Nicotine Can Damage Kidney Cells in Smokers, According to New Miller School Study

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Nicotine can damage kidney cells and contribute to the progression of diabetic nephropathy in people who smoke, according to a new study by the University of Miami Miller School of Medicine and several New York City academic institutions.

Figure A: Photomicrographs of kidney tissue showing marked increase of glomerular Fibronectin (dark staining) in diabetic mice with blood levels of nicotine like those achieved in smokers with either E-cigarettes or regular cigarettes.
Fig B: A semi-quantitative graphic representation of the changes described above.

“The nicotine in cigarettes and e-cigarettes has a toxic effect on podocytes, which play a crucial role in the kidneys’ filtering function,” said Leopoldo Raij, M.D., professor emeritus of medicine and former chief of nephrology at the Miami Veterans Administration Medical Center, and director of hypertension at the Katz Family Division of Nephrology and Hypertension. “If you have diabetic kidney disease, the nicotine in smoking vapors will increase your risk of renal failure.”

Dr. Raij was senior author of the collaborative study, “Nicotine, Smoking, Podocytes and Diabetic Nephropathy,” which was published recently in the American Journal of Physiology-Renal Physiology. Miller School co-authors were Runxia Tian, M.D., Alessia Fornoni, M.D., Ph.D., professor of medicine, chief of the Katz Family Division of Nephrology and Hypertension, and director of the Peggy and Harold Katz Family Drug Discovery Center, and Sandra Merscher, Ph.D., research associate professor. First author Edgar A. Jaimes, M.D., chief of renal service at Memorial Sloan Kettering Cancer Center in New York, formerly was a postdoctoral trainee with Dr. Raij, as well as senior faculty at UM.

The risks of podocyte loss

Podocytes filter proteins in plasma from leaking to the urine and are crucial for healthy functioning kidneys, Dr. Raij said. “If you lose too many podocytes, you are at risk for diabetic nephropathy and renal failure.”

About 40% of diabetics develop diabetic kidney disease, and previous research has shown that smoking is a significant risk factor.

“Prior to this study, the combustion effect of smoking cigarettes was known to contribute to the progression, and the role of nicotine was undetermined,” Dr. Raij said. “However, our study found that nicotine, which is habit forming, was actually toxic to the kidney cells. This finding is particularly relevant given the growing popularity in young people of e-cigarettes, which deliver as much nicotine as combustible tobacco products.”

The researchers performed the nicotine studies in both human podocytes and mouse models of diabetic nephropathy. They found a higher expression of the inflammatory enzyme COX2 and signs of oxidative stress, which can contribute to cellular injury. Nicotine also led to a rise of cell death and decreased the levels of synaptopodin, a protein that helps prevent podocyte damage or death. In diabetic mice, nicotine increased proteinuria and kidney damage, recognized markers of kidney disease progression.

Looking ahead, Dr. Raij said, “Future studies will be essential to further characterize the renal effects of nicotine in e-cigarette products and their safety in diabetics and other patients with chronic kidney disease.”

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