Protein Intake in Hemodialysis Patients Should Be Higher than 1.2 g/kg per Day: Commentary

Biruete and Kistler and Ozcan and Ikizler are to be congratulated for their thoughtful discussion on the dietary protein needs of maintenance hemodialysis (MHD) patients.^1,2 Both sets of authors identify factors that occur commonly in MHD patients and that affect their protein metabolism and potentially their dietary protein needs, including losses of amino acids during the hemodialysis procedure, inflammatory states, such hormonal and metabolic disturbances as insulin resistance and acidemia, low energy and protein intakes, and the sedentary state. Hemodialysis is also associated with peptide removal, adherence of protein to dialysis membranes and tubing, and blood losses. MHD patients are also subject to resistance to IGF-1 and growth hormone and to frequent intercurrent illnesses. The authors emphasize that muscle protein synthesis and often degradation are altered in people with ESKD, both during and independently of a hemodialysis treatment.^1,2 These authors raise intriguing questions regarding the appropriate amounts and optimal timing for dietary protein intake. Ozcan and Ikizler comment that protein catabolism stimulated by hemodialysis can be compensated by providing amino acids and energy during the actual hemodialysis procedure.²

Biruete and Kistler point out that although dietary needs for many essential nutrients are determined by body mass, protein needs are not the same for all bodily tissues and appear to be decidedly less for fat cells than, for example, skeletal muscle.¹ Since MHD patients are often obese or protein-energy wasted, simply basing protein needs on the body weight of patients may lead to overestimates or underestimates of protein needs. The authors suggest that it may be preferable to base dietary protein needs of MHD patients on bioelectrical impedance determinations of their lean body mass. An unmentioned question is how to determine the optimal body mass even if bioelectrical impedance is used. Biruete and Kistler allude to the Hamwi method to estimate ideal body weight.¹ To the best of my knowledge, there is no evidence that this method indicates the optimal body weight for people with advanced CKD.

Biruete and Kistler also comment that older healthy adults seem to require more protein intake to stimulate protein synthesis than younger adults,¹ and the average age of prevalent American MHD patients is older, 65.1±SD 13.8 years in one report.³ Whether older MHD patients also require more protein intake than younger MHD patients to stimulate the same magnitude of protein synthesis is not known.

The authors' comments presuppose we know the dietary protein needs of normal, presumably healthy people and that we know how to ascertain the protein needs of MHD patients. There is an underlying assumption in both papers that dietary protein requirements can be ascertained by assessing the relationship between dietary protein intake and body protein balance (e.g., nitrogen balance) or, in cohort studies, between estimates of protein intake and maintenance of normal body mass, muscle mass, or serum protein levels. Commonly, dietary protein needs are based on some measure of body mass^1,2 or possibly muscle protein content.² These approaches reflect the traditional ways that dietary protein requirements have been ascertained in normal healthy people.⁴

Traditionally, dietary protein requirements or allowances were determined in meticulously conducted nitrogen balance studies in normal healthy people who were fed varying amounts of protein.⁴ The results of these studies, performed in rather small numbers of volunteers, were confirmed by epidemiologic observations in much larger numbers of apparently normal individuals in whom dietary protein intake was compared with estimates of body protein or muscle mass, serum protein levels, and appearance of good health.⁵ Other techniques for assessing dietary protein needs include the factorial method and the indicator amino acid oxidation techniques.^6,7 Indicator amino acid oxidation involves giving a participant an isotopic carbon-labeled amino acid at each level of protein intake and monitoring the dietary protein level above which oxidation of that amino acid increases. Recent reports emphasize that each of these methods are imprecise, and they often lead to overestimation of dietary protein needs.^6,7

It is well recognized that there is much individual variation in the dietary needs for the essential nutrients, including protein.⁴ This and the imprecision in assessing dietary protein needs are reasons why the Dietary Reference Intakes have developed the following categories to characterize the dietary needs of essential nutrients, including protein:⁴

• “Recommended Dietary Allowances (RDA): the average daily dietary nutrient intake level sufficient to meet the nutritional requirement of nearly all (97%–98%) healthy individuals in a particular life stage and gender group.”

• “Adequate Intake: the recommended average daily intake based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate—used when the RDA cannot be determined.”

• “Estimated Average Requirement: the average daily nutrient intake level estimated to meet the requirement of half the healthy individuals in a particular life stage and gender group.”

• “Tolerable Upper Intake Level: the highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population. As intake increase above the upper intake level, the potential risk of adverse effects may increase.”

It is important to recognize that the RDA does not indicate the dietary protein requirement of an individual. The RDA indicates an amount of protein that should ensure that almost all healthy people will ingest sufficient protein. A related conundrum concerning the dietary protein needs in both healthy people and those with CKD is that almost all studies examining protein intake and outcomes are short term. More research is needed concerning the long-term effects of carefully measured protein intakes and nutritional and clinical outcomes.

The issues addressed in these two papers are highly relevant. Protein or protein-energy wasting is associated with decreased survival in MHD patients.^8,9 Moreover, nutritional support of MHD patients who have protein-energy wasting not only improves their nutritional status but may increase survival.⁹

These authors recognize that maintaining normal body protein mass may not be the only or optimal way to determine dietary protein needs.^1,2 Although the major locus of body protein is muscle, it is not obvious why in rather sedentary people, such as is the case for almost all MHD patients, a change in muscle protein mass, even to a substantial degree, should affect their morbidity, mortality, or quality of life. There should be more effective and precise methods for assessing the dietary needs of essential nutrients than simply measuring the relationship between intake and the balance, body content, or blood levels of these nutrients.

This may be as true for normal healthy humans as for patients with CKD and ESKD and for individuals with other disease conditions. It is likely that protein intake will affect clinical outcomes, including mortality, not so much by its ability to maintain muscle protein mass or total body protein as through its effects on specific cellular, biochemical, and molecular processes. This might be especially the case for those activities that facilitate immunologic function, antibody production, lymphocyte killer cell activity, inflammatory responses, host resistance, and ability to grow new tissues and heal wounds. These processes might be more likely to affect clinical outcomes if they involve such essential organs as heart, liver, lungs, brain, nerves, kidneys, and bone marrow rather than simply skeletal muscle. It may be time to reexamine dietary protein allowances in both healthy and ill people by investigating the effects of protein intake on these processes. Moreover, as was pointed out by these authors,^1,2 dietary protein needs also depend on intakes of other nutrients especially those providing for the energy needs. Much research is needed to investigate these questions.

What practical information can we take from these two thoughtful papers? It would seem MHD patients need to be prescribed at least 1.0–1.2 g protein/kg per day. Energy needs must be monitored and met with appropriate diets. Most importantly, since protein-energy needs of MHD patients can vary substantially, even at different times in the same patient as the clinical condition changes, the protein-energy status of MHD patients must be periodically assessed. If it is not optimal, nutritional interventions should be implemented.

Finally, the current level of sophistication of the basic biologic sciences and of outcomes research should enable us now to develop much more effective tools to examine both the short-term and long-term effects of different protein and energy intakes. This should allow a more precise assessment of the dietary needs of protein and other essential nutrients not only for MHD patients but also for healthy people and for people with other acute or chronic illnesses.

Disclosures

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/KN9/B256.

Author Contributions

Writing – original draft: Joel D. Kopple.

Writing – review & editing: Joel D. Kopple.

Funding

None.