Sete de 11 estudos (63,6%) identificaram valores médios da ingesta de cálcio dietético abaixo do recomendado para a idade, principalmente em escolares, com a progressão da faixa etária. Entre os pré-escolares, estudos com pesagem direta dos alimentos apresentaram maiores valores médios de cálcio dietético ingerido comparados aos obtidos com recordatório alimentar. Crianças frequentadoras de creches públicas em regime de meio período tiveram a maior inadequação da ingesta de cálcio. A ingesta de leite e derivados foi menor entre as crianças com idade mais avançada, principalmente em escolares. Conclusões: A inadequação da ingesta de cálcio dietético parece ser prevalente no Brasil, principalmente em escolares. Sendo assim, a avaliação da ingestão de leite e derivados é um ponto a ser observado para a realização de ações corretivas nessa faixa etária.

Three food pattern-based indices diagnose lactating women's nutritional inadequacies in Argentina: A clinimetric approach using diet quality indicators and breast milk biomarkers.

Diet is a health foundation that supports breastfeeding and enables lactating women's recovery. This study aimed to develop 3 valid diet adherence indices by clinimetric contrast with different parameters. We hypothesize that the 3 diet adherence-based indices are positively correlated with diet quality and milk biomarkers and directly related to calcium, fiber, and energy intake. A cross-sectional study recorded food frequency, anthropometric and dietary measures, and milk analysis to estimate correlations, sensitivity, and specificity (n = 284). Three reliable indices agreed by >75% with food frequency: macronutritional (MDI), phytochemical (PDI), and energetic (EDI), which correlated positively to the Fat Quality Index and Minimum Dietary Diversity for Women. MDI and EDI correlated negatively to the Healthy Plant-Based Diet Index (H-PBDI), whereas PDI correlated positively. MDI correlated positively to the protein-to-carbohydrate ratio, whereas EDI correlated negatively. Inadequate intakes of calcium, fiber, and energy were indicated by MDI <19, PDI <19, and EDI ≥19, respectively, in a sensitive and specific manner. Body fat was therefore positively associated with EDI. MDI was associated with increased protein and superoxide anion in milk, depending on its high protein-to-carbohydrate ratio and low H-PBDI. These indices allowed us to assess diet to diagnose maternal malnutrition promptly. Index validity was supported by significant dietary correlations and biological responsiveness. MDI and EDI promoted breast bioactivity and body adiposity, respectively, whereas PDI represented a healthier option.

[Nutritionnal complications and patients follow-up after bariatric surgery]. / Complications nutritionnelles de la chirurgie bariatrique et surveillance des patients opérés.

NUTRITIONNAL COMPLICATIONS AND PATIENTS FOLLOW-UP AFTER BARIATRIC SURGERYBariatric surgery is the most consistently effective method for sustained weight reduction and can result in a substantial improvement in overall survival in patients with severe obesity. Complex mechanisms underlying metabolic benefits could also drive preventable, but potentially life-threatening, long-term nutritional complications. Consequently, physicians should be familiar with the lifelong monitoring of patients after bariatric surgery and the potential long-term complications in this paradoxical situation where the long-awaited weight loss can lead to severe nutritional complications.

COMPLICATIONS NUTRITIONNELLES DE LA CHIRURGIE BARIATRIQUE ET SURVEILLANCE DES PATIENTS OPÉRÉS La chirurgie bariatrique est le traitement le plus efficace en termes de perte pondérale durable et de réduction de la morbi-mortalité en cas d'obésité sévère. Cependant, les modifications profondes de la physiologie digestive qui sous-tendent ces bénéfices métaboliques peuvent entraîner des carences nutritionnelles qui peuvent induire des complications sévères et irréversibles. La population des patients bariatriques étant en constante augmentation, tout médecin peut être amené à prendre un charge un patient opéré. Il devrait donc connaître les principes de la surveillance à vie et les possibles complications à long terme dans cette situation si paradoxale où la perte de poids tant attendue peut aussi s'associer à des carences potentiellement sévères.

Validation of the Updated Korean Calcium Assessment Tool.

BACKGROUND: We previously developed the Korean Calcium Assessment Tool (KCAT) for assessing the intake of calcium and vitamin D in Korean women. However, based on the Korea National Health and Nutrition Examination Survey (KNHANES) VI and VII (2013-2018), major food sources for calcium and vitamin D have changed, and the National Standard Food Composition database was updated. Therefore, the present study aimed to update the KCAT and validate the Updated KCAT. METHODS: A total of 285 women aged >19 years were asked to complete questionnaires of the KCAT and the Updated KCAT. RESULTS: Calcium intake did not differ significantly between the KCAT (566±245 mg/day) and the Updated KCAT (569±248 mg/day; P=0.343). A correlation coefficient of 0.99 indicated a positive correlation on calcium intake between the KCAT and the Updated KCAT, with an almost perfect agreement by Cohen's κ coefficients (0.95). Vitamin D intake assessed by the Updated KCAT was significantly higher than that assessed by the KCAT, which was positively correlated with a moderate agreement measured by Cohen's κ coefficients (0.41). CONCLUSIONS: The present study demonstrated that the Updated KCAT was a valid tool for the rapid evaluation of calcium and vitamin D intake for Korean women.

Calcium daily intake and the efficacy of a training intervention on optimizing calcium supplementation therapy: A clinical audit.

BACKGROUND AND AIMS: Calcium is an essential element for human health, with key roles in the prevention and therapy of multifactorial conditions. Calcium dietary intake is often insufficient in the general population. The aim of this study was to perform a clinical audit for general practitioners (GPs) to understand the efficacy of training intervention on doctors' awareness about dietary calcium and supplements. METHODS AND RESULTS: General practice outpatients were enrolled (Before Clinical Audit, BCA) from the same sanitary district, and calcium dietary intake was evaluated with a validated questionnaire, also collecting information about the consumption of calcium and vitamin D supplements. Then, a training intervention with a frontal lesson and discussion with GPs involved was performed. After one month of this intervention, a second outpatient enrolment was performed (Post Clinical Audit, PCA) in the same general practices to evaluate differences in nutritional suggestions and supplement prescription by GPs. In BCA, the calcium dietary intake was low, with nobody reaching 1000 mg as suggested by the guidelines. Only 6.6% and 24.5% took calcium and vitamin D supplements, respectively; in the PCA, these percentages increased to 28% and 78% for calcium and vitamin D supplements, respectively (p < 0.01 PCA vs BCA). There were no differences in calcium dietary intake between BCA and PCA. CONCLUSION: Training intervention on GPs was successful to sensitize them regarding calcium intake problems; GPs tended to increase the prescription of supplements but not to suggest changes in dietary habits.

Comparación de la bioaccesibilidad de calcio en leche de vaca, semillas de ajonjolí (Sesamun indicum) y almendra (Prunus amygdalus) / Comparison of calcium bioaccessibility in cow's milk, sesame seeds (Sesamun indicum) and almond (Prunus amygdalus)

RESUMEN Introducción. La biodisponibilidad de un nutriente refleja la fracción disponible para ser absorbido y utilizado. Resulta crítica al evaluar la calidad nutricional de un alimento. Objetivo. Comparar la bioaccesibilidad de calcio entre el ajonjolí (Sesamun indicum) y almendra (Prunus amygdalus) con la bioaccesibilidad de calcio de la leche de vaca utilizando un método in vitro. Métodos. Estudio de tipo observacional que evaluó la bioaccesibilidad mediante el método in vitro de dializabilidad. Resultados. La dializabilidad de calcio de la leche de vaca fue de 20,71%; en las semillas de ajonjolí y almendra fue 1% y 2,27%, respectivamente. Se determinó que la leche de vaca cubre entre el 2% - 4% del requerimiento total de calcio en niños de 1 a 6 años de edad y del 2% en adolescentes y adultos. En las semillas, la cobertura fue mínima. Conclusión. La bioaccesibilidad y aporte potencial de calcio de la leche entera de vaca fue superior en comparación con las semillas de almendra y ajonjolí.

ABSTRACT Introduction. The bioavailability of a nutrient reflects the fraction available to be absorbed and used. Is critical when evaluating the nutritional quality of a food. Objective. To compare the bioaccessibility of calcium between sesame (Sesamun indicum) and almond (Prunus amygdalus) with the bioaccessibility of calcium from cow's milk using an in vitro method. Methods. An observational study that evaluated bioaccessibility using the in vitro dialyzability method. Results. Calcium dialysability of cow's milk was 20,71%; in sesame and almond seeds it was 1% and 2,27%, respectively. It was determined that cow's milk covers between 2% - 4% of the total calcium requirement in children 1 to 6 years of age and 2% in adolescents and adults. In seeds the coverage was minimal. Conclusions. The bioaccessibility and potential calcium contribution of whole cow's milk was higher compared to almond and sesame seeds.

The effect of fructan-enriched diet on bone turnover parameters in ovariectomized rats under calcium restriction.

INTRODUCTION: Osteoporosis, the "quiet epidemic", is one of the most serious threats to public health. It is known that estrogen plays a significant role in the regulation of bone turnover, and its loss at menopause causes osteoporosis. Added to this, insufficient calcium intake accelerates bone mass loss, increasing the risk of fractures. OBJECTIVE: The study aimed to answer the question whether a fructan-enriched diet could be helpful in preventing from disturbances in bone turnover caused by calcium restriction combined with ovariectomy-induced estrogen deficiency. The differences related to the kind of fructan and 'matrix effect' of fructan action (form of addition) were also evaluated. MATERIAL AND METHODS: The study was conducted using sham-operated (control groups) or ovariectomized (OVX) rats fed a calcium restricted diet. The treatment diets contained one of three fructan sources - Jerusalem artichoke, yacon and Beneo Orafti Synergy1 - added alone or as an ingredient of strawberry sorbet, all in the amount providing 8% fructans. Analyses of biological material included: serum Ca, Mg and P concentrations, alkaline phosphatase activity (ALP), osteocalcin (OC) and C-telopeptide degradation products from type I collagen (CTX). Densitometric parameters of femora were also assayed. RESULTS: Among markers of bone turnover, the ALP activity depended both on the kind of fructan and the form of addition. The highest value was shown in the OVX group fed a low-calcium diet, whereas administration of diet enriched with Jerusalem artichoke led to an almost 50% decrease in the value of this parameter. Dietary fructans also lowered the OC level. Feeding rats with diet containing sorbet enriched in yacon or Jerusalem artichoke resulted in a decrease of CTX, compared to the diet containing yacon alone or fructan formulation in both forms No significant differences were observed in densitometric parameters between treatment groups. CONCLUSIONS: The obtained findings suggest that fructan administration with a calcium-restricted diet might exert a positive effect on bone turnover parameters. Regarding the form of their addition, it is possible that other constituents of sorbets contributed to the fructan action. It remains open whether this impact would be significant over a longer period of time.

Claudin-14 Gene Polymorphisms and Urine Calcium Excretion.

BACKGROUND AND OBJECTIVES: Claudin-16 and -19 are proteins forming pores for the paracellular reabsorption of divalent cations in the ascending limb of Henle loop; conversely, claudin-14 decreases ion permeability of these pores. Single-nucleotide polymorphisms in gene coding for claudin-14 were associated with kidney stones and calcium excretion. This study aimed to explore the association of claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms with calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective observational study of 393 patients with hypertension who were naïve to antihypertensive drugs, in whom we measured 24-hour urine calcium excretion; history of kidney stones was ascertained by interview; 370 of these patients underwent an intravenous 0.9% sodium chloride infusion (2 L in 2 hours) to evaluate the response of calcium excretion in three different 2-hour urine samples collected before, during, and after saline infusion. Genotypes of claudin-14, claudin-16, and claudin-19 were obtained from data of a previous genome-wide association study in the same patients. RESULTS: Thirty-one single-nucleotide polymorphisms of the 3' region of the claudin-14 gene were significantly associated with 24-hour calcium excretion and calcium excretion after saline infusion. The most significant associated single-nucleotide polymorphism was rs219755 (24-hour calcium excretion in GG, 225±124 mg/24 hours; 24-hour calcium excretion in GA, 194±100 mg/24 hours; 24-hour calcium excretion in AA, 124±73 mg/24 hours; P<0.001; calcium excretion during saline infusion in GG, 30±21 mg/2 hours; calcium excretion during saline infusion in GA, 29±18 mg/2 hours; calcium excretion during saline infusion in AA, 17±11 mg/2 hours; P=0.03). No significant associations were found among claudin-16 and claudin-19 single-nucleotide polymorphisms and calcium excretion and between claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms and stones. Bioinformatic analysis showed that one single-nucleotide polymorphism at claudin-14 among those associated with calcium excretion may potentially influence splicing of transcript. CONCLUSIONS: Claudin-14 genotype at the 3' region is associated with calcium excretion in 24-hour urine and after the calciuretic stimulus of saline infusion.

Fibroblast Growth Factor 23 Associates with Death in Critically Ill Patients.

BACKGROUND AND OBJECTIVES: Dysregulated mineral metabolism is a common and potentially maladaptive feature of critical illness, especially in patients with AKI, but its association with death has not been comprehensively investigated. We sought to determine whether elevated plasma levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), are prospectively associated with death in critically ill patients with AKI requiring RRT, and in a general cohort of critically ill patients with and without AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured plasma FGF23 and other mineral metabolite levels in two cohorts of critically ill patients (n=1527). We included 817 patients with AKI requiring RRT who enrolled in the ARF Trial Network (ATN) study, and 710 patients with and without AKI who enrolled in the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study. We hypothesized that higher FGF23 levels at enrollment are independently associated with higher 60-day mortality. RESULTS: In the ATN study, patients in the highest compared with lowest quartiles of C-terminal (cFGF23) and intact FGF23 (iFGF23) had 3.84 (95% confidence interval, 2.31 to 6.41) and 2.08 (95% confidence interval, 1.03 to 4.21) fold higher odds of death, respectively, after adjustment for demographics, comorbidities, and severity of illness. In contrast, plasma/serum levels of parathyroid hormone, vitamin D metabolites, calcium, and phosphate were not associated with 60-day mortality. In the VALID study, patients in the highest compared with lowest quartiles of cFGF23 and iFGF23 had 3.52 (95% confidence interval, 1.96 to 6.33) and 1.93 (95% confidence interval, 1.12 to 3.33) fold higher adjusted odds of death. CONCLUSIONS: Higher FGF23 levels are independently associated with greater mortality in critically ill patients.

Vitamin D status in prepubertal children with isolated idiopathic growth hormone deficiency: effect of growth hormone therapy.

Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels <30 ng/mL and 20 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. 25(OH)D was lower in cases than controls. Forty per cent of children with GHD were 25(OH)D insufficient and 44% deficient, while 16% were sufficient at baseline. There was a positive correlation between 25(OH)D and peak GH levels. Peak GH was a significant predictor of 25(OH)D levels. After 1 year of GH therapy, 25(OH)D increased (18.42±5.41 vs 34.5±10.1 ng/mL; P<0.001). Overall, 22% of cases remained insufficient and 24% deficient, with an increase in prevalence of children with normal levels (54%; P<0.001). 25(OH) correlated negatively with PTH (r=-0.71, P=0.01). In conclusion, hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy. 25(OH)D should be assessed in children with GHD at diagnosis and during follow-up.

Cálcio e vitamina D em adultos atendidos em ambulatório de nutrição / Calcium and vitamin D in adults attending an outpatient nutrition clinic / Calcio y vitamina D en adultos asistidos en ambulatorio de nutrición

Objetivo: Avaliar o consumo de cálcio e vitamina D de pacientes atendidos em um ambulatório de Nutrição de referência. Métodos: Estudo transversal quantitativo realizado no período de novembro de 2015 a junho de 2016 avaliou 1.000 recordatórios alimentares de pacientes na faixa etária de 20 a 59 anos do ambulatório de Nutrição de um centro universitário do interior do Rio Grande do Sul, Brasil. Excluíram-se os recordatórios com medidas caseiras incompletas. Para a padronização dessas medidas utilizou-se registro fotográfico de um livro de medidas caseiras. Utilizou-se como referência para análise de ingestão do cálcio e vitamina D a Dietary Reference Intakes. Os dados foram analisados por meio de estatística descritiva e inferencial com nível de significância de 5%. Resultados: O consumo de cálcio e de vitamina D foi simétrico, apresentando 89,5% (n=895) de inadequação do consumo de vitamina D e 86,6% (n=866) de inadequação do consumo de cálcio, portanto, abaixo da recomendação diária. Homens apresentaram ingestão significativamente maior de cálcio em comparação às mulheres (p<0,001), enquanto o consumo de vitamina D não apresentou diferença significativa entre os sexos (p=0,307). Conclusão: Verificou-se elevada inadequação quanto à ingestão de cálcio e vitamina D pela população estudada.

Objective: To assess calcium and vitamin D intake in patients attending a reference outpatient nutrition clinic. Methods: Quantitative cross-sectional study carried out from November 2015 to June 2016 to analyze 1,000 dietary recalls of patients aged 20 to 59 years attending an outpatient nutrition clinic of a university center in the countryside of Rio Grande do Sul. Recalls with incomplete household measures were excluded. Measures were standardized using pictures from a household measures book. The analysis of calcium and vitamin D intake was based on the Dietary Reference Intakes. Data were analyzed using descriptive and inferential statistics with a significance level of 5%. Results: Calcium and vitamin D intake was symmetrical, with 89.5% (n=895) of inadequate vitamin D intake and 86.6% (n=866) of inadequate calcium intake, i.e., below the daily recommendation. Men presented significantly higher calcium intake compared to women (p<0.001), while vitamin D intake showed no significant differences between genders (p=0.307). Conclusion: There was a high inadequacy of calcium and vitamin D intake in the population analyzed.

Objetivo: Evaluar el consumo de calcio y vitamina D de pacientes asistidos en un ambulatorio de nutrición de referencia. Métodos: Estudio transversal cuantitativo realizado en el período entre noviembre de 2015 y junio de 2016 evaluó 1.000 recordatorios alimentarios de pacientes en la franja de edad entre 20 y 59 años del ambulatorio de nutrición de un centro universitario de un pueblo de Rio Grande do Sul, Brasil. Se excluyeron los recordatorios con las medidas caseras incompletas. Para la estandarización de esas medidas se utilizó el registro fotográfico de un libro de medidas caseras. Se utilizó como referencia para el análisis de la ingesta de calcio y vitamina D la Dietary Reference Intakes. Los datos fueron analizados a través de la estadística descriptiva e inferencial con el nivel de significación del 5%. Resultados: El consumo de calcio y vitamina D ha sido simétrico presentando el 89,5% (n=895) de inadecuación para el consumo de vitamina D y el 86,6% (n=866) de inadecuación para el consumo de calcio, por lo tanto, abajo de la recomendación diaria. Los hombres presentaron ingesta significativamente mayor de calcio en comparación con las mujeres (p<0,001) mientras el consumo de vitamina D no ha presentado diferencia significativa entre los sexos (p=0,307). Conclusión: Se verificó una elevada inadecuación de la ingesta de calcio y vitamina D de parte de la población estudiada.

Calcium and Cardiovascular Disease.

Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate Binders.

BACKGROUND AND OBJECTIVES: Prior studies have shown that sevelamer attenuates progression of arterial calcification and may reduce the risk of death compared with calcium-based phosphate binders. In clinical practice, however, sevelamer is used not only as an alternative but also as an add-on therapy in patients already being treated with calcium-based phosphate binders. We analyzed the Dialysis Outcomes and Practice Patterns Study (DOPPS) data to test the hypothesis that the initiation of sevelamer is associated with improved survival in patients on hemodialysis treated with calcium-based phosphate binders. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We included 12,564 patients from DOPPS phase 3 and phase 4 (2005-2011) who were prescribed calcium-based phosphate binders at baseline or before sevelamer treatment. Mortality risk was assessed using a sequential stratification method to identify as-yet-untreated patients who were appropriately matched to the newly treated patients on the basis of their risk of death. RESULTS: Of 12,564 patients, 2606 were subsequently treated with sevelamer hydrochloride or sevelamer carbonate. After beginning sevelamer therapy, mean serum phosphorus levels decreased by 0.3 mg/dl in the first 4 months and gradually decreased thereafter. We matched 2501 treated patients with at least one as-yet-untreated patient. Patients treated with sevelamer had a 14% lower risk for mortality compared with as-yet-untreated patients (hazard ratio, 0.86; 95% confidence interval, 0.76 to 0.97). Similar results were observed in the sensitivity analyses when changing the matching calipers or the treated and as-yet-untreated ratios, and by using propensity score matching. CONCLUSIONS: The use of sevelamer as an add-on or alternative therapy to calcium-based phosphate binders is associated with improved survival in patients on maintenance hemodialysis.

Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. RESULTS: We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). CONCLUSIONS: Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion.

Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33-4.66 mg/dl (0.75-1.50 mmol/L) or a liberalized target of 6.20-7.75 mg/dl (2.00-2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks. RESULTS: Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275-3000) mg in the intensive group, and 0 (0-500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events. CONCLUSIONS: It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.

Facility Practice Variation to Help Understand the Effects of Public Policy: Insights from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Recent Centers for Medicare & Medicaid Services policies have used dialysis facility practice variation to develop public ratings and adjust payments. In the Dialysis Facility Compare star rating system (DFC SRS), facility-relative rates of performance-based clinical measures varied nearly two-fold for mortality (standardized mortality ratio; 10th/90th percentiles: 0.71, 1.34) and hospitalization (standardized hospitalization ratio; 10th/90th percentiles: 0.64, 1.37), and nearly four-fold for transfusion (standardized transfusion ratio; 10th/90th percentiles: 0.43, 1.65). Medicare claims data (from July of 2014) demonstrate that facility variation for the proportions of patients on hemodialysis hospitalized (10th/90th percentiles: 27%, 50%) and transfused (10th/90th percentiles: 3%, 17%) within 6 months that far exceeds relatively modest recent overall longitudinal trends. DFC SRS-rated facility variation is also substantial for fistula (10th/90th percentiles: 50%, 78%) and catheter use >90 days (10th/90th percentiles: 3%, 19%). By contrast, DFC SRS-rated facility distributions for adult hemodialysis Kt/V>1.2 (10th/90th percentiles: 84%, 97%) and total serum calcium >10.2 mg/dl (median, 1%; 75th/90th percentiles: 3%, 5%) are quite narrow and may be of questionable value. Likewise, variation in the US Dialysis Outcomes and Practice Patterns Study is over two-fold for facility median serum parathyroid hormone (10th/90th percentiles: 290 pg/ml, 629 pg/ml) and ferritin (10th/90th percentiles: 469 ng/ml, 1143 ng/ml) levels, and facility mean treatment time varies by 30 minutes (10th/90th percentiles: 204 minutes, 234 minutes). Rising serum parathyroid hormone and ferritin levels, and generally short dialysis treatment time, represent areas unchecked by existing policy; both overall trends and facility variation in these values may reflect unintended consequences of policy or reimbursement pressures and therefore raise concern. Additionally, outcomes in the transition period from advanced CKD to dialysis remain poor, and policy initiatives and performance accountability in this area remain insufficient. Innovative models of comprehensive care in advanced CKD and the early dialysis period which are more amenable to policy oversight are needed. In summary, facility variation is typically larger than prevailing longitudinal trends, and should not be overlooked. The combination of nationally representative observational databases (e.g., the Dialysis Outcomes and Practice Patterns Study) and ESRD registries can provide policy makers with additional tools to evaluate facility variation, develop policies, and monitor unintended effects.

Calcium and Cardiovascular Disease

Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults.

BACKGROUND AND OBJECTIVES: Patiromer is a nonabsorbed potassium-binding polymer that uses calcium as the counterexchange ion. The calcium released with potassium binding has the potential to be absorbed or bind phosphate. Because binding is not specific for potassium, patiromer can bind other cations. Here, we evaluate the effect of patiromer on urine ion excretion in healthy adults, which reflects gastrointestinal ion absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed the effect of patiromer on urine potassium, sodium, magnesium, calcium, and phosphate in two studies. Healthy adults on controlled diets in a clinical research unit were given patiromer up to 50.4 g/d divided three times a day for 8 days (dose-finding study) or 25.2 g/d in a crossover design as daily or divided (two or three times a day) doses for 18 days (dosing regimen study). On the basis of 24-hour collections, urinary ion excretion during the baseline period (days 5-11) was compared with that during the treatment period (days 13-19; dose-finding study), and the last 4 days of each period were compared across regimens (dosing regimen study). RESULTS: In the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium (P<0.01 for each). Patiromer at 25.2 g/d decreased urine potassium (mean±SD) by 1140±316 mg/d, urine magnesium by 45±1 mg/d, and urine sodium by 225±145 mg/d. Urine calcium increased in a dose-dependent manner, and urine phosphate decreased in parallel (both P<0.01). Patiromer at 25.2 g/d increased urine calcium by 73±23 mg/d and decreased urine phosphate by 64±40 mg/d. Urine potassium, urine sodium, and urine magnesium were unaffected by dosing regimen, whereas the increase in urine calcium was significantly lower with daily compared with three times a day dosing (P=0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing (P<0.05). CONCLUSIONS: In healthy adults, patiromer reduces urine potassium, urine sodium, urine magnesium, and urine phosphate, while modestly increasing urine calcium. Compared with divided dosing, administration of patiromer once daily provides equivalent reductions in urine potassium, urine sodium, and urine magnesium, with less effect on urine calcium and urine phosphate.