BOSTON (FRONTLINE MEDICAL NEWS) – Maintaining or improving cardiorespiratory fitness during the year following an intensive lifestyle intervention contributed to the prevention of advanced chronic kidney disease over 4 years among participants in Look AHEAD, according to findings from a substudy of that randomized clinical trial.

During the first 4 years of follow-up in 4,906 of the 5,145 original study subjects, the incidence of advanced chronic kidney disease – after adjustment for age, race, ethnicity, and disease-related baseline covariates – was reduced by nearly 60% in those who received the intervention in the original study, compared with those who received diabetes support and education (hazard ratio, 0.59), Dr. Margareta I. Hellgren reported at the annual scientific sessions of the American Diabetes Association.

At 1-year follow-up, fitness level was unchanged in 77% of the lifestyle intervention group patients, compared with 58% of those in the diabetes support and education group, and in a model that used the same covariates, plus 1-year fitness change, and which included annually updated weight, blood pressure, and hemoglobin A1c, both intervention group participation and unchanged or improved fitness predicted lower incidence of advanced CKD over 4 years (HR, 0.69, 0.49, respectively), said Dr. Hellgren of the University of Gothenburg, Sweden.

The multicenter Look AHEAD trial included overweight adults with type 2 diabetes who were followed for about 10 years. The findings, which were published in 2013, showed no difference between intensive lifestyle intervention – including physical activity and reduced calorie intake – and diabetes support and education for reducing the incidence of cardiovascular events (the primary outcome measure), but did demonstrate a benefit with intensive lifestyle intervention for a number of secondary outcomes, including nephropathy.

A secondary analysis published in The Lancet in 2014 showed that the incidence of advanced kidney disease was reduced by 31% over 8 years in those in the intervention group, compared with those in the diabetes care and intervention group – an effect that was partly attributable to reductions in body weight, HbA1c, and systolic blood pressure, she noted.

The outcome of the current substudy was very high risk kidney disease (classified according to the Kidney Disease Improving Global Outcomes Guidelines), which is an important cause of disability and high costs and is associated with high mortality, Dr. Hellgren said.

Study subjects had a mean age of 58.6 years at baseline, 59% were women, and 66% were non-Hispanic whites. Known diabetes duration was 6.7 years.

Fitness assessment was based on estimated metabolic equivalents (METs) during a graded treadmill exercise test at baseline and at 1 year. A significant association was seen between baseline fitness and class of chronic kidney disease, Dr. Hellgren said, noting that 31% of those with the lowest fitness level had abnormal kidney function, compared with 14% of those with the highest level.

“Physical fitness at baseline was positively associated with kidney function. Maintaining or improving fitness during the first year was associated with lower incidence of very high risk kidney disease in both intervention groups, with a 51% reduction overall,” she said, adding that the lifestyle intervention effect was only partially attenuated after accounting for fitness change and annually updated wight, blood pressure, and HbA1c, which suggests that an additional unknown mechanism is responsible for the benefits of intervention.

The National Institute of Diabetes and Digestive and Kidney Diseases sponsored Look AHEAD. Dr. Hellgren reported having no disclosures.