Frontier Program Spotlights Diagnostic Innovation for Kidney Stone Disease Patients

Kidney stone disease occurs when hard deposits of minerals and salts crystalize inside the kidneys to form stones. The CHOP Kidney Stone Center is working to transform disease management for children.

Discovery, innovation, clinical integration. These are the key themes of the CHOP Kidney Stone Center, according to Gregory Tasian, MD, MSc, MSCE, an attending urologist at Children's Hospital of Philadelphia and one of the Center's co-leaders.

Now, with the Center's designation as a Frontier Program, researchers are hard at work studying the emergence of early-onset kidney stone disease to create new solutions for diagnostic testing that will reveal why stones could be forming and inform new treatment options for pediatric patients.

Historically, kidney stone disease was most prevalent in middle-aged, white men, but the last 30 years have seen a rapid rise in children and adolescents with stones. One study found that the incidence rate increased by 4% per calendar year between 1984 and 2008.

"As we move forward, the goal is to translate our knowledge into something that could yield new diagnostic tests for not only children treated at CHOP but also throughout the United States," Dr. Tasian said.

Frontier Programs conduct visionary research that translates into clinical care, and they are often at the forefront of breakthroughs in new therapies, surgical techniques, and diagnostic testing to improve care for some of the most challenging pediatric conditions. The goal of the CHOP Kidney Stone Center is to develop new kidney stone diagnostic tests that use a single urine sample collected at home or in the clinic. This will be achieved through the expertise of the Center's leaders alongside multi-omics research, data science, and machine learning. Patient samples also will be collected in a biorepository to help build the data infrastructure needed for comparative effectiveness studies, developing diagnostic testing, and eventually organizing clinical trials.

"This is a disease that will often exist for many patients over their lifespan, so we need to develop new solutions when individuals are affected early in life," Dr. Tasian said. "As we encounter the boundaries of our knowledge in clinical care, our goal is to produce new knowledge that can be incorporated back into clinical care."

Kidney stone disease occurs when hard deposits of minerals and salts crystalize inside the kidneys to form stones that are often painful to pass. Diet and certain medical conditions and medications can cause kidney stones, which affect around 11% of Americans.

Typically, researchers analyze the urine chemistries of urine collected from a patient over the course of 24 hours to determine the amount of calcium and other molecules such as citrate, and the amount voided. This is only a small amount of information on a condition that could diagnostically offer much more, Dr. Tasian said. Digging deeper and identifying the metabolomic and proteomic signatures of calcium kidney stone disease could help contribute to new techniques for diagnoses and personalized interventions.

The Kidney Stone Center has partnered with the Penn-CHOP Microbiome Program over the last several years to begin this work by studying patients' gut and urine microbiomes and metabolomes in an effort to characterize the proteins unique to early-onset kidney stone disease. These efforts have led to the discovery of signatures that not only differentiate between individuals who develop stones and those who don't, but also between individuals who have more severe disease and those who have less.

Investigators also plan to leverage their relationships with 30 medical institutions that participate in the Pediatric KIDney Stone Care Improvement Network to conduct multi-center clinical trials and create a sustainable platform for personalized management of the disease.

"The ability to integrate research and clinical care to create something that is truly state of the art where patients can participate in discovery is something that very few, if any other, places can offer at the scale that CHOP can," Dr. Tasian said.

Heading the Frontier program alongside Dr. Tasian are Michelle Denburg, MD, MSCE, Director of Research in the Division of Nephrology, and Stephen Master, MD, PhD, Division Chief and Director of Metabolic and Advanced Diagnostics in the Department of Pathology and Laboratory Medicine, and leader of the new Center for Diagnostic Innovation that will work closely with the CHOP Kidney Stone Center as they embark on the translation of new testing.