Urinary calcium and uric acid excretion in children with vesicoureteral reflux

Abstract

Urolithiasis is relatively common in children, and identifiable predisposing factors for stone formation, including metabolic and structural derangements, can be established in most cases. Vesicoureteral reflux (VUR) is a common cause of kidney stone formation. The pathophysiological mechanism of urolithiasis in reflux is related to urinary tract infection and urinary stasis, both of which promote urinary crystal formation, but metabolic causes, such as crystallurias (mostly hypercalciuria), may also be involved in this process. However, few studies on urinary calcium and uric acid excretion in children with VUR have been conducted. We have studied the frequency of hypercalciuria and hyperuricosuria in children with VUR and compared the results with those from a control group. The VUR group comprised 108 children with VUR (19 boys, 89 girls; age range 3 months to 12 years), and the control group comprised 110 healthy children without any history of reflux or urinary tract infection (30 boys, 80 girls; age range 2 months to 12 years). Fasting urine was analyzed for the calcium/creatinine (Ca/Cr) and uric acid/creatinine (UA/Cr) ratios. Hypercalciuria was more frequently diagnosed in the VUR patients than in the control group (21.3 vs. 3.6%; P = 0.0001). Significant differences between the two groups were also found for the mean Ca/Cr and UA/Cr ratios (P = 0.0001 and P = 0.0001, respectively). No differences were found in the urinary Ca/Cr or UA/Cr ratios related to VUR grading or unilateral/bilateral VUR in the patient group, with the exception of those for hypercalciuria and mild VUR (P = 0.03). The association of urinary stones and microlithiasis in the VUR group was 29.6%. Our results demonstrate that the frequency of hypercalciuria and hyperuricosuria was higher in pediatric patients with VUR than in healthy children. Knowing this relationship, preventive and therapeutic interventions for stone formation in VUR could be greatly expanded.

Idiopathic hypercalciuria in children with urinary tract infection

“…12 Other studies reported a higher prevalence of IH in patients with VUR, although at a lower rate (17%-21%). 7,13 Similarly, our patients with VUR showed a high IH prevalence, but with no significant differences when compared to patients without VUR (26% versus 16%, respectively, p= 0.24). This finding is consistent with what has been reported by Biyikli.…”

“…For example, four Iranian studies reported that IH prevalence was 0.2%, 3.6%, 11.4%, and 13.3%, respectively. 8,7,10,13 More interestingly, in Argentina, Alconcher, et al 30 studied 220 healthy school children and found 28 cases (12.7%) with a urinary calcium excretion level higher than the globally accepted cut-off value (4 mg/kg/day); 22,23 however, in relation to the upper limit observed in their own patients (4.74 mg/kg/day), only 12 (5.5%) had IH.…”

“…15,22,23 The calcium to creatinine ratio was used in an isolated urine sample to estimate calcium excretion because it shows an adequate correlation with a 24-hour urine collection, 24 it can be done in children who have neither bladder nor bowel control, and also because there is more pediatric information on normal urinary calcium values for this ratio than for the 24-hour urine collection. 15 Although it has been reported that calciuria measured in a fasting second morning void sample is more representative than the 24-hour urine collection, 25 we decided to use the first morning void sample because it has been widely accepted in the literature, 6,[9][10][11][12][13]20 especially taking into account how difficult it may be to keep infants fasting until their second void.…”

“…2,3 IH is a common pediatric disorder (3%-10%) [4][5][6] which predisposes to the development of UTI because the oversaturation of urine with calcium oxalate microcrystals may damage mucous membranes of the urinary tract. 7 Consequently, different studies have demonstrated an increase in IH prevalence in patients with UTI, 6,[8][9][10][11][12][13] although some authors have not been able to confirm such association. 7 The main determining factor o f u r i n a r y c a l c i u m e x c r e t i o n is the concomitant elimination of sodium, which in turns depends on salt intake.…”

“…14 In addition, calcium excretion is affected by other extrinsic factors (protein intake, mineral content of water) and intrinsic factors (ethnicity), 15 and this is reflected on the great geographic variability observed in IH prevalence, both in healthy children and in those with UTI. 6,[8][9][10][11][12][13] To our knowledge, there are no local data on IH prevalence in children with UTI; for this reason, we conducted this study with two main objectives: 1) to estimate IH prevalence in patients treated for UTI at a children's hospital; and 2) to assess whether such prevalence differs in relation to VUR presence or absence. Additionally, we studied the association between IH and salt intake.…”