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Treating malnutrition in patients on hemodialysis.

Malnutrition is common in patients on hemodialysis and is a powerful predictor of morbidity and mortality. Although much progress has been made in recent years in identifying the causes and pathogenesis of malnutrition in patients on hemodialysis, as well as recognizing the link between malnutrition and morbidity and mortality, no consensus has been reached concerning its management (Bossola et al., 2005).

There are many causes of inadequate nutritional intake in the population receiving dialysis. Taste abnormalities, such as dry mouth, acuity, metal flavors, and changes in taste, are often seen in patients with uremia. Anorectic factors, such as inflammation and/or infection, medications, psychological issues (including depression), poverty, and alcohol and drug addiction, all contribute to malnutrition in this population. Other factors associated with the dialysis process, including post-dialysis fatigue, poor dialysis adequacy (inadequate Kt/V), and cardiovascular instability, all have an adverse effect on nutritional status as well. Anorexia is present in approximately one-third of patients receiving hemodialysis and is the consequence of multiple complex and only partially defined disturbances involving inflammation and altered hormonal and amino acid patterns (Bossola et al., 2005).

Nutrition screening, dietary counseling, and dialytic adequacy have a critical role in malnutrition prevention. Pharmacological interventions have been used, and this article reviews approaches to increase appetite and weight gain in the hemodialysis population.

Appetite Stimulants

Use of Megestrol Acetate

The most widely prescribed appetite stimulant is megestrol acetate (Megace[R]) generically. Megace was approved in 1993 for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of AIDS. By 1999, nearly one million prescriptions had been written for Megace Oral Suspension (Bristol-Meyers Squibb Co, Princeton, NJ). Megestrol acetate is a semisynthetic progestational steroid that was originally used as a therapeutic modality for metastatic breast cancer. In addition to improving appetite and food intake, megestrol acetate has also been found to have significant anti-inflammatory properties. Few studies have been conducted on its use in patients on hemodialysis. In one study in which megestrol acetate was administered long-term, many side effects, such as headaches, dizziness, confusion, diarrhea, and hyperglycemia, were observed. It is well known that megestrol acetate can induce thromboembolic phenomena, uterine bleeding, peripheral edema, and adrenal insufficiency (Boccanfuso, Hutton, & McCallister, 2000). As reported by Boccanfusso et al. (2000), weight gain is due to an increase in fat mass not muscle mass, and it is also related to edema.

In another study, megestrol acetate was administered for 6 months to 17 patients on dialysis. Although neither serum albumin nor other laboratory parameters changed significantly, subjective global assessment, dry weight, and sense of well-being all showed improvement (Boccanfuso et al., 2000). Appetite improved in two patients and was stable in a third. There were significant side effects that were dose-related and resolved as doses were reduced or the megestrol acetate was stopped. The optimal dose for patients with Stage 5 chronic kidney disease (CKD) is 400 mg twice a day (Boccanfuso et al., 2000). Megestrol acetate and its metabolites are primarily excreted in the urine, and their dialyzability has not been determined. One explanation for the large number of side effects is that the population studied was elderly and was taking a larger number of other medications (Boccanfuso et al., 2000). The occurrence of diarrhea after starting megestrol acetate is documented in the literature, and many of the participants in this study experienced it as well (Bossola et al., 2005). Dry weight increases were mostly adipose tissue. Confusion and hallucinations associated with the use of megestrol acetate were also noted. These symptoms cleared when the medication was stopped and recurred when it was restarted.

The maximum benefit of megestrol acetate appears to be that it manifests itself at about 3 months of use. This is in conjunction with a high incidence of side effects and indicates that megestrol acetate may be useful for short-term use; there is a detrimental shift in the risk benefit equation with long-term use (Boccanfuso et al., 2000). Lastly, patient adherence to the treatment plan was widely variable. Some dosage reductions during this study period were initiated by patients and not by physician orders.

The entire healthcare team must work closely together, communicating and educating the therapeutic goals and strategies with the patient, and in so doing, making the patient a fully informed member of the team.

A new oral formulation of megestrol acetate has recently become commercially available, known as Megace ES. This formulation may have some advantages over the older suspension. The newer formulation calls for one-quarter the volume to provide the same dosing. Preliminary data in patients with HIV suggest that this new formulation may lead to weight gain in a larger percentage of patients than the older version of the medication. In addition, side effects are similar to the older formulation.

Dronabinol as an Appetite Stimulant

Dronabinol (Marinol[R]), a marijuana derivative, has been described as a potentially effective agent for appetite stimulation in patients with cancer. In a large 469-patient trial, Jatoi and colleagues (2002) found this agent did not provide appetite stimulation to the same extent as megestrol acetate. Dronabinol is approved by the Food and Drug Administration (FDA) for nausea and vomiting associated with cancer, and is also FDA-approved for anorexia associated with weight loss in patients with AIDS. The major side effect of dronabinol is impaired cognition, in addition to some physiologic effects, such as tachycardia, hypotension, delayed gastric emptying, and decreased muscle strength. These symptoms are typically dose-related, show considerable inter-patient variability, and are worse in older adults (Wilner & Arnold, 2006).


The only class of agents that appears somewhat comparable to megestrol acetate is corticosteroids. Dexamethasone (Decadron[R]) has been tested in patients with about the same increases in appetite as those treated with megestrol acetate. This class of agents is perhaps best used for patients with cancer who have a poor prognosis. Challenging side effects, such as myopathy and gastric/duodenal irritation, can occur with long-term use.

Malnutrition and Inflammation

Malnutrition and inflammation together are known as the malnutrition-inflammation complex syndrome, and this syndrome is believed to be associated with higher mortality and longer hospitalizations in patients on maintenance dialysis (Rammohan, Kalantar-Zadeh, Hang, & Ghossein, 2005). Weight gain and improvement in serum albumin persisted for longer than 3 months in patients after completion in a megestrol acetate trial in the dialysis population (Rammohan et al., 2005). Although food intake decreased abruptly after the return of anorexia, a subsequent decrease in body weight happened over a longer period of time (Rammohan et al., 2005). Serum albumin did not decrease in the first 2 to 3 months post-trial. It is quite possible, although not supported in this study, that anti-inflammatory effects of megestrol acetate persist for a longer time, whereas its appetite-stimulating effect diminishes more abruptly on its discontinuation (Rammohan et al., 2005).

Future Management of Malnutrition

Large, randomized controlled trials are warranted to define the exact role of megestrol acetate in preventing and treating anorexia in patients on hemodialysis who are malnourished. First-line approaches in managing the malnourished patient on hemodialysis include:

* Ensuring adequate dialysis.

* Discontinuing any medications that may be causing anorexia.

* Treating gastroparesis.

* Offering nutritional guidance that encourages the use of nutritional supplements.

Until further studies are completed, the administration of megestrol acetate, 400 mg twice daily, may be an effective intervention to correct anorexia, mitigate inflammation, and improve the nutritional state of patients on dialysis who are hypoalbuminemic (Rammohan et al., 2005).

Additional Reading

Jatoi, A., Kumar, S., Sloan, J., & Nguyen, P. (2000). On appetite and its loss. Journal of Clinical Oncology, 18, 2930-2932. Par Pharmaceuticals, Inc. (2007). Magase ES: Megestrol acetate. Retrieved January 18, 2009, from


Boccanfuso, J., Hutton, M., & McAllister, B. (2000). The effects of megestrol acetate on nutritional parameters in a dialysis population.Journal of Renal Nutrition, 10, 36-43.

Bossola, M., Muscaritoli, M., Tazza, L., Giungi, S., Tortorelli, A., Fanelli, F., et al. (2005). Malnutrition in hemodialysis patients: What therapy? American Journal of Kidney Diseases, 46, 371-386.

Jatoi, A., Windschitl, H.E., Loprinzi, C.L., Sloan, J.A., Dakhil, S.R., Mailliard, J.A., et al. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A North Central Cancer Treatment Group study. Journal of Clinical Oncology, 20(12), 2912-2913.

Rammohan, M., Kalantar-Zadeh, K., Liang, A., & Ghossein, C.

(2005). Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. Journal of Renal Nutrition, 15, 345-355.

Wilner, S., & Arnold, R. (2006).Cannabinoids in the treatment of symptoms in cancer and AIDS. Journal of Palliative Medicine, 9, 802-803.

Therese Shumaker, MS, RD, LD, is a Renal Dietitian, the Mayo Clinic, Rochester, MN.
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Title Annotation:Issues in Renal Nutrition: Focus on Nutritional Care for Nephrology Patients
Author:Shumaker, Therese
Publication:Nephrology Nursing Journal
Geographic Code:1USA
Date:Jan 1, 2009
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