Citraturia en pacientes pediátricos con urolitiasis / Citraturia in pediatric patients with urolithiasis

La urolitiasis en niños y adolescentes es etiológicamente multifactorial, incluyendo bajo volumen urinario o desequilibrio entre factores promotores e inhibidores de la cristalización urinaria. La hipocitraturia es una alteración bioquímica relacionada con pH urinario acido y dietas ricas en proteínas o deficientes en frutas y hortalizas. Objetivos: determinar los valores urinarios de citrato y de algunos promotores de la cristalización (calcio, ácido úrico y fósforo) en pacientes menores de 18 años con urolitiasis. Métodos: se incluyeron 68 pacientes menores de 18 años con diagnóstico de urolitiasis en quienes se realizaron los siguientes estudios: examen general de orina (muestra aislada), calcio, fosforo, ácido úrico y citrato (recolección de 24 horas), gases venosos, electrolitos séricos y ecosonograma renovesical. En los pacientes hipocitratúricos también se determinó la citraturia después de seis meses de tratamiento con citrato de potasio. Los pacientes se dividieron en dos grupos: grupo A, pacientes normocitratúricos y grupo B, pacientes hipocitratúricos. Resultados: cuarenta y tres pacientes (63%) presentaron antecedentes familiares de litiasis. valores de citraturia (mgs/24hrs): grupo total: X:280±108,8; grupo A: 488,503±112,4; grupo B: X:169,5±95,2. Se evidenció hipocitraturia en 44 pacientes (64,71%). Alteraciones asociadas (n/%): acidosis metabólica (23/33%), de los cuales 20 pacientes (87%) tuvieron hipocitraturia; hiperuricosuria (16/23,52%); hipercalciuria (15/22,05%); hiperfosfaturia (09/13,23%); pH urinario ácido (35/51%) y alcalino o neutro (33/49%); pH urinario persistentemente acido (18/41%). en 28 pacientes (41,17%) se encontraron alteraciones metabólicas mixtas. Conclusiones: la hipocitraturia se encontró en más de la mitad de los pacientes estudiados y se asoció de manera significativa con otras alteraciones metabólicas litogénicas(AU)

Urolithiasis in children and adolescents is etiologically multifactorial, including low urinary volume or imbalance between urinary crystallization promoting and inhibiting factors. Hypocitraturia is a biochemical alteration related to urinary acid pH and diets high in protein or low in fruits and vegetables. Objectives: to determine urinary values of citrate and crystallization promoters (calcium, uric acid and phosphorus) in patients less than 18 years of age with urolithiasis. Methods: sixty-eight patients under 18 years of age with a diagnosis of urolithiasis were submitted to the following studies: urinalysis (isolated urine sample), calcium, phosphorus, uric acid and citrate (24-hour collection), venous gases, serum electrolytes and abdominal ultrasonogram. In hypocytraturic patients, citraturia was also determined after six months of treatment with potassium citrate. Patients were divided into two groups: group A, normocytraturic patients, and group B, hypocytraturic patients. Results:. Forty-three patients (63%) had a family history of urolithiasis. urinary citrate values (mgs/24hrs): total group: X:280±108.8; group A: 488,503±112.4; group B: X:169.5±95.2. hypocitraturia was observed in 44 patients (64.71%). Associated alterations (n/%): metabolic acidosis (23/33%), of which 20 patients (87%) had hypocitraturia; hyperuricosuria (16/23.52%); hypercalciuria 15/22.05%; hyperphosphaturia 9/13.23%; urinary acid pH (35/51%) and alkaline or neutral (33/49%); persistently urinary acid pH (18/41%). Mixed metabolic alterations were found in 28 patients (41.17%). Conclusions: hypocitraturia was found in more than half of the patients and was significantly associated with other lithogenic metabolic alterations(AU)

Composición de las urolitiasis y trastornos metabólicos renales en adultos cubanos / The composition of urolithiasis in Cuban adult patients and its relationship with renal metabolic disorders

Introducción: La litiasis urinaria es una enfermedad común, cuya prevalencia se incrementa a escala nacional y planetaria. Objetivos: Conocer la composición de las urolitiasis en pacientes adultos cubanos y su relación con los trastornos metabólicos renales. Métodos: Estudio descriptivo, transversal. Universo constituido por los pacientes cubanos de 19 años y más de edad, que se realizaron estudio de composición de urolitiasis en el Instituto de Nefrología Dr. Abelardo Buch, de La Habana, Cuba, en el período comprendido de 2011-2020. De ellos 443 se habían realizado estudio metabólico renal. Los datos fueron recogidos de los informes de resultados, de composición de litiasis y de estudio metabólico. Se utilizó análisis de distribución de frecuencias, y para identificar las relaciones, el test independencia. Resultados: En cuanto a la composición química, predominaron las litiasis de oxalato de calcio. Los trastornos metabólicos más frecuentes fueron excreción de sodio aumentada (46,7 por ciento) y volumen urinario bajo (29,3 por ciento). La frecuencia de pacientes con litiasis cálcicas, fue superior en los que tuvieron excreción de sodio aumentada (78,3 por ciento), y en los que presentaron hipercalciuria (83,3 por ciento), en contraste con las frecuencias de este tipo de litiasis, en los que no presentaron dichos trastornos (p=0,03 en ambos casos). Conclusiones: Las urolitiasis más comunes en adultos cubanos son las cálcicas, especialmente las de oxalato de calcio. Los trastornos metabólicos más frecuentes son: excreción urinaria aumentada de sodio, volumen urinario bajo y pH urinario ácido. La presencia de litiasis cálcicas se relaciona con excreción urinaria aumentada de sodio y con hipercalciuria(AU)

Introduction: Urinary lithiasis is a common disease, whose prevalence is increasing on a national and planetary scale. Objectives: To know the composition of urolithiasis in Cuban adult patients and its relationship with renal metabolic disorders. Methods: Descriptive, cross-sectional study. Universe constituted by Cuban patients aged 19 and over, who underwent a composition study of urolithiasis at the Dr. Abelardo Buch Institute of Nephrology, in Havana, Cuba, in the period 2011-2020. In 443 of them, a renal metabolic study had also been carried out. The data were collected from the results reports of stone composition and metabolic study. Frequency distribution analysis was used, and the independence test was used to identify relationships. Results: Regarding chemical composition, calcium oxalate stones predominated. The most frequent metabolic disorders were increased sodium excretion (46.7percent) and low urine volume (29.3percent). The frequency of patients with calcium stones was higher in those with increased sodium excretion (78.3percent) and in those with hypercalciuria (83.3percent), in contrast with the frequencies of this type of lithiasis, in those who did not present these disorders (p=0.03 in both cases). Conclusions: The most common urolithiasis in Cuban adults are calcium ones, especially those of calcium oxalate. The most common metabolic disorders are: increased urinary sodium excretion, low urinary volume and acid urinary pH. The presence of calcium lithiasis is related to increased urinary sodium excretion and hypercalciuria(AU)

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.

High Prevalence of Hypocitraturia in Stone Formers from the Maya Region of Yucatan, Mexico.

BACKGROUND: Urinary Stone Disease (USD) arises from an interaction of genetic and environmental factors. Urinary metabolic abnormalities are well described as risk factors. In Mexico, the Maya region holds the highest prevalence of USD. Treatment of these abnormalities lowers the risk of recurrences. AIM: Assess the underlying metabolic abnormalities of patients with USD to provide a rationale to lead further prevention strategies. METHODS: Clinical and demographical data from patients coming to the Stone Clinic were prospectively collected along with a 24 h urinary panel to identify metabolic abnormalities. All participants signed consent and the study was approved by the hospital's institutional review board. RESULTS: A total of 126 patients were included, with a mean age of 47.2 ± 13 years, 75.4% were female. A positive family history of stones was observed in 40 and 87.3% were overweight/obese. The frequency of hypocitraturia, hypercalciuria, hypomagnesuria, hyperoxaluria, and hyperuricosuria was 91.3, 68.5, 42.1, 36.5, and 26.6%, respectively. Median urinary citrate was 79.5 (37.5-160) mg/24 h and was inversely correlated to glycemia. Urine Calcium/Creatinine index was correlated with Hounsfield units (HU) (p = 0.01). Oxalate was correlated with HU and stone burden. Interestingly, dietary distribution of macro- and micronutrients were similar between groups. Patients with a single kidney had lower citrate and higher urinary calcium. CONCLUSIONS: Interestingly, a shortage of inhibitors such as citrate and magnesium are highly prevalent in patients with USD from the Maya region and seems to be influenced by other metabolic conditions as malnutrition next to the genetic component.

Principais distúrbios metabólicos em adolescentes portadores de nefrolitíase / Main metabolic disorders in adolescents with nephrolithiasis

Introdução: Os cálculos renais compreendem uma das mais comuns patologias do trato urinário e têm apresentado maior incidência em adolescentes nos últimos anos. Objetivos: Identificar os distúrbios metabólicos causadores de cálculo renal mais prevalentes em adolescentes. Métodos: Foram analisados os prontuários de 135 indivíduos portadores de nefrolitíase, com idade entre 12 e 18 anos, de ambos os sexos. Na análise laboratorial, incluiu-se: duas amostras de urina de 24 horas, contendo cálcio, citrato, oxalato e ácido úrico; uma amostra sanguínea, contendo creatinina, paratormônio, ácido úrico e cálcio; pH urinário após 12 horas de restrição hídrica e jejum; urocultura e cistinúria qualitativa. Resultados: 88 pacientes apresentaram hipercaIciúria (65,2%), 42 apresentaram hipocitratúria (31,1%) e 29 hiperuricosúria (21,5%). As demais alterações observadas foram: volume urinário reduzido (14,8%), infecções do trato urinário (9,6%), hiperoxalúria (5,2%), hiperparatireoidismo (1,5%) e acidose tubular renal (1,5%). Os distúrbios metabólicos mais frequentemente observados nos adolescentes portadores de cálculo renal foram hipercalciúria, hipocitratúria e hiperuricosúria

Introduction: Kidney stones are one of the most common pathologies of the urinary tract and have had a higher incidence in adolescents in recent years. Objectives: To identify the most prevalent metabolic disorders that cause kidney stones in adolescents. Methods: The medical records of 135 individuals with nephrolithiasis, aged between 12 and 18 years, of both sexes, were analyzed. The laboratory analysis included: two 24-hour urine samples containing calcium, citrate, oxalate and uric acid; a blood sample, containing creatinine, parathyroid hormone, uric acid, and calcium; urinary pH after 12 hours of fluid restriction and fasting; uroculture and qualitative cystinuria. Results: 88 patients had hyperuricosuria (65.2%), 42 had hypocitraturia (31.1%) and 29 had hyperuricosuria (21.5%). The other changes observed were: reduced urinary volume (14.8%), urinary tract infections (9.6%), hyperoxaluria (5.2%), hyperparathyroidism (1.5%) and renal tubular acidosis (1.5 %). Conclusions: The metabolic disorders most frequently observed in adolescents with kidney stones were hypercalciuria, hypocitraturia and hyperuricosuria.

Trastornos metabólicos urinarios en pacientes urolitiásicos con enfermedad renal poliquística y sin ella / Urinary metabolic disorders in urolithiasis patients with and without polycystic kidney disease

Introducción: La urolitiasis se ha incrementado en las últimas décadas. La enfermedad renal poliquística autosómica dominante (ERPAD), enfermedad renal hereditaria más frecuente, ocupa un lugar preponderante. Objetivos: Identificar la frecuencia de presentación de los trastornos metabólicos urinarios en pacientes litiásicos cubanos con ERPAD y sin ella Métodos: Estudio descriptivo, transversal. Fueron estudiados 579 pacientes adultos sin ERPAD, seleccionados por muestreo simple aleatorio y los 21 pacientes con ERPAD, del total de pacientes con litiasis urinaria que se realizó estudio metabólico renal en el Laboratorio de Fisiopatología Renal del Instituto de Nefrología, en el periodo 2010-2015. Los datos fueron tomados de la historia clínica y del informe de estudio metabólico renal. La información se procesó de forma automatizada (SPSS 22.0). Se utilizó el promedio, desviación estándar, análisis de distribución de frecuencias y el test de homogeneidad. Resultados: En los pacientes con ERPAD predominó el sexo femenino (57,1 por ciento), mientras que en los pacientes sin ERPAD, el masculino (63,4 por ciento). Los trastornos más frecuentes en la población no poliquística fueron hipercalciuria (45,3 por ciento) e hipofosfatemia (17,1 por ciento). En los poliquísticos, aclaramiento aumentado de ácido úrico (38,1 por ciento) e hipercalciuria (23,8 por ciento). Se encontraron diferencias estadísticamente significativas para aumento del aclaramiento de ácido úrico (p = 0,01) e hiperfosfatemia (p = 0,04). Conclusiones: Los principales trastornos metabólicos de los pacientes litiásicos, tanto poliquísticos como no poliquísticos, son el aclaramiento de ácido úrico aumentado, hipercalciuria, hiperuricosuria e hipofosfatemia, aunque el orden de presentación es diferente. El aclaramiento de ácido úrico aumentado y la hiperfosfatemia se presentan con mayor frecuencia en los pacientes litiásicos poliquísticos(AU)

Introduction: Urolithiasis has increased in recent decades. Autosomal dominant polycystic kidney disease (ADPKD), the most common of all hereditary kidney diseases, occupies a predominant position in terms of incidence. Objectives: Identify the frequency of occurrence of urinary metabolic disorders in Cuban urolithiasis patients with and without ADPKD. Methods: A descriptive cross-sectional study was conducted of 579 adult patients without ADPKD selected by simple random sampling, and 21 patients with ADPKD, from the total urolithiasis patients undergoing renal metabolic evaluation at the Renal Physiopathology Laboratory of the Institute of Nephrology in the period 2010-2015. Data were obtained from medical records and reports of renal metabolic studies. Information was processed with the statistical software SPSS version 22.0. Average and standard deviation were estimated and use was made of frequency distribution analysis and homogeneity testing. Results: A predominance was found of female sex among patients with ADPKD (57.1 percent) and male sex among patients without ADPKD (63.4 percent). The most common disorders were hypercalciuria (45.3 percent) and hypophosphatemia (17.1 percent) in the non-polycystic population, and increased uric acid clearance (38.1 percent) and hypercalciuria (23.8 percent) in polycystic patients. Statistically significant differences were found in uric acid clearance increase (p = 0.01) and hyperphosphatemia (p = 0.04). Conclusions: The main metabolic disorders of lithiasis patients, polycystic as well as non-polycystic, are increased uric acid clearance, hypercalciuria, hyperuricosuria and hypophosphatemia, with a varying order of presentation. Increased uric acid clearance and hyperphosphatemia are more common in polycystic lithiasis patients(AU)

Litiasis renal en niños / Renal lithiasis in children

Resumen Justificación y objetivo: La litiasis renal se debe a la precipitación de cristales por un desequilibrio en la orina entre sustancias promotoras y las sustancias inhibitorias. Es una patología con una prevalencia entre 2-10% en la población pediátrica, con una incidencia que ha aumentado en los últimos 25 años; razón por la cual este estudio pretende conocer la prevalencia, las manifestaciones clínicas y metabólicas de la litiasis renal en la población pediátrica del Hospital Nacional de Niños de Costa Rica. Métodos: Es un estudio retrospectivo, descriptivo y observacional, mediante la revisión de expedientes de pacientes menores a 18 años con el diagnóstico de litiasis renal, atendidos en el Hospital Nacional de Niños, en el periodo comprendido entre enero del año 2000 al 2018. Resultados: Se incluyeron un total de 106 pacientes. El 57,5% hombres, la edad promedio al diagnóstico de 6,6 ± 3,8 años; la frecuencia de casos se ha incrementado en 5,5 veces en los últimos 5 años. Factores de riesgo detectados: anormalidades del tracto urinario 22,6% y antecedentes familiares de litiasis 17,9%. El análisis metabólico mostró un gasto urinario bajo en el 74,3%, hiperfosfaturia en un 43,2%, hipomagnesuria 39,2% e hipercalciuria 37,8%. Etiologías determinadas: metabólica 54,7%, malformaciones de las vías urinarias 16% e idiopática en un 30,9%. La litotricia intracorpórea se aplicó en un 61,2%. La recidiva se observó en el 28,5% de los casos, se encontró relación entre la incidencia de recidiva con el tamaño del lito (p = 0,001) y el tratamiento quirúrgico. (p = 0,010). Conclusiones: Existe un aumento en la frecuencia de casos de litiasis pediátrica con una etiología multifactorial en el Hospital Nacional de Niños de Costa Rica.

Abstract Background and aim: Renal lithiasis is due to the precipitation of crystals due to an imbalance in the urine between promoter substances and inhibitory substances. It is a pathology with a prevalence between 2-10% in the pediatric population, with an incidence that is increasing in the last 25 years, because of that, this study pretend to know the prevalence, the clinical and metabolic, manifestation of the renal lithiasis in the pediatric population. Methods: It is a retrospective, descriptive and observational study, by reviewing records of patients under 18 years of age with a diagnosis of renal lithiasis, treated at the Hospital Nacional de Niños, in the period of 2000 to 2018. Results: A total of 106 patients were included, 57,5% men, the average age at diagnosis of 6,6+- 3,8 years, the frequency of cases has increased 5,5 times in the last 5 years. Risk factors detected: urinary trac abnormalities 22,6% and family history of nephrolithiasis 17,9%. The metabolic analysis showed a low urinary flow rate in 74,3%, hyperphosphaturia in 43,2%, hypomagnesuria 39,2% and hypercalciuria 37,8%. Etiologies determined: metabolic 54,7%, malformations of the urinary trac 16% and idiopathic in 30,9%. Intracorporeal lithotripsy was applied in 61,2%. Recurrence was observe in 28,5 % of cases, a relationship was found between the incidence of recurrence with the size of litho (p= 0.001) and surgical treatment (p= 0.01). Conclusions: There is a significant increase in the incidence of pediatric lithiasis cases with a multifactorial etiology.

Aspectos clínicos, epidemiológicos y terapéuticos en niños y adolescentes con hipercalciuria idiopática / Clinical, epidemiological and therapeutic aspects in children and adolescents with idiopathic hypercalciuria

Introducción: La hipercalciuria idiopática es un trastorno metabólico frecuente y poco reconocido, cuyo curso clínico depende en gran medida de cambios en los hábitos dietéticos desde la infancia. Objetivo: Caracterizar a niños y adolescentes con hipercalciuria idiopática según variables clínicas, epidemiológicas y terapéuticas. Métodos: Se realizó una investigación observacional, longitudinal y prospectiva de 44 pacientes con hipercalciuria idiopática, atendidos en el Servicio de Miscelánea del Hospital Pediátrico Docente Sur Antonio María Béguez César de Santiago de Cuba, desde enero de 2014 hasta diciembre de 2015. Resultados: Las formas sintomáticas de la enfermedad resultaron ser las más frecuentes (68,2 %); asimismo, predominó el sexo masculino (72,7 %) y el promedio de edad fue de 7,2 ± 4 años. Existió asociación estadística entre las edades preescolar y escolar en cuanto al diagnóstico de hipercalciuria idiopática. La hematuria macroscópica recurrente fue el síntoma más usual en la mayoría de los casos (59,1 %); en tanto, 25,0 % de los pacientes presentó litiasis renal y el tratamiento no farmacológico a base de líquidos y dieta se relacionó con una evolución satisfactoria en 68,2 % de los afectados, a pesar de que el restante 31,8 % necesitó tratamiento medicamentoso. Conclusiones: Las características clínicas y epidemiológicas de los pacientes con hipercalciuria idiopática de esta casuística no difirieron de las registradas a nivel mundial, considerando que este trastorno metabólico es relativamente frecuente en los servicios de pediatría.

Introduction: The idiopathic hypercalciuria is a frequent and not very recognized metabolic disorder which clinical course depends in great extent on changes in the dietary habits from the childhood. Objective: To characterize children and adolescents with idiopathic hypercalciuria according to the clinical, epidemiological and therapeutic variables. Methods: An observational, longitudinal and prospective investigation was carried out in 44 patients with idiopathic hypercalciuria, assisted in the Miscellaneous Service of Antonio María Béguez Cesar Southern Teaching Children Hospital in Santiago de Cuba, from January, 2014 to December, 2015. Results: The symptomatic forms of the disease were the most frequent (68.2 %); also, the male sex prevailed (72.7 %) and the average age was 7.2 ± 4 years. Statistical association existed among the preschool and school ages as for the diagnosis of idiopathic hypercalciuria. The recurrent macroscopic hematuria was the most usual symptom in the majority of cases (59.1 %); as long as, the 25.0 % of patients presented renal lithiasis and the diet and liquids-based non pharmacological treatment was associated with a satisfactory evolution in 68.2 % of the affected patients, although the remaining 31.8 % needed drugs treatment. Conclusions: The clinical and epidemiological characteristics of patients with idiopathic hypercalciuria of this case material didn't differ from the ones registered worldwide, taking into account that this metabolic disorder is relatively frequent in pediatric services.

Hypomagnesemia with Hypercalciuria Leading to Nephrocalcinosis, Amelogenesis Imperfecta, and Short Stature in a Child Carrying a Homozygous Deletion in the CLDN16 Gene.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disease caused by mutations in the CLDN16 or CLDN19 gene; however, few cases develop classical amelogenesis imperfecta. Herein, we report the case of a boy with early clinical renal manifestations that started at 1 year of age and presenting with dental hypoplasia and growth delay. The patient presented with vomiting, polyuria, and polydipsia. Apart from recurrent sterile leukocyturia, erroneously treated as infectious, he was normal, except for short stature and amelogenesis imperfecta with gradually discolored teeth. Laboratory tests revealed hyperparathyroidism, hypomagnesemia, severe hypercalciuria, and hypermagnesuria on 24-h urine testing. Helical computed tomography confirmed nephrocalcinosis. We performed whole-exome sequencing (WES) to test the hypothesis of FHHNC and oligogenic inheritance of amelogenesis. Analysis of the WES binary sequence alignment/map file revealed the presence of exon 1 of the CLDN16 and absence of the other exons [c.325_c918*? (E2_E5del)]. We confirmed a CLDN16 E2_E5 homozygous deletion by multiplex ligation-dependent probe amplification and polymerase chain reaction assays. Although most mutations causing FHHNC are missense and nonsense mutations in the CLDN16 or CLDN19 gene, large deletions occur and may be misled by WES, which is generally used for genetic screening of oligogenic disorders. The patient received cholecalciferol, magnesium oxide and potassium citrate. Later, the combination with hydrochlorothiazide plus amiloride was prescribed, with a good response during follow-up. Our report broadens the phenotype of FHHNC, including severe early-onset amelogenesis and short stature, and reinforces the phenotype-genotype correlation of the large deletion found in CLDN16.

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 .

Renal manifestations of sarcoidosis: from accurate diagnosis to specific treatment

ABSTRACT Sarcoidosis is a multisystem granulomatous disease characterized by epithelioid noncaseating granulomas associated with clinical and radiologic findings. The cause of this disease is still uncertain. Sarcoidosis affects mostly lungs and lymph nodes and is not usually considered a urological disease, therefore, this etiology may be overlooked in several urological disorders, such as hypercalcemia, hypercalciuria and nephrolithiasis. It affects all races and genders. This review aims to describe the urological manifestations of sarcoidosis and to elucidate how the disease may affect the management of numerous urological conditions.

Renal manifestations of sarcoidosis: from accurate diagnosis to specific treatment.

Sarcoidosis is a multisystem granulomatous disease characterized by epithelioid noncaseating granulomas associated with clinical and radiologic findings. The cause of this disease is still uncertain. Sarcoidosis affects mostly lungs and lymph nodes and is not usually considered a urological disease, therefore, this etiology may be overlooked in several urological disorders, such as hypercalcemia, hypercalciuria and nephrolithiasis. It affects all races and genders. This review aims to describe the urological manifestations of sarcoidosis and to elucidate how the disease may affect the management of numerous urological conditions.

Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers.

The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D3 [1,25(OH)D] levels exceed the values of controls in some but not all hypercalciuric stone formers (HSF). We aimed to evaluate serum 1,25(OH)D levels, the expression of VDR, CYP27B1, and CYP24A1 hydroxylases in HSF in comparison with normocalciuric stone formers (NSF) and healthy subjects (HS). Blood samples, 24-h urine collections and a 3-day dietary record were obtained from 30 participants from each of the groups. The expression of VDR, CYP27B1, and CYP24A1 was measured by flow cytometry. HSF presented significantly higher urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Calcium intake was lower in HSF versus NSF and HS (442 ± 41 vs 594 ± 42 and 559 ± 41 mg/day, respectively, p = 0.027). Ionized calcium was significantly lower in HSF than NSF (1.29 ± 0.0 vs 1.31 ± 0.0 mmol/L, p < 0.01). Serum 1,25(OH)D was significantly higher in HSF and NSF than HS (22.5 ± 1.2; 22.2 ± 1.2 vs 17.4 ± 1.2 pg/ml, p = 0.007) but serum 25(OH)D, PTH, klotho and plasma FGF-23 did not differ between groups. VDR expression was higher in HSF and NSF than HS (80.8 ± 3.2; 78.7 ± 3.3 vs 68.6 ± 3.2%, p = 0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio of 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43 ± 0.25 and 0.56 ± 0.10 vs 0.34 ± 0.06, p = 0.00). Stone formers, regardless of urinary calcium excretion, had higher VDR expression and 1,25(OH)D levels than HS, even in ranges considered normal. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.

[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.

Hipercalciuria hidiopática como factor predisponente de infección urinaria / Idiopathic hypercalciuria as predisposing factor of urinary infection

Introducción: La hipercalciuria idiopática es una alteración metabólica relativamente frecuente y existen escasas publicaciones de su relación con la infección del tracto urinario. Objetivos: Precisar si existe asociación entre la infección urinaria e hipercalciuria idiopática para determinar si esta alteración metabólica constituye un factor de riesgo de infección urinaria. Métodos: Estudio descriptivo longitudinal prospectivo en pacientes de edad pediátrica con diagnóstico de infección urinaria atendidos en el Hospital Pediátrico Universitario William Soler entre 1ro. enero de 2016 y 31 de diciembre de 2017. Dos semanas después de controlada la infección se recogió muestra de orina de la primera micción del día para determinación de índice calcio/creatinina y precisar la excreción de calcio en 24 horas. Si esta prueba arroja resultados positivos, entre dos y cuatro semanas posteriores, se repite la muestra y si ambas son positivas y el calcio en sangre es normal se diagnostica hipercalciuria idiopática. Resultados: Se incluyeron en el estudio 130 pacientes. En 43,8 por ciento se encontró hipercalciuria idiopática. En su primer episodio infeccioso se estudiaron 52,3 por ciento y los restantes con antecedentes de infección o recurrencia. En 86,2 por ciento la infección fue catalogada como pielonefrítica. La distribución por sexo de la hipercalciuria no mostró diferencia y el síntoma hematuria con dolor abdominal recurrente resultó sugestivo de infección asociada a hipercalciuria (p < 0,05). El germen infectante no contribuye a pensar en hipercalciuria. Conclusión: La hipercalciuria idiopática constituye un factor predisponente de infección del tracto urinario(AU)

Introduction: Idiopathic hypercalciuria is a relatively frequent metabolic alteration and there are scarce publications on its relation with the urinary tract´s infection. Objective: To specify if there is a relation between urinary infection and idiopathic hypercalciuria, in order to determine if this last one constitutes a risk factor of urinary infection. Methods: Prospective, descriptive and longitudinal study in pediatric age's patients with a diagnosis of urinary infection that were attended in William Soler University Pediatric Hospital from January 1st, 2016 to December 31st, 2017. After two weeks of the infection being controlled, a urine sample from the first micturition of the day was collected to determine calcium/creatinine index and to specify calcium excretion in 24 hours. If this test shows positive results, after two to four weeks the sample is repeated, and if both are positive and calcium level in blood is normal, so idiopathic hypercalciuria is diagnosed. Results: 130 patients were included in the study. In 43.8 percent idiopathic hypercalciuria was found. 52.3 percent were studied during the first infectious episode, and there is presented a history of infection or recurrence. In 86.2 percent of the patients, the infection was catalogued as pyelonephritis. Hypercalciuria´s gender distribution didn't show any differences, and the symptom called hematuria with recurrent abdominal pain was suggestive to an infection related to hypercalciuria (p < 0.05). The infectious germ does not induce to think in hypercalciuria. Conclusions: Idiopathic hypercalciuria constitutes a predisposing factor of urinary tract's infection(AU)

Calcitriol and FGF-23, but neither PTH nor sclerostin, are associated with calciuria in CKD.

PURPOSE: The recent observation that urinary calcium excretion (UCE) drops considerably with CKD and that this effect may occur beyond compensation for reduced intestinal calcium absorption suggests that CKD per se is a state of sustained positive calcium balance, a mechanism likely to contribute to vascular calcification and CVD in CKD. However, the determinants of UCE reduction in CKD are not well understood and there is a lack of clinical studies, particularly in the CKD population. Therefore, in this study, we aimed to evaluate variables associated with UCE in a CKD cohort. METHODS: Baseline data on 356 participants of the Progredir Study, Sao Paulo, Brazil, essentially composed of CKD G3a-G4, were analyzed according to UCE (24 h urine collection). RESULTS: Median 24 h UCE was 38 mg/day (IQR 21-68 mg/day) and 0.48 mg/kg/day (IQR 0.28-0.82 mg/kg/day). In univariate analysis, UCE was inversely related to age, phosphorus, 1-84 PTH, FGF-23 and sclerostin, and positively associated with eGFR, DBP, 1,25(OH)2-vitamin D, calcium, bicarbonate, total calorie intake and spironolactone use. After adjustments for age, sex and eGFR, only 1,25(OH)2-vitamin D, calcium, FGF-23, bicarbonate and total calorie intake remained associated with it, but not PTH nor sclerostin. Lastly, in a multivariable model, eGFR, serum 1,25(OH)2-vitamin D, calcium, and FGF-23 remained associated with UCE. Similar results were observed when calcium fractional excretion was used instead of UCE, with eGFR, 1-25-vitamin D and FGF-23 remaining as independent associations. CONCLUSION: Our results showed that CKD is associated with very low levels of UCE and that 1,25(OH)2-vitamin D, serum calcium and FGF-23 were independently associated with UCE in this population, raising the question whether these factors are modulators of the tubular handling of calcium in CKD.

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.

Etiología de la hematuria monosintomática en pediatría / Etiology of monosymptomatic hematuria in Pediatrics

Introducción: La hematuria es el hallazgo clínico más frecuente entre las enfermedades genitourinarias, después de las infecciones del tracto urinario a cualquier edad. Objetivo: Identificar las características generales y etiología de la hematuria monosintomática en pacientes pediátricos. Métodos: Investigación descriptiva longitudinal y prospectiva con los pacientes atendidos con hematuria monosintomática en el Servicio de Nefrología del Hospital Pediátrico Docente William Soler entre el primero de enero de 2014 y 31 de diciembre de 2015. Resultados: Se reclutaron 45 pacientes. Predominó en escolares (40 por ciento) y adolescentes (40 por ciento), sexo masculino (55,5 por ciento). Se recogió el antecedente personal o familiar de hematuria en 44,5 por ciento y 55,5 por ciento, respectivamente. La urolitiasis familiar estuvo presente en 37,7 por ciento. El tipo de hematuria más frecuente fue la macroscópica (75,8 por ciento), no glomerular (71,2 por ciento), sin proteinuria (77,8 por ciento), y hematíes eumórficos (62,2 por ciento). La causa más frecuente fue la hipercalciuria idiopática (51,1 por ciento) y el 80 por ciento de todos los pacientes solo recibió tratamiento higieno-dietético. En 20 por ciento de los pacientes no se pudo precisar la causa etiológica. Conclusiones: La causa más frecuente de hematuria fue no glomerular (hipercalciuria idiopática) y en aquellos con hematuria cuya causa etiológica no se pudo precisar, es obligado mantener un seguimiento prolongado(AU)

Introduction: Hematuria is the most frequent clinical finding among genitourinary diseases afterwards urinary tract infection at any age. Objective: To identify general characteristics and etiology of monosymptomatic hematuria in in pediatrics patients. Methods: Descriptive, longitudinal and prospective research of the patients by monosymptomatic hematuria attended at the Nephrology service in William Soler Teaching Pediatric Hospital from January 1, 2014 to December 31, 2015. Results: 45 patients were recruited. Schoolchildren (40 percent) were predominant and adolescents (40 percent), and males (55.5 percent). It was collected personal or familial records of hematuria in 44.5 percent and 55.5 percent, respectively. Familial urolithiasis was present in 37.7 percent. The most common type of hematuria was the macroscopic (75.8 percent), non-glomerular (71.2 percent), without proteinuria (77.8 percent) and with eumorphic hematies (62.2 percent). The most frequent etiological cause was idiopathic hypercalciuria (51.1 percent), and 80 percent of all patients only received hygiene-dietetic treatment. In the 20 percent of the patients was not possible to determine the etiological cause. Conclusions: The most frequent cause of hematuria was non-glomerular (idiopathic hypercalciuria); and in those patients with hematuria of non-precised etiological cause, it is mandatory to keep long-term follow-up(AU)

Effects of Tributyltin (TBT) on Rat Bone and Mineral Metabolism.

BACKGROUND/AIMS: Tributyltin (TBT) is an organotin (OTs) and biohazard organometallic pollutant. Recently our group has shown that TBT, even in very low doses, has deleterious effects on several tissues most likely due to its role as an endocrine-disrupting molecule. Other studies have confirmed that OT exposure could be responsible for neural, endocrine, and reproductive dysfunctions via in vitro and in vivo models. However, TBT effects on bone lack concise data despite the fact that bone turnover is regulated by endocrine molecules, such as parathormone (PTH), estrogen (E2), etc. Our group has already shown that TBT disrupts adrenal and female gonadal functions. METHODS: We studied the effects of TBT on bone metabolism and structure using DXA, microCT scan, and SEM. We also determined the calcium (Ca²âº) and phosphate (Pi) metabolism in TBT-treated rats as well as some biomarkers for bone formation and resorption. RESULTS: Surprisingly, we found that TBT leads to higher bone mineral density (BMD) although lesions in spinal bone were observed by either microCT scan or SEM. Biomarkers for bone resorption, such as the urinary deoxipyridinolines (DPD) excretion ratio was increased in TBT-treated animals versus mock-treated controls. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone formation and are also elevated suggesting that the bone matrix suffers from a higher turnover. Serum Ca²âº (total and ionized) do not changed by TBT treatment although hypercalciuria is observed. CONCLUSION: It is known that Sn atoms have three valence states (Sn²âº, Sn³âº, and Sn4⁺); hence, we hypothesized that Sn (more likely Sn²âº) could be competing with Ca²âº and/or Mg²âº in hydroxyapatite mineral matrix to disturb bone turnover. Further work is needed to confirm this hypothesis.