Rats could eat a salty diet without sodium levels rising
By keeping sodium out of circulation, an experimental drug might protect against high blood pressure and possibly heart failure, both of which are linked to a high-salt diet. Researchers report that the candidate drug can usher a good portion of sodium out of the body before it reaches the bloodstream and the kidneys.
A salty diet can tilt the sodium balance in the blood and hamper kidney function. The experimental drug, called tenapanor, can block sodium from passing through membranes of the gut into the bloodstream. The findings, published in the March 12 Science Translational Medicine, show that tenapanor inhibits a protein that facilitates sodium’s passage. In the end, much of the salt flushes out of the body with feces, tests in rats and people show.
The idea of controlling sodium in the body by blocking its absorption in the intestine is “really amazing,” says Nicholas Zachos, a molecular biologist at Johns Hopkins University who wasn’t involved in this study. Tenapanor’s developers describe it as a “first-in-class” drug candidate, meaning it would do something no other med has done. At present, the only way to limit sodium absorption in the gut is through a low-salt diet.
The researchers gave the experimental drug to dozens of healthy people for seven days and gave others a placebo. Tenapanor increased the amount of sodium exiting in feces and reduced sodium excreted in urine, indicating that volunteers on the experimental drug absorbed less salt and processed less through their kidneys. Tenapanor itself didn’t show up in the blood of most people taking it, suggesting the compound often goes no farther than the intestines. That’s important because sodium plays fundamental roles in the body and wiping it out elsewhere would be dangerous, Zachos says. No adverse effects were reported in the human tests.
By lowering sodium levels in the blood, tenapanor has downstream effects. Kidneys filter the blood, but excess sodium in the bloodstream reduces the kidneys’ ability to remove water. Retaining water contributes to high blood pressure, which is why some people with hypertension take diuretics, or water pills. Keeping sodium out of circulation mitigates this cycle and would help people with kidney disease, says study coauthor Dominique Charmot, a chemist and cofounder of Ardelyx, a biotechnology company in Fremont, Calif., which developed the experimental drug. “The whole idea is to lessen the burden on the kidneys.”
Tenapanor binds to and neutralizes a compound called NHE3, part of a complex of biomolecules that orchestrates sodium passage through the membranes of the small intestine.
In an experiment on rats consuming a high-salt diet, the researchers found that tenapanor worked well with the drug enalapril, or Vasotec, which is prescribed for high blood pressure, kidney problems and heart failure.
Charmot is cautious. Although hundreds of people have taken the new drug safely in early studies, he stresses the need for further research. Tenapanor is now being tested against a placebo in people with kidney disease.
A.G. Spencer et al. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Science Translational Medicine. Vol. 6, March 12, 2014, p. 227ra36. doi: 10.1126/scitranslmed.3007790.
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S. Vegter et al. Sodium intake, ACE inhibition, and progression to ESRD. Journal of the American Society of Nephrology. Vol. 23, January 1, 2012, p. 165. doi:10.1681/ASN.2011040430.