Monday, April 07, 2014
Dr. Schelling Releases Study On Chronic Kidney Disease
Dr. Jeffrey Schelling, researcher at The MetroHealth System and Professor of Medicine at Case Western Reserve University School of Medicine, led an important study recently published in The Journal of Clinical Investigation
that provided new insight on the progression of kidney disease affecting people with diabetes (diabetic nephropathy).
Over 26 million Americans suffer from chronic ki¬dney disease, approximately half of whom are diabetic. While chronic kidney disease is usually initiated by injury to the glomerulus, a “filter” that removes toxins, loss of the downstream tubules is a stronger predictor of kidney failure.
Currently the best clinical marker for diabetic nephropathy is the appearance of small amounts of protein leaking into the urine. Dr. Schelling’s research examined how fatty acids bound to the leaked protein might be the actual cause of harm to tubules.
“Our study clarifies a new disease pathway, which then has the potential to identify novel therapeutic targets,” Dr. Schelling said. “Almost all current diabetic kidney disease research is focused on the glomerulus. This new data suggests that there could be an additive beneficial effect of treatments directed toward the glomerulus and tubules.”
The studies have the greatest implication for patients with diabetes, who tend to have higher blood levels of fatty acids. The fatty acids taken up by the tubules are initially metabolized to molecules called “long chain acyl CoAs.” The problem with long chain acyl CoAs is that when present in large amounts they compete with a structurally similar molecule, called PI(4,5)P2, for binding with NHE1, a protein of interest to the Schelling lab for over a decade.
In cases of stress, NHE1 controls the environment within the cell by exchanging sodium and hydrogen ions. NHE1 needs to interact with PI(4,5)P2 to function properly. When long chain acyl CoAs accumulate and interfere with this interaction, NHE1 fails and the cell’s ability to survive is thrown into peril.
Dr. Schelling’s research provides the clearest picture yet of how fatty acids might endanger tubule cell survival and thus lead to chronic kidney disease progression.
His research was funded, in part, by the National Institute of Health, a taxpayer-funded institution. Dr. Schelling’s lab is currently focusing on how fatty acids make their way from the glomeruli and are taken up by tubules. In the future, he hopes to identify mechanisms for inhibiting the fatty acid uptake, as a potential therapy for diabetic nephropathy. This research will require continued collaboration between Dr. Schelling and other Case Western Reserve University faculty members.
Dr. Schelling is part of the Rammelkamp Center for Education and Research and Department of Medicine. Rammelkamp features more than 80,000 square feet of space on the MetroHealth campus, and is dedicated to research that will ultimately better the lives of MetroHealth patients as well as patients worldwide. MetroHealth has partnered with Case Western Reserve University School of Medicine since 1914, bolstering both its research and education programs. Dr. Schelling is a graduate of the Case Western Reserve School of Medicine.