Normal-to-high levels may be associated with increased mortality.

LONDON, Ont.—Patients referred to Canadian nephrologists with CKD stage 3-5 and normal-to-high phosphate levels are at greater risk of kidney failure and death than are those with low phosphate levels, a study has revealed.

In a study funded through the Kidney Foundation of Canada, re-searchers at the 31 centers participating in the Canadian Care Prior to Dialysis study examined 482 patients (average age 70 years). Of these patients, 39.5% and 52% had CKD stage 3 or 4, respectively. In addition, most subjects had at least one comorbidity. Eighty percent had hypertension, 43% had diabetes, and 31% had coronary artery disease.

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Patients’ average BP at baseline was 147/76 mm Hg, their estimated glomerular filtration rate (eGFR) was 29 mL/min/1.73 m2, average he-moglobin level 121 g/L, average albumin level 36 g/L, and average phosphate level 1.3 mmol/L.

After a mean follow-up of 28 months, 78 subjects had died; none of these individuals had begun dialysis. An additional 35 people were undergoing hemodialysis, 19 were on peritoneal dialysis, and one had undergone a pre-emptive transplant.

The investigators found that three parameters were significantly correlated with death. Each 1.0 mmol/L increment in phosphate was associated with a 3.48-fold higher risk of death. This is a large magnitude of effect, noted lead investigator Adeera Levin, MD, professor of medicine at the University of British Columbia in Vancouver.

Each additional year of age was associated with an 8% increased risk of death, and each additional 1 g/L of hemoglobin was associated with a 2% increased death risk. In addition, the researchers found that proteinuria was a significant and independent predictor of a decline in GFR.

Dr. Levin presented research findings here at the Canadian Society of Nephrology’s annual meeting on behalf of her co-investigators Bryan Curtis, MD, and Brendan Barrett, MD. She was not surprised that phosphate levels predicted mortality, she said.

Brad Astor, PhD, MPH, assistant professor of epidemiology and medicine at Johns Hopkins University in Baltimore, said that the phosphate finding dovetails with other research on the poor outcomes associated with mineral-metabolism disturbances, specifically phosphate, that has appeared in recent years.

“In aggregate, these results support placing a greater emphasis on controlling phosphate levels and possibly focusing less on calcium,” Dr. Astor said.