Nutrition and Chronic Kidney Disease

Denis Fouque; Solenne Pelletier; Denise Mafra; Philippe Chauveau


Kidney Int. 2011;80(4):348-357. 

In This Article

Chronic Kidney Disease: Which Protein Intake Before Maintenance Dialysis?

There is now evidence that patients with chronic kidney disease (CKD) should control their protein intake to reach optimal body protective values.[6] After an extensive review of the literature, most of the scientific societies worldwide recommend a daily allowance of 0.6–0.8 g protein/kg/day for CKD patients with or without diabetes.[7–11] Clinical trials confirmed by meta-analyses on large numbers (e.g., more than 2000 patients) show that it is effective and safe to reduce protein intake from the western-type diet, which contains about 1.3–1.4 g protein/kg/day to a nutritionally and metabolically optimal intake of 0.6–0.8 g protein/kg/day.[12,13] This is particularly important in patients with proteinuria, including those with diabetic nephropathy, as any increase in protein intake will increase proteinuria, which per se, is a risk factor for CKD progression.[14,15] Furthermore, reducing protein intake decreases proteinuria as efficiently as angiotensin-converting enzyme inhibitors,[16,17] improves serum lipid profile,[18] and has an additional effect on proteinuria reduction to that of angiotensin-converting enzyme inhibitors.[19] Thus, based solely on proteinuria, there is a strong rationale to control protein intake.

Limiting protein intake is associated with an instant decrease in wasted products and uremic toxins, blood urea nitrogen levels, and acid load. Metabolic consequences of restricted protein diet have been extensively reviewed:[6] reduction in oxidative stress, amelioration of insulin resistance, better control of metabolic bone disorders in response to a reduced phosphate load, and subsequent improvement in anemia control.[20–23]

Nutritional Safety of a Controlled Protein Intake

As CKD is associated with protein–energy wasting,[24] the nutritional safety of such a protein reduction has been questioned.[25] Muscle wasting is associated with CKD and increases dependency, mortality, and morbidity in this population.[26] From a basic point of view, one should find a direct relationship between reduced protein intake and muscle wasting. Unfortunately, this approach is not clinically relevant: muscle wasting in chronic diseases is mainly due to an imbalance between protein synthesis and degradation, and is further worsened by inactivity.[27] In addition, acidosis and activation of the ubiquitin–proteasome pathway associated with inflammation and insulin resistance represent the main factors of muscle wasting.[26,28] Reducing protein intake has been shown to improve all these catabolic conditions. Indeed, a better control of metabolic acidosis due to a lower acid load leads to a normalization of the adaptive responses to dietary protein restriction, as it has been clearly demonstrated in animals models, CKD, and dialysis patients,[29–31] and seems beneficial on the progression of CKD.[31] Insulin resistance is associated with muscle protein breakdown in end-stage renal disease patients[32] and rapidly improves after 3 months of low-protein diet (LPD).[22] Recent experimental data suggest that an increase in blood urea nitrogen induces reactive oxygen species production and enhances insulin resistance.[33]

Protein Intake and Oxidative Stress

Oxidative stress and upregulation of oxidative metabolism are among the main factors responsible for sarcopenia in chronic disease and in aging. Recent data suggest that oxidative stress is associated with severe disturbances of muscle function even without muscle atrophy.[34] Moreover, oxidative stress is probably one of the main factors that aggravate glomerulosclerosis and fibrosis during CKD. A low-protein intake confers a protection against oxidative stress in experimental studies.[35,36] Finally in CKD patients treated with LPD or supplemented very low-protein diet (SVLPD), long-term studies on body composition did not find any adverse effect of such diets on muscle or lean body mass.[37–39]

Quality of protein intake (and not only quantity) should also be addressed. First, despite debate and controversies, clinical studies in patients receiving LPD (0.6–0.8 g/kg/day) or SVLPD (0.3–0.6 g/kg/day, supplemented with amino acids or keto-analogs) are nutritionally safe. No case of malnutrition occurred, in response to an adequate metabolic adaptation.[13,17] In the Modification of Diet in Renal Disease study, 9 months after completion of the study, the mean serum albumin was 42 g/l, and in the 239 patients of the Bordeaux cohort, only two patients stopped an SVLPD diet for reason of malnutrition, whereas the mean cohort serum albumin at start of renal replacement therapy was 39 g/l.[40,41]

Beneficial Effects of a Nutritional Support

Most patients who start renal replacement therapy without prior dietary follow-up do present symptoms of malnutrition, for example, loss of body weight, altered anthropometry, and laboratory nutritional parameters.[42] The occurrence of a previous nutritional care plan appears to be the main protective factor against this progressive wasting. First, nutritional support and patient information are key factors to ensure motivation and adherence to the diet. This fact has been clearly demonstrated by Campbell et al.,[43] using body composition analysis and subjective global assessment. Second, in clinical studies, an LPD is usually composed of 50% protein of high biological value (such as meat, fish, or egg). In the case of SVLPD, no malnutrition occurred and long-term survey during or after the start of renal replacement therapy did not show a greater relative risk of death.[41]

Third, animal experiments and studies in elderly patients renewed attention on protein quality and the importance of essential amino acids intake. Indeed, in the elderly, a protein intake higher than 0.8 g/kg/day is recommended to avoid sarcopenia due to a relative resistance of muscle to the anabolic effect of an amino-acid load.[44] However, this resistance could be inhibited using amino-acid mixtures, particularly those enriched in branched-chain amino acids, that is, leucine, isoleucine, and valine.[45] An indirect evidence of the effect of amino acids on CKD-associated sarcopenia is reflected by the observation that, in dialysis patients, resistance training effect on muscle metabolism is enhanced when combined with intradialytic parenteral nutrition.[46] In elderly, sarcopenia is partly explained by enhanced oxidative stress. In nephrectomized rat, increased oxidative stress caused by protein malnutrition impairs the glomerular filtration barrier and a supplementation with ketoacids reduced kidney and oxidative stress injury.[35]

Finally, clinical studies using LPD or SVLPD bear a great attention on energy intake. Specific dietary survey is provided to ensure a sufficient amount of calories, for example, ~35 kcal/kg/day. This is not always the case in most renal units where time of dietitian is lacking. In conclusion, the beneficial effects of reducing protein intake to optimal values are obscured by the lack of physician confidence, dietitian time, and patient education. Although immediately costly and sometimes tricky to set up, nutritional support should be provided for the patient's sake and is clearly cost-effective over the long term.[47]


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