Oxidative Stress May Be Why High Phosphorus Ups Mortality

ATLANTA—Oxidative stress may play a role in the association between high serum phosphorus levels and increased mortality risk, according to study findings presented at the American Society of Nephrology's Kidney Week 2013.

Essam F. Elsayed, MD, and colleagues at the University of Texas Southwestern Medical Center in Dallas studied 19 subjects with a mean age of 53 years. All were men and 60% were African American. The researchers were randomly assigned to a low phosphate (Pi) intake and high Pi intake phase.

After a washout period, subjects were switched to the other arm. Participants took a phosphate supplement during the high Pi intake phase and a phosphate binder during the low Pi intake phase. The outcome measure was the level of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA oxidative stress.

Participants had a mean serum phosphorus level was 3.7 mg/dL and a mean fraction excretion of phosphate (FePi) of 19.1%. They had a mean estimated glomerular filtration rate of 73 mL/min/1.73 m2. Nine subjects (47%) had stage 3 chronic kidney disease.

Each 1% increase in FePi was associated with a significant 0.7 ng/mL increase in 8-OHdG.

The researchers noted that the concept of “phosphotoxicity” is supported by animal studies. “Induction of high levels of oxidative stress and oxidative DNA damage are potential mechanisms by which Pi might affect cellular aging,” the authors concluded. The findings of this pilot study extend these findings to humans.

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