Nearly 70 million people in the United States have been diagnosed with high blood pressure, putting them at risk for heart attack, stroke and heart failure. And one-third of those individuals with hypertension also will eventually develop kidney disease.
Researchers at The University of Toledo are taking steps to better understand the relationship between high blood pressure and kidney disease to more effectively treat those patients.“Dr. Christopher Cooper, dean of the College of Medicine and Life Sciences, served as the principal investigator of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions clinical trial, which determined the best treatment options for renal artery stenosis, or blockage in the renal arteries of the kidney. However, the molecular mechanisms leading to renal dysfunction in this disease remain largely unknown,” said Dr. Steven Haller, assistant professor of medicine. “We knew that the protein Cd40 played an important role in inflammation and clotting in the body, but had not yet identified how it contributed to renal fibrosis.”
Renal fibrosis is a progressive condition that is the direct consequence of the kidney’s limited ability to regenerate after injury. The scarring of the kidney tissue results in a loss of function that can potentially lead to life-threatening kidney failure.
“My team collaborated with Dr. Bina Joe in UT’s Department of Physiology and Pharmacology to develop a rat model to explore the role of Cd40 in this scarring,” Haller said. “We found that by interrupting this protein, the rats had a significant reduction in renal fibrosis and demonstrated an improvement in renal function.”
These results mean that the Cd40 protein not only contributes to inflammation, but also may contribute to renal fibrosis and can be considered as playing a critical role in the development of hypertensive renal disease, he said.
“It has been an exciting project to be a part of,” Haller said. “I have enjoyed collaborating with the other experts we have within UT’s Center for Hypertension and Personalized Medicine to take an interdisciplinary approach to research in our quest to learn more about disease and developing preventative and therapeutic treatments.”
While medications and human trials are still several years away, Haller and his colleagues plan to take the next steps in exploring the most effective and safest ways to interrupt Cd40 and reduce renal fibrosis.
The results of the study were presented in a paper titled “Targeted Disruption of Cd40 in a Genetically Hypertensive Rat Model Attenuates Renal Fibrosis and Proteinuria, Independent of Blood Pressure,” and published in Kidney International in August.