Negative association between 25-hydroxyvitamin D and inflammatory markers in rheumatologic diseases / Asociación negativa entre 25-hidroxi vitamina D y los marcadores inflamatorios en enfermedades reumatológicas

Objective: The main purpose of this study was to evaluate serum 25-hydroxyvitamin D (25OHD) levels and its association with in"ammatory markers in patients with rheumatologic diseases (RD). Methods: A cross-sectional study in 154 women with RD (rheumatoid arthritis, spondyloarthritis and other connective tissue diseases) and 112 healthy individuals as a control group (CG) was carried out. Results: No differences in serum and urine calcium, serum phosphate, and urinary deoxypyridinoline were found. RD group had lower 25OHD and higher PTH compared to CG. RD group had higher C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) compared to CG. The overall mean level of 25OHD (ng/ml) was 26.3±12.0 in the CG and 19.4±6.8 in the RD group (p<0.0001). Moreover, CG had lower percentage of individuals with 25OHD de!ciency compared to RD (29.9% vs 53.2%). The femoral neck BMD was signi!cantly lower in postmenopausal RD women compared to CG. 25OHD levels signi!cantly correlated with ESR and CRP as in"ammatory markers. Age, BMI, presence of RD, and CRP were signi!cantly and negatively associated with 25OHD levels through linear regression analysis. According to univariate logistic regression analysis for 25OHD deficiency (<20 ng/ml), a significant and negative association with BMI, presence of RD, ESR and CRP were found. Conclusion: Patients with RD had lower 25OHD levels than controls and the presence of a RD increases by 2.66 the risk of vitamin D de!ciency. In addition, 25OHD has a negative correlation with ESR and CRP as in"ammatory markers. (AU)

Objetivo El objetivo principal de este estudio fue evaluar los niveles séricos de 25-hidroxivitamina D (25OHD) y su asociación con marcadores inflamatorios en enfermedades reumatológicas. Materiales y métodos: Se realizó un estudio transversal en 154 mujeres con enfermedades reumatológicas (artritis reumatoide, espondiloartritis y otras enfermedades del tejido conectivo) y 112 individuos sanos como grupo control (GC). Resultados: No se encontraron diferencias en el calcio sérico y urinario, el fosfato sérico y la desoxipiridinolina urinaria entre el GC y los sujetos con enfermedades reumatológicas. El grupo de pacientes con enfermedades reumatológicas tenía 25OHD más bajo y PTH más alto en comparación con el GC. Asimismo, el grupo de individuos con enfermedades reumatológicas tenía proteína C reactiva (PCR) y velocidad de eritrosedimentación (VES) más altas en comparación con el GC. El nivel de 25OHD (ng/ml) fue 26,3±12,0 en el GC y 19,4±6,8 en el grupo con enfermedades reumatológicas (p<0,0001). Además, el GC presentó un porcentaje menor de deficiencia de 25OHD en comparación con el grupo con enfermedades reumatológicas (29,9% vs 53,2%). La DMO del cuello femoral fue significativamente menor en las mujeres posmenopáusicas con enfermedades reumatológicas en comparación con el GC. La 25OHD correlacionó significativamente con la VES y la PCR como marcadores inflamatorios. El análisis de regresión lineal mostró que la edad, el IMC, la presencia de una enfermedad reumatológica y la PCR se asociaron significativa y negativamente con los niveles de 25OHD. Mientras que el análisis de regresión logística univariada mostró que la deficiencia de 25OHD (<20 ng/ml), se asoció significativa y negativamente con el IMC, la presencia de una enfermedad reumatológica, la VES y los niveles de PCR. Conclusiones: Los pacientes con enfermedades reumatológicas tenían niveles de 25OHD más bajos que los controles y la presencia de una enfermedad reumatológica aumenta en 2.66 el riesgo de deficiencia de vitamina D. Además, la 25OHD mostró correlación negativa con la VES y la PCR como marcadores inflamatorios. (AU)

Digital radiography as an alternative method in the evaluation of bone density in uremic rats / Radiografia digital como método alternativo na avaliação da densidade óssea em ratos urêmicos

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.

Chronic kidney disease is a main confounding factor for 25-vitamin D measurement / A doença renal crônica é um importante fator de confusão para a dosagem de 25-hidroxivitamina D

Abstract Background: Current guidelines recommend assessment of 25-vitamin D status in patients with chronic kidney disease (CKD). Although significant differences among assays have been described, the impact of CKD on this variability has never been tested. Methods: We tested the variability between two 25-vitamin D assays in patients with CKD (eGFR < 60 mL/min/1.73m2) who had consecutive 25-vitamin D measurements in 2015 (Assay 1 - Diasorin LIASON 25 TOTAL - D assay®) and 2016 (Assay 2 - Beckman Coulter Unicel Xl 800®). The cohort consisted of 791 adult patients (122 with normal renal function and 669 with CKD - 33, 30, and 37% in stages 3, 4, and 5 on dialysis, respectively). Results: Levels of 25-vitamin D were lower and the prevalence of hypovitaminosis D using assay 1 was higher than using assay 2 in patients with CKD, regardless of similar levels of calcium, phosphate, and parathyroid hormone. As kidney function decreased, the percentage of disagreement between the assays increased. Conclusion: There is a noteworthy variability between assays in patients with CKD such that the diagnosis of hypovitaminosis D is modified. The mechanism behind this result is still unclear and might be due to a possible interference in the analytical process. However, the clinical significance is unquestionable, as the supplementation of vitamin D can be erroneously prescribed to these patients.

Resumo Antecedentes: As diretrizes atuais recomendam a avaliação do estado da 25-hidroxivitamina D em pacientes com doença renal crônica (DRC). Embora significativas diferenças entre os ensaios tenham sido descritas, o impacto da nesta variabilidade DRC nunca foi testado. Métodos: Testamos a variabilidade entre dois ensaios de 25-hidroxivitamina D em pacientes com DRC (TFGe < 60 mL/min/1,73 m2) que realizaram medidas consecutivas de 25-hidroxivitamina D em 2015 (Ensaio 1 - Diasorin LIASON 25 TOTAL - D assay® ) e 2016 (Ensaio 2 - Beckman Coulter Unicel Xl 800®). A coorte consistiu de 791 pacientes adultos (122 com função renal normal e 669 com DRC - 33, 30 e 37% nos estágios 3, 4 e 5 em diálise, respectivamente). Resultados: Os níveis de 25-hidroxivitamina D foram menores e a prevalência de hipovitaminose D foi maior utilizando o ensaio 1 do que com o ensaio 2 em pacientes com DRC, independentemente dos níveis similares de cálcio, fosfato e paratormônio. Quando a função renal diminuiu, a porcentagem de discordância entre os ensaios aumentou. Conclusão: Existe uma notável variabilidade entre os ensaios em pacientes com DRC, de modo a modificar o diagnóstico de hipovitaminose D. O mecanismo por trás desse resultado ainda não está claro e pode ser devido a uma possível interferência no processo analítico. Entretanto, o significado clínico é inquestionável, pois a suplementação de vitamina D pode ser erroneamente prescrita a esses pacientes.

Metabolic and volume status evaluation of hemodialysis patients with and without residual renal function in the long interdialytic interval / Avaliação metabólica e volêmica no maior intervalo interdialítico de pacientes em hemodiálise com e sem função renal residual

Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.

Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.

Hipercalcemia e hipofosfatemia en prematuros que reciben nutrición parenteral agresiva / Hypercalcemia and hypophosphatemia among preterm infants receiving aggressive parenteral nutrition

Introducción. La nutrición parenteral agresiva constituye un estándar de cuidado en prematuros de muy bajo peso. Sin embargo, investigaciones recientes evaluaron su impacto en los resultados a corto plazo, como la homeostasis mineral y electrolítica. El objetivo fue comparar la prevalencia de hipercalcemia e hipofosfatemia en prematuros que recibían nutrición parenteral agresiva o estándar. Métodos. Estudio observacional retrospectivo que comparó a un grupo de prematuros menores de 1250 gramos que recibían nutrición parenteral agresiva con un grupo control histórico. Se calculó la prevalencia de hipercalcemia y se buscó la asociación con nutrición parenteral agresiva ajustando por confundidores. Se estimó la media de fosfatemia del grupo control mediante regresión lineal y se la comparó con el otro grupo. Resultados. Se incluyeron 40 pacientes por grupo. La prevalencia de hipercalcemia fue mayor en el grupo de nutrición parenteral agresiva (87,5% vs. 35%, p= 0,001). La nutrición parenteral agresiva se asoció con hipercalcemia al ajustar por peso al nacer, restricción del crecimiento intrauterino, aporte de aminoácidos y calorías (ORa 21,8; IC 95%: 3,7-128). La media de calcemia fue diferente entre ambos grupos (p= 0,002). El grupo de nutrición parenteral agresiva presentó más sepsis sin alcanzar significancia estadística y su fosfatemia media resultó menor que la estimada para el grupo control (p= 0,04). La prevalencia de hipofosfatemia en este grupo fue de 90% (IC 95%: 76-97%). Conclusiones. Nuestros datos muestran una asociación entre hipercalcemia/hipofosfatemia y nutrición parenteral agresiva. Se recomienda monitorizar la calcemia y la fosfatemia frecuentemente, ya que pueden estar asociadas con resultados clínicos adversos.

Introduction. Aggressive parenteral nutrition is the standard of care among very-low-birth weight preterm infants. However, in recent studies, its impact on short-term outcomes, has been evaluated. The objective was to compare the prevalence of hypercalcemia and hypophosphatemia among preterm infants receiving aggressive or standard parenteral nutrition. Methods. Observational, retrospective study comparing a group of preterm infants weighing less than 1250 grams who received aggressive parenteral nutrition with a historical control group. The prevalence of hypercalcemia was estimated and its association with aggressive parenteral nutrition was searched adjusting by confounders. The mean phosphate level was estimated for the control group by linear regression and was compared to the value in the other group. Results. Forty patients per group were included. The prevalence of hypercalcemia was higher in the group who received aggressive parenteral nutrition (87.5% versus 35%, p= 0.001). Aggressive parenteral nutrition was associated with hypercalcemia when adjusting by birth weight, intrauterine growth restriction, amino acid, and calorie intake (adjusted odds ratio: 21.8, 95% confidence interval -amp;#91;CI-amp;#93;: 3.7-128). The mean calcium level was different between both groups (p= 0.002). Infants who received aggressive parenteral nutrition had more sepsis without reaching statistical significance and the mean phosphate level was lower than that estimated for the control group (p= 0.04). The prevalence of hypophosphatemia in this group was 90% (95% CI: 76-97%). Conclusions. Our data show an association between hypercalcemia/hypophosphatemia and aggressive parenteral nutrition. It is recommended to frequently monitor calcium and phosphate levels since they might be associated with adverse clinical outcomes.

Lamivudine, Entecavir, or Tenofovir Treatment of Hepatitis B Infection: Effects on Calcium, Phosphate, FGF23 and Indicators of Bone Metabolism

ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

Evaluación de la respuesta densitométrica en pacientes con osteoporosis posmenopáusica tratadas con ranelato de estroncio o denosumab / Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr. (AU)

Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of "responders" was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR. (AU)

Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications

ABSTRACT Objectives To identify a clinical profile and laboratory findings of a cohort of hypoparathyroidism patients and determine the prevalence and predictors for renal abnormalities. Materials and methods Data from medical records of five different visits were obtained, focusing on therapeutic doses of calcium and vitamin D, on laboratory tests and renal ultrasonography (USG). Results Fifty-five patients were identified, 42 females and 13 males; mean age of 44.5 and average time of the disease of 11.2 years. The most frequent etiology was post-surgical. Levels of serum calcium and creatinine increased between the first and last visits (p < 0.001 and p < 0.05, respectively); and serum levels of phosphate decreased during the same period (p < 0.001). Out of the 55 patients, 40 had USG, and 10 (25%) presented with kidney calcifications. There was no significant difference in the amount of calcium and vitamin D doses among patients with kidney calcifications and others. No correlation between serum and urinary levels of calcium and the presence of calcification was found. Urinary calcium excretion in 24h was significantly higher in patients with kidney calcification (3.3 mg/kg/d) than in those without calcification (1.8 mg/kg/d) (p < 0.05). Conclusions The reduction of hypocalcemia and hyperphosphatemia suggest an effectiveness of the treatment, and the increase in serum creatinine demonstrates an impairment of renal function during follow-up. Kidney calcifications were prevalent in this cohort, and higher urinary calcium excretion, even if still within the normal range, was associated with development of calcification. These findings suggest that lower rates of urinary calcium excretion should be aimed for in the management of hypoparathyroidism.

Hypocalcemia development in patients operated for primary hyperparathyroidism: Can it be predicted preoperatively?

ABSTRACT Objective Primary hyperparathyroidism (PHP) is a common endocrine disease, and its most effective treatment is surgery. Postoperative hypocalcemia is a morbidity of parathyroid surgeries, and it may extend hospitalization durations. The purpose of this study is to determine the predictive factors related to the development of hypocalcemia and hungry bone syndrome (HBS) in patients who underwent parathyroidectomy for PHP. Materials and methods Laboratory data comprising parathyroid hormone (PTH), calcium, phosphate, 25-OHD, albumin, magnesium, alkaline phosphatase (ALP), blood urea nitrogen (BUN), and thyroid stimulating hormone (TSH) of the patients were recorded preoperatively, on the 1st and 4th days postoperatively, and in the 6th postoperative month, and their neck ultrasound (US) and bone densitometry data were also recorded. Results Hypocalcemia was seen in 63 patients (38.4%) on the 1st day after parathyroidectomy. Ten patients (6.1%) had permanent hypocalcemia in the 6th month after surgery. Out of the patients who underwent parathyroidectomy for PHP, 22 (13.4%) had HBS. The incidence of postoperative hypocalcemia was higher in patients who underwent parathyroidectomy for PHP, who had parathyroid hyperplasia, and who had osteoporosis. Preoperative PTH, ALP, and BUN values were higher in those patients who developed HBS. Furthermore, HBS was more common in patients who had osteoporosis, who had parathyroid hyperplasia, and who underwent thyroidectomy simultaneously with parathyroidectomy. Conclusions As a result, patients who have the risk factors for development of hypocalcemia and HBS should be monitored more attentively during the perioperative period.

Requests of laboratory tests for the diagnosis and management of calcium-phosphate disorders in Spain / Solicitud de pruebas de laboratorio para el diagnóstico y manejo de los desórdenes del metabolismo fosfocálcico en España

Background: Knowledge about the variability in the request of calcium-phosphate metabolism laboratory tests in primary care is important to design strategies to improve health system efficiency. Aim: To compare the inter-practice variability in calcium-phosphate metabolism laboratory tests requested by general practitioners from diverse regions across Spain. Material and Methods: One hundred and forty one clinical laboratories were invited to participate in an observational cross-sectional study. They informed the number of serum calcium, phosphate, parathyroid hormone and 25-hydroxyvitamin D requested by general practitioners. Appropriateness indicators were calculated as number of test requests per 1,000 inhabitants and ratio of related tests requests. The differences according to hospital setting, region and type of management were analyzed. Results: We recruited 76 laboratories (17,679,195 inhabitants). General practitioners requested 3,260,894 calcium-phosphate metabolism tests. The rate of request ranged from 2.97 per 1,000 inhabitants for 25-hydroxyvitamin D to 98.89 per 1,000 inhabitants for calcium. The rates of request for calcium, phosphate, parathyroid hormone in some areas were 30, 100 and 340 times higher than in other areas. Parathyroid hormone and 25-hydroxyvitamin D were highly requested in private management areas. There were also differences in phosphate, parathyroid hormone and 25-hydroxyvitamin D requesting between regions across Spain. Conclusions: The high variability observed is difficult to explain by differences in patient case mix between regions. Depending on the area, calcium could be under requested to detect primary hyperparathyroidism.

Objetivo: Conocer la variabilidad en la solicitud de pruebas de laboratorio en atención primaria es importante para diseñar estrategias que mejoren la eficiencia del sistema de salud. La propuesta de este estudio fue comparar la variabilidad en la solicitud de pruebas para la evaluación del metabolismo fosfocálcico por médicos de atención primaria de diversas regiones de España. Material y Método: Se invitó a participar a 141 laboratorios clínicos de diversas regiones españolas. Completaron una encuesta con el número de determinaciones de calcio, fósforo, hormona paratiroidea y 25-hidroxivitamina D solicitadas por médicos de atención primaria de sus áreas. Se calcularon las tasas en relación a la población y se construyeron indicadores de adecuación. Los resultados se compararon por características del hospital, región y tipo de gestión. Resultados: Obtuvimos los datos de 76 laboratorios (17.679.195 habitantes). Los médicos de atención primaria solicitaron 3.260.894 pruebas de metabolismo fosfocálcico. La tasa de solicitud varió de 2,97 por 1.000 habitantes de 25-hidroxivitamin D a 98,89 por 1.000 habitantes de calcio. Las tasas de calcio, fósforo, hormona paratiroidea en algunas áreas fue 30, 100 y 340 veces más alta respecto a otras. Hormona paratiroidea y 25-hidroxivitamina D fueron más solicitadas significativamente en hospitales con gestión privada. También hubo diferencias en fósforo, hormona paratiroidea y 25-hidroxivitamina D solicitas entre distintas regiones de España. Discusión: La alta variabilidad observada es difícil de explicar por las diferencias de las características de los pacientes. Dependiendo de la región podría haber una infra solicitud para la detección del hiperparatiroidismo primario.

La diabetes mellitus experimental produce aumento en la expresión de iNOS y altera la vía paracelular de la absorción intestinal de calcio / Experimental diabetes mellitus produces increased iNOS expression and alters the paracellular pathway of intestinal calcium absorption

Previamente hemos demostrado que la diabetes mellitus tipo 1 experimental (D.m.1) inducida por estreptozotocina (STZ) produce estrés oxidativo intestinal en las primeras etapas de la enfermedad, lo que conduce a la inhibición de la absorción intestinal de Ca+2, alterando la vía transcelular del transporte del catión. El objetivo de este trabajo fue estudiar la vía paracelular del transporte del Ca+2 y analizar si la D.m.1 induce estrés nitrosativo a nivel duodenal. Se utilizaron ratas Wistar machos a las que se inyectaron 60 mg STZ/kg de peso corporal; se sacrificaron a los 30 días postratamiento. Se determinó la expresión génica y proteica de claudina 2 y 12, proteínas involucradas en el transporte paracelular del Ca+2. En la mucosa duodenal se determinó el contenido de óxido nítrico (NO) y la expresión proteica de óxido nítrico sintasa inducible (iNOS). Los resultados revelaron que la expresión génica de claudina 2 en las ratas diabéticas fue más del doble en comparación con la de los controles, mientras que la expresión génica de claudina 12 fue similar en ambos grupos. La expresión proteica de claudina 2 y 12 aumentó en las ratas diabéticas. El contenido de NO fue similar en ambos grupos; sin embargo, la expresión proteica de iNOS fue mayor en las ratas diabéticas en comparación con la de las ratas controles. En conclusión, la D.m.1 experimental se acompaña de estrés oxidativo y de aumento en la expresión proteica de iNOS, alterándose la vía paracelular de absorción de Ca+2 como un mecanismo compensatorio. (AU)

We have previously shown that experimental type 1 diabetes mellitus (D.m.1) produced by streptozotocin (STZ) in rats causes intestinal oxidative stress in the early stages of the disease, which leads to the inhibition of intestinal Ca2+ absorption, altering the transcellular Ca2+ pathway. The aim of this work was to study the paracellular Ca2+ pathway and analyze if D.m.1 induces duodenal nitrosative stress. The animals were assigned to two groups: 1) control rats, and 2) STZ-induced diabetic rats (60 mg/kg b.w.). Rats were sacrificed 30 days after induction of diabetes. The gene and protein expression of claudin 2 and 12, proteins involved in paracellular Ca2+ pathway, was determined as well as the nitric oxide (NO) content and protein expression of iNOS in rat duodenum mucosa. The results revealed that claudin 2 expression was more that double in diabetic rats compared to control rats at 30 days, while the gene expression of claudin 12 was similar in both groups. The protein expression of claudin 2 and 12 increased in the diabetic rats. NO content was similar in both groups, but the iNOS protein expression was enhanced in diabetic rats. To conclude, the experimental type I D.m.1 is accompanied by duodenal oxidative stress, increase iNOS protein expression and alteration of the paracellular Ca2+ pathway as a compensatory mechanism. (AU)

Efecto de la suplementación con vitamina D en monodosis en niños con parálisis cerebral: Estudio preliminar controlado y aleatorizado / Effect of supplementation with a single dose of vitamin D in children with cerebral palsy: Preliminary randomised controlled study

Introducción: Los niños con parálisis cerebral (PC) tienen mayor riesgo de deficiencia de vitamina D (VD). Aunque existen bastantes estudios sobre VD en PC, hay limitada información sobre suplementación con VD en estos pacientes. Objetivo: Evaluar el efecto de la suplementación con VD en monodosis en las concentraciones plasmáticas de 25-hidroxi-vitamina-D (25OHD) en niños con PC. Pacientes y método: Estudio controlado, prospectivo y aleatorizado. Se estudiaron 30 niños chilenos (19 varones) con PC, mediana de edad de 9,9 años (6,2-13,5). Se registraron las variables clínicas y bioquímicas incluyendo 25OHD (tiempo 0 y 8 semanas). El grupo suplementado (S) recibió 100.000 UI D3 oral (tiempo 0), comparado con el grupo placebo (P). Resultados: Entre las características clínicas destaca: gastrostomizados (60%), desnutrición (30%), postración (93,3%), uso de antiepilépticos (70%) y uso de antiepilépticos inductores del metabolismo de VD (43,3%). Las mediciones basales de variables bioquímicas fueron normales. La 25OHD fue insuficiente en 4/30 y deficiente en 6/30. No hubo asociación de 25OHD con las variables estudiadas. Completaron el estudio 8 pacientes en el grupo S y 10 en el P. En ambos grupos no se observaron diferencias significativas en las variables basales. A las 8 semanas la calcemia, la fosfemia y la fosfatasa alcalina fueron normales en ambos grupos, la 25OHD en el grupo P fue normal en 6/10 e insuficiente + deficiente en 4/10 y normal en 8/8 en el grupo S (test exacto de Fisher, p = 0,07). Conclusiones: Una monodosis de 100.000 UI de VD podría normalizar las concentraciones de 25OHD en niños con PC. Se necesitan más estudios para confirmar estos resultados.

Introduction: Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients. Objective: To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP. Patients and method: Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group. Results: Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bedridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient + deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P = .07). Conclusions: A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results.

Vitamin D deficiency in risk groups living in tropical curaçao / Deficiencia de vitamina D en los grupos de riesgo de curazao tropical

OBJECTIVE: Curaçao (12 degrees 10N, 69 degrees 0W) is characterized by whole year abundant sunshine (8-10 hours/day). We challenged the automatic assumption that people living in tropical countries do not have a high risk of vitamin D deficiency, and investigated the vitamin D status in a tropical environment. METHODS: For this, we selected fiftytwo elderly people with little or no exposure to direct sunlight [median 84 (60-96) years; 34 females, 18 males] and who were cared for by community nurses or lived in retirement or nursing homes. Furthermore, six rehabilitating orthopaedic patients [median 72 (38-90) years; one female, five males] were included. Serum 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and creatinine were measured. Those exhibiting elevated creatinine, PTH or both had their 1,25dihydroxyvitamin D [1,25(OH)2D] examined. RESULTS: Serum levels of 25(OH)D below 25, 50 and 75 nmol/L were detected in, respectively, seven (12%), 22 (38%) and 48 (83%) of the fiftyeight persons. Four persons had combined high creatinine and PTH, and low 1,25(OH)2D, which was not known by their caregivers. CONCLUSION: Abundant sunshine outdoors is no guarantee for vitamin D sufficiency. More attention is needed for vitamin D deficiency in risk groups living in tropical areas and elderly persons with poor kidney function.

OBJETIVO: Curazao (12 grados 10N, 69 grados 0W) se caracteriza por su abundante luz solar durante todo el año (8-10 horas/día). Ponemos en duda la suposición automática de que los habitantes de países tropicales no poseen un alto riesgo de deficiencia de vitamina D, e investigamos los niveles de vitamina D en un ambiente tropical. MÉTODOS: Para ello, seleccionamos a cincuenta y dos personas de avanzada edad [mediana 84 (60-96) años; 34 mujeres, 18 hombres] con poca o ninguna exposición directa a la luz solar, cuidados por enfermeras comunitarias o que vivían en hogares de ancianos o casas de retiro. Además, se incluyeron seis pacientes bajo rehabilitación ortopédica [mediana 72 (38-90) años; una mujer, cinco hombres]. Se les realizaron las siguientes mediciones: 25(OH)D en suero, calcio, fosfato, hormona paratiroidea (HPT), y creatinina. A todos aquellos que mostraron niveles elevados de creatinina, de HPT, o de ambas, se les realizó un examen de 1,25dihidroxivitamina D [1,25(OH)2D]. RESULTADOS: Se detectaron niveles séricos de 25(OH)D por debajo de 25, 50 y 75 nmol/L en siete (12%), 22 (38%) y 48 (83%) de las cincuenta y ocho personas, respectivamente. Cuatro personas presentaron una combinación de elevada creatinina y HPT, y bajo 1,25(OH)2D, datos desconocidos para sus cuidadores. CONCLUSIÓN: La abundancia de luz solar exterior no es garantía de suficiencia de vitamina D. Se necesita prestar mayor atención a la deficiencia de vitamina D en los grupos de riesgo que viven en áreas tropicales, así como a las personas de edad avanzada con pobre función renal.

Serum 25-hydroxyvitamin D and biochemical markers of bone metabolism in patients with juvenile idiopathic arthritis

Our objective was to evaluate the concentrations of serum 25-hydroxyvitamin D [25(OH)D], serum calcium, serum phosphorus, alkaline phosphatase, and parathormone (PTH) in patients with polyarticular juvenile idiopathic arthritis (JIA) and to associate them with disease duration and activity, bone mineral density and use of medications. In a cross-sectional and controlled study, 30 patients with polyarticular JIA were evaluated and compared to 30 healthy individuals matched for age and gender. Clinical status, anthropometry, laboratory markers in both patients and controls, and bone mineral density, only in the patients, were measured. Of the 30 patients included in the study, 23 (76.7%) were female and 16 (53.3%) non-Caucasian; mean age was 14 years (range = 4 to 20 years). Mean disease duration was 5 years (range = 1 to 12 years). The mean concentrations of serum albumin-corrected calcium (9.04 ± 0.41 mg/dL) and alkaline phosphatase (153.3 ± 100.1 IU) were significantly lower in patients with JIA than in controls (P < 0.0001 and P = 0.001, respectively). No differences in 25(OH)D, PTH or serum phosphorus were observed between JIA and control subjects. Regarding 25(OH)D concentration, 8 patients (26.7%) and 5 controls (16.7%) had 25(OH)D concentrations compatible with deficiency (lower than 20 ng/mL) and 14 patients (46.7%) and 18 controls (60%) had concentrations compatible with insufficiency (20-32 ng/mL). These values were not associated with disease activity, use of medications or bone mineral density. We observed a high frequency of 25(OH)D insufficiency and deficiency in the study sample. The compromised bone metabolism emphasizes the importance of follow-up of JIA patients.

Effectiveness of an i-PTH Measurement in Predicting Post Thyroidectomy Hypocalcemia: Prospective Controlled Study

PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy. The purpose of this study was to determine whether measurement of intact parathyroid hormone (i-PTH) level in thyroidectomy patients could predict hypocalcemia. MATERIALS AND METHODS: We performed a prospective study of patients undergoing total thyroidectomy. Serum concentration of i-PTH, total calcium (Ca), ionized calcium (Ca2+), phosphate (P), magnesium (Mg), and albumin were measured preoperatively and at 0 hour, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours postoperatively. RESULTS: 108 patients were recruited to the study. A total of 50 patients (46%) experienced hypocalcemia. The serum i-PTH concentration was linearly related to the time of measurement, while concentrations of P, Mg, albumin, Ca, and Ca2+ were not. We compared odds ratios, and found that the concentration of i-PTH at 6 hours post operation was the most closely related to the occurrence of hypocalcemic symptom. On ROC analysis using i-PTH level at 6 hours, an i-PTH level of 10.6 mg/dL was found to maximize both sensitivity and specificity at the same time point. CONCLUSION: We found that i-PTH was a predictor of hypocalcemia, and that the earliest predictor of hypocalcemic symptoms was an i-PTH concentration lower than 10.6 mg/dL obtained 6 hours after total thyroidectomy.

Effects of a Face-to-face Self-management Program on Knowledge, Self-care Practice and Kidney Function in Patients with Chronic Kidney Disease before the Renal Replacement Therapy

PURPOSE: The purpose of this study was to examine the effects of a face-to-face self-management educational program on knowledge, self-care practice and kidney function in patients with chronic kidney disease (CKD) before kidney replacement therapy. METHODS: This study employed a nonequivalent control group, non-synchronized design. Data were collected from 61 patients with CKD visiting an outpatient department of nephrology in a university hospital in Seoul, South Korea. The experimental group (n=31) took the pre-test, then after 3 weeks, face-to-face education and individualized consultation (1st intervention), after a week of self-practice, the 1st post-test, followed by re-enforcement education and consultation (2nd intervention), and 4 weeks later, the 2nd post-test. The control group (n=30) took the pre-test and post-tests at 4 and 8 weeks. RESULTS: Scores for knowledge of CKD and self-care practice over time improved significantly in the experimental group compared to the control group. Kidney function did not improve significantly in the experimental group. CONCLUSION: Health care providers can identify various and individualized needs, and provide effective education and consultation through face to face self-management for patients with chronic irreversible illnesses. Nurses can coordinate for these program by designing and providing systematic and effective education.

Vitamin D status in patients with Behcet's Disease

OBJECTIVES: This study investigated the serum 25-hydroxyvitamin D levels of patients with Behcet's Disease. DESIGN AND METHODS: Thirty-two patients with Behcet's Disease and 31 matched healthy controls were enrolled in this study. The erythrocyte sedimentation rate (ESR) and the levels of C-reactive protein (CRP), serum 25-hydroxyvitamin D, calcium (Ca), phosphate (P), and total alkaline phosphatase (ALP) were measured in both groups. RESULTS: There were no significant differences between the two groups regarding demographic data. The serum 25-hydroxyvitamin D levels of patients and controls were 13.76 (range: 4.00-35.79) and 18.97 (range: 12.05-36.94) ng/ml, respectively. In patients with Behcet's Disease, 25-hydroxyvitamin D values were significantly lower than those of the healthy controls (p<0.001). Serum Ca, P, and ALP levels were similar in both groups. Serum ESR and CRP levels were significantly higher in patients than controls (p<0.05). There was no correlation between 25-hydroxyvitamin D levels and age, body mass index (BMI), disease duration, ESR, or CRP levels. Multivariate regression analysis parameters showed that smoking, alcohol intake, and use of colchicine were the main predictors of 25-hydroxyvitamin D levels. Of the parameters studied, the largest impact was due to colchicine therapy (p<0.001). We did not find a significant relationship between the use of corticosteroids and 25-hydroxyvitamin D levels. CONCLUSION: Our results suggest that serum 25-hydroxyvitamin D levels are decreased in patients with Behcet's Disease. Smoking, alcohol intake, and use of colchicine appear to affect vitamin D levels.

Serum and urinary calcium in stone formers and non-stone formers

Geographical variation in the rates of kidney stones has been observed for many years. Pakistan is situated in stone belt. Calculus diseases is endemic in Pakistan, perhaps the incidence in Pakistan is highest in the world. To evaluate etiology and biochemical risk factors [inorganic phosphate] in the Peshawar. Study was conducted at LHR and Hayatabad Hospitals of Peshawar for the period of nine months. Two hundred patients and same number of controls were selected. The mean value of mean inorganic phosphate in non stone formers were less than that of stone formers. The mean of urinary inorganic phosphate excretion in stone formers was greater than that of non-stone formers. We conclude that inorganic phosphate is an independent risk factor for renal stone formation

Can calcium, phosphate, calcium phosphate product and intact parathyroid hormone levels be appropriately controlled in dialysis patients?

To review the target levels of calcium [Ca], phosphate [P], calcium phosphate products [Ca x P] and intact parathyroid hormone [iPTH] levels in patients undergoing hemodialysis [HD] and peritoneal dialysis [PD] and compare them with the Kidney Disease Outcome Quality Initiative [K/DOQI] recommendations. Three hundred and fifty-seven patients who had been undergoing dialysis for more than 3 months were included. Patients who had undergone a parathyroidectomy were excluded. The levels of Ca, P, iPTH and Ca x P were monitored for the last 3 months. The Ca and P levels were measured by standard techniques, and iPTH was assessed by the intact molecule assay. Between HD and PD patients, there was no statistically significant difference for age, duration of dialysis or primary disease causing end-stage renal disease. The percentage of patients whose serum Ca, P, Ca x P product and iPTH were within K/DOQI recommended target ranges were 61.2, 66.4, 82.2 and 28.3% in HD patients, and 56.3, 60.6, 85.9 and 22.5% in PD patients, respectively. When all results for each group - HD and PD - were analyzed, 12.8% of patients had all 4 markers within the target range. Achieving target ranges of mineral markers is important in dialysis patients, but reaching K/DOQI target levels is difficult. Hence, physicians should be careful in using P binders and vitamin D analogs to achieve the normal ranges

A novel GNAS mutation in an infant boy with pseudohypoparathyroidism type Ia and normal serum calcium and phosphate levels / Mutação nova no GNAS em um menino com pseudo-hipoparatireoidismo tipo Ia e dosagens séricas normais de cálcio e fósforo

The objective of this study was to describe a new mutation in GNAS in a family with pseudohypoparathyroidism type Ia (PHP Ia), a rare osteometabolic disease. An 8-month-old boy was seen by an Endocrinologist due to obesity and low growth velocity. Noteworthy, his mother exhibited typical Albright hereditary osteodystrophy (AHO) phenotype. The clinical diagnosis of PHP Ia was suspected. The GNAS coding region from mother and son was amplified and directly sequenced. A novel heterozygous missense mutation (c.673T>C) was identified in exon 5 in both patients. In this family, the mother's clinical picture was the clue for the son's diagnosis. Molecular analysis of GNAS confirmed the diagnosis of PHP Ia in both patients and the child's early diagnosis was possible. Moreover, this novel missense substitution expands the spectrum of GNAS mutations associated with this disorder and allows for genetic counseling of this family.

O objetivo deste estudo foi descrever uma nova mutação no GNAS em uma família com pseudo-hipoparatireoidismo tipo Ia (PHP Ia), doença osteometabólica rara. Um garoto de oito meses foi visto por um endocrinologista por obesidade e baixa velocidade de crescimento. Chamava a atenção o fato de sua mãe apresentar fenótipo típico da osteodistrofia hereditária de Albright (OHA). O diagnóstico clínico de PHP Ia foi suspeitado. A região codificadora do GNAS da mãe e do filho foi amplificada e submetida ao sequenciamento direto. Uma nova mutação missense em heterozigose (c.673T>C) foi identificada no éxon 5 em ambos. O quadro clínico materno foi a pista para o diagnóstico do filho. A análise molecular do GNAS confirmou o diagnóstico de PHP Ia nos dois pacientes possibilitando o diagnóstico precoce da criança. Além disso, essa nova substituição missense expande o espectro de mutações no GNAS associadas a essa doen­ça e permite o aconselhamento genético nesta família.