Mild reduction in food intake slows development of autosomal-dominant polycystic kidney disease

A small reduction in food intake—less than required to cause weight loss—dramatically slowed the development of a common genetic disorder called autosomal-dominant polycystic kidney disease (ADPKD) in mice, a new study in American Journal of Physiology—Renal Physiology reports.

ADPKD affects approximately 400,000 people in the U.S. About half of these individuals will go on to kidney failure, also known as end-stage kidney disease, after which they will require life-long dialysis or a kidney transplant. There are no approved treatments for ADPKD in the U.S. Several drug trials are underway, and a new drug called tolvaptan was approved in Japan, Europe and Canada. Tolvaptan use is controversial, however, because of its side effects, potential toxicity and extreme cost, says Thomas Weimbs, of the University of California, Santa Barbara (UCSB) and lead investigator of the study. Having very low side effects is important because ADPKD is a slow, progressive, chronic disease, and therapy would continue for years or decades, according to Weimbs.

Treatment through food reduction "would be an ideal therapy because it would be expected to be free of side effects and extremely cost-effective," Weimbs says. In addition to the new UCSB findings, researchers at the Mayo Clinic also found that reduced food intake 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," Weimbs explains.

Before moving to clinical trials, the next step is to understand why reduced food intake was so effective. "We do not know whether this is due to caloric restriction or due to restriction of a particular nutrient group, such carbohydrates, lipids or protein. The next step would be to identify, in mouse studies, the most effective dietary modification. Once we have this information, a clinical trial would be warranted," Weimbs says.

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