Newswise — Obesity increases the risk of acute kidney injury (AKI) following cardiac surgery, according to a Vanderbilt study published in the Journal of the American Society of Nephrology.

Considered common after cardiac surgery, AKI represents a fivefold increase in mortality risk within 30 days after the procedure and is associated with longer hospital stays and a range of complications.

The study, led by anesthesiologist Frederic T. (Josh) Billings IV, M.D., M.Sc., followed a sample of 455 cardiac surgery patients at Vanderbilt University Hospital and Brigham and Women’s Hospital in Boston. Some 25 percent of the patients developed AKI after their procedure.

The study found that patients with a higher body mass index (BMI) had a much greater risk. After adjusting for several other risk factors, the odds of AKI increased a staggering 26.5 percent for every five-point increase in a patient’s BMI.

Billings and colleagues used a statistical technique called mediation analysis to discover that oxidative stress could be the mechanism by which obesity influences acute kidney injury. Oxidative stress is the toxic overabundance of reactive oxygen species, brought on by excess generation or insufficient elimination.

“By identification of this mechanism, we now may be able to target intraoperative oxidative stress with the hope of reducing kidney injury following cardiac surgery. That may be particularly appropriate for obese individuals,” Billings said.

The authors noted that the finding is “consistent with the hypothesis that oxidative stress partially mediates the association between BMI and AKI.”

“I think we learned something really important by doing the mediation analysis,” said biostatistician Jonathan Schildcrout, Ph.D., one of the study’s authors. “You could have just examined the BMI and AKI association, and everybody would have said, ‘OK, obese people have higher risk of AKI.’

“When you learn the mechanism, you can start to learn how to intervene to prevent the injury,” Schildcrout said.

The study was funded by the National Institutes of Health (RO1HL77389, RO1HL65193, and UL1RR024975). Clinical Trial Registration: NCT00141778.

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HOUSTON—Lifestyle modifications that lead to weight loss may help reduce the prevalence of low testosterone levels by almost 50% in overweight, prediabetic middle-aged men, according to a new study presented at The Endocrine Society's 94th Annual Meeting.

“Doctors should first encourage overweight men with low testosterone levels to try to lose weight through diet and exercise before resorting to testosterone therapy to raise their hormone levels,” said study co-author Frances Hayes, MD, Professor of Medicine at St. Vincent's University Hospital, Dublin, Ireland.

The study involved 891 men with impaired glucose tolerance (IGT) from the Diabetes Prevention Program (DPP). The men were not on medications that interfere with testosterone levels. Of the 891 subjects, 293 were randomized to lifestyle modification, 305 were randomized to receive metformin, and 293 were randomized to placebo. Because overweight men are more likely to have low testosterone levels, Dr. Hayes and her colleagues studied the impact of changes in body weight and insulin sensitivity on serum testosterone levels in men. In a previous study, the researchers had shown that increasing insulin resistance was associated with a decrease in Leydig cell testosterone secretion.

The researchers analyzed anthropometric variables (body mass index [BMI], waist circumference), physical activity (metabolic equivalent hours/week), insulin sensitivity (homeostatic model assessment (HOMA-IR) and reproductive hormone levels (testosterone and luteinizing hormone [LH]) at baseline and at 12 months. Men were excluded from the study if they had a known diagnosis of hypogonadism or were taking medications that could interfere with testosterone levels. Lifestyle modifications consisted of exercising for 150 minutes a week and eating less fat and fewer calories.

The mean age of the men at baseline was 53.9 years and the mean BMI was 31.9 kg/m2.  The researchers observed that the mean testosterone levels (407 ng/dL) were not significantly different among treatment groups at baseline and in the group as a whole did not change (417 ng/dL at 12 months). However, the men randomized to lifestyle modification had a 15% increase in testosterone levels (417 vs. 460 ng/dL). The researchers observed no change in LH (3.1 vs. 3.1 IU/L). Testosterone levels were unchanged in the other two treatment groups.

The overall prevalence of hypogonadal testosterone levels (below 300 ng/dL) at baseline was 23.7%. Through lifestyle modification, the prevalence of hypogonadal testosterone levels decreased from 20.4% to 11.1%, a 46% decline. The prevalence was not significantly changed in the metformin group (24.8% vs. 23.8%) and the placebo group (25.6% vs. 24.6%). Reduction in body weight was greater with lifestyle modification than metformin (-7.8 vs. -2.8 kg), as was the decrease in HOMA-IR (7.0 to 5.2 with lifestyle modification vs. 7.2 to 6.0 with metformin).

Changes in testosterone levels correlated with changes in body weight, waist circumference, and HOMA-IR. They observed no relationship between change in testosterone and physical activity levels. “We didn't see any benefit with exercise. That surprised us. I thought that it would lead to some improvement in testosterone, but we were not able to see any relationship there,” Dr. Hayes told Renal & Urology News.

Men in the lifestyle modification group lost an average of about 17 pounds (7.8 kg) over the one-year study. “Losing weight not only reduces the risk of prediabetic men progressing to diabetes but also appears to increase their body's production of testosterone,” Dr. Hayes said.

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