Protein Recommendations for Individuals
With CKD Stages 1-4

Sharon Stall

The prevalence of chronic kidney disease (CKD) has increased in the U.S. population from 20 million to 26 million people during 1999-2004, according to the recently studied National Health and Nutrition Examination Survey (NHANES) (Coresh et al., 2007). Diabetes and hypertension, which have also increased, may explain this 30% rise. The staging of CKD (see Table 1) based on estimated glomerular filtration rate (eGFR) (an estimate of kidney function) and albuminuria (provides evidence of kidney damage) gives a paradigm for classification of CKD (National Kidney Foundation [NKF], 2002) and facilitates identification of this population. Analysis of NHANES III 1988-1994 data shows that patients with CKD Stage 3 often die of cardiovascular death before they need dialysis (NKF, 2007). One public health response to these alarming statistics is education of professionals and the public on the risks of CKD and its treatment. Interventions to delay progression of CKD include, but are not limited to, use of angiontensin-converting enzyme (ACE) inhibitors or angiotensin-2-receptor blockers (ARBs), blood sugar control, and blood pressure control (NKF, 2002). Diet and lifestyle are also components of the treatment plan (NKF, 2002). This article will review dietary protein recommendations for individuals with Stage 1-4 CKD.

Protein recommendations are orchestrated depending on the stage of CKD to:

• Maintain nutritional health.
• Reduce the end products of protein metabolism, thus controlling uremia.
• Delay progression of CKD (Hirschberg & Kopple, 1988).
  

Protein 101: To Maintain Nutritional Health
Adequate energy intake is essential for protein to be used for growth and repair of lean tissue. In an absence of sufficient energy, protein is diverted from its important functions to supply energy (4 calories/gram), the primary nutrient need of the body (Matthews, 2006). The Kidney Disease Outcome Quality Initiative (K/DOQI) Clinical Practice Guidelines for Nutrition in Chronic Renal Failure suggest energy intake at 35 kcal/kg body weight/day for patients younger than 60 years of age and 30 to 35 kcal/kg body weight/day for patients older than 60 years of age, with GFR less than 25 mL/min (NKF, 2000). Energy recommendations for individuals with Stage 1 to 3 CKD are not outlined but are the same as for healthy adults (Fouque, 2005).

Since total energy intake is key to protein utilization by convention, the overall macronutrient distribution of the diet is described. The Dietary Reference Intake, published by the National Academy of Sciences (Food and Nutrition Board, Institute of Medicine, 2002), suggests that acceptable macronutrient distribution for protein is 10% to 35% of energy intake, with 15% of calories from protein being the average adult intake in the U.S.  Total energy intake is based on energy expenditure and weight goals. The Recommended Daily Allowance (RDA) is 0.8 gm good-quality protein/kg body weight/day. This RDA is the amount to provide nitrogen balance for the population at large and gives assurance of protein health. The RDA for protein is derived from the estimated average requirement (EAR) for protein. The EAR of 0.66 gm protein/kg, which meets the estimated nutrient needs of half the individuals in a group, is increased by 2 standard deviations from the mean, then rounded up to 0.8 gm protein/kg to obtain the RDA for reference protein. (Food and Nutrition Board, 2002; Matthews, 2006). This is why some patients can do well on less protein; since 0.8 gm protein/kg may actually be more than they need, with the provision they receive adequate calories. 

The RDA of protein, 0.8 gm/kg body weight/day (or 10% of calories), is much less than most Americans eat. The NHANES 1999-2000 indicated that the majority of Americans consume 15% of total calories or approximately 1.04 gm/kg body weight/day as protein (NKF, 2007).  Good quality protein contains all nine indispensable amino acids and promotes growth. These foods are meat, poultry, fish, eggs, milk, cheese, and soy.

To Control Uremia
Nitrogenous waste products of protein metabolism, as well as inorganic ions such as phosphorus, are eliminated by the kidney. Historically, low protein diets have been used to treat patients with advanced kidney disease who are not on dialysis. By modulating protein intake, uremic symptoms may be controlled. Research studies show that 0.6 g protein/kg/day, with at least 50% of the protein of high biologic value, may be prescribed if adequate energy of 35 kcal/kg is consumed (Fouque, 2005). A protein amount of 0.28 g/kg/day supplemented with essential amino acids, or with keto acid supplements and adequate energy, have also been used (Mitch, 1988). These latter two diets have grown out of favor. When protein energy malnutrition and low albumin were identified as a predictor of morbidity and mortality in patients receiving maintenance dialysis, many practitioners switched their emphasis from limiting protein prior to the initiation of dialysis to maintaining adequate nutritional status (Owen, Jr., Lew, Liu, Lowrie, & Lazarus, 1993). However, there is the argument that under good nutritional supervision, and motivation by the patient, low protein diets may be maintained. The 2000 KDOQI Nutrition in Chronic Renal Failure Guidelines recommended 0.6 gm to 0.75 gm protein/kg body weight for GFR less than 25 mL/min, with emphasis on adequate energy intake and maintenance of good nutritional status (NKF, 2000).

To Delay Progression of CKD
Brenner and colleagues postulated that protein increases renal plasma blood flow and GFR leading to glomerular hyperfiltration and hypertension, and over time, results in kidney injury (Brenner, Meyer, & Hostetter, 1982). It is well known that a high protein load acutely increases GFR, renal plasma flow, and proteinuria in animals and humans (Bernstein, Treyzon, & Zhaoping, 2007). Reducing the protein load may stop kidney scarring in experimental situations. In addition, proteinuria has been identified as an independent risk factor for CKD progression. Protein intake can regulate proteinuria; therefore lowering protein intake may reduce proteinuria and have an impact on the progression of CKD.

The KDOQI Clinical Practice Guidelines for Chronic Kidney Disease:  Evaluation, Classification, and Stratification (NKF, 2002) suggest 0.75 gm protein/kg/day for a GFR greater than 30 mL/min/1.73 m2. The guidelines are clear in stating that there is insufficient evidence to suggest this amount of protein delays progression (NKF, 2002).

The hypothesis of a low protein diet and strict blood pressure control in delaying the progression of CKD was tested with The Modification of Diet in Renal Disease (MDRD) study.  This was a large clinical trial to determine if the protein-modified diet delayed progression of CKD in a population without diabetes using three different study diets in two different kidney function groups. The study results did not show statistical significance of diet intervention, and essentially, the modified protein diet was debunked. However, a recent secondary analysis of the MDRD study population, with a 6-year follow up, showed that the low protein diet with tight blood pressure control may have a beneficial effect on delaying progression in CKD Stages 3 to 4 (Levey et al., 2006). Although further long-term analyses beyond 6 years were not as convincing, the investigators concluded with suggesting 0.6 to 0.8 gram protein/kg body weight/day for GFR less than 60 mL/min/1.73m2. This study also raises the effect of time on the protein-modified diet and time needed to assess the protective effect of diet on kidney function based on clinical outcomes.

To clarify the MDRD study result, Fouque, Laville, and Boissel (2006) did a meta-analysis for the Cochrane group. Only eight trials met the rigorous criteria for inclusion. The analysis showed that protein modification in Stages 3 and 4 delayed progression to the clinical outcomes of dialysis, transplantation, or death by 31%. It seems that there is a role for protein modification in Stages 3 to 4 CKD, but the specific amount of protein to recommend is uncertain and ranges from 0.6 to 0.8 g/kg/day.

Protein restriction for persons with diabetes is less clear. A meta-analysis by the Cochrane group concluded “that restricted protein intake appeared to slow progression of diabetic kidney disease, but not by much on average” (Robertson, Waugh, & Robertson, 2007, p. 2). There was, however, variability among individuals with some showing benefit from the low protein diet. There are few studies in diabetic kidney disease, and the studies that exist are short term, done in a small group with limited documentation. There is some evidence to suggest that rather than limiting the amount of protein in the diet, consuming white meat and fish or vegetables as opposed to red meat may also provide benefits (Robertson et al., 2007).

CKD Stages 1 and 2
The emerging public health awareness of CKD and cardiovascular disease (CVD), as well as the obesity and diabetes epidemics, has fueled interest in the dietary treatment of CKD. There is an important focus on CVD risk reduction. Dietary and lifestyle recommendations for the general population have been published by major health organizations and may be adapted to this population.  Good blood sugar control, blood pressure reduction, maintenance of a healthy weight, control of lipids, avoidance of tobacco, and moderate physical activity are goals for managing diabetes, controlling hypertension, and addressing CVD risk, and are consistent with strategies to delay progression of CKD. Dietary modification is adapted on an individual basis.

Diabetes
The KDOQI Clinical Practice Guidelines for Diabetes and Chronic Disease, published in 2007, suggest target dietary protein intake for people with diabetes and CKD Stage 1 to 4 of 0.8 gm/kg body weight, the RDA (NKF, 2007). The guidelines state, “They [The Diabetes Work Group] selected this amount because of evidence of kidney and survival benefit of approximately the RDA level in diabetes and CKD Stages 1 and 2. They conclude that a protein intake that meets but does not exceed the RDA would be prudent at earlier stages of CKD” (NKF, 2007, p. S105). This is a huge step in guidance to the population with CKD and diabetes.

High-protein diets, already described as potentially damaging to the kidney, have even more effect on kidney hemodynamics and kidney damage in patients with diabetes. These guidelines recommend that people with diabetes and CKD should avoid high-protein diets. This should also be a consideration for high-protein diets that have been popular for weight loss (Kent, 2006).

Hypertension
The KDOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease describe the Dietary Approaches to Stop Hypertension (DASH) diet (NKF, 2004). DASH is a dietary pattern of fruits, vegetables, low-fat dairy foods, whole grains, poultry and fish, with smaller amounts of red meat, which has been recommended for the general population for treatment of high blood pressure. This may also be used for CKD Stages 1 and 2. The 1.4 gram protein/kg recommended in this diet is adjusted to 0.6 to 0.8 gm/kg body weight in Stages 3 and 4 and further adjustments for phosphorus and potassium are given (NKF, 2004). 

CVD
The American Heart Association guidelines state “CKD, which precedes end-stage kidney disease, substantially increases the risk of CVD.  Dietary therapies recommended for the general population are also recommended for persons with early stages of CKD, consistent with the individualized guidance provided by the patient’s health care provider” (Lichtenstein et al., 2006, p. 2189).

Summary
In CKD Stages 1 and 2, diet and lifestyle interventions are key for their potential to delay progression of kidney failure and reduce CVD risk. The recommendations are to prudently lower protein in the diet to the RDA. Although the research supporting this data may still be considered uncertain about the efficacy of a low protein diet on slowing the progression of CKD, it may also be considered safe since it is the RDA (Levey et al., 2006). Other interventions may include control of proteinuria, of high blood pressure, and blood sugar, and the use of an ACE inhibitor or ARB. In CKD Stages 3 and 4, there are more enthusiastic recommendations regarding protein, potassium, and phosphorous that influence diet decision making but are not necessarily employed in the earlier stages of CKD.

In addition, we cannot neglect that these patients, despite our best efforts, often progress to Stage 5 CKD treated with peritoneal dialysis or hemodialysis. We must maintain an optimum nutritional status along the continuum of CKD Stages 1 to 5. Protein energy malnutrition is a predictor of morbidity and mortality in patients on dialysis (NKF, 2000). The goal for these patients is to be well nourished and kidney protected, which is a balancing act. Medicare supports medical nutrition therapy for registered dietitian (RD) services for patients with GFRs of 15 to 50 mL/min/1.73m2 (NKF, 2007). The RDs in nephrology are effective in reviewing the diet options and providing necessary guidance and support to individuals with CKD. These RDs are the nutrition information resource for practitioners treating patients with Stages 1 to 4 CKD.

References
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Brenner B.M., Meyer T.W., & Hostetter T.H. (1982). Dietary protein intake and the progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive sclerosis in aging renal ablation and intrinsic renal disease. New England Journal of Medicine, 307, 652-659.

Coresh, J., Selvin E, Stevens L.A., Manzzi, J, Kusek J.W., Eggers P., et al. (2007). Prevalence of chronic kidney disease in the United States. Journal of the American Medical Association, 298(17), 2038-2047.

Fedje, L., & Karalis, M. (2004). Nutrition management in early stages of chronic kidney disease. In L. Byham-Gray & K. Wiesen (Eds.), A clinical guide of nutrition care in kidney disease. (pp. 21-28). Chicago: American Dietetic Association.

Food and Nutrition Board, Institute of Medicine. (2002). Proteins and amino acids. Dietary reference intakes for energy, carbohydrates, fiber, fat, fatty acids, cholesterol, protein and amino acids (macronutrients). Washington, DC: National Academies Press.

Fouque D., Laville M., & Boissel J.P. (2006). Low protein diets for chronic kidney disease in non diabetic adults (Review). Cochrane Database of Systematic Reviews, 2, 1-17.

Fouque, D. (2005). Nutritional strategies for progressive renal insufficiency.  In. W.E. Mitch, & S. Klahr (Eds.), Handbook of nutrition and the kidney (5th ed., pp. 176-195). Philadelphia: Lippincott, Williams & Wilkins.

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Lichtenstein A.H., Appel, L.J., Brands, M., Carnethon, M., Daniels, S., Franch, H.A., et al. (2006). Summary of American Heart Association diet and lifestyle recommendations revision 2006. Arteriosclerosis Thrombosis Vascular Biology, 26, 2186-2191.

Matthews, D.E. (2006). Proteins and amino acids.  In. M.E. Shils, M. Shike, A.C. Ross, B. Caballero, & R. J. Cousins (Eds.), Modern nutrition in health and disease (10th ed., pp. 23-61).  Philadelphia:  Lippincott, Williams & Wilkins.

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Robertson L., Waugh N., & Robertson A. (2007). Protein restriction for diabetic renal disease (review). Cochrane Database of Systematic Reviews, 4, 1-19.