(NEW YORK – JULY 31, 2015) –– Patients with higher levels of a key protein are at greater risk for severe kidney disease, according to a study published today in Nature Communications and led by researchers from the Icahn School of Medicine at Mount Sinai. The study, which was conducted in mice, suggests that variations in the gene RTN1 led to greater production of the related RNT1 protein, which caused kidney cells to self-destruct.
“We are excited because these findings will shape our upcoming research efforts and hopefully lead to future classes of therapeutics,” said John Cijiang He, MD, PhD, the Irene and Dr. Arthur M. Fishberg Professor of Medicine and Chief of the Division of Nephrology in the Department of Medicine at the Icahn School of Medicine at Mount Sinai. “We believe we have found a target for the development of drugs to prevent chronic kidney disease from becoming severe.”
The findings contribute to a better understanding of kidney disease, which is commonly caused by diabetes, high blood pressure and cancer. When healthy, the kidneys filter blood, divert waste into urine and return useful proteins to the bloodstream. Chronic kidney disease (CKD) affects about 10 percent of American adults, and eventually progresses to end-stage renal disease that requires dialysis or a kidney transplant.
In the study, researchers found that when RTN1 gene is overexpressed, or activated more than normal, it causes an excess of a protein called reticulon to be built. This in turn changes the shape of the endoplasmic reticulum, part of the protein-building machinery in kidney cells, which signals cells to self-destruct as part of disease. The research team examined which genes were expressed more and less in study mice as kidney damage grew more severe. Genes whose level of expression correlated with the intensity of renal damage were catalogued, including RTN1. To ensure that the results were relevant to human kidney disease, researchers then confirmed that similar genetic differences are seen in human kidney disease. Before this study, RTN1 had never been examined in the context of kidney disease.
“Right now, therapeutic options for chronic kidney disease are limited, and only offer partial protection against disease protection,” said Dr. He. “Therefore, there is an urgent need to identify key causes and mediators of chronic kidney disease progression so that we can find the best way to fight it.” About the Mount Sinai Health System The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services— from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,100 primary and specialty care physicians; 12 minority-owned free-standing ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. Seven departments at The Mount Sinai Hospital and one at the New York Eye and Ear Infirmary (NYEE) ranked nationally in the top 25 in the 2015-2016 “Best Hospitals” issue of U.S. News & World Report. Mount Sinai’s Kravis Children’s Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report.
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