Abstract

BackgroundHypocitraturia 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.MethodsThe 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 m2, and as the calcium/citrate index.ResultsSimilar 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 m2/24 h for males and 250 mg/1.73 m2/24 h for females as lower cut-off values appeared to be reliable from a practical perspective.ConclusionsWe 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.

Highlights

  • Further prospective studies are warranted to elucidate whether this difference represents a differentiated risk of urolithiasis

  • Low urinary citrate excretion is recognized as a major risk factor for calcium stone formation

  • The exclusion criteria included abnormalities in dipstick urinalysis (Bayer Diagnostic, Bridgend, UK), any infections or medications, diseases known to affect urinary citrate excretion, and inadequate 24-h urine collection assessed with urine creatinine excretion according to Remer et al [16]

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Summary

Introduction

Low urinary citrate excretion is recognized as a major risk factor for calcium stone formation. The inhibitory effects of citrate on crystal formation in urine are complex. Citrate creates soluble complexes with calcium, thereby effectively reducing urinary calcium supersaturation and preventing the nucleation of both calcium oxalate and calcium phosphate [1, 2]. Citrate enhances the inhibitory effect of Tamm– Horsfall protein on calcium oxalate aggregation and may reduce the expression of urinary osteopontin, which is a common component of the urinary stone matrix [5]. Changes in urinary citrate level are predominantly influenced by the acid–base status. Both systemic and intracellular acidosis may inhibit renal citrate output if the citrate reabsorption and metabolism in the proximal tubule becomes upregulated in order to counteract those disorders. 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

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