Key Points

  • After adjusting for age and gender, children with vesicoureteral reflux (VUR) had a 4.5 times and 6.9 times increased likelihood of hypercalciuria and hyperuricosuria, respectively.
  • Hypercalciuria and hyperuricosuria were found in 46.9% and 31.2% of VUR patients with urinary stones, respectively.
  • Researchers postulate the existence of a genetic link between VUR in children and hypercalciuria.

High calcium and uric acid excretion are associated with vesicoureteral reflux (VUR) in children, and this could increase their risk for urinary stones, new findings suggest. Consequently, children with VUR should be closely followed for the development of urinary stones, investigators concluded.

In a study comparing 108 children with VUR (19 boys and 89 girls) and 110 healthy children (30 boys and 80 girls) with no history of reflux or urinary tract infection, Iranian researchers found that a significantly higher proportion of the VUR group had hypercalciuria and hyperuricosuria (21.3% vs. 3.6% and 18.5% vs. 1.8%, respectively). Both hypercalciuria and hyperuricosuria combined occurred in 6.5% of the VUR group but not in any of the controls.

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After adjusting for age and gender, VUR was associated with a significant 4.5 times and 6.9 times increased likelihood of hypercalciuria and hyperuricosuria, respectively. After further adjustment for independent variables and hyperuricosuria, VUR patients had a 4.4 times increased likelihood of hypercalciuria.

Thirty-two VUR patients (29.6%) had urinary stones; of these, 15 (46.9%) had hypercalciuria and 10 (31.2%) had hyperuricosuria. No child in the control group had a urinary stone.

In a report in Pediatric Nephrology (2012;27:95-99), the researchers, led by Nooshin Kermani, MD, of the Children’s Hospital Medical Center of Tehran University of the Medical Sciences, noted that the medical literature provides no evidence of a genetic link between hypercalciuria and VUR, “but as both conditions are inheritable, we assume there is some linkage between these conditions.”

The investigators determined calcium and uric excretion using the calcium/creatinine and uric acid/creatinine ratios.

VUR is a common cause of kidney stone formation, the authors noted. The pathophysiological mechanism of urolithiasis in VUR patients is related to UTIs and urinary stasis, both of which promote urinary crystal formation. The researchers also observed that VUR is commonly identified in children with urolithiasis, and they cited studies showing that the estimated prevalence of VUR in patients is between 8% and 18%.

Joshua Zaritsky, MD, PhD, an Assistant Professor in Division of Pediatric Nephrology at UCLA Medical Center, said the study’s findings “are not completely novel, as an increased incidence of metabolic abnormalities [previously] has been found in children with VUR.”

The cross-sectional study, however, is unique in that the investigators included a separate case-control group instead of comparing cases to population norms, Dr. Zaritsky said. Additional study strengths included a multivariate analysis to adjust for age and gender.

“This cross-sectional study could provide a starting point for future prospective trials of measures to prevent urolithiasis in patients with VUR,” he said.

Still, as a result of the new findings, Dr. Zaritsky observed, pediatric nephrologists may want to consider that not all urolithiasis in children with VUR is attributable to this structural abnormality, but could be related to metabolic causes that are potentially amenable to treatment.

Dr. Zaritsky noted that the high ratio of female to male patients in the study likely reflects the higher incidence of VUR in females, but he stated that “the overall incidence of urinary stones tends to be higher in boys than girls.”

Further, Dr. Zaritsky said he does not understand why the investigators did not measure uric acid excretion correcting for glomerular filtration rate, but instead used a fixed uric acid/creatinine ratio, which can be very high normally in children younger than three years.