One in 10 people in their lifetime will have a kidney stone — a small, hard deposit of mineral and acid salts that can obstruct the drainage of urine, cause intense pain and, if not treated properly, lead to long-term kidney issues. Kidney stones are relatively uncommon in children, but the number of cases over the past two decades has risen.
The treatment for kidney stones has remained the same for decades — increased fluid intake, limited sodium intake, diuretics and potassium citrate therapy. Lifestyle factors are typically blamed for kidney stones, yet twin studies suggest a genetic component. In fact, new research supports pursuing a genetic diagnosis for this common condition, especially in kids.
“The minute we find a mutation that causes disease, we have the cause of disease in hand,” says Friedhelm Hildebrandt, MD, chief of the Division of Nephrology at Boston Children’s Hospital. “And finding the cause has consequences for therapy.”
Single-gene causes of kidney stones
In 2014, a study led by Hildebrandt identified a causative single-gene mutation in a surprising 21 percent of children and 11 percent of adults. “We therefore wanted to study a pediatric cohort of our own patients at Boston Children’s Hospital,” Hildebrandt says.
In early-onset urinary stone disease, it is advisable to perform a clinical genetics examination for mutations as routinely as people do urine chemistry analysis.
In a second study, he and his colleagues analyzed 30 known causative genes in 143 children with kidney stones (nephrolithiasis) or nephrocalcinosis, a related condition in which calcium deposits form directly in the kidney tissue. As reported in the January 2016 Clinical Journal of the American Society of Nephrology, they found a similarly high percentage of patients (17 percent) with causative mutations, including children with only one stone so far.
“Our findings have a strong potential for personalization of treatment or prophylaxis and should therefore be implemented in clinical practice for pediatric patients with nephrolithiasis or nephrocalcinosis,” Hildebrandt says. “In early-onset urinary stone disease, it is advisable to perform a clinical genetics examination for mutations as routinely as people do urine chemistry analysis.”
Hildebrandt’s lab at Boston Children’s offers a test panel for single-gene causes of urinary stone disease on an experimental basis. If a causative mutation is found, a clinical-grade, CLIA-certified clinical genetics testing lab can convert that finding into a clinical report.
Kidney stone genetics: practical implications
Knowing the genetic diagnosis has value beyond counseling families and focusing preventive measures. It can change therapy.
Certain stone-causing mutations have been associated with other treatable medical complications. People with CYP24A1 mutations, for example, should avoid vitamin D supplements, whereas calcium supplementation should be considered in people with VDR mutations. Mutations in some genes are accompanied by defects in other organ systems, such as eye problems in patients with OCRL mutations or hearing loss in patients with ATP6V1B1 mutations. Patients with mutations in those genes should be specifically screened for these complications, Hildebrandt says.
Learn more about the Boston Children’s Kidney Stone Program