Phosphorus-lowering approach in dialysis patients could reduce survival.

Lowering serum phosphorus in maintenance hemodialysis (MHD) patients by restricting dietary protein, a routinely used strategy, may do more harm than good, according to a study.

The finding is based on a three-year evaluation of 30,075 MHD patients monitored for six months. Compared with patients whose serum phosphorus and protein intake both increased, subjects whose serum phosphorus decreased but whose protein intake increased had a significant 10% reduction in death risk. Patients whose phosphorus levels increased and protein intake decreased and those whose phosphorus levels and protein intake both decreased had significant 11% and 6% increases in death risk, respectively.

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Foods high in protein are a main source of dietary phosphorus, so imposing dietary phosphorus restriction often leads to decreased dietary protein intake, the authors explained. This can result in malnutrition and protein-energy wasting, which can increase the risk of death in MHD patients.

The researchers postulated that “the risk of controlling serum phosphorus by imposing dietary protein restriction may outweigh the benefit of phosphorus control in MHD patients. The persistent association between low protein intake and worse survival may indicate that methods other than restricting protein intake should be sought to restrict dietary phosphorus intake.”

Christian S. Shinaberger, MD, then a doctoral student at the University of California at Los Angeles (UCLA), and colleagues measured subjects’ protein intake indirectly using the normalized protein equivalent of total nitrogen appearance (nPNA), also known as the normalized protein catabolic rate.

The researchers measured serum phosphorus, nPNA, and most other laboratory values monthly for six months. A decline in nPNA was associated incrementally with higher mortality, the researchers reported in The American Journal of Clinical Nutrition (2008;88:1511-1518). Each decrease in nPNA of 0.1 g/kg-1/day-1 was associated with an 18% increased death risk. In addition, each 1 mg/dL rise in serum phosphorus was associated with a 13% increased death risk.

“Because higher protein intake and a concurrent decline in serum phosphorus appear to be associated with the lowest mortality, diligent use of potent phosphorus binders may be helpful, especially if these binders do not lead to an excessive calcium load or pill burden, although binder choice remains a topic of debate,” the study authors wrote.

In addition to phosphate binders, another alternative is to restrict nondietary phosphorus from such sources as food additives and preservatives, all of which contain relatively large amounts of phosphorus, said principal investigator Kamyar Kalantar-Zadeh, MD, PhD, MPH, associate professor of medicine and pediatrics at the UCLA David Geffen School of Medicine and director, Dialysis Expansion & Epidemiology, at the Harbor-UCLA Division of Nephrology & Hypertension. “

We have just started an initiative to lobby the FDA to add phosphorus content and the proportion of nonprotein phosphorus on all food labels,” said Dr. Kalantar-Zadeh, who also is the medical director for nephrology at Renal & Urology News. A third alternative is to use more frequent dialysis.