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      Urinary citrate excretion in healthy children depends on age and gender

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          Abstract

          Background

          Hypocitraturia is considered a major risk factor for calcium stone formation. However, there is no widely accepted reference database of urinary citrate excretion in children. The aim of our study was to determine the amount of citrate eliminated in the urine over a 24-h period in a pediatric cohort and to determine an optimal unit reflecting excretion.

          Methods

          The study cohort comprised 2,334 healthy boys and girls aged 2–18 years. The levels of urinary citrate were assessed by an enzymatic method in 24-hour urine and expressed in absolute values, as urinary concentration, citrate/creatinine ratio, per kilogram of body weight, in relation to 1.73 m 2, and as the calcium/citrate index.

          Results

          Similar incremental age-related citraturia rates were observed in both male and female subjects until puberty during which time citrate excretion became significantly higher in girls. Urinary citrate adjusted for creatinine and for body weight showed a significantly decreasing trend with increasing age in both sexes. Urinary citrate corrected for body surface was weakly correlated with age. Thus, the assumption of 180 mg/1.73 m 2/24 h for males and 250 mg/1.73 m 2/24 h for females as lower cut-off values appeared to be reliable from a practical perspective.

          Conclusions

          We found distinct sex-dependent differences in citraturia at the start of puberty, with significantly higher values of urinary citrate in girls than in boys. Further prospective studies are warranted to elucidate whether this difference represents a differentiated risk of urolithiasis.

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          Most cited references23

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          Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research.

          Urinary creatinine reference values that take anthropometric data into account, which is mandatory during growth, are not available for healthy white children. We sought to establish anthropometry-based reference values for 24-h urinary creatinine excretion in healthy white children aged 3-18 y. Anthropometric variables and 24-h urinary creatinine excretion rates were determined cross-sectionally (225 boys and 229 girls). Age and sex dependency of 24-h creatinine excretion (crude and related to individual anthropometric variables) were assessed to derive appropriate creatinine reference values. The applicability of these creatinine reference values for estimation of daily excretion of certain analytes was assessed in 40 additional children. Sex-specific, body-weight-related creatinine reference values were derived for the following age groups: 3, 4-5, 6-8, 9-13, and 14-18 y. The 5th percentile exceeded 0.1 mmol x kg(-1) x d(-1) in all age groups >3 y. The use of these creatinine reference values for estimating average 24-h excretion rates of certain analytes (determined as the ratio of analyte to creatinine in spot urine samples) yielded reasonable estimates of mean 24-h urinary excretion rates actually analyzed (spot and 24-h urine samples from the same children). Ideal 24-h creatinine excretion values for height were also derived for a potential determination of the creatinine height index. Established anthropometry-based creatinine reference values are recommended as a convenient, simple tool to 1) identify severe 24-h urine collection errors, 2) calculate average 24-h excretion rates of certain analytes (from respective ratios of analyte to creatinine) determined in spot urine samples, and 3) assess somatic protein status by determining the creatinine height index.
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            Renal handling of citrate.

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              Citrate excretion: a window on renal metabolism.

              The rate of intracellular metabolism of citrate plays a major role in determining the amount of citrate excreted in the urine. Fractional excretion of citrate can be increased either by increasing intracellular citrate synthesis from precursors or by inhibiting mitochondrial citrate metabolism. Increased excretion secondary to increased synthesis of citrate occurs when citric acid cycle precursors such as malate or succinate are infused. Increased excretion resulting from inhibition of citrate metabolism occurs when malonate, maleate, or fluorocitrate is administered. Systemic acid-base changes cause striking changes in citrate clearance and metabolism. Recent evidence suggests that the effects of acid-base changes are mediated by alteration in the pH gradient across the inner mitochondrial membrane. Metabolic alkalosis causes cytoplasmic pH and bicarbonate to increase, resulting in a decrease in the mitochondrial pH gradient. This change inhibits the tricarboxylate carrier, slowing entry of citrate into the mitochondrial matrix compartment. The level of citrate in the cytoplasm increases, tubular and peritubular citrate uptake are reduced, and citrate clearance increases. Opposite changes occur in acidosis. Change in the mitochondrial pH gradient provides a sensitive mechanism for regulating renal substrate metabolism.
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                Author and article information

                Contributors
                tporowski@biaman.pl
                Journal
                Pediatr Nephrol
                Pediatr. Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0931-041X
                1432-198X
                3 April 2014
                3 April 2014
                2014
                : 29
                : 9
                : 1575-1582
                Affiliations
                [ ]Department of Pediatric Nephrology, Medical University of Bialystok, Waszyngtona Street 17, 15-274 Bialystok, Poland
                [ ]Department of Pediatric Surgery, Medical University of Bialystok, Bialystok, Poland
                [ ]Department of Pediatrics and Developmental Disorders, Medical University of Bialystok, Bialystok, Poland
                [ ]Department of Urology, Regional Hospital of Bialystok, Bialystok, Poland
                [ ]Department of Pediatrics, Division of Pediatric Nephrology, University of Bonn, Bonn, Germany
                Article
                2806
                10.1007/s00467-014-2806-7
                4147207
                24696006
                253022c5-a906-4ce5-a64c-4a53748702c2
                © The Author(s) 2014

                Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 2 January 2014
                : 28 February 2014
                : 6 March 2014
                Categories
                Original Article
                Custom metadata
                © IPNA 2014

                Nephrology
                children,citraturia,normative values,urolithiasis
                Nephrology
                children, citraturia, normative values, urolithiasis

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