Role of claudins in idiopathic hypercalciuria and renal lithiasis.

Paracellular transport in the kidney is mediated by a family of proteins located in the tight junctions called claudins which confers its ionic selectivity. Claudin-2 is highly expressed in the proximal tubule and descending limb of Henle and mediate paracellular reabsorption of sodium and calcium cations. In the thick ascending limb of Henle (TALH) calcium is reabsorbed by a paracellular channel formed by Claudin-16 and-19. Claudin-16 mediates cationic permeability while Claudin-19 increases the cationic selectivity of Claudin-16 by blocking anionic permeability. On the other hand, Claudin 14, that is also located in TALH, inhibits the paracellular permeability of Claudin-16 to calcium. Recent wide genomic association analysis studies have detected four common synonymous variants (genetic polymorphisms of a single nucleotide, SNPs) at the locus of Claudin-14 gene that were significantly associated with the presence of renal lithiasis. Another study of wide genomic association and nephrolithiasis was carried out in the general population but including chromosome X, where claudin-2 gene is located. They detected nine SNPs that had a significant association with renal lithiasis risk. A greater knowledge of the paracellular pathway controlled by claudins and its regulation will allow us to develop future new treatments for idiopathic hypercalciuria and renal lithiasis.

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.

Sarcopenia in hemodialysis patients from Buenos Aires, Argentina.

OBJECTIVES: Sarcopenia is the loss of skeletal muscle mass and function that occurs with aging that can lead to greater morbidity and mortality. Chronic kidney disease and hemodialysis (HD) favors the development of sarcopenia. We studied the prevalence of sarcopenia and its components using European Working Group on Sarcopenia in Elderly People 2 proposed criteria and risk factors for its development in HD patients. METHODS: In 100 adult HD patients, we evaluated: hand grip strength (HGS), muscle mass by dual energy X-ray absorptiometry and physical performance (gait-speed and sit-stand test). RESULTS: Sixty patients were male and 40 were female; mean age 55.6 years. Prevalence of sarcopenia was 16% (11.1% in males and 25% in females; P = 0.05); 7% had severe sarcopenia. Prevalence of low HGS was 33% in males and 28% in females; low muscle mass was 30% in males but 70% in females and low physical performance 23% in males and 45% in females. Falls were reported by 23 patients. Patients with lower HGS had a higher prevalence of falls in the last year (40% two or more falls; P = 0.03). Only females with sarcopenia had lower bone mineral content. Neither age, body mass index, time on dialysis, or prevalence of diabetes predicted sarcopenia. CONCLUSIONS: A significant proportion of dialysis patients had sarcopenia, more frequent in females. Low HGS was associated with a higher prevalence of falls. Only females with sarcopenia had lower bone mineral content.

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 .

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

Kidney stones: Composition, frequency and relation to metabolic diagnosis.

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.

Kidney stones: composition, frequency and relation to metabolic diagnosis

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.

Metabolic risk factors in children with asymptomatic hematuria.

BACKGROUND: Idiopathic or benign hematuria is diagnosed in children after all other possible causes have been ruled out and test results for renal or urologic pathologies are negative. METHODS: To identify possible urinary risk factors for hematuria in children, we retrospectively evaluated clinical onset, family history, and metabolic risk factors of 60 children with idiopathic hematuria but without renal stones or other pathologic conditions that could explain the hematuria. All patients followed the same ambulatory protocol at that used to evaluate kidney stone-formers. RESULTS: Seven patients had microhematuria, three patients each had microhematuria and gross hematuria, and the remaining 50 patients had gross hematuria onset. A family history of stone disease was found in 63 % of the children. At least one urinary metabolic abnormality was present in 49 patients, while 11 patients had no metabolic abnormality. The most common urinary risk factor was idiopathic hypercalciuria (single or associated), which was found in 43.5 % of patients, followed by hypocitraturia (single or associated), present in 31.7 %. Unduly acidic urine pH as a single abnormality was found in 10 % of this pediatric patient population. We also found hyperoxaluria and, less frequently, hypomagnesuria, and hyperuricosuria. CONCLUSIONS: Asymptomatic idiopathic hematuria in pediatric patients may often be associated to different urinary biochemical abnormalities, similar to what is observed in pediatric kidney stone-formers.

Aspectos metabólicos y complicaciones de la hiperuricemia / Metabolic aspects and complications of hyperuricemia

El resultado de observaciones epidemiológicas inicia en la actualidad una reevaluación del ácido úrico en diferentes enfermedades metabólicas, enfermedad cardiovascular y renal. El rol de la hiperuricemia como factor de riesgo cardiovascular independiente es difícil de evaluar aún en análisis de modelos multivariados, dado que existen resultados inconclusos e inconsistentes en la mayoría de los estudios. Esta dificultad se observa por la fuerte asociación del ácido úrico con otros factores clásicos de riesgo cardiovascular que no permiten diferenciar el riesgo. Durante muchos años se lo consideró una sustancia biológicamente inerte, pero posteriormente se encontró que tiene muchas propiedades biológicas que podrían ser beneficiosas o perjudiciales para los seres humanos. Existen en la actualidad una controversia sobre si su rol es protector por tener propiedades anti-oxidante o lesivo por sus propiedades pro-oxidantes en la placa arterioesclerótica y en tejido adiposo lo que podría determinar que no solo se trate de un marcador de riesgo, sino que conforme un factor causal en las enfermedades metabólicas como la diabetes mellitus, el síndrome metabólico, las enfermedades cardiovasculares y/o renales. En esta revisión hemos actualizado estos conceptos de manera de intentar esclarecer dicho rol, para en un futuro se pueda instituir normas, que actualmente no están establecidas, para decidir si se debe tratar la hiperuricemia, en qué casos, con que niveles de corte y cuáles serían sus objetivos terapéuticos en cada circunstancia.

The results of epidemiological observations have led to a revaluation of uric acid role in different metabolic, cardiovascular and renal illnesses. The role of hyperuricemia as an independent cardiovascular risk factor is difficult to evaluate even in multivariate models analysis, since there are inconclusive and weak results in most studies. This difficulty is observed due to the strong association of uric acid with other classic cardiovascular risk factors which do not allow its distinction as an independently risk factor. For many years it was considered a biologically inert substance, but later, it was found that it has many biological properties which could be beneficial or harmful for human beings. Nowadays there is a controversial discussion about its role, whether it is protective for having anti-oxidant properties or harmful due to its pro-oxidants in the atherosclerotic plaque and in adipose tissue which could determine that it is not only a risk marker, but also a causal factor for metabolic illnesses as diabetes mellitus, metabolic syndrome, cardiovascular and/or renal illnesses. In this consensus we have updated these concepts trying to clarify the mentioned role, so that in the future, regulations could be introduced, which are not established so far, in order to decide whether hyperuricemia must be treated, in which cases, which cut-off levels must be used and which should be the therapeutic objectives in each circumstance.

Biochemical diagnosis in 3040 kidney stone formers in Argentina.

Nephrolithiasis is a frequent condition in urology that has an important recurrence and high impact in health economy. Knowing the biochemical abnormalities implicated in its pathogenesis is mandatory to establish therapeutic aims. Our objectives are to present the results in 3040 kidney stone formers in Argentina. All patients were selected after completing an ambulatory metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with a mean age of 45±12 years, and 1323 women, (43.52%), mean age 44±12 years. 2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily divided in two groups: those who had only one (single) biochemical abnormality (n=2156) and those who had associated abnormalities (n=625). No biochemical abnormalities were found in 259 patients (8.51%). The abnormalities present, single and associated, in order of frequency, were idiopathic hypercalciuria, (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%), hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone composition and found calcium oxalate stones related to idiopathic hypercalciuria predominantly while uric acid stones to unduly acidic urine. In conclusion, the biochemical abnormalities described are similar to those found in a previous series of our own and to those reported in the literature. Its diagnosis is important to therapeutic purposes to avoid eventual recurrence.

Experiencia inicial con cinacalcet en Argentina / Inicial experience with cinacalcet in Argentina

Introducción: el hiperparatiroidismo secundarioes una complicación frecuente de laenfermedad renal crónica. Cinacalcet, un moduladoralostérico del receptor sensor del calcio incrementasu sensibilidad a la activación por partedel calcio iónico extracelular, demostró ser efectivoen reducir los niveles de PTH. Objetivo:Evaluar la eficacia de cinacalcet en pacientes enhemodiálisis con HPTS. Material y métodos: Se realizó un estudio retrospectivo, multicéntrico, observacional, en 76 pacientes que recibieronal menos 3 meses de cinacalcet como tratamientodel HPTS...

Introduction: secondary Hyperparathyroidism is a frequent chronic renal disease complication. Cinacalcet, an allosteric modulator of the calcium sensing receptor, increases its sensitivity to activation by extracellular calcium ions, proved to be effective in reducing PTH levels. Objetive: To evaluate cinacalcet effectiveness in hemodialysis patients with HPTS. Methods: A retrospective, multicenter, observational study was carried out, on 76 patients who received Cinacalcet for at least 3 months, as a treatment for HPTS...

Weekly high-dose ergocalciferol to correct vitamin D deficiency/insufficiency in hemodialysis patients: a pilot trial.

Controversy exists on which vitamin D (D2 or D3) and which dosage scheme is the best to obtain and maintain adequate 25 OH D levels in dialysis patients safely. We tried to determine whether high-dose vitamin D2 supplementation could obtain optimal vitamin D status without inducing hypercalcemia. We studied 82 patients on dialysis not taking active vitamin D therapy and supplemented them with oral vitamin D2 72,000 IU/week for 12 weeks followed by 24,000 IU/week as maintenance therapy during 36 weeks. By week 12, serum 25(OH)D increased from 15.2 ± 5.4 to 42.5 ± 13.2 ng/mL (P < 0.01) at week 12 and remained optimal (34.7 ± 12.0); 84.8% of the patients reached values ≥30 ng/mL. iPTH and alkaline phosphatase did not change at 48 weeks compared with baseline, but bone alkaline phosphatase decreased significantly (54.3 ± 46.0 to 44.3 ± 25.0; P = 0.02). Uncorrected serum Ca increased significantly at the end of follow-up (9.03 ± 0.42 to 9.14 ± 0.62; P = 0.04); hypercalcemia was presented in two patients in the first control visit (week 12), in one patient in the second control (week 30), and in one patient in the third control (week 48). In 222 serum calcium determinations during follow-up, hypercalcemia was observed in only 1.8% of cases. This vitamin D2 oral regimen with initial high doses was safe and sufficient to obtain and maintain optimal serum 25(OH)D concentrations and prevent vitamin D insufficiency in chronic kidney disease patients on dialysis.

Hypercalcemia secondary to granulomatous disease caused by the injection of methacrylate: a case series.

Association of dysregulated calcium homeostasis and granulomatous disease is well established. There exist reports in the literature of granulomatous reactions produced by silicones associated with hypercalcemia. In this case series we report four young women that underwent methacrylate injections in gluteus, thighs and calves that developed granulomas with posterior appearance of hypercalcemia. This complication presented as subacute around 6 months after the procedure. The four patients have as common elements the presence of moderate to severe renal insufficiency, suppressed PTH and elevated calcitriol levels for the degree of renal function. In the image studies, two patients presented in the nuclear magnetic resonance of the gluteus hypodense nodular images compatible with granulomas. Two patients had a positron emission tomography performed showing increased metabolic activity in the muscles of the gluteal region compatible with granulomas. Two patients had a partial surgical resection of the gluteal lesions with the finding of methacrylate associated to foreign body granulomas. In these patients hypercalcemia was treated with oral or local injections of corticoids, intravenous bisphosphonates or ketoconazole with good response. Although the prevalence of this complication with methacrylate injection is not common, hypercalcemia secondary to granulomas should be considered in the differential diagnosis of patients with hypercalcemia when there is a history of this procedure, and especially if they have a reduction in their renal function.