Identifying Which Children with Nephrotic Syndrome Will Respond to Steroids

Identifying Which Children with Nephrotic Syndrome Will Respond to Steroids 1024 683 Mary Bates, PhD

New research identifies potential biomarkers in the plasma of children with steroid resistant nephrotic syndrome.

Nephrotic syndrome is among the most common forms of kidney disease in children. Although glucocorticoids (i.e., steroids) are the primary treatment, approximately 10 to 20% of children with nephrotic syndrome present with or develop steroid resistance. This is only discovered after they fail to respond to several weeks of daily steroid therapy, resulting in prolonged exposure to the drugs’ toxic side effects with little to no clinical benefit.

Unfortunately, there are no validated biomarkers able to predict which patients will be steroid resistant at the time of initial clinical presentation. To help address this, researchers from Nationwide Children’s performed plasma cytokine profiling in children with steroid sensitive nephrotic syndrome and children with steroid resistant nephrotic syndrome. The results were recently published in the journal Kidney International Reports.

The researchers collected plasma samples from children with nephrotic syndrome from sites across North America through the Pediatric Nephrology Research Consortium (PNRC). They obtained paired blood samples from 26 children with steroid sensitive nephrotic syndrome and 14 children who turned out to have steroid resistant nephrotic syndrome, collected both at the time of initial presentation (before any steroid therapy) and again after approximately seven weeks of glucocorticoid treatment, when doctors determined whether the patients were steroid sensitive or steroid resistant.

The researchers performed plasma cytokine profiling using a 27-cytokine panel, using the patients’ pre- and post-treatment plasma samples to identify biomarkers that might be able to predict steroid resistance.

“From this panel of 27 cytokines, we identified 13 that were significantly different between the pre-treatment samples of children who were steroid sensitive and those who were steroid resistant,” says William E. Smoyer, MD, vice president and director for the Center for Clinical and Translational Research at the Abigail Wexner Research Institute at Nationwide Children’s and one of the study’s authors.

From there, the team used sophisticated statistical modeling to identify a panel of three cytokines (interleukin-7 (IL-7), interleukin-9 (IL-9), and monocyte chemoattractant protein-1 (MCP-1)) that were able to discriminate at disease presentation between children with steroid sensitive nephrotic syndrome and steroid resistance nephrotic syndrome.

“This trio of cytokines represents the smallest number of cytokines that we could use to successfully predict whether a patient was likely to respond to steroids or not,” says Dr. Smoyer, who is also the Robert Kidder Chair in Clinical and Translational Research, and professor of Pediatrics at The Ohio State University College of Medicine.

Shipra Agrawal, PhD, a principal investigator in the Center for Clinical and Translational Research at Nationwide Children’s and the lead author of the study, says that this study, although small, is encouraging.

“This was a preliminary study in which we identified candidate biomarkers that still require further validation in a larger cohort of children,” says Dr. Agrawal. “It’s not ready to go into clinical use, but it is an important step forward and will be helpful to other doctors and researchers.”

The researchers say this study lays a foundation for future work confirming the ability of this three-cytokine biomarker panel to predict steroid resistance at initial disease presentation, which could benefit patients by decreasing unnecessary steroid exposure and enabling an earlier transition to more effective alternative treatments.

In addition, this work may help shed light on the molecular mechanisms regulating steroid resistance in nephrotic syndrome, which remain unclear.

“These findings are not only relevant to the clinic, but they could also be used in basic research to understand the biology of steroid resistance,” says Dr. Agrawal, who is also an assistant professor in the department of pediatrics at The Ohio State University College of Medicine. “There is still a lot to learn about why some children with nephrotic syndrome are resistant to treatment with steroids and the mechanisms underlying that.”

 

Reference:

Agrawal S, Brier ME, Kerlin BA, Smoyer WE, Mahan J, Patel H, Ransom RF, Pan C, Geary DF, Chang ML, Gibson KL, Iorember FM, Brophy PD, Srivastava T, Greenbaum LA. Plasma cytokine profiling to predict steroid resistance in pediatric nephrotic syndrome. Kidney International Reports. 2021;6(3):785-795. Doi: 10.1016/j.ekir.2020.12.027.

About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.