Smoking might raise the risk of kidney disease in people with diabetes

New research published in the August issue of the American Journal of Renal Physiology shows that the nicotine in cigarette smoke might hasten kidney disease in diabetics. Previous epidemiological studies have established smoking as a risk factor in the progression of diabetic kidney disease, but none looked at the mechanisms that caused the progression, said University of Alabama at Birmingham researcher Edgar Jaimes, M.D. This is the first research to link a specific compound in cigarette smoke to the worsening of the disease.

"We knew going into this study the impact of smoking on the progression of chronic kidney disease in diabetics, but we needed to figure out why so we can work toward finding ways to slow the disease and reduce the likelihood a patient will need dialysis or suffer from other complications of the disease," said Jaimes, an associate professor in the UAB Division of Nephrology.

Diabetes is the single leading cause of kidney failure in the United States, according to the National Kidney Foundation, accounting for about 44 percent of the people who start treatment for kidney failure each year, and about 38 percent of all Americans being treated for kidney failure. Complications include high blood pressure, anemia and blindness.

Jaimes, the study's senior author, and his colleagues exposed diabetic mice to nicotine and compared their kidney function to diabetic mice not exposed to nicotine. The mice exposed to nicotine had levels of cotinine in their blood comparable to those of human smokers. Cotinine is a metabolite of nicotine and the amount of it in a person's blood is proportionate to the amount of exposure to cigarette smoke, making it an important indicator of tobacco smoke exposure.

The mice with the comparable cotinine levels had more fibrosis, or scarring of the kidneys (a marker of kidney disease), and more proteinuria, the amount of protein found in the urine, another marker of kidney disease, than mice not exposed to nicotine. The mice in the two groups did not show significant differences in blood pressure, body composition or blood glucose.

"Not having changes in blood pressure is a significant finding because it suggests the effects of nicotine on renal injury are not explained away by changes in systemic blood pressure," Jaimes said. "Even though this is an animal study and was not done in humans, there are enough similarities between the animal model we used and humans to show that nicotine is an important link between smoking and the progression of diabetic kidney disease."

Jaimes said the findings are of particular concern, not just for diabetics who smoke, but for those trying to kick the habit as well.

"Nicotine patches are used as a means of smoking cessation and that strategy is designed to be used for just a few weeks," Jaimes said. "But if a diabetic were to stay on nicotine patches for a very long time, in theory, there is a possibility that it could be detrimental to their kidney function."

Jaimes said much more work is needed to explain why nicotine affects diabetic kidney disease and to find out what other derivatives of cigarette smoke could also cause renal injury.

"There are several things we are doing now in terms of how we're going continue our study," he said. "We're going to continue to look at the mechanisms by which nicotine is doing this. We are testing other animal models of kidney disease to try to determine whether or not nicotine has similar effects in other models.

"We also are looking at other compounds present in smoke that may have similar effects, as well as studying the exposure to tobacco smoke itself and comparing that to other components in tobacco to determine if there are some differences there," Jaimes added.

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