Tumoregenic kidneys are larger and show abnormal coloring than healthy kidneys.

Tumoregenic kidneys are larger and show abnormal coloring than healthy kidneys.

Polycystic Kidney Disease (PKD) is a genetic disease, characterized by giant fluid-filled cyst growing in the kidneys, which enlarges the organ to potentially fatal sizes. Treatment for slowing or stopping cyst growth caused by PKD is at the moment nonexistent. However, a team of researchers at the University of California, Santa Barbara, directed by Thomas Weimbs, Ph.D, a professor in molecular, cellular and developmental biology (MCBD) and in the Neuroscience Research Institute at UCSB, has recently discovered that reducing food intake in mice can substantially dampen the rapid proliferation of cyst growth in the kidneys and in turn preserve kidney function.

PKD currently affects 15 million people worldwide and is considered one of the most common life-threatening genetic diseases. PKD is slowly progressive and usually affects its patients in their forties of fifties, but if growth is left unchecked, the aberrant cyst growth will ultimately progress to kidney failure, forcing many with PKD to undergo kidney transplants or dialysis.

The findings on Weimbs’ research focus on the inhibition of the mTOR pathway, a biological signaling pathway activated in times of wound healing, whose main function facilitates cell proliferation and cell growth. In PKD, the protein that the mutation has encoded for interacts with the mTOR pathway causing the mTOR pathway in the kidney to be aberrantly active, facilitating cysts to grow and proliferate uncontrollably. Due to this overly active and unregulated mTOR pathway, the kidneys, which are normally the size of human fists, enlarge to the size of footballs in PKD patients, thereby causing pain, disrupting proper renal functions and eventually leading to kidney failure.

“Rapamycin, a drug that targets and down regulates the mTOR signaling pathway, has tested effective in reducing polycystic kidney growth in rodents but unfortunately comes with unwanted and harmful side effects such as weakened immunity.” Weimbs said. “We thought about other measures we could take to dampen the mTOR pathway, such as reduction in food intake. It is well studied that the mTOR pathway is strongly regulated by nutrients and the energy status of cells. Therefore we chose a mild reduction in food intake, around 23%, and discovered that it negatively affected polycystic kidney growth while having no negative effect on normal body growth.”

The findings have also shown that mice administered with a 23% reduction in diet, exhibited a 41% reduction in kidney weight growth over the course of a 7-week period. Meanwhile, the mice that were administered the normal non-reduced diet exhibited an increase of 151% kidney weight growth also in the same 7-week time period. The researchers also discovered that the cyst-lining cells in the reduced diet mice proliferated 7.7% while the non-reduced diet mice had their cyst-lining cells proliferate at 15.9%. Further examination of the mTOR pathway also revealed that the mice that had been administered the reduced diet had two of their activating signaling branches of mTOR suppressed. This would make reduction in diet more effective than pharmaceutical rapalogues, such as rapamycin, which only suppresses one activating signaling branch.

“This would be fantastic if we could achieve these results in patients. Because of the slowly progressive nature of the disease, the kidneys keep growing over years and decades, but kidney function remains relatively normal to the very end. The idea therefore is that cyst growth doesn’t have to be completely stopped or reversed but slowed substantially enough to retain kidney function until old age, essentially curing the patients,” Weimbs said.

The future of the study will be attributed to finding specific dietary restrictions that will benefit PKD patients.

According to Dr. Weimbs,” The goal now is to find which nutrients are important to reduce. For example should we reduce carbohydrate, lipid, or protein intake, since we do not want to put patients through unnecessary dietary restrictions.”

A version of this story appeared on p. 14 of the Thursday, Feb. 25 print edition of the Daily Nexus.