Upper metastable limit osmolality of urine as a predictor of kidney stone formation in children.

High fluid intake has been universally recommended for kidney stone prophylaxis. We evaluated 24-h urine osmolality regarded as the best biomarker of optimal hydration and upper metastable limit osmolality after water evaporation from urine sample to the onset of spontaneous crystallization and its usefulness as a new risk index that would describe an individual lithogenic potential. We collected 24-h urine from 257 pediatric patients with kidney stones and 270 controls. After volume and osmolality assessment, the urine samples were subjected to volume reduction in vacuum rotavapor continued to the onset of an induced urinary crystallization. The upper metastable limit osmolality of urine sample was calculated based on its initial osmolality value and the amount of water reduction. Pediatric stone formers presented with higher urine volume and lower urine osmolality than healthy controls. Despite that, their urine samples required much lower volume reduction to induce the spontaneous crystallization than those of controls. The ROC analysis revealed an AUC for the upper metastable limit osmolality of 0.9300 (95% CI 0.9104-0.9496) for distinguishing between stone formers and healthy subjects. At the cutoff of 2696 mOsm/kg, the test provided sensitivity and specificity of 0.8638 and 0.8189, respectively. 24-h urine osmolality provided the information about current hydration status, whereas evaporation test estimated the urinary potential to crystalize dependent on urine composition. Upper metastable limit osmolality may estimate the individual lithogenic capability and identify people at risk to stone formation when exposed to dehydration.

Does obesity or hyperuricemia influence lithogenic risk profile in children with urolithiasis?

BACKGROUND: There are indications that obesity and hyperuricemia may influence the formation and composition of urinary stones. The aim of our study was to determine the effect of obesity and hyperuricemia on the urinary lithogenic risk profile in a large cohort of pediatric patients. METHODS: The study population comprised 478 children with urolithiasis and 517 healthy children (reference group). We studied the effects of obesity on the lithogenic profile by dividing the patients with urolithiasis into two groups based on body mass index Z-score (patients who were overweight/obese vs. those with normal weight for age) and comparing the two groups. To study the effect of hyperuricemia on the lithogenic profile, we divided the patients with urolithiasis into two groups based on the presence or not of hyperuricemia (110 patients with urolithiasis accompanied by hyperuricemia vs. 368 patients with urolithiasis and normal serum uric acid levels) and compared the groups. RESULTS: Among the children and adolescents with urolithiasis and hyperuricemia, there was a significantly lower excretion of crystallization inhibitors (citrates, magnesium). We also found significantly negative correlations between serum uric acid levels and the urine citrate/creatinine ratio (citrate/cr.; r = -0.30, p < 0.01), as well as the magnesium/cr. ratio (Mg/cr.; r = -0.33, p < 0.01). There was no statistically significant differences in the urinary excretion of oxalates, citrates, calcium, phosphorus, magnesium and uric acid between children with urolithiasis who were either overweight or obese and children with urolithiasis who had a normal body weight. CONCLUSIONS: In our pediatric patient cohort, hyperuricemia was associated with a decrease in the excretion of crystallization inhibitors in the urine, but the clinical relevance of this observation needs to be confirmed in future studies. Obesity and overweight had no direct influence on the lithogenic risk profile in the urinary stone formers in our study, but there was an indication that higher serum uric acid may be associated with impairment in renal function, which in turn could influence the excretion of lithogenic parameters.

Urinary citrate excretion in healthy children depends on age and gender.

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 m2, 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 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. 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.

An association between kidney stone composition and urinary metabolic disturbances in children.

OBJECTIVE: To determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors. PATIENTS AND METHODS: We studied 135 pediatric patients with upper urinary tract lithiasis in whom excreted or extracted stones were available for analyses. Composition of stones was analyzed. A 24-hour urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate. RESULTS: Calcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. The calcium oxalate content in calculi showed a strong relationship with calciuria, and moderate association with oxaluria, magnesuria and acidification of urine. The percent content of struvite presented reverse and lower correlations with regard to the above parameters. Calcium phosphate stone proportion had low associations with urinary risk factors. CONCLUSIONS: Calciuria, oxaluria, magnesuria and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. Relationships of urinary risk factors with calculi calcium phosphate content were of unclear significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.

Correspondence between Ca²âº and calciuria, citrate level and pH of urine in pediatric urolithiasis.

BACKGROUND: Hypercalciuria and hypocitraturia are considered the most important risk factors for urolithiasis. Citrate binds to urinary calcium to form a soluble complex which decreases the availability of ionized calcium (Ca(2+)) necessary for calcium oxalate formation and phosphate crystallization. The aims of this study were to assess the Ca(2+) fraction in relation to total calciuria, citraturia and urinary pH and to determine whether urinary Ca(2+) concentration is a helpful biomarker in metabolic evaluation of children with urolithiasis. METHODS: We collected 24-h urine samples from 123 stone-forming children and adolescents with hypocitraturia and from 424 healthy controls. Total calciuria (total calcium, Catotal), Ca(2+), pH, citrate, oxalate and Bonn Risk Index (BRI) were assessed and compared between the two groups. RESULTS: Total calciuria and Ca(2+) content were higher in stone-formers than in the healthy children. In both stone-formers and controls, Ca(2+) content was inversely related to citraturia and urinary pH, whereas the Ca(2+)/Catotal ratio differed slightly between the groups. A large variability in Ca(2+) level was found across individuals in both groups. The BRI increased with increasing calciuria and urine acidity. CONCLUSIONS: Compared to controls, stone-formers with hypocitraturia demonstrated a higher urinary Ca(2+) concentration, but this was proportional to calciuria. The large individual variability in urinary Ca(2+) content limits its practical use in metabolic evaluation of children with urolithiasis. However, the Ca/Citrate ratio may be a useful clinical tool in evaluating children with urolithiasis.

Assessment of lithogenic risk in children based on a morning spot urine sample.

PURPOSE: The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on 24-hour urine collection. We studied whether the Bonn Risk Index could be measured in spot urine samples and which part of the day is most suitable for this purpose. MATERIALS AND METHODS: We collected total and fractionated 24-hour urine (in a 6-hour nocturnal portion and 9 consecutive 2-hour diurnal samples) in 42 children and adolescents with calcium oxalate urolithiasis and 46 controls. Bonn Risk Index values determined from each of the urine fractions were compared to those obtained from related 24-hour urine collections. RESULTS: Both groups exhibited similar circadian patterns of Bonn Risk Index values. Median Bonn Risk Index for the nighttime portion of urine in the stone group was 1.4 times higher than that obtained from the total 24-hour urine. The morning hours between 08:00 and 10:00 showed the peak lithogenic risk, and this fraction had the highest sensitivity and selectivity regarding discrimination between stone formers and healthy subjects. The afternoon hours demonstrated lower and less fluctuating crystallization risk. Despite diurnal fluctuations in Bonn Risk Index, there was still a well-defined cutoff between the groups. CONCLUSIONS: Bonn Risk Index determined from urine samples collected between 08:00 and 10:00 appears optimal in separating stone formers from healthy subjects, and appears as useful as the value determined from 24-hour urine collection. Investigation of this diurnal sample simplifies diagnosis in pediatric stone disease without loss of clinical information.