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Bringing Pediatric Trials for Rare Kidney Diseases to California

As basic scientists unraveled the biology of podocyte cells and their role in the kidneys’ glomerular function and structure over the past few decades, the numbers of clinical trials in glomerular kidney diseases exploded. Novel agents targeting key pathways in kidney diseases dramatically increased treatment options for adults as studies reached completion.

As with any new area of research, however, work with adults came first, and pediatric trials have been few and far between. Now, clinician-researchers at Cedars-Sinai Guerin Children’s are working hard to ensure more trial opportunities are available in Southern California for children with rare kidney diseases.

“Not many studies address the needs of children with glomerular disease,” said Elaine Kamil, MD, former division director of Pediatric Nephrology and now a part-time staff physician at Guerin Children’s. Kamil now leads the program’s work in glomerular disease clinical trials. “I want children in this part of the country to be able to access the trials that are really advancing the available therapies.”

One such trial is the EPPIK Study, sponsored by Travere Therapeutics, which is currently enrolling. This study evaluates sparsentan (an endothelin and angiotensin II receptor antagonist) for safety and efficacy in children as young as 1 year old with focal segmental glomerulosclerosis (FSGS), minimal change disease, immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis or Alport syndrome.

The EPPIK Study comes on the heels of DUPLEX, a large Phase III study that evaluated sparsentan in adult and pediatric FSGS patients as young as age 8. Cedars-Sinai recently completed the last study visit for their final DUPLEX patient, although an open-label extension study is still ongoing.

Preliminary results have been promising, and it is expected the company will seek U.S. Food and Drug Administration approval for sparsentan for FSGS. The therapy was just approved under the brand name Filspari for adults with IgAN.

Advancing Care Beyond the Big-Name Studies

The Pediatric Nephrology team at Guerin Children’s also provides a wide range of pediatric research opportunities for patients with nephrotic syndrome and glomerular diseases, including for APOL1-mediated kidney disease, a serious condition for which about 13% of African Americans possess the genetic risk factor.

The team is also conducting work to continue improving transplant success in highly immunologically sensitized or challenging patients, such as children who are receiving a second transplant or who have required numerous blood transfusions in the past. The pediatric nephrologists at Guerin Children’s collaborate closely with the Cedars-Sinai Comprehensive Transplant Center, which treats some of the nation’s most complex adult and pediatric kidney transplant cases—nearly half of whom are highly sensitized.

“We are at an exciting time in the field of pediatric nephrology research,” said Helen Pizzo, MD, staff nephrologist at Guerin Children’s and a member of the clinical research team for pediatric kidney disease and transplant trials. “So much is emerging in the treatment realm, and there is still so much that is unknown. Cedars-Sinai is a great place to be, because the support for research is fantastic and we have amazing collaboration opportunities with immunology experts and the greater hospital community.”

Pizzo and her colleagues recently published their findings on donor kidneys impacted by cytomegalovirus, COVID-19 and angiotensin II type 1 receptor antibodies—a serious risk factor for organ rejection in adults—and their repercussions in pediatric recipients.

In addition, the team’s work includes investigating biomarkers to detect early organ rejection, and it plans to research biomarkers to detect organ injury before there is permanent damage. The Pediatric Nephrology team at Cedars-Sinai Guerin Children’s was the first to publish the utility of donor-derived cell-free DNA in pediatric kidney transplant recipients. Although great strides have been made in developing blood-based tests to indicate early rejection, they are now hoping to investigate a less-invasive, urine-based biomarker, as well.

Improving Care Through More—and Better—Research

“At the moment, children often pay a price for the treatments they need,” said Kamil. She points to recent data that found immunosuppressants used prior to kidney transplant may result in increased malignancy risk down the line. “If we can get better, more precise tests and therapies, that would be major progress—the right therapy for the right patient at the right time.”

To this end, Kamil and colleagues at a handful of institutions across the country formed a pediatric kidney research registry about seven years ago, which operates out of the University of Michigan.

In addition to collecting clinical data on more than 1,200 cases of glomerular disease, the registry has enabled numerous research endeavors with much larger cohorts than would be feasible at a single center. Studies to date have examined mood disorders, antihypertensive medication use and thrombotic complications among patients with nephropathies and even resulted in a more objective clinical rating system for edema.

As the number of sponsored pediatric trials and investigator-initiated endeavors grows, the future is bright for children with these rare and complex glomerular diseases.

“We are hopeful that these emerging therapies and enhanced clinical approaches will improve disease control and prolong the time children have healthy, functioning kidneys,” said Pizzo. “Ideally, we can get more children healthy enough to avoid transplants altogether.”

Of course, this success requires the collaboration of patients, parents and physicians.

“Physicians need to be aware of clinical trials and treatment guidelines,” said Kamil to her fellow nephrologists. “Always remember that if there is no good treatment option, or if recommended therapies fail, a clinical trial is the best way to go. Be proactive in referring patients and remember that families are your partners—their participation is critical to getting answers.”


  1.       Pizzo H, Mirocha J, Choi J, et al. Pre-transplant angiotensin II receptor type I antibodies in pediatric renal transplant recipients: An observational cohort study. Pediatr Transplant. 2022 Dec;26(8):e14400.
  2.       Pizzo H, Shin B, Garrison J, et al. Development of CMV-specific cytotoxic T cells (CMV-Tc) in pediatric renal transplant recipients with CMV viremia. Pediatr Transplant. 2021 Dec;25(8):e14119.
  3.       Pizzo H, Soni PR, Nadipuram S, et al. Utilization of SARS-CoV-2-positive donors in pediatric renal transplantation. Pediatr Transplant. 2022 Dec 14:e14451.
  4.       Puliyanda DP, Swinford R, Pizzo H, et al. Donor-derived cell-free DNA (dd-cfDNA) for detection of allograft rejection in pediatric kidney transplants. Pediatr Transplant. 2021 Mar;25(2):e13850.
  5.       Steggerda JA, Pizzo H, Garrison J, et al. Use of a donor-derived cell-free DNA assay to monitor treatment response in pediatric renal transplant recipients with allograft rejection. Pediatr Transplant. 2022 Jun;26(4):e14258.