Kidney Stone Disease: A Disorder of Mineral Metabolism on the Rise

Case

A 15-year-old previously healthy girl developed sudden onset of left flank pain and vomiting, which worsened over 2 to 3 hours, and then diminished. The pain returned the next morning, this time slightly lower and radiating to the left lower quadrant. She came to her local hospital emergency department where a CT was performed, which demonstrated a 5mm stone in the distal left ureter. She was discharged on analgesics and tamsulosin to facilitate stone passage.

Image 2: 6mm stone in the mid right ureter demonstrated by (a) gray-scale and (b) Doppler ultrasound imaging. She returned to the ED 3 days later with worsening pain. She was transferred to CHOP where an ultrasound revealed left hydronephrosis and a stone at the ureterovesical junction. (See Image 2.) She was admitted due to refractory pain and underwent ureteroscopy the next day to remove the ureteral stone. She now returns to clinic 1 month after surgery wanting to know why she formed these stones and how to prevent recurrence.

Discussion

Passing a kidney stone is exquisitely painful and is how most patients learn they have nephrolithiasis. For this reason, treatment of kidney stone disease historically focused on removing the offending stone. However, surgical intervention should be only the introduction to the comprehensive, multidisciplinary care that children with nephrolithiasis need.

Nephrolithiasis is a disorder of mineral metabolism that is punctuated by symptomatic events. Other than rare conditions such as cystinuria and primary hyperoxaluria, approximately 50% of the risk of developing nephrolithiasis is heritable, with the remaining risk determined by exposures that impact mineral metabolism, such as diet and systemic disease (eg, Crohn’s disease). The prevalence of nephrolithiasis in the United States is similar to diabetes, affecting 1 in 11 people in their lifetime. Although nephrolithiasis is more common among adult men, nephrolithiasis is more common among adolescent girls. Approximately 85% of stones are calcium-based, with most composed primarily of calcium oxalate. Individuals who develop a first stone during childhood have a 50% risk of having another symptomatic stone in the next 5 years.

Over the past 15 years, the prevalence of kidney stone disease has nearly doubled, with disproportionate increases found among historically lower-risk groups, including children, women, and African-Americans. The incidence of kidney stone disease has risen most rapidly among adolescents, with a recent study reporting an increasing incidence of 5% per year. The causes are unknown; contributing factors likely include changes in diet, the environment, and other as yet unknown exposures.

Nephrolithiasis is associated with an increased risk of coronary heart disease, chronic kidney disease, diabetes mellitus, and hypertension among adults, with the greatest risk generally found for younger individuals. These findings raise the concern that children with nephrolithiasis may be at particularly high risk for these adverse health states, considering the long lifespan over which they may develop and because early onset nephrolithiasis may represent a more severe form of the disease. Children with nephrolithiasis have also been shown to have increased carotid artery wall thickness and are at increased risk of low bone mineral density and fracture. Evaluation of children with nephrolithiasis should consider these associations, although at this time it is unknown whether they are causal or due to shared risk factors.

In response to the rising incidence of kidney stone disease among children and the recognition of substantial health implications, the divisions of Urology and Nephrology at Children’s Hospital of Philadelphia developed the Pediatric Kidney Stone Center. The mission of the center is to deliver comprehensive surgical and medical care for children with kidney stones and to provide personalized treatments to decrease risk of kidney stone recurrence. These treatments depend on the stone type and underlying urinary metabolic profile, but always include increasing fluid intake and decreasing sodium intake. Recommendations for stone prevention and the follow-up plan are sent to the referring and primary care provider.

The Kidney Stone Center has also developed and published pathways for the outpatient and emergency care of children with kidney stones. These pathways virtually eliminated the use of CT as the first diagnostic study in the CHOP Emergency Department, which is a notable achievement considering that approximately 80% of children elsewhere in the United States first have a CT during the initial evaluation.

Research is also critical to the mission of the Kidney Stone Center. Urologist Gregory Tasian MD, MSc, MSCE, and nephrologists Larry Copelovitch, MD, and Michelle Denburg, MD, MSCE, are leading National Institutes of Health-supported clinical trials of interventions to decrease stone recurrence among patients of all ages and other clinical research studies to elucidate modifiable risk factors for kidney stone disease that may help explain and, ultimately, stop the rising incidence of pediatric nephrolithiasis.

References and suggested readings

Tasian GE, Ross ME, Song L, et al. Annual incidence of nephrolithiasis among children and adults in South Carolina from 1997 to 2012. Clin J Am Soc Nephrol. 2016;11(3):488-496.

Tasian GE, Pulido JE, Keren R, et al. Use of and regional variation in initial CT imaging for kidney stones. Pediatrics. 2014;134(5):909-915.