Researchers at City of Hope have discovered new biomarkers that could predict kidney failure in patients with type 1 diabetes (T1D), according to a study published today in Science Translational Medicine.
The study, led by Rama Natarajan, PhD, deputy director of the Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope, marks the first epigenome-wide association analysis conducted in patients with diabetic kidney disease.
By examining DNA methylation activity—a process that can modify the activity of DNA segments without changing their sequence—the researchers identified novel associations with the risk of developing kidney failure over several years.
T1D affects an estimated 9 million people worldwide and is associated with a heightened risk of kidney disease, which can progress to kidney failure. Kidney failure in turn, leads to dialysis or renal transplantation and higher rates of morbidity and mortality among T1D patients. “Finding mechanisms leading to kidney failure in diabetes, as well as biomarkers for early detection, is crucial for facilitating prompt intervention,” Natarajan emphasized.
Epigenetics, the study of how behaviors and environmental factors can cause reversible changes in gene expression and activity, played a central role in this research. Specifically, the team focused on methylation, a type of epigenetic modification that can influence gene expression and contribute to disease. Using blood samples from 277 participants in the Joslin Kidney Study, an extensive study of diabetic patients, the researchers pinpointed regions of the genome where DNA methylation was associated with kidney failure risk.
Natarajan noted the stability of these biomarkers: “Key locations of kidney failure-associated DNA methylation variations remained remarkably stable in the same person with T1D over several years.” The study also provided insights into the molecular mechanisms related to DNA methylation that are linked to major clinical conditions associated with kidney disease and failure.
The research team integrated various data types—genetic, protein, and noncoding RNA markers—through multiomics integrative analyses, enhancing their understanding of the combined influences on disease processes. Importantly, because the researchers made strong associations between DNA methylation and kidney failure using blood samples alone, their findings suggest the potential for a new noninvasive prognostic test for T1D patients with kidney disease.
“We demonstrated that DNA methylation at some of the identified genomic sites can be used as noninvasive biomarkers to improve the prediction of kidney failure,” said Nancy Chen, MD, first author of the paper and assistant research professor in City of Hope’s Department of Diabetes Complications & Metabolism.
“This has important translational implications for early detection and prevention of kidney failure in at-risk patients with T1D.”
Looking ahead, the researchers plan to conduct further experimental studies to verify the molecular mechanisms identified and to validate their findings in larger cohorts of both type 1 and type 2 diabetes patients. Their ultimate goal is to develop a risk score test for predicting kidney failure in diabetes using several epigenetic biomarkers.
“In the future, DNA methylation at the identified genomic locations could not only be used as biomarkers to predict kidney failure development but could also be targeted to prevent diabetic kidney disease progression to kidney failure, which is a major unmet need in the field,” Chen concluded in a press statement.
