Routine nutritional assessments of patients new to dialysis frequently uncover individuals with large weight losses. National Health and Nutrition Examination Survey data show that dietary intake of patients with CKD spontaneously declines as they progress toward end-stage renal disease (ESRD) (Kidney Int. 2004;65:1031-1040).

This decline may be explained by an increase in uremic symptoms, such as nausea and anorexia. Anorexia, defined as a loss of the desire to eat or a loss of appetite, develops in 10%-25% of patients with CKD (J Ren Nutr. 1999; 9:129-132) and increases in severity as the patient nears ESRD.

Patients on dialysis experience appetite loss or anorexia as well. In the Hemodialysis (HEMO) trial, Burrowes et al found that approximately 32% of dialysis patients had fair or poor appetite (Nephrol Dial Transplant. 2005;20:2765-2774).

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Additionally, Lopes et al found that 45% of the hemodialysis patients participating in Dialysis Outcomes and Practice Patterns Study (DOPPS) I and II reported being moderately, very much, or extremely bothered by a lack of appetite (Nephrol Dial Transplant. 2007;22:3538-3546). Appetite has been suggested as a possible link between protein energy wasting and inflammation.

Inflammation, which is characterized by an increase in cytokines, such as interleukin (IL)-1, IL-6, or tumor necrosis factor-α, is present in many patients with CKD before they start and while they are on dialysis. Cytokines interfere with the satiety center, resulting in a loss of appetite (Contrib Nephrol. 1998;16:76-82). A logical extension of that connection leads to conjecture that appetite may be a useful predictor of protein energy wasting.

Loss of appetite

Nutrition parameters, hospitalization, and mortality have all been associated with loss of appetite in CKD patients. In the appetite and diet assessment tool (ADAT) designed by Burrowes and colleagues and used in the HEMO trial, the initial three questions relate to appetite.

The first is, “During the past week, how would you rate your appetite?” Patients are asked to respond with “very good, good, fair, poor, or very poor.” In the HEMO trial, patients who ranked their appetite as poor or very poor  had serum albumin levels, normalized protein catabolic rates, and serum creatinine concentrations that were significantly lower than those in patients who ranked their appetite as very good, good, or fair.

Using the same initial question from the HEMO trial, Kalantar-Zadeh et al found that patients with self-reported diminished appetite had significantly worse nutritional status as measured by the malnutrition inflammation score and were taking higher synthetic erythropoietin doses. These patients were also more likely to be hospitalized and had a higher rate of mortality (Am J Clin Nutr. 2004;80:299-307).

Finally, Carrero et al used the self-reported appetite component of Subjective Global Assessment to evaluate the appetite of hemodialysis patients in Sweden (Am J Clin Nutr. 2007;85:695-701). In this study, appetite was hypothesized to have gender differences. Forty-four percent of these dialysis patients reported their appetite to be sometimes, often, or always bad.

Fewer men reported having poor appetite than women. Appetite was positively associated with serum albumin, hemoglobin, high-sensitivity C-reactive protein (CRP), and IL-6 levels. Additionally, patients with poor appetite had significantly lower BMI, mid-arm muscle circumference, fat mass, and lean body mass.

Signs of uremic anorexia

As outlined by Carrero et al, the clinical signs of uremic anorexia are food aversion, gastric problems, oral manifestations, dental problems, impaired olfactory function, and weight or muscle loss. Biochemical signs of uremic anorexia are reduced oral and protein intake seen as a decreased normalized protein catabolic rate, serum albumin, and creatinine; decreased insulin growth factor-1 from muscle mass loss; increased CRP, IL-6, IL-1, and tumor necrosis factor-α due to inflammation; decreases in branched-chain amino acids; increases in leptin and visfatin resulting from altered adipokine balance; and altered appetite peptides, such as increased ghrelin and peptide YY and decreased neuropeptide Y and cholecystokinin (J Ren Nutr. 2009;19:10-15).

Although measurement of many of the biochemical signs of uremic anorexia is not routinely done in clinical settings, assessment of the clinical signs is easy and should be done on a regular basis. As dietitians or other members of the health-care team work with patients to achieve optimal outcomes, methods to increase appetite in patients who report anorexia should become routine.

Some simple ways to increase dietary intake and stimulate appetite are dining on small, frequent meals; eating cold foods, such as puddings or custards, which give off little aroma; and adding calorie-dense foods to meals or snacks so that every bite has nutritional value.

A commonly used and effective practice is having patients take their daily pills with liquid nutritional supplements. Even 2-4 oz of a calorie-dense nutritional supplement can provide needed protein, micronutrients, and calories.

When diet alterations are insufficient to increase dietary intake, a trial of an appetite-stimulating medication may be warranted. Finally, if both diet alteration and medication fail to increase caloric and protein intake, clinicians need to consider enteral (such as tube feeds) or parenteral (such as intradialytic parenteral nutrition) methods to ensure that CKD patients are receiving sufficient nutrients.

Dr. Steiber is Coordinator of the Dietetic Internship/Master’s Degree Program at Case Western Reserve University in Cleveland.