Kidney stones, hypercalciuria, and recent insights into proximal tubule calcium reabsorption.

PURPOSE OF REVIEW: Most kidney stones are composed of calcium, and the greatest risk factor for kidney stone formation is hypercalciuria. Patients who form kidney stones often have reduced calcium reabsorption from the proximal tubule, and increasing this reabsorption is a goal of some dietary and pharmacological treatment strategies to prevent kidney stone recurrence. However, until recently, little was known about the molecular mechanism that mediates calcium reabsorption from the proximal tubule. This review summarizes newly uncovered key insights and discusses how they may inform the treatment of kidney stone formers. RECENT FINDINGS: Studies examining claudin-2 and claudin-12 single and double knockout mice, combined with cell culture models, support complementary independent roles for these tight junction proteins in contributing paracellular calcium permeability to the proximal tubule. Moreover, a family with a coding variation in claudin-2 causing hypercalciuria and kidney stones have been reported, and reanalysis of Genome Wide Association Study (GWAS) data demonstrates an association between noncoding variations in CLDN2 and kidney stone formation. SUMMARY: The current work begins to delineate the molecular mechanisms whereby calcium is reabsorbed from the proximal tubule and suggests a role for altered claudin-2 mediated calcium reabsorption in the pathogenesis of hypercalciuria and kidney stone formation.

The emerging roles and therapeutic potential of cyclin M/CorC family of Mg2+ transporters.

Cyclin M (CNNM) and its prokaryotic ortholog CorC belong to a family of proteins that function as Mg2+-extruding transporters by stimulating Na+/Mg2+ exchange, and thereby control intracellular Mg2+ levels. The Mg2+-extruding function of CNNM is inhibited by the direct binding of an oncogenic protein, phosphatase of regenerating liver (PRL), and this inhibition is responsible for the PRL-driven malignant progression of cancers. Studies with mouse strains deficient for the CNNM gene family revealed the importance of CNNM4 and CNNM2 in maintaining organismal Mg2+ homeostasis by participating in intestinal Mg2+ absorption and renal reabsorption, respectively. Moreover, CNNM proteins are involved in various diseases, and gene mutations in CNNM2 and CNNM4 cause dominant familial hypomagnesemia and Jalili syndrome, respectively. Genome wide association studies have also revealed the importance of CNNM2 in multiple major diseases, such as hypertension and schizophrenia. Collectively, the molecular and biological characterizations of CNNM/CorC show that they are an intriguing therapeutic target; the current status of drug development targeting these proteins is also discussed.

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.

Parathyroidectomy improves hypercalciuria in patients with primary hyperparathyroidism.

BACKGROUND: Hypercalciuria is an important manifestation of primary hyperparathyroidism and may contribute to the risk of nephrolithiasis. This study examined the impact of parathyroidectomy on 24-hour urinary calcium (24-hour UCa) levels and rates of resolution of hypercalciuria after surgery. METHODS: A retrospective cohort study was performed of patients who underwent curative parathyroidectomy for primary hyperparathyroidism from 2007 to 2017. Baseline and postoperative urine and serum biochemistry levels were analyzed. The relationship between preoperative 24-hour UCa levels and the absolute decrease in postoperative UCa excretion was assessed using Spearman's rank correlation coefficient. RESULTS: Of 110 patients, 84 (76.4%) experienced a ≥20% decrease in 24-hour UCa level postoperatively. These patients had a higher baseline median 24-hour UCa level (293.5 vs 220.5 mg/24-hour; P = .001), higher baseline mean serum parathyroid hormone (106.5 vs 83; P = .05) and were more likely to have single gland disease (85.7% vs 65.4%, P = .04) compared with patients in whom 24-hour UCa excretion did not improve. Of the 28 patients (25%) who were hypercalciuric (24-hour UCa >400 mg/day) at baseline, 22 (79%) became normocalciuric postoperatively. A linear correlation was observed between preoperative 24-hour UCa levels and the decline in 24-hour UCa excretion after surgery (R2 = 0.59, P < .0001) such that the degree of improvement could be predicted using the following equation: absolute decrease in postoperative 24-hour UCa = 0.68 × preoperative 24-hour UCa-68. CONCLUSION: Parathyroidectomy reduces 24-hour UCa excretion in the majority of patients with PHPT and restores normocalciuria in 79% of patients with hypercalciuria at baseline.

Educational review: role of the pediatric nephrologists in the work-up and management of kidney stones.

BACKGROUND: The incidence of nephrolithiasis in children and adolescents is increasing and appears to double every 10 years. The most important role of the pediatric nephrologist is to diagnose and modify various metabolic and non-metabolic risk factors, as well as prevent long-term complications especially in the case of recurrent nephrolithiasis. OBJECTIVE: The purpose of this review is to summarize the existing literature on the etiology and management of pediatric nephrolithiasis. RESULTS: The incidence of kidney stones is increasing; dietary and environmental factors are probably the main causes for this increased incidence. In most pediatric patients, the etiology for the kidney stones can be identified. Metabolic factors, such as hypercalciuria and hypocitraturia, urinary tract infection, and urinary stasis, constitute leading causes. Herein, we review the etiologies, diagnostic work-up, and treatment options for the most prevalent causes of kidney stones. The detrimental effects of excessive dietary sodium, reduced fluid intake, and the benefits of plant-based over animal-based protein consumption on urinary crystal formation are discussed. We also review the long-term complications. CONCLUSIONS: Pediatric nephrologists have an important role in the diagnostic work-up and prevention of recurring nephrolithiasis.

Resumen ejecutivo del documento de consenso SEORL CCC-SEEN sobre hipoparatiroidismo postiroidectomía / Executive summary of the SEORL CCC-SEEN consensus statement on post-thyroidectomy hypoparathyroidism

El hipoparatiroidismo es la complicación más frecuente tras la tiroidectomía total. Se define por la presencia de hipocalcemia con unos niveles de hormona paratiroidea (PTH) bajos o inadecuadamente normales. La hipocalcemia aguda es una complicación potencialmente grave. Su tratamiento se basa, según la gravedad del cuadro, en la administración de calcio por vía oral o intravenosa, pudiendo requerir asimismo calcitriol oral. El riesgo de hipocalcemia sintomática tras una tiroidectomía es muy bajo si la PTH postoperatoria desciende menos del 80% respecto de la preoperatoria. Estos pacientes podrían ser dados de alta sin tratamiento, aunque los umbrales son variables entre laboratorios y recomendamos extremar la vigilancia en los casos de riesgo aumentado (enfermedad de Graves, grandes bocios, reintervenciones o constancia de la extirpación de alguna paratiroides). El tratamiento a largo plazo busca controlar los síntomas manteniendo la calcemia en el límite bajo de la normalidad, vigilando el producto calcio-fósforo y la aparición de hipercalciuria

Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria

Executive summary of the SEORL CCC-SEEN consensus statement on post-thyroidectomy hypoparathyroidism. / Resumen ejecutivo del documento de consenso SEORL CCC-SEEN sobre hipoparatiroidismo postiroidectomía.

Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria.

Clinical and Metabolic Correlates of Calcium Oxalate Stone Subtypes: Implications for Etiology and Management.

Introduction: Calcium oxalate (CaOx) is the predominate component within renal calculi and can be divided into two subtypes: CaOx-monohydrate (COM) and CaOx-dihydrate (COD). COM and COD form in differing urinary environments, which suggest differential underlying metabolic abnormalities associated with each subtype. We compared clinical and metabolic findings in CaOx stone formers to delineate factors differentiating COD and COM stone formers and the implication this holds in terms of etiology and treatment. Patients and Methods: We identified CaOx stone formers that had passed their stones or had undergone endoscopic extraction between October 2014 and December 2018. Only patients who had a predominant subtype (≥80% COM or COD) and who had a 24-hour urine evaluation before medical management were included. Clinical and metabolic factors were compared in the two subgroups. Results: Out of 157 stone formers, 121 were COM and 36 were COD. COD formers were younger than COM formers with a mean age of 53 ± 16 vs 59 ± 15, respectively (p = 0.038). There were no observable differences in gender, body mass index, hypertension, diabetes mellitus, or hyperlipidemia. COM formers exhibited higher rates of hypocitraturia and hyperoxaluria, p = 0.022 and p = 0.018, respectively. Conversely, COD formers had significantly higher rates of hypercalciuria (47% vs 28%, p = 0.012). Multivariate analysis found hypercalciuria to independently predict COD (p = 0.043) and hyperoxaluria to predict COM stones (p = 0.016). Conclusion: COM formers are more likely to have hyperoxaluria, hypocitraturia, and elevated urinary oxalate levels compared to COD formers. COD formers exhibited higher incidence of hypercalciuria. These data suggest that all CaOx stones are not alike and that distinct metabolic and clinical etiological differences exist that may guide future management and prevention.

A comparison of induced effects on urinary calcium by thiazides and different dietary salt doses: Implications in clinical practice. / Comparación de los efectos inducidos sobre la calciuria por tiazidas y diferentes dosis de sal en la dieta: implicaciones en la práctica clínica.

INTRODUCTION: Both dietary restriction of sodium chloride (NaCl) and treatment with thiazides have been used in hypercalciuric patients. OBJECTIVES: To calculate regular salt intake and investigate the correlation between natriuresis and urinary calcium with usual diet (B) and after changing the amount of NaCl intake and administration of thiazides. MATERIAL AND METHODS: Nineteen healthy young individuals had their diet replaced by 2l of Nutrison® Low Sodium (500mg sodium/day) daily for two days. Then, 5g of NaCl were added every two days («5¼, «10¼ and «15¼), administering 50mg (H50) and 100mg (H100) of Higroton® on the last two days. Blood sodium, plasma renin activity (PRA) and aldosterone were determined in venous blood samples, as were urinary sodium and calcium. STATISTICAL ANALYSIS: Wilcoxon t-test and the Pearson linear correlation were calculated. RESULTS: Urinary Na (mEq/24h): 210.3±87.6 («B¼); 42.7±20.4 («5¼); 135.5±50.6 («10¼); 225.5±56.7 («15¼). Urinary calcium (mg/24h): 207.8±93.6 («B¼); 172.8±63.1 («5¼); 206.2±87.7 («10¼); 227.4±84.1 («15¼). A positive correlation was observed between natriuresis and urinary calcium in «10¼ (r=0.47) and «15¼ (r=0.67). After Higroton®, natriuresis: 232.3±50.7; 377±4 (H50); 341.1±68.4 (H100); Ca in urine: 209.8±57.4; 213.2±67.6 (H50); 159.1±52.2 (H100). CONCLUSIONS: Salt intake in the population studied was estimated to be 14.9±4.9g/day with a positive correlation found between sodium and calcium urine output with daily intakes of 11.25 and 16.25g of salt. With the usual intake, for each gram of salt, urinary calcium increased by 5.46 mg/24 h and with 100mg of Higroton® it decreased by 50.7mg/24h. These data could be useful for the management of patients with excretory hypercalciuria or hypoparathyroidism.

[The long-term results of the treatment of renal hypercalciuria - a report of two cases]. / Odlegle wyniki leczenia hiperkalciurii nerkowej ­ prezentacja dwóch przypadków.

In recent years there can be observed a growing number of cases of urolithialis, both in children and in adults. Many pathogenic mechanisms of forming stones have been recognized and there is possible profounder diagnostics. Facing increasing problem of urolithialis in children, it is necessary to seek all possible causes of the disease to prevent forming stones, relapses and its further consequences. In most cases it is possible to diagnose metabolic abnormalities, of which the most frequent is hypercalciuria (excessive excretion of calcium in urine). In children, idiopathic hypercalciuria occurs the most frequently. It is possible to diagnose different types of hypercalciuria (absorptive, renal or resorptive) and apply appropriate treatment. A CASE REPORT: We present two cases of patients with urolithialis and diagnosed renal hypercalciuria. Time of observation of the first patient was more than 6 years, of the second one - 9 years. In both cases there has been applied appropriate treatment, however it was the proper realization of the recommendations that influenced long-term results of the treatment. Even the most detailed examination cannot assure effectiveness if the patient and the parents do not have positive approach to the treatment.

Kidney Calculi: Pathophysiology and as a Systemic Disorder.

The pathophysiology of urinary stone formation is complex, involving a combination of metabolic, genetic, and environmental factors. Over the past decades, remarkable advances have been emerged in the understanding of the pathogenesis, diagnosis, and treatment of calcium kidney calculi. For this review, both original and review articles were found via PubMed search on pathophysiology, diagnosis, and management of urinary calculi. These resources were integrated with the authors' knowledge of the field. Nephrolithiasis is suggested to be associated with systemic disorders, including chronic kidney insufficiency, hematologic malignancies, endocrine disorders, autoimmune diseases, inflammatory bowel diseases, bone loss and fractures, hypertension, type 2 diabetes mellitus, metabolic syndrome, and vascular diseases like coronary heart diseases and most recently ischemic strokes. This is changing the perspective of nephrolithiasis from an isolated disorder to a systemic disease that justifies further research in understanding the underlying mechanisms and elaborating diagnostic-therapeutic options.

Primary hyperparathyroidism, hypercalciuria, and bone recovery after parathyroidectomy.

BACKGROUND: In primary hyperparathyroidism, successful parathyroidectomy leads to improved bone mineral density in the majority of cases. Our aim was to further explore the relationship between hypercalciuria, kidney function, and bone recovery after parathyroidectomy. METHODS: Bone mineral density, estimated glomerular filtration rate, and 24-hour urinary calcium were analyzed before and one year after parathyroidectomy in a cohort of 150 primary hyperparathyroidism patients (119 women; median age 60 [range 30-80] years) taking part in a clinical trial. The patients were randomized to 1-year daily treatment with either cholecalciferol 1,600 IU and calcium carbonate 1,000 mg or calcium carbonate alone. RESULTS: Baseline 24-hour urinary calcium correlated directly with s-calcium, parathyroid hormone, 25-OH-D, the bone markers beta C-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide, and estimated glomerular filtration rate (r = 0.19-0.30; P < .05) and inversely with age (r = -0.25; P = .004); 24-hour urinary calcium decreased and bone mineral density in lumbar spine and hip increased similarly in the 2 groups. Baseline 24-hour urinary calcium in the highest quartile (>10 mmol/d) was associated with greater increases in all locations. In a multivariable model adjusting for age, sex, smoking, diabetes, body mass index, estimated glomerular filtration rate, baseline bone mineral density, and vitamin D group, the increase in total hip bone mineral density remained independently associated with baseline 24-hour urinary calcium in the highest quartile (>10 mmol/d) and with plasma parathyroid hormone. Patients with persistent increases in 24-hour urinary calcium at follow-up (14%) had similar bone mineral density improvement. CONCLUSION: Overall, 24-hour urinary calcium > 10 mmol/d was an independent determinant of improvement in bone mineral density and should be taken into account when considering parathyroidectomy.

Inherited and acquired disorders of magnesium homeostasis.

PURPOSE OF REVIEW: Magnesium (Mg) imbalances are frequently overlooked. Hypermagnesemia usually occurs in preeclamptic women after Mg therapy or in end-stage renal disease patients, whereas hypomagnesemia is more common with a prevalence of up to 15% in the general population. Increasing evidence points toward a role for mild-to-moderate chronic hypomagnesemia in the pathogenesis of hypertension, type 2 diabetes mellitus, and metabolic syndrome. RECENT FINDINGS: The kidneys are the major regulator of total body Mg homeostasis. Over the last decade, the identification of the responsible genes in rare genetic disorders has enhanced our understanding of how the kidney handles Mg. The different genetic disorders and medications contributing to abnormal Mg homeostasis are reviewed. SUMMARY: As dysfunctional Mg homeostasis contributes to the development of many common human disorders, serum Mg deserves closer monitoring. Hypomagnesemic patients may be asymptomatic or may have mild symptoms. In severe hypomagnesemia, patients may present with neurological symptoms such as seizures, spasms, or cramps. Renal symptoms include nephrocalcinosis and impaired renal function. Most conditions affect tubular Mg reabsorption by disturbing the lumen-positive potential in the thick ascending limb or the negative membrane potential in the distal convoluted tubule.

El cociente calcio/creatinina de ayunas en pacientes con litiasis cálcica y su relación con la hipercalciuria y el metabolismo fosfocálcico / The fasting calcium/ creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism

OBJETIVO: Determinar la importancia del cociente calcio/creatinina de ayunas en pacientes con litiasis cálcica y su relación con la hipercalciuria y metabolismo fosfocálcico. MÉTODOS: Estudio transversal que incluye 143 pacientes divididos en dos grupos según calcio/creatinina en ayunas. Grupo 1:66 pacientes (calcio/creatinina<0,11); Grupo 2:77 pacientes (calcio/creatinina>0,11). Se realiza estudio comparativo entre grupos de parámetros del metabolismo fosfo-cálcico y excreción de marcadores litogénicos en orina. Estudio de correlación lineal calciuria- calcio/creatinina en ayunas. Estudio estadístico con SPSS 17.0, considerando p≤0,05. RESULTADOS: Destaca en los pacientes del grupo 2 una excreción aumentada de calcio en orina de 24 h respecto grupo 1 (229,3 vs 158,1; p = 0,0001) y de calcio/citrato (0,47 vs 0,34; p = 0,001). Existe correlación lineal positiva y significativa entre niveles de calcio en orina de 24 h y cociente calcio/creatinina en ayunas (R=0,455; p = 0,0001) y se establece un punto de corte en 0,127 del cociente (sensibilidad 72% y especificidad 66%) para determinar hipercalciuria (excreción mayor 260 mg en 24 h). CONCLUSIONES: La elevación del calcio/creatinina en ayunas determina mayor excreción de calcio en 24 h, aunque la sensibilidad y especificidad para determinar hipercalciuria no es elevada

OBJECTIVE: To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism. METHODS: Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p≤0.05. RESULTS: It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p = 0.0001) and calcium/citrate (0.47 vs 0.34; p = 0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p = 0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h). CONCLUSIONS: Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high

Family history influences clinical course of idiopathic calcium nephrolithiasis: case-control study of a large cohort of Italian patients.

AIM: To evaluate the contribution of family history of stones (FHS), up to second-degree relatives, on clinical course (age of first renal colic, bilateral disease, retained calculi, recurrences, urological procedures) of idiopathic calcium nephrolithiasis (ICN) and urinary parameters of lithogenic risk, a case-control study was carried out. METHOD: Clinical records of 2080 patients with ICN were evaluated and categorized according to FHS. Data about clinical course of disease and urinary parameters of lithogenic risk were collected. Student's t, Chi square tests and binary logistic regression were applied to discriminate groups with vs. without FHS. RESULTS: FHS was associated with an earlier onset of stone disease (age at first episode 32 ± 13 vs. 37 ± 15 years, p <0.001), particularly in females. After adjustment for multiple covariates, FHS was significantly associated to a higher risk of recurrence [odds ratio (OR) 1.2, 95 % confidence interval (1.1-1.4), p = 0.04], retained stones [OR 1.3, CI (1.1-1.5), p = 0.004], bilateral stones [OR 1.2, 95 % CI (1.1-1.5), p = 0.022] and urological procedures [OR 1.2, 95 % CI (1.1-1.5), p = 0.034]. FHS did not influence urinary parameters of lithogenic risk, except for calcium excretion in females. CONCLUSION: A positive family history influences the clinical course of ICN with some significant gender-related differences, substantially irrespective of urinary parameters of lithogenic risk.

A Practical Approach to Hypocalcaemia in Children.

Hypocalcaemia is one of the commonest disorders of mineral metabolism seen in children and may be a consequence of several different aetiologies. These include a lack of secretion or function of parathyroid hormone, disorders of vitamin D metabolism and abnormal function of the calcium-sensing receptor. A practical approach to the investigation, diagnosis and subsequent management of hypocalcaemic disorders is presented.

Hypercalciuria in a child with acral peeling skin syndrome: a case report.

We present a case of 3-year-old Caucasian boy who developed monthly cyclic attacks of skin peeling of the palms and soles over 1.5 years. The skin peeling was associated with hypercalciuria. No mutation was present in TGM5 and CSTA genes, but the typical clinical picture and the biopsy from flaccid blisters on the feet confirmed the acral peeling skin syndrome (APSS). The possible associations of rare genetic disorders and metabolic conditions in the course of APSS need to be investigated.

Early postnatal calcium and phosphorus metabolism in preterm infants.

OBJECTIVES: Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake. METHODS: Preterm infants, included on their first day of life, received standard PN, providing a maximum Ca/P intake of 3/1.92 mmol · kg(-1) · day(-1) on day 3. Ca/P content of formula was 2.5/1.6 mmol/dL, and fortified human milk was 2.4/1.95 mmol/dL. PN supplied 80 IU · kg(-1) · day(-1) vitD. Formula and fortified human milk contained 200 IU/dL of vitD. During a 5-week period, serum concentrations and urinary excretion of Ca/P were registered and related to the intake of minerals and vitD. RESULTS: During 12 months, 79 infants (mean gestational age 29.8 ± 2.2 weeks, mean birth weight 1248 ± 371 g) were included. The recommended intake for minerals was achieved by day 5 and for vitD by 4 weeks. Infants developed hypercalcaemia, hypercalciuria, and hypophosphataemia during the first postnatal week, leading to the additional P supplementation in 49 infants. The renal tubular reabsorption of P was >95% until day 9 but decreased <70% after the second week. Alkaline phosphatase was normal at birth, increased to a maximum of 450 IU/L by day 14, and remained above the normal range for the remaining period. CONCLUSIONS: Parenteral intake of P appeared to be too low, leading to mineral imbalances in the early postnatal period, and vitD intake was also below recommendations.