Sumit Ranjan Monu, DVM, Ph.D., assistant professor of Physiology at the Wayne State University School of Medicine, has received a Career Development Award from the American Heart Association to fund his study into the mechanism underlying kidney disease in obesity.
The $231,000 grant will help fund “Impaired Glomerular Hemodynamics in Pre-diabetic Obesity: Uncovering a Novel Distal Tubular Mechanism.”
Obesity plays a factor in 20% to 25% or renal disease, which can lead to kidney failure. The only available treatment for renal failure are dialysis or transplantation, which are financially burdensome, difficult to secure donors for, and are mentally and physically taxing, Dr. Monu said. While weight reduction is ideal for treating obesity-related renal injury, it is challenging.
Previous research conducted by Dr. Monu found that impaired glomerular hemodynamics, specifically higher glomerular capillary pressure, or, glomerular hypertension, and its resulting damage begins in the early stages of obesity. His laboratory, one of only about four labs in the world capable of performing in vivo renal micropuncture — a gold standard technique for studying single nephron function — has observed these impairments in pre-diabetic obesity. But the underlying mechanism remains unclear/
His data suggest that a novel distal tubule renal mechanism may be responsible for the early increase in glomerular capillary pressure in obesity, even when glucose levels are nearly normal, as seen in pre-diabetic obesity. He will test a hypothesis that impaired glomerular hemodynamics is driven by a mechanism initiated by the epithelial sodium channel, or ENaC, in the distal tubule. Using advanced techniques such as RNA sequencing on dissected tubules, patch clamp techniques and in vivo silencing of potential proteins via adenoviral methods, his lab will investigate the molecular basis of this mechanism and determine if normalizing renal hemodynamics can mitigate renal damage.
“Given that approximately 43% of the U.S. adult population is obese, this study is crucial for enhancing our understanding of the mechanisms leading to renal damage in pre-diabetic obesity,” said Dr. Monu, who also serves as a research scientist/instructor in the Hypertension and Vascular Research Division of Henry Ford Hospital. “This research may uncover potential targets to normalize glomerular hemodynamics and prevent subsequent renal damage associated with the alarming rise in obesity rates.”
His research focuses on unveiling a novel distal tubular mechanism responsible for altering renal hemodynamics and subsequent injury in pre-diabetic obesity, where glucose levels are almost normal. An understanding of these mechanisms could lead to new prevention and treatment options.
“This work may promote the use of drugs that inhibit the epithelial sodium channel and its downstream signaling mechanisms in the kidneys of at-risk patients,” he said. “Ultimately, this research may identify pharmacological targets to normalize the distal tubule-initiated Af-Art dilatory mechanism, treating pre-diabetic renal complications and reducing medical expenditures. This is my hope for the future.”