24 Hour urine metabolic differences between solitary and multiple stone formers: Results of the Collaboration on Urolithiasis in Pediatrics (CUP) working group.

INTRODUCTION: Specific factors associated with the risk of developing pediatric urinary stone disease remain unclear, especially those that may be associated with recurrent stone disease.

OBJECTIVE: We compared the results of 24-h urine collections in children with a solitary stone episode to those with multiple stone episodes to determine if there is a difference that may be associated with multiple stone formation in children.

STUDY DESIGN: A multi-institutional retrospective analysis was completed to assess 24-h urinary metabolic profiles in children with urolithiasis aged 2-18 years old. Differences in mean urine collections between the two groups were assessed using chi-square tests to test the associations among gender, stone type, and multiple stone status, as well as multivariate analyses using general linear models.

RESULTS: We analyzed 142 solitary stone patients and 136 multiple stone patients from four centers were included. Multiple stone patients were older than solitary stone patients (mean 13.4 ± 3.6 years vs. 12 ± 3.9 years, p = 0.002). Females were more likely to have multiple stones (58% vs. 39%, p = 0.002). BMI was not associated with multiple stones (p = 0.8467). Multiple stone formers had lower urine volumes, although this did not reach statistical significance when compared with solitary stone formation (20.4 mL/kg/day ± 11.5 vs. 22.9 ± 13.0, p = 0.0880). Higher values for super-saturation of calcium oxalate were associated with multiple stone disease in univariate (p = 0.0485) and multivariate analysis (p = 0.0469) (Figure). Centers located in the Southeast of the United States saw a higher proportion of children with multiple stones (Tennessee 62.7%, Virginia 44.4%, Oregon 31.6%, Michigan 27.3%, p < 0.0001).

DISCUSSION: In a large multi-institutional retrospective analysis we found that multiple stone disease was associated with higher super-saturations of calcium oxalate. Many urinary parameters changed with patient age, highlighting that the values should be interpreted with respect to patient age. The inability to comment on follow-up because of the nature of our dataset is a limitation of this study.

CONCLUSION: Multiple stone disease in children is associated with higher super-saturation calcium oxalate, while lower urinary volume may also be associated with multiple stones; however, further study is required. Early metabolic evaluation may help risk stratify children likely to form multiple stones.