Nutrition and Chronic Kidney Disease

Denis Fouque; Solenne Pelletier; Denise Mafra; Philippe Chauveau

Disclosures

Kidney Int. 2011;80(4):348-357. 

In This Article

Inflammation: A Double-Edge Catabolic and Anorectic Sword

Chronic inflammation has been identified in CKD in the mid-nineties[97–99] and was thought to be the primarily cause for low-serum albumin concentrations in these patients. There is a linear risk between serum C-reactive protein (CrP) and coronary heart disease, stroke and mortality in the general population,[100] and in a healthy elderly population.[101] In maintenance dialysis, Kaysen et al.[102] reported a double dependency of serum albumin, positive one with protein intake as a source of amino acids mandatory to protein synthesis, and negative one with serum CrP as a marker of chronic inflammation. More recent reports have confirmed the major interdependency between inflammation, cardiovascular risk, and malnutrition.[103,104] As serum albumin is a strong predictor for mortality, it is tempting to analyze the potential impact of inflammation on CKD patients' survival.[24]

Low-grade chronic inflammation is present in about 30–65% of maintenance dialysis patients.[105] Inflammation seems to increase with age, and in 2008, maintenance hemodialysis patients aged over 75 years had a median CrP of 6 mg/l, which was significantly greater than those aged under 75 years.[106] The CrP threshold used to define inflammation is unclear, and varies between 5 and 10 mg/l among studies. In many reports, other inflammatory markers such as interleukin-1, -6, or tumor necrosis factor-α have been shown to be elevated and elicit comparable side effects.[107,108] However, these markers are more difficult to collect and more expensive to measure, and on a routine basis, it seems acceptable to use CrP. Thus, whatever the cause,[99] inflammation appears to be a common condition of CKD, and until now, no dialysis technique or medication has been successful in correcting or even improving inflammation.

The impact of inflammation on nutritional status is twofold (Figure 4). Inflammation may induce additional catabolism in CKD patients, as shown by Avesani et al.[90] Indeed, any 1 mg/l CrP elevation results in a 30 kcal increase in daily energy expenditure.[90] Besides being catabolic, inflammation is also responsible for anorexia. Experimental injection of recombinant interleukin-1 in rats dramatically reduces spontaneous food intake.[109] In maintenance hemodialysis patients, serum CrP is negatively linked with appetite.[49,50] Indeed, Kalantar-Zadeh et al.[49] reported in 331 Californian maintenance hemodialysis patients a significant inverse relationship between an appetite score and serum CrP. Visfatin, a new adipocyte-derived factor sensitive to inflammation,[110] may also be involved in anorexia in CKD.[111] Based on an appetite questionnaire in 246 maintenance hemodialysis patients in Sweden, a high-serum visfatin (for example, greater than 40 ng/ml) was associated with poor appetite and a lower plasma amino-acid profile. Appetite was also influenced by visfatin genotype.[111]

Figure 4.

The double impact of inflammation on wasting. The role of inflammation in chronic kidney disease, responsible for increased catabolism and anorexia, both actions that may induce protein–energy wasting and loss of body proteins, which can be counteracted by nutrients.

Chronic inflammation is linked with more impaired nutritional status. In a 5-year follow-up of 310 Swedish patients, mortality was greater in patients with a CrP >10 mg/l and a subjective global assessment greater than 2, indicating a worse nutritional status.[112] It is interesting to note that, depending on the way inflammation will impact on metabolism, a slow process with muscle and fat loss without hypoalbuminemia may apply if only food intake is reduced as a consequence of anorexia, whereas a more rapid wasting and hypoalbuminemia will occur as a consequence of catabolic events induced by a more active inflammation[112] (Figure 4). This may partly explain why in a maintenance hemodialysis population some inflamed patients may have a less severe wasting state than others.

Is this chronic inflammatory-wasting state an irreversible situation? First, when survival is analyzed according to nutritional status (for example, subjective global assessment, normalized protein nitrogen appearance, or serum albumin) and CrP, patients with a high CrP and a good nutritional status always survive better than those with a low CrP and a more impaired nutritional status, conferring some protection of a better nutritional state to the deleterious effects of inflammation.[112] Second, fortunately, there seems to exist a therapeutic response to this inflammatory-induced wasting. Recent interventional studies have shown anabolic responses to either oral and/or parenteral nutritional supplements in hemodialysis patients.[113–115] Importantly, these responses also occurred in patients with CrP above 10 mg/l.[113–115] In the FINE study after receiving 1 year of supplemental nutrition, serum albumin and prealbumin of the malnourished inflamed patients did respond better than in the noninflamed patients.[114] Thus, after a careful check-up aimed at solving obvious inflammation causes, inflamed patients presenting with protein–energy wasting should be aggressively treated with nutritional supplements as well (Figure 4).

Is nutrition responsible for inflammation? The food content may possibly be responsible for production or additional accumulation of inflammatory compounds. Plasma advanced glycosylated end-products have been shown to increase during advanced CKD and could be increased not only from endogenous metabolism but also from dietary sources.[116] Indeed, about 10% of ingested advanced glycosylated end-products may be absorbed and ~60% of this absorbed amount will be incorporated in tissues.[117] Ingesting food low in advanced glycosylated end-products content resulted in a plasma advanced glycosylated end-products reduction.[118] As a follow-up to this observation, does a protective diet exist? A potential response may be found in the Mediterranean diet. This diet is rich in vegetables, fruit, olive oil, and fish, and poor in red meat. It has been associated with reduced cardiovascular mortality, increased longevity, and more recently with decreased dementia.[119] A Mediterranean diet possesses anti-inflammatory properties, improves lipid profile and reduces oxidant stress. For example, olive oil has been shown to reduce CrP and oxidized low-density lipoprotein cholesterol.[120,121] Whether this Mediterranean diet possesses protective properties in CKD should be further studied. Indeed, in maintenance dialysis, attention should be focused on potassium intake that could be slightly increased by these diets rich in fruit and vegetables.

In summary, it appears that inflammation is not only catabolic but may also induce protein–energy wasting from a reduction in appetite.[24] Interestingly, by contrast to a generally admitted opinion, inflammation-induced protein–energy wasting can be reversed by nutritional supplements.

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