While both disorders are associated with poor clinical outcomes, including high mortality, MBD and PEW are usually assumed to have distinct and unrelated etiologies and to act through different clinical pathways. MBD is associated with high phosphorus levels, while PEW is believed to result from inadequate protein intake due to anorexia from the uremic state (Am J Clin Nutr. 2004;80:299-307) and other conditions that restrict oral food ingestion in dialysis patients.

Thus, restricting dietary phosphorus intake and increasing dietary protein intake are recommended to most individuals with advanced CKD, especially those undergoing dialysis treatment. However, the resulting prevention of MBD may be at the expense of worsening PEW, and vice versa, because higher protein in-take may lead to increased serum phosphorus concentrations (see chart).

This therapeutic conundrum is encountered frequently during the medical care of dialysis patients. Many nephrologists and dietitians are not sure whether they should reinforce dietary restrictions in their dialysis patients (which often includes significant protein restriction to achieve a serum phosphorus level within the recommended target zone) or whether they should liberalize or encourage protein intake to improve nutritional status and prevent hypoalbuminemia (which is associated with an elevated death risk).

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Indeed, the lower mortality in African-American dialysis patients may be related to their higher protein intake even at the expense of worsening hyperphosphatemia (Nat Clin Pract Nephrol. 2007;3:493-506). The recent findings by Shinaberger et al further support the idea that the risk of controlling serum phosphorus by imposing dietary protein restriction may outweigh its benefit.

However, the authors admitted that reduced protein intake may also be the result of poor appetite, which is common in sicker dialysis patients, independent of restricting or liberalizing dietary intake.

The Shinaberger study also found that higher baseline nPCR was associated with lower mortality, consistent with some previous studies (Am J Kidney Dis. 2006;48:37-49). The nPCR is a urea kinetic-based estimate of dietary protein intake in dialysis patients, assuming minimal or no residual renal function (Kidney Int. 1997;52:486-494).

However, the nPCR is collinear with Kt/V because both nPCR and Kt/V are calculated using the same urea nitrogen levels. Higher protein intake may indeed lead to lower mortality by virtue of improv-ing nutritional status.

While a moderate rise in nPCR was associated with reduced mortality, a more drastic rise in nPCR exhibited a paradoxical trend toward higher mortality. The latter association may result from worsening hyperphosphatemia caused by higher-than-usual protein intake, once again illustrating the countervailing risks and benefits of high protein intake.   

In conclusion, it is plausible that the risk of controlling serum phosphorus by imposing dietary protein restriction outweighs its benefit in dialysis 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.

More attention to nonprotein sources of phosphorus, such as food additives or highly processed convenience foods, is warranted (Semin Dial. 2007;20:295-301). Because increased protein intake with a concurrent decline in serum phosphorus appears to be associated with the lowest mortality, diligent use of potent phosphorus binders may be helpful, especially binders that do not lead to increased calcium load or high pill burden, although binder choice remains a topic of debate.

In any event, the findings of Dr. Shinaberger and colleagues underscore the need for clinical trials to determine which treatment protocols offer the greatest survival advantage for dialysis patients and whether nondietary control of phosphorus or restricting nonprotein sources of phosphorus is safer and more effective.

Dr. Kalantar-Zadeh is associate professor of medicine, pediatrics, and epidemiology at the David Geffen School of Medicine at the University of California-Los Angeles (UCLA) and director of Dialysis Expansion & Epidemiology in the Harbor-UCLA Division of Nephrology & Hypertension. He is also the Renal & Urology News medical director for nephrology.