June 17, 2013
By C.J. Janovy
|Xiaogang Li, Ph.D., and Xia Zhou, Ph.D.|
Despite decades of research, treatments for polycystic kidney disease remain elusive. Now a new study by KU Medical Center researchers suggests that one mechanism for controlling the ravages of the disease might be found in vitamin B3.
Polycystic kidney disease is one of the most common life-threatening genetic diseases, affecting 600,000 Americans and 12.5 million people worldwide. People who inherit PKD develop kidney cysts that grow and multiply slowly over time — patients in their 20s might have few symptoms, but by the time they are into their 40s or 50s, normally fist-sized kidneys containing these fluid-filled sacs can grow to the size of a football, causing pain and destroying kidney function. With a research program dating back to the 1950s, KU Medical Center scientists are internationally recognized experts on the disease — and acutely aware that there is still no cure.
Recently, however, Xiaogang Li, Ph.D., an associate professor of Nephrology and Hypertension and a member of the KU Kidney Institute, found that vitamin B3 helped naturally inhibited the activity of a protein called Sirt1 that influences the formation and growth of cysts. Li and colleagues were able to show that vitamin B3 slowed the creation of cysts and restored kidney function in mice with PKD. The results were published in the June 17, 2013 Journal of Clinical Investigation (and earned a spot in the American Society of Nephrology's June 25 "In the Loop" daily news briefing).
Li's discovery is the second recent breakthrough from KU Medical Center scientists.
In November 2012, the New England Journal of Medicine reported that a clinical trial of 1,445 patients with PKD, conducted over three years at multiple international sites, showed that the drug tolvaptan slows the enlargement of cystic kidneys while also slowing the loss of kidney function. Tolvaptan was developed as a result of KU Medical Center research.
Because vitamin B3 is a commonly used supplement with little reported toxicity, Li hopes that efforts to test its effectiveness might bypass the early phase clinical trials that test toxicity in humans. "Promising therapies with vitamin B3 might rapidly be translated into human phase III clinical trials without years of normally required drug testing," Li says.
Especially exciting, he says, is that after large-scale clinical trials confirm that vitamin B3 therapies are safe and effective for treating PKD, those therapies might also work for infants who are genetically at risk for developing the disease. "We may someday be able to safely treat mothers of fetuses with established genetic risks of developing PKD during their pregnancy to prevent the earliest stages of PKD development throughout fetal life," he says. "We believe that administration of Vitamin B3 to a neonate, toddler or adolescent will effectively prevent or delay cyst formation and can be used for a lifetime."
Li's collaborators at the University of Kansas Medical Center are Xia Zhou, Ph.D., and Lucy X. Fan. William E. Sweeney, Jr. and Ellis D. Avner of the Medical College of Wisconsin and John M. Denu of the University of Wisconsin also contributed to the study.
This study was supported by the National Institutes of Health (grant DK084097) and the PKD Foundation.