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)

Hipercalciuria idiopática ¿se pueden evitar los diuróticos? / Idiopathic hypercalciuria: can the diuretics be avoided?

La hipercalciuria idiopática se define como la excreció;n de calcio superior a 220 y 300 mg/día en mujeres y hombres respectivamente o bien mayor a 4 mg/kg peso. En mujeres con osteoporosis se observa en el 19% de los casos, mientras que en litiasis renal varía entre el 50 y 70%. Seleccionamos 206 pacientes hipercalció;ºricos, de nuestra base de datos, con y sin litiasis renal, a los que se les había indicado una dieta restringida. Luego los dividimos, de acuerdo a la respuesta, en dieta dependiente y dieta independiente. De estos solo consideramos 122 pacientes con diagnó;sticos de hipercalciuria dieta-dependiente (105 mujeres y 17 hombres), que fueron seguidos con control dietario (800 mg de calcio, alrededor de 1 g de proteínas animales y < 100 mEq de sodio diarios). No se consideró; la aparició;n de cálculos, o la recurrencia de los mismos, como tampoco el compromiso ó;seo. Luego de una media de 17 meses todos tenían controlada la calciuria e incluso hubo 16 (13%) que luego de 42 meses de seguimiento persistían normocalció;ºricos solo con dieta. Concluimos que es fundamental la divisió;n de las hipercalciurias, segó;ºn su respuesta a una dieta restringida, con el fin de evitar o postergar el uso de diuró;©ticos y sus efectos adversos, con una administració;n adecuada de la dieta.

Idiopathic hypercalciuria is defined as calcium excretion greater than 220 and 300 mg / day in women and men respectively, or greater than 4 mg / kg body weight. In women with osteoporosis it is observed in 19% of cases, while in kidney stones cases varies between 50 and 70%. We selected 206 hypercalciuric patients from our database, with and without renal lithiasis, to whom a restricted diet had been indicated. We divided them, according to the response, into a dependent diet and an independent diet. We considered 122 patients with diagnosis of hypercalciuria diet dependent (105 women and 17 men), which were followed with dietary control (800 mg of calcium, around 1 g of animal proteins and < 100 mEq sodium a day). The appearance of stones, or the recurrence of stones, was not considered, nor was bone involvement. After an average of 17 months, everyone had their calciuria controlled and there were even 16 (13%) who, after 42 months of follow-up, continued to be normocalciuric only on a diet. We conclude that the division of the hypercalciurias is fundamental, according to their response to a restricted diet, in order to avoid or postpone the use of diuretics and its adverse effects, with an adequate management of the diet.

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

ABSTRACT Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

Effect of vitamin D supplementation on 24-hour urine calcium in patients with calcium Urolithiasis and vitamin D deficiency

ABSTRACT Purpose: Hypercalciuria is one of the risk factors for calcium kidney stone formation (the most common type of urinary stones). Although vitamin D deficiency is prevalent among urolithiasis patients, the effect of vitamin D supplementation on urine calcium in these patients is still unclear. Materials and Methods: In this retrospective study, medical and laboratory tests records of 26 patients with recurrent calcium kidney stones and vitamin D deficiency treated with 50000IU vitamin D per week for 8-12 weeks were analyzed. The changes in 24-hour urine calcium (24-h Ca), serum 25-hydroxyvitamin D (25 (OH) D), serum parathormone (PTH), other 24-hour urine metabolites and calculated relative supersaturations of calcium oxalate (CaOxSS), calcium phosphate (CaPSS) and uric acid (UASS) were assessed. Moreover, correlations between changes in 24-h Ca and other aforementioned variables were assessed. Results: Serum 25 (OH) D and 24-h Ca increased after vitamin D supplementation, while serum PTH decreased (p < 0.001, for all analyses). The levels of 24-hour urine sodium and urea increased significantly (p = 0.005 and p = 0.031, respectively). The levels of CaOxSS and CaPSS increased, but the changes were not significant (p = 0.177, and p = 0.218, respectively). There were no correlations between the changes in 24-h Ca and serum 25 (OH) D or PTH. Conclusions: The result of current study suggests that although urine Ca increased in vitamin D supplemented patients, this increase was not associated with the increase in serum vitamin D and may be due to other factors such as dietary factors. Further randomized clinical trials considering other factors associated with urine Ca are warranted.

Seasonal variations in urinary calcium, volume, and vitamin D in kidney stone formers

ABSTRACT Objectives: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. Materials and Methods: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. Results: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. Conclusions: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: a perspective for disease prevention

ABSTRACT Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking. Objective: To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis. Materials and Methods: We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar's test for categorical variables. Significance was set at 5%. Results: Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24-hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057). Conclusions: P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi.

Índice calcio-creatinina en una muestra matutina de orina para la estimación de hipercalciuria asociada con hematuria no glomerular observada en las edades infanto-juveniles / Calcium-creatinine ratio in a morning urine sample for the estimation of hypercalciuria associated with non-glomerular hematuria observed in children and adolescents

Resumen Introducción: La hipercalciuria suele revelarse durante el diagnóstico diferencial de la hematuria que acompaña a la litiasis renal. La exactitud diagnóstica de la excreción urinaria de calcio puede afectarse por las insuficiencias asociadas con la colección de orina de 24 horas. En este estudio se evaluó la utilidad diagnóstica del índice calcio/creatinina (ICaCre) en la estimación de la hipercalciuria asociada con hematuria y litiasis renal. Método: Se calculó el ICaCre de las concentraciones urinarias de calcio (mmol/l) y creatinina (µmol/l) en una alícuota de colección de 24 horas de orina en 169 niños y adolescentes atendidos por hematuria no glomerular (HNG) o litiasis renal (LR). La calciuria de 24 horas > 4.0 mg/kg en 24 horas se distribuyó según la presencia de HNG o LR. Resultados: El ICaCre promedio fue de 0.2 ± 0.1 mg/mg. La excreción urinaria de calcio estimada del ICaCre fue significativamente superior a la obtenida en colección de orina de 24 horas (p < 0.05). Los métodos de determinación de la calciuria concordaron en la frecuencia de hipercalciuria (ICaCre 39.5% vs. colección de 24 horas 32.1%; p > 0.05). Según la presencia de HNG o LR, la hipercalciuria se distribuyó de la siguiente manera: no HNG + no LR: 59%; no HNG + LR: 60% (diferencia: +1.0%); HNG + no LR: 68.2% (diferencia: +9.2%); HNG + LR: 73.3% (diferencia: +14.4%). Conclusiones: El ICaCre para estimar la excreción urinaria de calcio puede ser efectivo en el estudio de la hipercalciuria asociada con HNG y LR.

Abstract Background: Hypercalciuria might be revealed during the differential diagnosis of hematuria accompanying renal lithiasis (RL). In spite of this, diagnostic accuracy of calcium urinary excretion might be affected by incomplete 24-hour urine collections. In the present study, the diagnostic utility of calcium/creatinine (ICaCre) index for determining hypercalciuria associated with non-glomerular hematuria (NGH) and RL was assessed. Method: ICaCre (mg/mg) index was calculated from calcium (mmol/l) and creatinine (µmol/l) concentrations in an aliquot from a 24-hour urine collection in 169 children and adolescents with NGH or RL. Calciuria values > 4.0 mg/kg in 24 hours were distributed according to the presence of NGH or RL. Results: Mean ICaCre index was 0.2 ± 0.1 mg/mg. Calciuria values estimated from ICaCre were statistically higher to those from 24-hour urine collection (p < 0.05). The frequency of hypercalciuria was independent from the measurement method (estimated from ICaCre 39.5% vs. 24 h collection 32.1%; p > 0.05). Hypercalciuria distribution was as follows: no NGH + no RL: 59.0%; no NGH + RL: 60.0% (∆ = +1.0%); NGH + no RL: 68.2% (∆ = +9.2%); NGH + RL: 73.3% (∆ = +14.4%). Conclusions: The use of ICaCre index for determining calcium urine excretion might be effective in the study of hypercalciuria associated with NGH and RL.

Metabolic investigation in patients with nephrolithiasis / Investigação metabólica em pacientes com nefrolitíase

ABSTRACT: Objective: To evaluate the prevalence of metabolic disorders associated with nephrolithiasis in a female population. Methods: A retrospective study on 1,737 patients with evidence of recent formation of renal stones, being 54% females. The laboratory investigation consisted of at least two samples of blood and 24-hour urine to assess calcium, uric acid, citrate and creatinine levels, qualitative cystinuria, urinary pH following fasting and 12-hour water restriction, urine culture, serum creatinine and parathyroid hormone. Results: The most frequent alterations were hypercalciuria (40.9%), urinary tract infection (23.2%), hypocitraturia (22.4%), low urinary volume (20.5%) and hyperuricosuria (16%). Conclusion: The most frequent metabolic alterations in females were hypocitraturia, urinary tract infection, low urinary volume and hyperuricosuria.

RESUMO Objetivo: Avaliar a prevalência dos distúrbios metabólicos associados à nefrolitíase em uma população feminina. Métodos: Foi realizado um estudo retrospectivo em 1.737 pacientes com evidência de formação recente de cálculos renais, sendo 54% do sexo feminino. A avaliação laboratorial constou de duas ou mais amostras de sangue e urina de 24 horas com dosagens de cálcio, ácido úrico, citrato e creatinina cistinúria qualitativa, pH urinário em jejum e restrição hídrica de 12 horas, urocultura, creatinina e paratormônio séricos. Resultados: As alterações mais encontradas foram hipercalciúria (40,9%), infecção do trato urinário (23,2%), hipocitratúria (22,4%), baixo volume urinário (20,5%) e hiperuricosúria (16%). Conclusão: As alterações metabólicas mais frequentes na população feminina foram hipocitratúria, infecção do trato urinário, baixo volume urinário e hiperuricosúria.

Bone turnover after bariatric surgery

ABSTRACT Objective The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. Subjects and methods This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. Results Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. Conclusion The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.

Hipercalcemia hipocalciurica familiar en una paciente con mutación del receptor de calcio: forma atípica de presentación y tratamiento con cinacalcet / Familial hypocalciuric hypercalcemia in a patient with calcium-sensing receptor mutation: atypical clinical presentation and treatment with cinacalcet

El hiperparatiroidismo familiar y la hipercalcemia hipocalciúrica familiar (HHF) constituyen un subgrupo heterogéneo de trastornos con herencia mendeliana, que representan en conjunto el 5% de las causas de hipercalcemia PTH dependiente. La HHF se asocia con mutaciones del gen del receptor sensor de calcio (CaSR). Esta entidad se manifiesta, en la mayoría de los casos, con la presentación asintomática y familiar de hipercalcemia e hipocalciuria y valores elevados o normales de hormona paratiroidea (PTH). Los avances en la biología molecular han contribuido al diagnóstico, evaluación del fenotipo de cada entidad y elección del tratamiento. Se describe el caso de una paciente con hipercalcemia estudiada a partir de una tumoración de cuello asociada con una glándula paratiroides quística. Luego de un exhaustivo proceso diagnóstico se halló en el estudio genético una mutación inactivante en el gen CaSR. Teniendo en cuenta la presencia de la relación clearance calcio/clearance creatinina <0,01 y la falta de respuesta al tratamiento quirúrgico, se consideró la entidad de HHF con forma de presentación atípica. La paciente, sin tratamiento, presentaba un progresivo incremento de la calcemia luego de la cirugía de las glándulas paratiroides, que no se controló con el uso de bifosfonatos y evolucionó con episodios de mareos y desmayos frecuentes sin causa neurológica o cardiovascular detectada. Por lo tanto, se inició el tratamiento con cinacalcet, con el cual se obtuvo una buena respuesta terapéutica: descenso de la calcemia y mejoría de la sintomatología luego de un año de su comienzo. El cinacalcet es una herramienta terapéutica de importancia en estos raros casos de HHF. (AU)

Familial hyperparathyroidism including familial hypocalciuric hypercalcemia (FHH) is an heterogeneous subgroup of disorders with Mendelian inheritance, that account for 5% of PTH dependent hypercalcemia. FHH is associated with mutations of the calcium receptor (CaSR) gene. This entity is manifested by hypercalcemia with hypocalciuria and high or normal levels of parathyroid hormone (PTH) generally asymptomatic and with familial presentation. Advances in molecular biology have contributed to the diagnosis, evaluation of the phenotype of each entity and the choice of treatment. We describe a patient with hypercalcemia diagnosed following the finding of a neck tumor associated with cystic parathyroids. After an exhaustive diagnostic process, an inactivating mutation in the CaSR gene was found. Considering the presence of a ratio clearance calcium / clearance creatinine <0.01 and the lack of response to surgical treatment, HHF entity with atypical presentation was considered. The patient exhibited progressive increase in serum calcium following parathyroid surgery, which was not controlled with the use of bisphosphonates and evolved into episodes of frequent dizziness and fainting, without neurological or cardiovascular causes. Treatment with cinacalcet was initiated, with a good therapeutic response. The use of cinacalcet is a useful therapeutic tool in these rare cases of FHH. (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.

Evaluation of preoperative ultrasonographic and biochemical features of patients with aggressive parathyroid disease: is there a reliable predictive marker?

ABSTRACT Objective Parathyroid cancer (PC) represents < 1% of cases of PHPT. Tumors demonstrating atypical histopathologic features and don’t fulfill criteria for carcinoma are classified as atypical adenomas (APA). The purpose of this study was to determine a biochemical or ultrasonographic feature that can predict aggressive disease requiring more extensive surgery and closer follow-up. Subjects and methods Twenty eight patients operated for PHPT and diagnosed with atypical adenoma (23 patients) or carcinoma (5 patients) were enrolled in this study. The control group consisted of 102 patients operated between the same dates and diagnosed with classical PA. Classical adenomas, atypical adenomas, and carcinomas were compared according to their biochemical and ultrasonographic parameters. Results Serum Ca levels were significantly higher in the PC group compared with the APA and classical PA groups. Serum median PTH, Serum ALP and UCa was significantly higher in the APA and carcinoma groups compared to the classical PA group. ROC analysis was made to determine the best cut off values for predicting aggressive disease were 12.45 mg/dL, 265.05 pg/mL, 154.5 IU/l, 348.5 mg/day and 21.5 mm for Ca, PTH, ALP, UCa and the adenoma diameter, respectively. Multivariate analysis showed that serum Ca, ALP and isoechoic/cystic appearance were independent predictors for aggressive disease. Conclusion Preoperatively high PTH, ALP, and UCa levels and large lesions with isoechoic or cystic appearances may be predictive of atypical adenoma or carcinoma in patients being evaluated for PHPT. In such cases, surgeons may prefer en bloc parathyroidectomy to minimally invasive surgery.

Perfil de riesgo litogénico en pacientes con urolitiasis en Paraguay / Lithogenic risk in patients from Paraguay with urolithiasis

The lithogenic risk profile is a graphical representation of metabolic factors and urinary saturation involved in the stone formation with their respective critical values. Aim: To determine the lithogenic risk profile in patients with urolithiasis. Material and Methods: Personal data such as anthropometric, history of diseases and family history of urolithiasis were recorded. Different compounds acting as promoters or inhibitors of crystallization were measured in serum and urine samples, and the data obtained were used to calculate urinary saturation using Equil software. Results: We included 30 men and 43 women with a median age of 45 (34-54) years. Overweight and family history of urolithiasis was reported in 63 and 32% respectively. Crystallization risk was detected in 74% of participants. The most common urinary abnormalities were hypocitraturia in 48% and hypercalciuria in 40%. Conclusions: The lithogenic profile revealed urinary saturation compatible with crystallization risk in 74% of the studied patients.

Hiperparatiroidismo primario normocalcémico

Presentamos las características clínicas, bioquímicas y densitométricas de 35 pacientes con hiperparatiroidismo primario (HPP) normocalcémico, que se caracteriza por un nivel elevado de hormona paratiroidea intacta (PTHi) con el calcio sérico y iónico persistentemente normales, una vez descartadas posibles causas de hiperparatiroidismo secundario. Del total, 30 fueron mujeres (90%) y 5 varones (10%). Se seleccionó un grupo control de 55 pacientes con hiperparatiroidismo primario hipercalcémico: 51 mujeres (93%) y 4 varones (7%). El promedio de edad al diagnóstico de HPP normocalcémico fue de 61.4 ± 11.7 años y del HPP hipercalcémico de 56.4 ± 11.3 años. Además de las diferencias esperables de la calcemia, el calcio iónico, el fósforo y la calciuria de 24 horas, no encontramos cambios significativos en el resto de las variables bioquímicas. Tampoco encontramos diferencias en los valores densitométricos, la presencia de osteopenia u osteoporosis y el número de fracturas entre ambos tipos de HPP. Sí hubo una diferencia significativa en la presencia de litiasis renal entre el HPP normocalcémico (11.4%) vs el HPP clásico (49.1%), p < 0.0005, en parte vinculada a la presencia de hipercalciuria en el HPP clásico. Dos de los 35 pacientes con HPP normocalcémico evolucionaron al HPP hipercalcémico durante un seguimiento de 4 años. Nuestros resultados apoyan la hipótesis que el HPP normocalcémico podría ser una forma temprana del HPP clásico, teniendo ambos similares repercusiones clínicas a nivel renal y óseo.

This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

Influence of clinical therapy and nutritional counseling on the recurrence of urolithiasis

PURPOSE: To evaluate the influence of combined clinical therapy and nutritional guidance on the recurrence of urolithiasis. METHODS: From our registry of patients with recurrent urolithiasis we selected 57 who had at least 5-years of follow-up. We collected 24h urine samples in order to analyze Ca, Na, uric acid, citrate, oxalate, and Mg concentrations and to assess urine volume. Patients filled out a clinical questionnaire before treatment, and abdominal radiographs and/or ultrasound were performed both before treatment and during the follow-up period. During follow-up, specific and individualized dietary advice was given based on the individual's metabolic disorders. Patients also received specific pharmacological treatment for their metabolic alterations. Outcome measures were metabolites in urine and the urolith recurrence rate. Pre- and post- intervention values were compared using tests as appropriate. RESULTS: Fifty six of the patients were male and the majority of patients were overweight. The mean BMI was 27 kg/m2. Urinary excretion of calcium, uric acid and sodium decreased significantly over the five year follow-up period. The number of uroliths that formed during the 5-year follow-up also decreased significantly compared to pre-treatment values. CONCLUSION: Individualized dietary advice combined with pharmacological treatment significantly reduces long-term urolithiasis recurrence. .

Tratamiento de la osteoporosis grave con teriparatide / Severe osteoporosis treatment with teriparatide

El objetivo de este trabajo retrospectivo fue evaluar el tratamiento de la osteoporosis grave con teriparatide (PTH) y comparar nuestros resultados con los publicados en la literatura médica. Se incluyeron cuarenta y seis pacientes, cuarenta y dos mujeres y cuatro varones, edad: 69.15 ± 9.43 años. Seis eran vírgenes de tratamiento y cuarenta tratados previamente con bisfosfonatos. Treinta y dos pacientes habían tenido 93 fracturas de las cuales 86 vertebrales. Cuarenta y seis recibieron PTH 6 meses, 29 pacientes durante 12 meses y 20 completaron los 18 meses sugeridos. La densidad mineral ósea (DMO) de columna lumbar aumentó significativamente desde el primer control a los 6 meses (p < 0.0001). La DMO de cuello de fémur alcanzó un incremento significativo al final del tratamiento (p = 0.002). La osteocalcina aumentó significativamente al mes, seguido por el ß crosslaps (beta-CTx, prueba en suero) al tercer mes y la fosfatasa alcalina ósea, regresando los marcadores de recambio óseo a niveles basales a los 18 meses. Las calcemias y las calciurias no se modificaron significativamente, pero 8 pacientes tuvieron hipercalcemias leves y tres hipercalciurias asintomáticas. El tratamiento fue bien tolerado y no se registraron efectos adversos graves que requirieran suspender el tratamiento. En conclusión, la PTH es una alternativa útil y segura para el tratamiento de la osteoporosis grave. Nuestros resultados concuerdan con los previamente publicados en la literatura médica.

The primary objective of this retrospective study was to evaluate the treatment of severe osteoporosis with teriparatide (PTH) and to compare our results with those published in the literature. We included 46 patients, 42 women and four men, mean age: 69.15 ± 9.43 years. Six patients were treatment naive and forty previously treated with bisphosphonates. Thirty-two patients had had 93 fractures of which 86 vertebral. Forty-six received PTH for 6 months, twenty-nine for 12 months and twenty completed the 18 months suggested. Bone mineral density (BMD) of the lumbar spine increased significantly at the first control performed at six months of treatment (p < 0.0001), and the femoral neck BMD reached a significant increase at the end of treatment (p = 0.002). Serum osteocalcin values significantly increased from the first month of treatment, followed by ß crosslaps (beta-CTx, serum test) and bone-specific alkaline phosphatase, returning all the markers of bone turnover to baseline levels at 18 months. Serum and urinary calcium did not change significantly at any time, but 8 (17.9%) patients developed mild hypercalcemia and 3 (6.5%) asymptomatic hypercalciuria. The treatment was well tolerated and there were no serious adverse events requiring discontinuation. In conclusion, PTH is a safe and useful alternative for the treatment of primary severe osteoporosis. Our results agree with those previously reported in the literature.

Nephrocalcinosis induced by hyperoxaluria in rats

PURPOSE: To investigate nephrocalcinosis due to hyperoxaluria induced by two different inducing agents in rats. METHODS: Forty Sprague-Dawley male rats were randomly distributed into four groups: Group1 (Clinical control, n = 10); Group 2 (0.5% Ethylene Glycol + Vitamin D3, n = 10); Group 3 (1.25% Ethylene Glycol, n = 10); and Group 4 (5%Hydroxy L-proline, n = 10). Five animals from each group were euthanized after one week of follow-up (M1 Moment) and the remaining, after four weeks (M2 Moment). All animals underwent 24h urine dosages of calcium, oxalate, uric acid, citrate and serum creatinine. Histology and histomorphometric analyses were performed using Image J program in the hematoxylin-eosin stains. Calcium deposits in the renal parenchyma were quantified by PIXE technique (Proton Induced X-Ray Emission). RESULTS: 24h urinary parameters did not show any significant variations after 28 days of experiment except by hyperoxaluria that was significantly higher in Group 3. Histomorphometric analyses showed a significantly higher nephrocalcinosis in Group 2 (p<0.01). The calcium deposits in the renal parenchyma were 10 and 100 times higher in Group 2 in comparison to other groups in the M1 and M2 moments, respectively. CONCLUSION: The Group 2 (vitamin D3+Ethylene Glycol 0.5%) was the best model to induce nephrocalcinosis in rats after 28 days.

Natriuria and calciuria levels in preeclampsia: a cross-sectional study / Valores de natriúria e calciúria na pré-eclâmpsia: estudo transversal

CONTEXT AND OBJECTIVE Sodium excretion abnormalities in preeclampsia have been studied in relation to several factors. The objective of this study was to compare natriuria (mEq/24 h) and calciuria levels (mg/24 h) in preeclamptic patients. DESIGN AND SETTING An analytical cross-sectional study with a control group was conducted in the obstetric center and the high-risk pregnancy outpatient clinic at a university hospital in southern Brazil, and in a primary healthcare unit in the same city, including pregnant women with mild preeclampsia, severe preeclampsia or chronic hypertension, and women with normal pregnancies (14 patients in each group). METHOD Natriuria was measured using an ion-selective electrode in an automated clinical chemistry analyzer (Hitache 917, Roche). All the patients collected 24-hour urine, at home or at the hospital, for analysis of proteins, creatinine, calcium, sodium and uric acid. Quantitative variables with asymmetrical distribution were described using the median, minimum and maximum, and were compared using the Kruskal-Wallis test. The results were logarithmically transformed, with one-way analysis of variance (ANOVA) by ranks and then the post-hoc Tukey test, and were analyzed by means of the Spearman correlation and receiver operating characteristic (ROC) curve. The significance level used was 0.05. RESULTS There were significant differences between the groups in comparing severe preeclampsia with chronic hypertension and severe preeclampsia with controls (P < 0.0001 for both measurements). CONCLUSION Natriuria levels may be lower in preeclampsia when associated with calciuria. Natriuria assessment is an additional test for differential diagnosis of hypertensive diseases in pregnancy, but is a poor predictor when used alone. .

CONTEXTO E OBJETIVO Alterações na excreção de sódio têm sido estudadas na pré-eclâmpsia relacionadas a vários fatores. O objetivo deste estudo foi comparar natriúria (mEq/24 h) com os níveis de calciúria (mg/24 h) em pacientes pré-eclâmpticas. ESTUDO E LOCAL Estudo transversal analítico com grupo controle foi realizado no Centro Obstétrico e no Ambulatório de Gestação de Alto Risco em um hospital universitário no sul do Brasil, e na Unidade Básica de Saúde na mesma cidade, incluindo gestantes com pré-eclâmpsia leve e grave, hipertensão crônica e gestações normais, com 14 pacientes em cada grupo. MÉTODO A natriuria foi dosada através da medida de íon eletrodo seletivo, utilizando analizadores automáticos de química clínica (Hitache 917 Roche). Todas as pacientes coletaram urina de 24 h, em casa ou no hospital, para análise de proteínas, creatinina, cálcio, ácido úrico e sódio. As variáveis quantitativas com distribuição assimétrica foram descritas por mediana, mínimo e máximo, e comparadas por teste Kruskal-Wallis. Os resultados foram transformados logaritmicamente, com ANOVA one-way por ranking e, posteriormente, teste post-hoc de Tukey, e foram analisados por médias de correlações de Spearman e curva ROC (receiver operating characteristic). O nível de significância adotado foi de 0.05. RESULTADOS Foram encontradas diferenças significativas entre os grupos quando comparados pré-eclâmpsia grave com hipertensão crônica e pré-eclâmpsia grave com controles (P < 0.0001 para ambas as medidas). CONCLUSÃO Natriúria pode estar reduzida na pré-eclâmpsia ...

Calcium renal lithiasis: metabolic diagnosis and medical treatment / Litiase renal cálcica: diagnóstico metabólico e tratamento médico

Calcium renal lithiasis is a frequent condition that affects the worldwide population and has a high recurrence rate. Different metabolic changes may trigger the onset of calcium stone disorders, such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other very prevalent disorders that are associated with calcium calculi, such as arterial hypertension, obesity and loss of bone mineral density. A correct diagnosis needs to be obtained through examining the serum and urinary parameters of mineral metabolism in order to carry out adequate prevention and treatment of this condition. Once the metabolic diagnosis is known, it is possible to establish dietary and pharmacological treatment that may enable monitoring of the disease and prevent recurrence of stone formation. Some advances in treating this pathological condition have been made, and these include use of sodium alendronate in patients with calcium renal lithiasis and osteopenia/osteoporosis, or use of a combination of a thiazide with a bisphosphonate. In summary, calcium renal lithiasis often requires multidrug treatment with strict control and follow-up of patients.

Litíase renal cálcica é uma doença comum que afeta a população no mundo todo e tem alta taxa de recorrência. Diferentes alterações metabólicas podem desencadear o aparecimento de distúrbios de pedras de cálcio, como hipercalciúria, hiperoxalúria, hiperuricosúria, hipocitratúria e outros. Existem também doenças altamente prevalentes associadas à doença de cálculo de cálcio, como hipertensão, obesidade e perda de densidade óssea mineral. Para realizar prevenção e tratamento adequados, é necessário diagnóstico correto, examinando o metabolismo mineral sérico e urinário. Depois de conhecer o diagnóstico metabólico, é possível estabelecer um tratamento dietético e farmacológico que permita controlar a doença e prevenir a recorrência de cálculos biliares. Há alguns avanços no tratamento dessa doença e incluem o uso de alendronato de sódio em pacientes com nefrolitíase de cálcio e osteopenia/osteoporose, ou a combinação de um tiazídico com um bifosfonato. Em resumo, litíase renal cálcica exige, muitas vezes, um tratamento multidroga com rigorosos controle e acompanhamento de pacientes.

Random Urinary Calcium/Creatinine Ratio for Screening Hypercalciuria in Children with Hematuria

BACKGROUND: Hypercalciuria is one of the most common causes of unexplained isolated hematuria. The diagnostic methods for hypercalciuria have not yet been standardized. The aim of this study was to assess whether random urinary calcium/creatinine ratio could be used as a screening tool for hypercalciuria in children with hematuria. METHODS: This prospective study included 264 children with primary hematuria for whom both random and 24 hr urinary evaluations were performed. Pearson correlation and ROC curve were used to assess the correlations. A multiple linear regression model was used to analyze effects of age, weight, height, body mass index, and body surface area on random urinary calcium/creatinine ratio. RESULTS: There was a moderately strong correlation between random urinary calcium/creatinine ratio and 24 hr urinary calcium excretion (r=0.584, P<0.001). The most appropriate cutoff value of random urinary calcium/creatinine ratio for the estimation of hypercalciuria was 0.075 mg/mg (sensitivity, 77.8%; specificity, 64.3%; area under the curve, 0.778). Body mass index and 24 hr urinary calcium excretion significantly affected random urinary calcium/creatinine ratio with a low coefficient of determination (r2=0.380, P<0.001). CONCLUSIONS: Random urinary calcium/creatinine ratio is not suitable for screening hypercalciuria in children with hematuria. Twenty-four hour urinary analysis should be performed to diagnose hypercalciuria in children with hematuria.