Kidney stone matrix proteins: Role in stone formation.

Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors. Crystallization inhibitors include citrate, magnesium, zinc, and organic compounds such as glycosaminoglycans. In the urine, there are various proteins, such as uromodulin (Tamm-Horsfall protein), calgranulin, osteopontin, bikunin, and nephrocalcin, that are present in the stone matrix. The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis. Proteins are the most abundant component of kidney stone matrix, and their presence may reflect the process of stone formation. Many recent studies have explored the proteomics of urinary stones. Among the stone matrix proteins, the most frequently identified were uromodulin, S100 proteins (calgranulins A and B), osteopontin, and several other proteins typically engaged in inflammation and immune response. The normal level and structure of these macromolecules may constitute protection against calcium salt formation. Paradoxically, most of them may act as both promoters and inhibitors depending on circumstances. Many of these proteins have other functions in modulating oxidative stress, immune function, and inflammation that could also influence stone formation. Yet, the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.

Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism / Características clínicas, evaluación diagnóstica y respuestas al tratamiento de la enfermedad de Paget ósea en un centro especializado en metabolismo óseo

Abstract The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal cross-linked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

Resumen La epidemiología de la en fermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism.

The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal crosslinked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

La epidemiología de la enfermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de Β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Spectrum of Bacterial Pathogens from Urinary Infections Associated with Struvite and Metabolic Stones.

OBJECTIVE: The purposes of this multi-center study were to evaluate the rate of infection stones and to evaluate the urine cultures of patients with infection stones. MATERIALS: Charts of adulpatients with urinary stones were reviewed and data on stone analyses and urine cultures were collected. RESULTS: In total, 1204 renal stone formers (RSFs) from 10 countries were included (776 males, 428 females). Fifty-six patients (4.6%) had struvite stones. The highest frequency of struvite stones was observed in India (23%) and Pakistan (18%). Lower rates were reported in Canada (2%), China (3%), Argentina (3%), Iraq (3%), Italy (3.5%) and Poland (3%), and intermediate rates in Egypt (5.5%) and Bulgaria (5.4%). Urine cultures were retrieved from 508 patients. Patients with struvite stones had a positive culture in 64.3% of the samples and patients with other stones, in 26.7%. In struvite stones, the most common isolates were Escherichia coli (27.7%) and Proteus spp. (27.7%), followed by Klebsiella spp. (16.7%); in other types of stone, it was Escherichia coli (47.6%), followed by Gram-positive bacteria (14.0%) Conclusions: The struvite stone composition was associated with a urinary infection, although an infection was not demonstrable with a conventional midstream urine culture in about 30%.

Stone composition of renal stone formers from different global regions.

OBJECTIVE: To study urinary stone composition patterns in different populations around the world. MATERIALS AND METHODS: Data were collected by reviewing charts of 1204 adult patients of 10 countries with renal or ureteral stones (> 18 years) in whom a stone analysis was done and available. Any method of stone analysis was accepted, but the methodology had to be registered. RESULTS: In total, we observed 710 (59%) patients with calcium oxalate, 31 (1%) with calcium phosphate, 161 (13%) with mixed calcium oxalate/calcium phosphate, 15 (1%) with carbapatite, 110 (9%) with uric acid, 7 (< 1%) with urate (ammonium or sodium), 100 (9%) with mixed with uric acid/ calcium oxalate, 56 (5%) with struvite and 14 (1%) with cystine stones. Calciumcontaining stones were the most common in all countries ranging from 43 to 91%. Oxalate stones were more common than phosphate or mixed phosphate/oxalate stones in most countries except Egypt and India. The rate of uric acid containing stones ranged from 4 to 34%, being higher in Egypt, India, Pakistan, Iraq, Poland and Bulgaria. Struvite stones occurred in less than 5% in all countries except India (23%) and Pakistan (16%). Cystine stones occurred in 1% of cases. CONCLUSIONS: The frequency of different types of urinary stones varies from country to country. Calcium-containing stones are prevalent in all countries. The frequency of uric acid containing stones seems to depend mainly on climatic factors, being higher in countries with desert or tropical climates. Dietary patterns can also lead to an increase in the frequency of uric acid containing stones in association with high obesity rates. Struvite stones are decreasing in most countries due to improved health conditions.

Hipercalciuria idiopática: diagnóstico, clasificación y tratamiento / Idiopathic hypercalciuria: diagnosis, classification, and treatment

Resumen Introducción: La hipercalciuria idiopática se define como la excreción de calcio superior a 220 y 300 mg/día en mujeres y hombres respectivamente o bien mayor a 4 mg/kg peso bajo dieta habitual. Objetivo: Revisar el diagnóstico, clasificación y tratamiento del paciente hipercalciúrico con litiasis renal. Material y métodos: Se incluyeron 250 pacientes con litiasis renal e hipercalciuria idiopática y 80 individuos sanos como controles. Todos realizaron un estudio bioquímico para litiasis renal. Resultados: Si bien el estándar de oro es la medición de la calciuria en 24 h, en el presente estudio sugerimos considerar también la relación Ca/Kg >4 mg/Kg o bien el índice de calciuria >140 mg/gr de creatinina urinaria. Con respecto a los tipos de hipercalciuria, luego de someterlos a una dieta restringida, los dividimos en hipercalciuria dieta dependiente y dieta independiente del calcio. Con respecto al tratamiento sugerimos una diuresis entre 2 y 2 ½ litros/d. En casos de hipercalciuria dieta dependiente aconsejamos una dieta de 600-800 mg de calcio y moderada restricción de proteínas animales y sal. En caso de no respuesta y en aquellos con hipercalciuria dieta independiente, el agregado de tiazidas, clortalidona, indapamida y ocasionalmente bisfosfonatos pueden controlar la hipercalciuria con menor riesgo de recurrencia de litiasis renal y un mejor estado óseo. Conclusiones: Consideramos importante no solo tener en cuenta las distintas formas de diagnóstico de hipercalciuria sino también la clasificación de esta, que permita un tratamiento más específico.

Abstract Introduction: Idiopathic hypercalciuria is defined as urine calcium excretion greater than 220 mg/day in women and 300 mg/day in men, or greater than 4 mg/kg under regular dietary conditions. Objective: The aim of this study is to review the diagnosis, classification, and treatment of hypercalciuric patients with renal lithiasis. Methods: We enrolled 250 patients suffering from renal lithiasis and idiopathic hypercalciuria and 80 healthy subjects as control group. Lab tests were performed to diagnose renal lithiasis. Results: Although the 24-hour urine test is the gold standard to determine calciuria, in this study we propose considering the Ca/Kg >4 mg/Kg ratio or an index of >140 mg of Ca per gram urine creatinine. Regarding the different types of hypercalciuria, after following a strict diet, subjects were divided into two groups: diet-dependent and diet-independent hypercalciuria. Concerning the treatment, we suggest diuretic therapy to achieve a urine output of 2-2.5 liters per day. In the case of subjects with diet-dependent hypercalciuria, we advise an intake of 600-800 mg of calcium and a moderate reduction in animal protein and salt intake. In cases of non-response to treatment in subjects with diet-dependent hypercalciuria, thiazides, chlorthalidone, indapamide and, in some cases, bisphosphonates may help control hypercalciuria with a lower risk of lithiasis recurrence and healthier bones. Conclusions: We believe it is important to consider not only the methods to diagnose hypercalciuria but also its classification to provide a better treatment.

Obesity rates in renal stone formers from various countries.

OBJECTIVE: To collect evidence on the rate of obesity in renal stone formers (RSFs) living in different climatic areas and consuming different diets. MATERIALS AND METHODS: Data of adult renal stone formers were retrospectively collected by members of U-merge from 13 participant centers in Argentina, Brazil, Bulgaria (2), China, India, Iraq (2), Italy (2), Nigeria, Pakistan and Poland. The following data were collected: age, gender, weight, height, stone analysis and procedure of stone removal. RESULTS: In total, 1689 renal stone formers (1032 males, 657 females) from 10 countries were considered. Average age was 48 (±14) years, male to female ratio was 1.57 (M/F 1032/657), the average body mass index (BMI) was 26.5 (±4.8) kg/m2. The obesity rates of RSFs in different countries were significantly different from each other. The highest rates were observed in Pakistan (50%), Iraq (32%), and Brazil (32%), while the lowest rates were observed in China (2%), Nigeria (3%) and Italy (10%). Intermediate rates were observed in Argentina (17%), Bulgaria (17%), India (15%) and Poland (22%). The age-adjusted obesity rate of RSFs was higher than the age-adjusted obesity rate in the general population in Brazil, India, and Pakistan, whereas it was lower in Argentina, Bulgaria, China, Italy, and Nigeria, and similar in Iraq and Poland. CONCLUSIONS: The age-adjusted obesity rate of RSFs was not higher than the age-adjusted obesity rate of the general population in most countries. The relationship between obesity and the risk of kidney stone formation should be reconsidered by further studies carried out in different populations.

Postmenopausal women with sarcopenia have higher prevalence of falls and vertebral fractures / Las mujeres postmenopáusicas con sarcopenia tienen mayor prevalencia de caídas y fracturas vertebrales

Abstract Recently, a new consensus of the European Working Group on Sarcopenia in Older People (EWSOP2) recommended new cut-off points for the diagnosis of sarcopenia. The aim of the present manuscript was to assess the prevalence of sarcopenia in postmenopausal women and its relationship with bone mineral density, falls and fragility fractures according to EWGSOP2. In this cross-sectional study, 250 ambulatory postmenopausal women over 60 years of age were included. Lumbar spine and hip bone mineral density (BMD) and whole-body composition were assessed by dual-energy X-ray absorptiometry (DXA). Muscle strength was evaluated by handgrip dynamometry and physical performance by a 4-m walk gait speed and five-repetition sit-to-stand test. Sarcopenia was defined according to EWGSOP2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass index by DXA). A sarcopenia prevalence of 4% was found in the whole group increasing with age being 12.5% in ≥ 80year-old. A higher percentage of falls, prevalence of osteoporosis and vertebral fractures were found in the sarcopenic group. Sarcopenia increased 6.0-fold the likelihood of having a fragility fracture. Women with sarcopenia had significantly lower femoral neck BMD and higher frequency of falls and vertebral fractures. According to our results, identifying patients with sarcopenia might be a useful tool to detect adults at higher risk of falls and fractures.

Resumen Recientemente el grupo de trabajo europeo sobre sarcopenia en adultos mayores (EWGSOP2) recomendó nuevos criterios y valores de referencia para el diagnóstico de sarcopenia. El objetivo del presente trabajo fue evaluar la prevalencia de sarcopenia en mujeres postmenopáusicas en nuestro medio y su relación con densidad mineral ósea, caídas y fracturas por fragilidad. Este es un estudio de diseño transversal en el cual se incluyeron un total de 250 mujeres ambulatorias mayores de 60 años. La densidad mineral ósea (DMO) de columna lumbar y cadera y la composición corporal fueron evaluados por absorciometría dual de rayos X (DXA). La fuerza fue evaluada por dinamometría de puño; para el rendimiento físico se utilizó caminata de 4 m y la prueba de levantarse y sentarse de una silla (5 repeticiones). La sarcopenia se definió de acuerdo a EWGSOP2 como baja fuerza muscular (dinamometría) y baja masa muscular (índice de masa muscular esquelética por DXA). El 4% de las mujeres cumplía con los criterios de sarcopenia siendo aún mayor en aquellas ≥ 80 años. Las mujeres con sarcopenia presentaron significativamente mayor frecuencia de caídas, osteoporosis y fracturas vertebrales. El riesgo de fracturas por fragilidad se vio incrementado 6 veces en las mujeres con sarcopenia. El diagnóstico de sarcopenia podría considerarse una herramienta útil para identificar a aquellos adultos con riesgo incrementado de caídas y fracturas.

Postmenopausal women with sarcopenia have higher prevalence of falls and vertebral fractures.

Recently, a new consensus of the European Working Group on Sarcopenia in Older People (EWSOP2) recommended new cut-off points for the diagnosis of sarcopenia. The aim of the present manuscript was to assess the prevalence of sarcopenia in postmenopausal women and its relationship with bone mineral density, falls and fragility fractures according to EWGSOP2. In this cross-sectional study, 250 ambulatory postmenopausal women over 60 years of age were included. Lumbar spine and hip bone mineral density (BMD) and whole-body composition were assessed by dual-energy X-ray absorptiometry (DXA). Muscle strength was evaluated by handgrip dynamometry and physical performance by a 4-m walk gait speed and five-repetition sit-to-stand test. Sarcopenia was defined according to EWGSOP2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass index by DXA). A sarcopenia prevalence of 4% was found in the whole group increasing with age being 12.5% in = 80- year-old. A higher percentage of falls, prevalence of osteoporosis and vertebral fractures were found in the sarcopenic group. Sarcopenia increased 6.0-fold the likelihood of having a fragility fracture. Women with sarcopenia had significantly lower femoral neck BMD and higher frequency of falls and vertebral fractures. According to our results, identifying patients with sarcopenia might be a useful tool to detect adults at higher risk of falls and fractures.

Recientemente el grupo de trabajo europeo sobre sarcopenia en adultos mayores (EWGSOP2) recomendó nuevos criterios y valores de referencia para el diagnóstico de sarcopenia. El objetivo del presente trabajo fue evaluar la prevalencia de sarcopenia en mujeres postmenopáusicas en nuestro medio y su relación con densidad mineral ósea, caídas y fracturas por fragilidad. Este es un estudio de diseño transversal en el cual se incluyeron un total de 250 mujeres ambulatorias mayores de 60 años. La densidad mineral ósea (DMO) de columna lumbar y cadera y la composición corporal fueron evaluados por absorciometría dual de rayos X (DXA). La fuerza fue evaluada por dinamometría de puño; para el rendimiento físico se utilizó caminata de 4 m y la prueba de levantarse y sentarse de una silla (5 repeticiones). La sarcopenia se definió de acuerdo a EWGSOP2 como baja fuerza muscular (dinamometría) y baja masa muscular (índice de masa muscular esquelética por DXA). El 4% de las mujeres cumplía con los criterios de sarcopenia siendo aún mayor en aquellas = 80 años. Las mujeres con sarcopenia presentaron significativamente mayor frecuencia de caídas, osteoporosis y fracturas vertebrales. El riesgo de fracturas por fragilidad se vio incrementado 6 veces en las mujeres con sarcopenia. El diagnóstico de sarcopenia podría considerarse una herramienta útil para identificar a aquellos adultos con riesgo incrementado de caídas y fracturas.

Metabolismo óseo-mineral en 4620 pacientes prevalentes en hemodiálisis crónica en argentina / Bone-mineral metabolism in 4,620 prevalent patients in chronic hemodialysis in argentina

RESUMEN Introducción: Las anormalidades del metabolismo óseo-mineral comienzan desde las primeras etapas de la enfermedad renal crónica, produciendo el desarrollo de enfermedad ósea y el aumento de la morbimortalidad de los pacientes. Objetivos: Conocer en una muestra representativa de nuestra población en hemodiálisis, la prevalencia de pacientes en rango objetivo de valores de parathormona, hiperparatiroidismo secundario y enfermedad ósea adinámica, de acuerdo con las guías KDIGO, evaluando, además, el uso de diferentes medicamentos en el control de estas alteraciones. Material y métodos: Participaron 39 centros de hemodiálisis de nuestro país, quienes enviaron las últimas determinaciones de calcio, fósforo y parathormona, y la medicación recibida en el manejo del metabolismo mineral. Resultados: Se incluyeron 4620 pacientes prevalentes en hemodiálisis, > 18 años, edad media 57 años, hombres 57,4%. Las medias fueron: calcemia 8,6 y fosfatemia 4,9 mg/dl. De esta población, el 56,7% y el 50,3% estaban en rango de calcemia y fosfatemia, respectivamente. La parathormona promedio fue 601 y la mediana 437 pg/ml. El 50,5% tenía parathormona en rango, el 15% por debajo de 150 y el 34,5% por encima de 600 pg/ml. En relación a la medicación, el 47% de la población recibió quelantes cálcicos, con extremos en su uso, que van desde el 4,5% al 8% en algunos centros, y del 83% al 94% en otros. El 28,8% recibió Sevelamer, calcitriol el 38%, paricalcitol el 11% y cinacalcet el 20%, siendo su uso variable según los centros del 3% al 52%. Conclusiones: La presencia de hiperparatiroidismo secundario es más frecuente que la deseada, probablemente vinculado a la dificultad en el uso adecuado de medicamentos.

ABSTRACT Introduction : Abnormalities of bone mineral metabolism begin from the early stages of CKD, causing the development of bone disease and increased morbidity and mortality of patients. Objectives: To know, in a representative sample of our hemodialysis patients, the prevalence of patients in the target range of PTH values, secondary hyperparathyroidism and adynamic bone disease according to the KDIGO guidelines, also evaluating the use of different drugs in the control of these alterations. Methods: 39 hemodialysis centers from our country participated, who sent the latest determinations of calcium, phosphorus and PTH and the medication received in the management of mineral metabolism. Results: 4620 prevalent hemodialysis patients > 18 years were included, mean age 57 years, men 57.4%. The means were calcemia 8.6 and phosphatemia 4.9 mg/dl. 56.7% and 50.3% were in the calcemia and phosphatemia range, respectively. The average PTH was 601 and the median 437 pg/ml. 50.5% had PTH in range, 15% below 150 pg/ml and 34.5% above 600 pg/ml. In relation to medication, 47% of the patients received calcium chelators with extreme use ranging from 4.5-8% in some centers to 83-94%. 28.8% received Sevelamer, calcitriol 38%, paricalcitol 11% and cinacalcet 20%, its use being variable according to the centers from 3% to 52%. Conclusion: the presence of secondary hyperpartyroidism was more frequent than desired, probably linked to the difficulty in the adequate use of medications.

Metabolic risk factors in children with kidney stone disease: an update.

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 .

[Idiopathic hypercalciuria: can the diuretics be avoided?] / Hipercalciuria idiopática ¿Se pueden evitar los diuréticos?

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.

La hipercalciuria idiopática se define como la excreción 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 hipercalciúricos, 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 diagnósticos 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 aparición de cálculos, o la recurrencia de los mismos, como tampoco el compromiso óseo. 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 normocalciúricos solo con dieta. Concluimos que es fundamental la división de las hipercalciurias, según su respuesta a una dieta restringida, con el fin de evitar o postergar el uso de diuréticos y sus efectos adversos, con una administración adecuada de la dieta.

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.

Riñón en esponja y litiasis renal / Sponge kidney and renal lithiasis

Introducción: El riñón en esponja es una malformación renal, de los túbulos colectores, que se suele asociar a nefrocalcinosis o acidosis tubular distal. La asociación con la litiasis renal se observa entre un 4-20%. Objetivo: El objetivo de nuestro trabajo fue describir factores de riesgo bioquímicos para litiasis renales, en pacientes con riñón en esponja. Material y métodos: Se realizó un estudio retrospectivo, observacional de corte, entre los años 2000 y 2017 en donde se estudiaron 37 pacientes con riñón en esponja y litiasis renal (26 mujeres y 11 hombres) de 37.3 ± 13.2 años. El diagnóstico de riñón en esponja se hizo mediante urograma excretor. Resultados: Fue observada nefrocalcinosis en el 95%. El diagnóstico bioquímico más frecuente fue la hipercalciuria idiopática que como única y asociada alteración se observó en el 59.4%. La hiperuricosuria fue el segundo diagnóstico encontrado en el 32.4% (única y asociada) seguido por la, hipocitraturia, hipomagnesuria y el pHu persistentemente ácido. En los hombres llamó la atención que un 46.2% no presentaron alteración bioquímica. Conclusiones: En conclusión se destaca la asociación relativamente frecuente de riñón en esponja y litiasis renal. La hipercalciuria idiopática fue la alteración metabólica más frecuente como causa de litogénesis, seguida por la hiperuricosuria, similar a lo descripto en la literatura, aunque en menor proporción. Otras alteraciones, como la hipocitraturia, hipomagnesuria y pHu persistentemente ácido también deben ser consideradas en el estudio de estos pacientes.

Introduction: Sponge kidney is a renal malformation of the collecting tubules, which is usually associated with nephrocalcinosis or distal tubular acidosis. The association with renal lithiasis is observed between 4-20%. Objective: The aim of our work was to describe the biochemical risk factors of renal lithiasis in patients with sponge kidney. Methods: A retrospective, observational, cross-sectional study was conducted between 2000 and 2017, in which 37 patients with sponge kidney and renal lithiasis (26 women and 11 men), aged 37.3 ± 13.2 years, were studied. The diagnosis of sponge kidney was made by excretory urography. Results: Nephrocalcinosis was observed in 95% of patients. The most frequent biochemical diagnosis was idiopathic hypercalciuria, which was observed, as a single and associated alteration, in 59.4% of cases. Hyperuricosuria was the second diagnosis found in 32.4% (single and associated) followed by hypocitraturia, hypomagnesuria and persistently acid pHu. Surprisingly, 46.2% of men presented no biochemical alteration. Conclusions: Our findings highlight the relatively frequent association of sponge kidney and renal lithiasis. Idiopathic hypercalciuria was the most common metabolic alteration as the cause of lithogenesis, followed by hyperuricosuria, similar to that described in the literature, but to a lesser extent. Other alterations, such as hypocitraturia, hypomagnesuria and persistently acid pHu, should also be considered in the study of these patients.

Litiasis renal y riesgo cardiovascular / Nephrolithiasis and cardiovascular risk

La litiasis renal es una enfermedad frecuente cuya prevalencia ha aumentado en los últimos años. En la actualidad se la considera como una patología sistémica; no limitada al riñón y a las vías urinarias, sino relacionada en gran medida a diabetes mellitus, obesidad, hipertensión arterial, hiperuricemia, hipercolesterolemia y enfermedad renal crónica, todos factores de riesgo cardiovascular que suelen vincularse a eventos severos como accidentes cerebrovasculares, enfermedad coronaria o infarto agudo de miocardio. Numerosos estudios transversales y meta-análisis han demostrado la asociación entre estas dos entidades. En esta revisión intentaremos demostrar los mecanismos involucrados en la fisiopatología de la litiasis renal y su relación con enfermedad cardiovascular. Como mecanismos involucrados, se mencionan tres asociaciones. La primera se refiere al estrés oxidativo y la inflamación. La segunda asociación se refiere a la presencia de mecanismos litogénicos que contribuyen a la calcificación vascular. Como última teoría se realiza la asociación ya conocida, de obesidad, síndrome metabólico, diabetes e hipertensión arterial, todos factores de riesgo para el desarrollo de litiasis renal así como de enfermedad cardiovascular, recordando que la litiasis renal es causa, en un 8%, del desarrollo de enfermedad renal crónica, otro factor de riesgo para enfermedad y muerte cardiovascular. Como conclusión se confirma la teoría de que la litiasis renal no es una enfermedad limitada al riñón y la vía urinaria, si no que se trata de una enfermedad sistémica, con riesgo de eventos cardiovasculares tan severos que pueden llevar a la muerte.

Renal lithiasis is a frequent disease whose prevalence has increased in recent years. Nowadays it is considered as a systemic pathology, not limited to the kidney and the urinary tract, but largely related to diabetes mellitus, obesity, hypertension, hyperuricemia, hypercholesterolemia and chronic kidney disease; all cardiovascular risk factors that are usually linked to severe events such as stroke, coronary heart disease or acute myocardial infarction. Numerous cross-sectional studies and meta-analyzes have proved the association between renal lithiasis and cardiovascular disease. In this review we will try to demonstrate the mechanisms involved in the pathophysiology of these two entities. Three associations are mentioned. The first one refers to oxidative stress and inflammation. The second association refers to the presence of lithogenetic mechanisms contributing to vascular calcification. The last theory is the already known correlation with obesity, metabolic syndrome, diabetes and hypertension; all risk factors for the development of renal lithiasis as well as cardiovascular disease. Let us remember that renal lithiasis is the cause, in 8% of cases, of the development of chronic kidney disease, another risk factor for cardiovascular disease and death. In conclusion, the theory that renal lithiasis is not a disease limited to the kidney and the urinary tract is confirmed; it is rather a systemic disease, with a risk of cardiovascular events so severe that they can lead to death.

Respuesta de la calciuria a suplementos de vitamina D / Calcium response to vitamin D supplementation

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.

[Calcium response to vitamin D supplementation]. / Respuesta de la calciuria a suplementos de vitamina D.

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.

Antecedentes familiares y diagnóstico bioquímico en 1948 formadores de cálculos renales / Family history and biochemical diagnosis in 1948 kidney stone formers

INTRODUCTION: The presence of family history of nephrolithiasis is associated with an increased risk of renal lithiasis. Different epidemiological studies have shown a family component in the incidence of it, which is independent of dietary and environmental factors. The role of heredity is evident in monogenic diseases such as cystinuria, Dent's disease or primary hyperoxaluria, while a polygenic inheritance has been proposed to explain the tendency to form calcium oxalate stones. OBJECTIVE: Our objective was to evaluate the family history of patients with renal lithiasis and the correlation of family history with its corresponding biochemical alteration, considering only those with a single metabolic alteration. METHODS: a prospective and retrospective observational and analytical study that included 1948 adults over 17 years of age and a normal control group of 165 individuals, all evaluated according to an ambulatory protocol to obtain a biochemical diagnosis. They were asked about their family history of nephrolithiasis and classified into five groups according to the degree of kinship and the number of people affected in the family. RESULTS: a positive family history of nephrolithiasis was found in 27.4% of renal stone formers, predominantly in women, compared to 15.2% of normal controls. The family history of nephrolithiasis was observed especially in 31.4% of patients with hypomagnesuria and in 29.6% of hypercalciuric patients. The rest of the biochemical alterations had a positive family history between 28.6% in hyperoxaluria and 21.9% in hypocitraturia. The highest percentage of family history of nephrolithiasis was found in cystinuria (75%) although there were few patients with this diagnosis. CONCLUSIONS: the inheritance has a clear impact on urolithiasis independently of the present biochemical alteration. Family history of nephrolithiasis of the first and second degree was observed between 21 and 32% of patients with renal lithiasis, with hypercalciuria and hypomagnesuria being the biochemical alterations with more family history

INTRODUCCIÓN: La presencia de antecedentes familiares de nefrolitiasis se asocia con un mayor riesgo de litiasis renal. Diferentes estudios epidemiológicos han mostrado un componente familiar en la incidencia de la misma, que es independiente de los factores dietéticos y ambientales. El papel de la herencia es evidente en enfermedades monogénicas como la cistinuria, la enfermedad de Dent o la hiperoxaluria primaria, mientras que se ha propuesto una herencia poligénica para explicar la tendencia a la formación de cálculos de oxalato de calcio. OBJETIVO: Nuestro objetivo fue evaluar la historia familiar de los pacientes con litiasis renal y la correlación de los antecedentes familiares con su correspondiente alteración bioquímica, considerando solo aquellos con una única alteración metabólica. MATERIAL Y MÉTODOS: Estudio observacional y analítico prospectivo y retrospectivo que incluyó a 1948 adultos mayores de 17 años y un grupo control normal de 165 individuos, evaluados todos siguiendo un protocolo ambulatorio para obtener un diagnóstico bioquímico. Se les preguntó acerca de su historia familiar de nefrolitiasis y se clasificó en cinco grupos según el grado de parentesco y el número de personas afectadas en la familia. Resultados: Se encontró historia familiar positiva de nefrolitiasis en el 27,4% de los formadores de cálculos renales, predominando en mujeres, frente al 15,2% de los controles normales. La historia familiar de nefrolitiasis se observó especialmente en el 31,4% de los pacientes con hipomagnesuria y en el 29,6% de los hipercalciúricos. El resto de las alteraciones bioquímicas tuvo antecedentes familiares positivos entre el 28,6% en la hiperoxaluria y el 21,9% en la hipocitraturia. El porcentaje más alto de antecedentes familiares de nefrolitiasis se encontró en la cistinuria (75%) aunque hubo pocos pacientes con este diagnóstico. CONCLUSIONES: La herencia tiene un claro impacto en la urolitiasis independientemente de la alteración bioquímica presente. Se observan antecedentes familiares de nefrolitiasis de primer y segundo grado entre el 21 y 32% de los pacientes con litiasis renal, siendo la hipercalciuria y la hipomagnesuria las alteraciones bioquímicas con más antecedentes familiares

[Asymptomatic primary hyperparathyroidism in women]. / Hiperparatiroidismo primario asintomático en mujeres.

Primary hyperparathyroidism may have different characteristics. One is the asymptomatic form. This is a mild variant of hypercalcemic hyperparathyroidism, characterized by a calcemia not greater than 1 mg/dl above the upper limit of the method, a high intact parathyroid hormone (iPTH), absence of renal stones, renal function impairement, and osteoporosis, less than 50 years of age, and less than 400 mg/day calciuria. It is not a surgical entity, but its evolution may require it. Twenty-four postmenopausal women, all older than 50 years, with a diagnosis of asymptomatic hyperparathyroidism, were studied. Clinical manifestations, densitometric changes, biochemical parameters and bone remodeling were analyzed and the results were compared with the classic and normocalcemic variants of the disease. Diagnostic criteria were established and observed that only 2 (8.3%) of patients, during a follow up of 44 ± 12 months, had need for a parathyroidectomy. In conclusion, the asymptomatic primary hyperparathyroidism is a benign disorder, of periodic clinical follow-up, which rarely may require surgery.