Reducing food intake slows polycystic kidney disease in mice

Mice fed a little less than normal—less than required to cause weight loss—had significantly slower progression of autosomal-dominant polycystic kidney disease (ADPKD), according to research published online January 28, 2016 in American Journal of Physiology–Renal Physiology.

This finding suggests that a mild decrease in food intake might be able to slow ADPKD progression in humans, the authors said. In addition, the small level of food reduction didn’t affect body weight, cause malnutrition, or result in any other apparent side effects.

“Amazingly, the growth of polycystic kidneys was quite strongly inhibited with the reduced food intake, suggesting that these organs are much more sensitive to nutrients than the rest of the body,” said lead investigator Thomas Weimbs, PhD, professor in the Department of Molecular, Cellular, and Developmental Biology at the University of California, Santa Barbara (UCSB), in Santa Barbara, CA.

“If we translate this to a human population, the regimen should be something that would be potentially feasible for PKD patients to follow,” he added.

In this study, Dr. Weimbs and colleagues focused on the mTOR signaling pathway, which is highly activated in human and mouse renal cysts. Although other trials have investigated mTOR inhibitors, such as rapamycin, results in humans were disappointing due to its side effects and potential toxicity.

Because ADPKD is a slowly progressive disease in which therapy continues for years or decades, any treatment should ideally have minimal side effects, Dr. Weimbs said. He hypothesized that a dietary strategy might affect mTOR activity in the kidney because mTOR is regulated not only by growth factor signaling but also by nutrient availability and the energy status of cells.

Also, ADPKD treatment through food reduction “would be an ideal therapy because it would be expected to be free of side effects and extremely cost effective,” he noted.

The researchers compared two groups of PKD1 knockout mice. Those in the control group, who were fed a regular diet, developed an increase in kidney weight of 151% during the study period. Mice in the experimental group, which were fed 23% less than the control group, showed only a 41% gain in kidney weight.

“That’s pretty substantial,” Dr. Weimbs said. “The reduction is similar to what we would see with rapamycin treatment but without the side effects.”

Also, proliferation of cyst-lining cells was 15.9% in the control mice compared with 7.7% in the experimental mice. The mice with reduced food intake maintained kidney function and didn’t progress to end-stage renal disease, the researchers found.

A recent study by researchers at the Mayo Clinic in Rochester, MN, also found that reduced food intake (up to 40% in this study) led to improved outcomes in mice with ADPKD. “The fact that two laboratories independently came to the same conclusions using different models and methods is a very powerful argument that dietary restriction may also be effective in patients,” Dr. Weimbs said.