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Title
A National Multi-Institutional Cooperative on Urolithiasis in Children: Age is a significant predictor of urine abnormalities
Background:
The incidence of pediatric stone disease is rising across the United States. Herein we report 24-hour urinary analysis parameters in children with nephrolithiasis across four institutions.
Methods
A 24-hour urinary analysis was performed in children who presented between 2000-2013 with a history of nephrolithiasis and stratified by age ≤10 years and >10 years. Exclusion criteria included patients with a history of spina bifida, neurogenic bladder, cerebral palsy and patients on treatment medications before the first 24-hour urine analysis.
Results
We analyzed 206 children who met inclusion criteria with a mean age of 13 years (± 3.9). Females compromised 51.9% of the cohort. Metabolic abnormalities were present in 130 children (63.1%). All 24-hour urinary values were adjusted for weight or body surface area. The institutions were well matched with respect to metabolic disorders present, with hyperoxaluria in 15.5%, hypocitraturia in 14.6%, hypercalciuria in 16.0% or a combination of metabolic abnormalities in 17.0%. Low volume was present in 48.5%. Children ≤10 years compromised 31.1% of the cohort (n=64).
Univariate analysis was performed and revealed children ≤10 years were more likely to have normal volume, elevated urinary oxalate, elevated urinary calcium, elevated supersaturation of calcium phosphate and elevated supersaturation of calcium oxalate. Additionally children less than 10 years of age are overall more likely to have a metabolic abnormality present on urinary analysis (Table).
On multivariate analysis children ≤10 years were more likely to have hyperoxaluria (OR 2.229, 95% CI 1.044-4.758, p=0.0384), elevated supersaturation of calcium phosphate (OR 3.129, 95% CI 1.457-6.719, p=0.0034) and hypercalciuria, which trended towards significance (OR 2.081, 95% CI 0.971-4.461, p=0.0595). They were also less likely to have low volume (OR 0.46, 95% CI 0.215-0.98, p=0.0443) compared to children >10 years. Supersaturation of calcium oxalate and metabolic abnormalities were not significant on multivariate analysis.
Table: Univariate Analysis (Age ≤10 years vs Age >10 years

	Age		P-value
	≤10 (years)	>10 (years)
	n=64	n=142
Volume			0.0063
Low Volume (<20ml/kg/day)	22(34.4)	78(54.9)
Normal (>20 ml/kg/day)	42(65.6)	64(45.1)
Oxalate			0.0351
Yes (>40mg/1.73m2/day)	25(39.1)	35(24.7)
No (<40mg/1.73m2/day)	39(60.9)	107(75.3)
Calcium			0.0001
Elevated (>4 mg/kg/day)	31(48.4)	31(21.8)

Normal (<4 mg/kg/day)	33(51.6)	111(78.2)
Super Saturation Calcium Phosphate			0.0009
Elevated (>2)	49(76.6)	74(52.1)
Normal (0.5-2)	15(23.4)	68(47.9)
Super Saturation Calcium Oxalate			0.0024
Elevated (>10)	37(57.8)	50(35.2)
Normal (0.5-2)	27(42.2)	92(64.8)
Metabolic Abnormality			0.0443
Yes	48(75.0)	86(60.6)
No	16(28.0)	56(39.4)
Results are presented as n(%)

Conclusion
When treating children with nephrolithiasis, it is important to consider age when determining the cause of urolithiasis. This study represents a national profile of 24-hour urines in pediatric stone formers that is consistent across multiple institutions. Children who are less than 10 years are more likely to have a metabolic abnormality present including elevations in urinary calcium and oxalate as well as elevated supersaturation of calcium phosphate. This is important when considering treatment options in these patients since younger children may require medical therapy as opposed to dietary changes.