Newswise — Rockville, Md. (January xx, 2021)—New research suggests the toxic effects of nicotine on the kidneys’ filtering function are partly responsible for the progression of diabetes-related kidney disease in people who smoke. The study is published ahead of print in the American Journal of Physiology-Renal Physiology.

Previous research has shown that smoking is a risk factor for diabetes-related kidney (renal) disease and that progression to end-stage renal disease may be prevented by smoking cessation. However, the channels through which cigarette smoke and, potentially, e-cigarette vapor damage the kidneys in people with diabetes is unclear. E-cigarettes have become a widespread replacement for combustible tobacco products. “This is a critical issue since the blood concentration of cotinine, a stable metabolite of nicotine, achieved in smokers and [e-cigarette] users are similar,” the authors of a new study wrote.

The researchers analyzed human kidney cells called podocytes and also studied a mouse model of type 1 diabetes. Podocytes play a crucial role in maintaining the filtering function of the kidneys. The research team treated human podocytes with nicotine. In the animal model, groups of mice with and without diabetes drank nicotine-infused water for 10 weeks and were compared to controls that drank plain water. Blood levels of cotinine in the nicotine-exposed mice were comparable to those of an active smoker.

The research team found higher expression of the inflammatory enzyme COX2 and increased reactive oxygen species (ROS) in the nicotine-treated human podocytes. ROS is a sign of oxidative stress, a form of cell damage, and can play a role in the development of chronic illness. Nicotine also led to a rise of cell death and decreased the expression of synaptopodin, a protein that helps prevent podocyte damage or death. The nicotine-treated mice with diabetes also had a reduction of synaptopodin expression. In addition, the nicotine-treated mice—both those with and without diabetes—had scarring of the glomeruli, the functional unit of the kidneys that filters out toxins. While only half of the diabetes control group had scarring of the renal cortex where the glomeruli are located, all of the nicotine-exposed group with diabetes did.

“Our findings unveil novel mechanisms of injury induced by nicotine that may explain at least in part the deleterious effects of cigarette smoking in renal injury. These findings are particularly relevant given the growing popularity of non-combustible tobacco products, including [e-cigarettes], for nicotine delivery,” the researchers wrote. “Future studies in humans will be essential to characterize the renal effects of these products and their safety in subjects with chronic renal disease and especially in diabetics,” they added.

Read the full article, “Nicotine, smoking, podocytes and diabetic nephropathy,” published ahead of print in the American Journal of Physiology-Renal Physiology.

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