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BACKGROUND: The prevalence of kidney stones in children has significantly increased in the past few decades, with concomitant increased morbidity and healthcare costs worldwide. Assessing metabolic risk factors is essential for diagnosis and specific treatment. The objective of this retrospective study is to identify the epidemiological and clinical characteristics of children under 17 years of age, as well as the metabolic risk factors of nephrolithiasis. METHODS: A total of 300 children with kidney stone disease were included to undergo several clinical tests using a standardized protocol. RESULTS: The mean age was 11.2 years, and the male:female ratio was 1.15:1.0. Biochemical abnormalities were found in 89.3% of all cases. A single urine metabolic risk factor was present in 52.6% (n = 141) of the patients, and multiple risk factors were present in 36.7% (n = 106). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 47.0% and 39.6% of these patients, respectively. Renal colic and/or unspecified abdominal pain were the most frequent forms of presentation (76.9%), followed by hematuria in 64.4% with 97.5% of stones located in the upper urinary tract. A positive family history in first-degree and second-degree relatives was found in 64.8% of boys and 61.8% of girls. CONCLUSIONS: We conclude that specific urinary metabolic risk factors can be found in most children with kidney stones, with hypercalciuria and hypocitraturia being the most common diagnoses. Graphical abstract .

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Múltiples estudios muestran la importancia de mantener niveles suficientes de vitamina D para prevenir varias enfermedades crónicas. Sin embargo, la suplementación de vitamina D sobre la calciuria es controvertida. El objetivo de este trabajo prospectivo, intervencionista, fue evaluar la respuesta de la calciuria en mujeres con hipercalciuria y normocalciuria, luego de conseguir niveles adecuados de 25 OH D. Se estudiaron 63 mujeres con hipercalciuria idiopática (9 con litiasis renal) y 50 mujeres normocalciúricas. Ambos grupos presentaron déficit/insuficiencia de 25 OH D y fueron suplementadas con vitamina D2 o D3 semanales o vitamina D3 en dosis de 100 000 UI mensuales. A todas se les midió la calciuria basal y final al alcanzar el valor de 25 OH D deseado (> 30 ng/dl). No observamos cambios significativos en los valores de la calciuria inicial y final en las que recibieron vitamina D2 o D3 semanal ni en las que recibieron dosis mensuales. Sin embargo, un subgrupo de mujeres: 19% (n = 12) de las hipercalciúricas y 12% (n = 6) de las normocalciúricas (con vitamina D semanal) aumentaron la calciuria en forma significativa. Mientras que, con dosis mensuales, un 40% (n = 4/10) de las hipercalciúricas y 44% (n = 4/9) de las hipercalciúricas con litiasis renal aumentaron la calciuria. En conclusión, niveles adecuados de 25 OH D son seguros en la mayoría de las pacientes. En aquellas que requieren dosis de carga mensuales podrían observarse aumentos de la calciuria en forma significativa con riesgo de formar cálculos renales o perder masa ósea, cuando están genéticamente predispuestas.

Several studies show the importance of serum vitamin D sufficient levels to prevent multiple chronic diseases. However, vitamin D supplementation and its effects on urine calcium excretion remain controversial. The objective of this prospective and interventional study was to evaluate urine calcium excretion in women with normal calciuria or hypercalciuria, once serum vitamin D sufficiency was achieved. We studied 63 women with idiopathic hypercalciuria, (9 with renal lithiasis) and 50 normocalciuric women. Both groups had serum vitamin D levels low (deficiency or insufficiency). Baseline urine calcium excretion was measured before being supplemented with vitamin D2 or D3 weekly or vitamin D3 100.000 IU monthly. Once serum vitamin D levels were corrected achieving at least 30 ng/ml, a second urine calcium excretion was obtained. Although in the whole sample we did not observe significant changes in urine calcium excretion according to the way of supplementation, some of those with weekly supplementation had significant higher urine calcium excretion, 19% (n = 12) of hypercalciuric women and 12% (n = 6) of the normocalciuric group. Monthly doses, also showed higher urine calcium excretion in 40% of hypercalciuric women (n = 4/10) and in 44% (n = 4/9) of the renal lithiasis hypercalciuric patients. In conclusion, different ways of vitamin D supplementation and adequate serum levels are safe in most patients, although it should be taken into account a subgroup, mainly with monthly loading doses, that could increase the calciuria significantly eventually rising renal lithiasis risk or bone mass loss, if genetically predisposed.

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Several studies show the importance of serum vitamin D sufficient levels to prevent multiple chronic diseases. However, vitamin D supplementation and its effects on urine calcium excretion remain controversial. The objective of this prospective and interventional study was to evaluate urine calcium excretion in women with normal calciuria or hypercalciuria, once serum vitamin D sufficiency was achieved. We studied 63 women with idiopathic hypercalciuria, (9 with renal lithiasis) and 50 normocalciuric women. Both groups had serum vitamin D levels low (deficiency or insufficiency). Baseline urine calcium excretion was measured before being supplemented with vitamin D2 or D3 weekly or vitamin D3 100.000 IU monthly. Once serum vitamin D levels were corrected achieving at least 30 ng/ml, a second urine calcium excretion was obtained. Although in the whole sample we did not observe significant changes in urine calcium excretion according to the way of supplementation, some of those with weekly supplementation had significant higher urine calcium excretion, 19% (n = 12) of hypercalciuric women and 12% (n = 6) of the normocalciuric group. Monthly doses, also showed higher urine calcium excretion in 40% of hypercalciuric women (n = 4/10) and in 44% (n = 4/9) of the renal lithiasis hypercalciuric patients. In conclusion, different ways of vitamin D supplementation and adequate serum levels are safe in most patients, although it should be taken into account a subgroup, mainly with monthly loading doses, that could increase the calciuria significantly eventually rising renal lithiasis risk or bone mass loss, if genetically predisposed.

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Nephrolithiasis is one of the most frequent urologic diseases. The aim of this paper is to study the composition and frequency of 8854 patient kidney stones and in a subset of them their metabolic risk factors to be related to their type of calculi. Physicochemical and crystallographic methods were used to assess kidney stone composition. In a subset of 715 patients, we performed an ambulatory metabolic protocol with diagnostic purposes. From the total sample 79% of stones were made of calcium salts (oxalate and phosphate), followed by uric acid stones in 16.5%, calcium salts and uric acid in 2%, other salts in 1.9% and cystine in 0.6%. Male to female ratio was almost three times higher in calcium salts and other types of stones, reaching a marked male predominance in uric acid stones, M/F 18.8 /1.0. The major risk factors for calcium stones are idiopathic hypercalciuria, followed by unduly acidic urine pH and hyperuricosuria. In uric acid stones unduly acidic urine pH and less commonly hyperuricosuria are the most frequent biochemical diagnosis. Our results show that analysis of kidney stones composition and the corresponding metabolic diagnosis may provide a scientific basis for the best management and prevention of kidney stone formation, as well as it may help us to study the mechanisms of urine stone formation.

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RESUMO

Nephrolithiasis is one of the most frequent urologic diseases. The aim of this paper is to study the composition and frequency of 8854 patient kidney stones and in a subset of them their metabolic risk factors to be related to their type of calculi. Physicochemical and crystallographic methods were used to assess kidney stone composition. In a subset of 715 patients, we performed an ambulatory metabolic protocol with diagnostic purposes. From the total sample 79% of stones were made of calcium salts (oxalate and phosphate), followed by uric acid stones in 16.5%, calcium salts and uric acid in 2%, other salts in 1.9% and cystine in 0.6%. Male to female ratio was almost three times higher in calcium salts and other types of stones, reaching a marked male predominance in uric acid stones, M/F 18.8 /1.0. The major risk factors for calcium stones are idiopathic hypercalciuria, followed by unduly acidic urine pH and hyperuricosuria. In uric acid stones unduly acidic urine pH and less commonly hyperuricosuria are the most frequent biochemical diagnosis. Our results show that analysis of kidney stones composition and the corresponding metabolic diagnosis may provide a scientific basis for the best management and prevention of kidney stone formation, as well as it may help us to study the mechanisms of urine stone formation.

La litiasis renal es una de las enfermedades urológicas más frecuentes. El objetivo de este trabajo fue estudiar la composición y frecuencia de 8854 cálculos renales y evaluar en un subgrupo de ellos la relación de los factores de riesgo metabólicos con el tipo de cálculo hallado. Se utilizaron métodos fisicoquímicos y cristalográficos para evaluar la composición de los cálculos renales. En un subgrupo de 715 pacientes, se pudo realizar un protocolo metabólico ambulatorio con fines diagnóstico. De la muestra total, 79.0% de los cálculos fueron de sales de calcio (oxalato y fosfato), seguido por cálculos de ácido úrico en 16.5%, sales de calcio y ácido úrico en 2.0%, otras sales en 1.9% y cistina en 0.6%. La relación hombre/mujer fue casi tres veces mayor en las sales de calcio y otros tipos de cálculos, alcanzando un marcado predominio en varones con cálculos de ácido úrico, M/F 18.8/1.0. Los principales factores de riesgo para los cálculos de calcio fueron la hipercalciuria idiopática, seguida del pH urinario excesivamente ácido y la hiperuricosuria. En los cálculos de ácido úrico el pH urinario excesivamente ácido y con menor frecuencia la hiperuricosuria fueron los diagnósticos más frecuentes. Nuestros resultados muestran que el análisis de la composición de los cálculos renales y el correspondiente diagnóstico metabólico pueden proporcionar una base científica para el mejor manejo y prevención en la formación de cálculos renales, así como que nos puede ayudar a estudiar los mecanismos de formación de los mismos.

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Background: Decreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. It is not yet clear if thiazide treatment prevent these events. Methods: We retrospectively evaluated bone mass and biochemical markers of bone turnover in response to thiazide therapy in 52 consecutive female patients with idiopathic hypercalciuria and nephrolithiasis. Patients were divided in two subgroups according to their menopausal status: 25 were pre-menopausal (Group I) and 27 were postmenopausal (Group II). Results: Osteoporosis was found in 12 patients at baseline, 9 at the lumbar spine and 6 at the femoral neck. Two were pre-menopausal and 10 were postmenopausal. Patients with osteoporosis were analyzed separately (Group III). There was a significant and persistent reduction in urinary calcium with preservation of bone mass in all the groups after a median follow-up of 51 months. Few adverse effects were found using low doses of hydrochlorothiazide / amiloride. Only in the group III we found a statistcally significant an increase in BMD at the lumbar spine of 9.5% and an increase in BMD at femoral neck of 4.4% that did not reach statistical significance. Conclusions: We conclude that correction of hypercalciuria during long term treatment with low-dose hydrochlorothiazide//amiloride in women with nephrolithiasis prevents bone loss and in those with osteoporosis can lead to a significant increase in bone mineral density at the lumbar spine. Few adverse effects were seen during treatment and no interruption of therapy was necessary.(AU)

Introducción: Reducción de la densidad mineral ósea y aumento de la prevalencia de fracturas óseas se han encontrado en pacientes con hipercalciuria idiopática. Aún no está claro si el tratamiento con tiazidas prevenir estos eventos. Métodos: Evaluamos retrospectivamente la masa ósea y los marcadores bioquímicos de recambio óseo en respuesta a la terapia con tiazidas en 52 pacientes femeninos consecutivos con hipercalciuria idiopática y nefrolitiasis. Los pacientes fueron divididos en dos subgrupos de acuerdo a su estado de la menopausia : 25 fueron pre-menopáusicas (Grupo I) y 27 eran posmenopáusicas (Grupo II). Resultados: La osteoporosis se encontró en 12 pacientes al inicio del estudio, 9 en la columna lumbar y 6 en el cuello femoral. Dos eran premenopáusicas y 10 eran posmenopáusicas. Los pacientes con osteoporosis se analizaron por separado (Grupo III). Hubo una reducción significativa y persistente en el calcio urinario con la preservación de la masa ósea en todos los grupos después de una mediana de seguimiento de 51 meses. Pocos efectos adversos se encuentran utilizando dosis bajasde hidroclorotiazida / amilorida. Sólo en el grupo III encontramos un aumento estadísticamente significativo en la DMO de la columna lumbar del 9,5% y un aumento de la densidad mineral ósea en el cuello femoral de 4,4% que no alcanzó significación estadística. Conclusión: Llegamos a la conclusión de que la corrección de la hipercalciuria durante el tratamiento a largo plazo con dosis bajas de hidroclorotiazida / / amilorida en mujeres con nefrolitiasis previene la pérdida ósea y en aquellos con osteoporosis puede conducir a un aumento significativo en la densidad mineral ósea en la columna lumbar. Pocos se observaron efectos adversos durante el tratamiento y no hay interrupción de la terapia era necesario.(AU)

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RESUMO

Background: Decreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. It is not yet clear if thiazide treatment prevent these events. Methods: We retrospectively evaluated bone mass and biochemical markers of bone turnover in response to thiazide therapy in 52 consecutive female patients with idiopathic hypercalciuria and nephrolithiasis. Patients were divided in two subgroups according to their menopausal status: 25 were pre-menopausal (Group I) and 27 were postmenopausal (Group II). Results: Osteoporosis was found in 12 patients at baseline, 9 at the lumbar spine and 6 at the femoral neck. Two were pre-menopausal and 10 were postmenopausal. Patients with osteoporosis were analyzed separately (Group III). There was a significant and persistent reduction in urinary calcium with preservation of bone mass in all the groups after a median follow-up of 51 months. Few adverse effects were found using low doses of hydrochlorothiazide / amiloride. Only in the group III we found a statistcally significant an increase in BMD at the lumbar spine of 9.5% and an increase in BMD at femoral neck of 4.4% that did not reach statistical significance. Conclusions: We conclude that correction of hypercalciuria during long term treatment with low-dose hydrochlorothiazide//amiloride in women with nephrolithiasis prevents bone loss and in those with osteoporosis can lead to a significant increase in bone mineral density at the lumbar spine. Few adverse effects were seen during treatment and no interruption of therapy was necessary.

Introducción: Reducción de la densidad mineral ósea y aumento de la prevalencia de fracturas óseas se han encontrado en pacientes con hipercalciuria idiopática. Aún no está claro si el tratamiento con tiazidas prevenir estos eventos. Métodos: Evaluamos retrospectivamente la masa ósea y los marcadores bioquímicos de recambio óseo en respuesta a la terapia con tiazidas en 52 pacientes femeninos consecutivos con hipercalciuria idiopática y nefrolitiasis. Los pacientes fueron divididos en dos subgrupos de acuerdo a su estado de la menopausia : 25 fueron pre-menopáusicas (Grupo I) y 27 eran posmenopáusicas (Grupo II). Resultados: La osteoporosis se encontró en 12 pacientes al inicio del estudio, 9 en la columna lumbar y 6 en el cuello femoral. Dos eran premenopáusicas y 10 eran posmenopáusicas. Los pacientes con osteoporosis se analizaron por separado (Grupo III). Hubo una reducción significativa y persistente en el calcio urinario con la preservación de la masa ósea en todos los grupos después de una mediana de seguimiento de 51 meses. Pocos efectos adversos se encuentran utilizando dosis bajasde hidroclorotiazida / amilorida. Sólo en el grupo III encontramos un aumento estadísticamente significativo en la DMO de la columna lumbar del 9,5% y un aumento de la densidad mineral ósea en el cuello femoral de 4,4% que no alcanzó significación estadística. Conclusión: Llegamos a la conclusión de que la corrección de la hipercalciuria durante el tratamiento a largo plazo con dosis bajas de hidroclorotiazida / / amilorida en mujeres con nefrolitiasis previene la pérdida ósea y en aquellos con osteoporosis puede conducir a un aumento significativo en la densidad mineral ósea en la columna lumbar. Pocos se observaron efectos adversos durante el tratamiento y no hay interrupción de la terapia era necesario.

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Citrate is a powerful inhibitor of the crystallization of calcium salts. Hypocitraturia is a biochemical common alteration in calcium stone formation in adults and especially in children. The acid pH (systemic, tubular and intracellular) is the main determinant of citrate excretion in the urine. While the etiology of hypocitraturia is idiopathic in most patients with kidney stones, there are a number of causes for this abnormality including distal renal tubular acidosis, hypokalemia, diets rich in animal protein and / or diets low in alkali and certain drugs, such as acetazolamide, topiramate, ACE inhibitors and thiazides. Dietary modifications that benefit these patients include high intake of fluids and fruits, especially citrus, sodium and protein restriction, with normal calcium intake. Treatment with potassium citrate is effective in patients with primary or secondary hypocitraturia and acidification disorders, which cause unduly acidic urine pH persistently. Adverse effects are low and are referred to the gastrointestinal tract. While there are various preparations of citrate (potassium citrate, sodium citrate, potassium citrate, magnesium) in our country is available only potassium citrate powder that is useful to correct both the hypocitraturia and the low urinary pH and reduce markedly the recurrence of kidney stones.

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El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular) es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio) en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.(AU)

Citrate is a powerful inhibitor of the crystallization of calcium salts. Hypocitraturia is a biochemical common alteration in calcium stone formation in adults and especially in children. The acid pH (systemic, tubular and intracellular) is the main determinant of citrate excretion in the urine. While the etiology of hypocitraturia is idiopathic in most patients with kidney stones, there are a number of causes for this abnormality including distal renal tubular acidosis, hypokalemia, diets rich in animal protein and / or diets low in alkali and certain drugs, such as acetazolamide, topiramate, ACE inhibitors and thiazides. Dietary modifications that benefit these patients include high intake of fluids and fruits, especially citrus, sodium and protein restriction, with normal calcium intake. Treatment with potassium citrate is effective in patients with primary or secondary hypocitraturia and acidification disorders, which cause unduly acidic urine pH persistently. Adverse effects are low and are referred to the gastrointestinal tract. While there are various preparations of citrate (potassium citrate, sodium citrate, potassium citrate, magnesium) in our country is available only potassium citrate powder that is useful to correct both the hypocitraturia and the low urinary pH and reduce markedly the recurrence of kidney stones.(AU)

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RESUMO

El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular) es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio) en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.

Citrate is a powerful inhibitor of the crystallization of calcium salts. Hypocitraturia is a biochemical common alteration in calcium stone formation in adults and especially in children. The acid pH (systemic, tubular and intracellular) is the main determinant of citrate excretion in the urine. While the etiology of hypocitraturia is idiopathic in most patients with kidney stones, there are a number of causes for this abnormality including distal renal tubular acidosis, hypokalemia, diets rich in animal protein and / or diets low in alkali and certain drugs, such as acetazolamide, topiramate, ACE inhibitors and thiazides. Dietary modifications that benefit these patients include high intake of fluids and fruits, especially citrus, sodium and protein restriction, with normal calcium intake. Treatment with potassium citrate is effective in patients with primary or secondary hypocitraturia and acidification disorders, which cause unduly acidic urine pH persistently. Adverse effects are low and are referred to the gastrointestinal tract. While there are various preparations of citrate (potassium citrate, sodium citrate, potassium citrate, magnesium) in our country is available only potassium citrate powder that is useful to correct both the hypocitraturia and the low urinary pH and reduce markedly the recurrence of kidney stones.

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