Nutrition in the Kidney Transplant Recipient

Susan Weil

The nutritional management of the renal transplant recipient is an important determinant of outcome in terms of both morbidity and mortality. Diet can be used to prevent and ameliorate many transplant-related complications, although the precise nutrient requirements of kidney transplant recipients continue to be incompletely defined. The following recommendations provide a guide to nutrition care management in the pretransplantation, acute post-transplantation, and long-term post-transplantation periods.

PRETRANSPLANTATION NUTRITION MANAGEMENT

Major Concerns

In the pretransplantation period, a multidisciplinary approach should incorporate diet and lifestyle changes to help correct or improve malnutrition, dyslipidemia, obesity, renal osteodystrophy, and hypertension. To varying degrees, the presence of these comorbidities in the pretransplantation recipient is a predictor of related complications in the post-transplantation period. Although the etiology of these problems is multifactorial, it is reasonable to assume that appropriately aggressive nutritional management in the pretransplantation period may help minimize post-transplantation morbid events.

Malnutrition

The primary nutritional focus of the pretransplantation period is the prevention and treatment of malnutrition, some element of which has been identified in up to 70% of the dialysis population, in whom a low serum albumin level is a powerful predictor of mortality risk and morbidity. In data from the Centers for Medicare and Medicaid Services (CMS) 2006 Clinical Performance Measures Project, only 33% of adult hemodialysis and 19% of adult peritoneal dialysis recipients in the United States had albumin levels equal to or greater than 4 g/dL. Inadequate dialysis can compound the effect of malnutrition. In addition, chronic inflammation may cause low albumin, malnutrition, and progressive atherosclerotic cardiovascular disease in dialysis recipients. The causes of inflammation are multifactorial, but proinflammatory cytokines such as inter-leukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) may play a central role. Markers of inflammation, such as C-reactive protein, are elevated in both peritoneal and hemodialysis patients, and inflammation appears to be a cause of hypoalbuminemia through increased albumin catabolism.

It is not entirely clear how these findings before transplantation may affect transplant outcome. Low serum albumin levels and other evidence of poor protein status are predictors of surgical risk and risk for infection. Aggressive treatment of malnutrition with oral supplements, tube feeding, or parenteral nutrition, as well as careful attention to dialysis adequacy and intervening causes of poor intake, not only may ultimately improve transplant outcome but also may allow transplantation to be an option for recipients who may otherwise have been excluded.

Obesity, Dyslipidemia, and Cardiovascular Disease

The incidence of postoperative wound complications, delayed graft function, and decreased recipient and graft survival may be increased in recipients with pretransplantation obesity. Morbidly obese patients (body mass index [BMI] ≥35 kg/m²), have an increased risk for delayed graft function, prolonged hospitalization, acute rejection, and decreased overall graft survival compared with normal weight recipients ( BMI 18.5 to 24.9 kg/m²).

A BMI of greater than 30 kg/m² has also been associated with increased patient death and graft failure. Post-transplantation dyslipidemia, hypertension, and glucose intolerance have been observed in obese recipients and play a role in the development of cardiovascular disease. It has been suggested that obese recipients, particularly those with a coronary heart disease, should not undergo transplantation until weight loss has been achieved. However, it has not been established that a decrease in BMI while awaiting a transplant protects against graft loss or post-transplantation mortality.

Chronic kidney disease (CKD) stage V is associated with dyslipidemia, as evidenced by moderate hypertriglyceridemia with a normal total cholesterol; normal or increased triglyceride-rich low-density lipoprotein (LDL); decreased highdensity lipoprotein (HDL); increased cholesterol-rich very-low-density lipoprotein (VLDL); and increased susceptibility of LDL to oxidation. Decreased levels of apoprotein A-I and increased apoprotein B, apoprotein C-III, and lipoprotein(a) have also been described and contribute to the increased incidence of cardiovascular disease in this population. Attention to dialysis adequacy, treatment of anemia, dyslipidemia, secondary hyperparathyroidism, hypertension, diabetes, and possibly weight management in the transplant candidate can potentially improve outcomes. Decisions about transplantation suitability should be made on an individual basis taking numerous factors, including these, into consideration.

Renal Osteodystrophy

Abnormalities of mineral metabolism (elevated serum phosphorus, calcium, and calcium-phosphorus product), as well as secondary hyperparathyroidism, have been implicated in the etiology of nonatherogenic, medial calcification and cardiovascular disease in the CKD population. Abnormal bone and mineral metabolism and elevated parathyroid hormone levels have also been associated with increased risk for mortality in this population. Because these problems can persist and complicate the post-transplantation course (see Chapter 10), attempts should be made to control or correct them before transplantation.

Nutritional Assessment of the Transplant Candidate

Nutritional assessment of the transplant candidate should include the following:

▪ History—medical and dialysis history including comorbidities; current intake; gastrointestinal and appetite symptoms; use of medications, including vitamins and herbal preparations; physical activity and limitations; psychosocial and financial impediments to adherence to diet therapy; and allergies or food intolerance
▪ Physical and anthropometric assessment—height; weight; weight changes; evidence of muscle wasting and depletion of subcutaneous fat stores determined by subjective global assessment or other measurements; and physical evidence of vitamin deficiencies (triceps skin fold, arm muscle circumference, and midarm circumference may be unreliable as a consequence of variations in fluid status)
▪ Laboratory data—serum albumin and other plasma proteins such as prealbumin; lipid profile; anemia profile including hemoglobin, ferritin,
transferrin saturation; bone disease profile including parathyroid hormone, phosphorus, and calcium; markers of dialysis adequacy (Kt/V); glycosylated hemoglobin (HgbAlc) in diabetics.

ACUTE POST-TRANSPLANTATION NUTRITION MANAGEMENT

Major Concerns

Protein Catabolism

The acute post-transplantation period generally refers to the 4- to 6-week period after surgery when the stress of surgery combined with the use of corticosteroids can lead to severe protein catabolism, particularly in recipients with underlying malnutrition. The primary goal is to provide adequate protein and calories to counteract protein catabolism, promote wound healing, and decrease susceptibility to infection associated with protein malnutrition. Fortunately, modern immunosuppressive protocols have dramatically reduced the dose of corticosteroids typically employed in the postoperative period.

Fluid and Electrolyte Balance

During the postoperative period, fluid and electrolyte requirements vary depending on the level of renal function, volume status, and drug-nutrient interactions. Needs are assessed on an ongoing basis to balance between adequate hydration and volume overload. Specific guidelines are discussed under “Acute Post-transplantation Nutrient Requirements.”

Drug-Nutrient Interactions

Drug-nutrient interactions, important in the long-term management of the transplant recipient, should also be considered in the acute postsurgical period. Table 19.1 lists both short- and long-term side effects, including nutrient interactions, of immunosuppressive agents. A special concern is the interaction between grapefruit and immunosuppressive agents. Grapefruit or grapefruit juice contains furanocoumarins, which inhibit the metabolic activities of cytochrome P-450 CYP3A4 isoenzyme, the most abundant P-450 enzyme, which is found primarily in liver and intestinal epithelial tissues. Levels of cyclosporine, tacrolimus, and sirolimus increase when taken concomitantly with grapefruit. Additional drug-nutrient interactions are discussed under “Long-Term Nutrition Management.”

Acute Post-transplantation Nutrient Requirements

In the following sections, the recommendations listed as “per kilogram of body weight” should be based on actual body weight in the underweight or appropriate-weight patient, and possibly body weight adjusted for obesity in the obese patient, although evidence of the efficacy of such a correction is equivocal.

Protein

In the acute postoperative period, protein requirements are generally accepted to be 1.3 to 2 g/kg body weight. These levels are compatible with neutral or positive nitrogen balance, provided caloric intake is adequate. For recipients who continue to require dialysis, these levels of protein intake do not result in an increased dialysis requirement and therefore are used in patients with a functioning or nonfunctioning graft. With evidence of protein depletion, protein is provided at the upper end of the recommended range.

Calories

For the uncomplicated recipient, caloric requirements are 30 to 35 kcal/kg or 1.3 to 1.5 × basal energy expenditure (BEE) as determined by the Harris-Benedict
equation, although this equation has not been systematically studied in kidney transplant recipients. This calorie level appears to be compatible with maintaining or achieving neutral or positive nitrogen balance.

TABLE 19.1 Side Effects of Immunosuppressive Agents

Agent	Side Effect
Corticosteroids	Polyphagia, glucose intolerance, hyperlipidemia, osteoporosis, gastritis and peptic ulcer disease, fluid retention, hypertension, protein catabolism, altered mood
Cyclosporin	Nephrotoxicity, neurotoxicity, hypertension, glucose intolerance, hyperlipidemia, hyperkalemia, hypomagnesemia, hyperuricemia, gingival hypertrophy
Azathioprine	Leukopenia, thrombocytopenia, megaloblastic anemia, nausea and vomiting, hepatic dysfunction
Atgam and Thymoglobulin	Chills, fever, leukopenia, thrombocytopenia, hyperglycemia (rare), diarrhea, nausea, vomiting
OKT3	Chills, fever, arthralgias, hypertension, pulmonary edema, nephrotoxicity, headache, encephalopathy, nausea, vomiting, diarrhea
Tacrolimus	Anemia, leukocytosis, hypertension, hyperglycemia, hyperkalemia or hypokalemia, hyperuricemia, hypomagnesemia, nausea, abdominal pain, gas, vomiting, anorexia, constipation, diarrhea, leukopenia
Mycophenolate mofetil (MMF)	Anorexia, nausea, epigastric pain, gas, diarrhea, abdominal pain
Sirolimus	Hypertriglyceridemia, hypercholesterolemia, thrombocytopenia, leukopenia, hypokalemia, delayed wound healing (at high doses); diabetogenic
Basiliximab and daclizumab	Vomiting

Carbohydrates

About 50% to 60% of calories should be from carbohydrate sources, with diet modifications as needed in the presence of diabetes. Several small, early studies demonstrated that limitation of carbohydrates in combination with a high protein diet minimized cushingoid facies in renal transplant recipients; however, these studies have not been repeated in a larger population or on a long-term basis.

Fat

Diet modification for dyslipidemia, a key issue in the long-term management of transplant recipients, can be introduced in the early postoperative period, assuming calorie requirements are easily met. Up to 35% of calories from fat can be provided, in keeping with the National Heart, Lung, and Blood Institute Adult Treatment Panel III Guidelines and adapted by the Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation (Table 19.2).

Sodium

Hypertension and volume overload are common in the post-transplantation period. Calcineurin inhibitor-related hypertension is partly salt dependent. In
these circumstances, control of sodium intake to 2 g per day is appropriate. Normotensive recipients who are edema free do not require strict sodium restriction.

TABLE 19.2 Therapeutic Lifestyle Changes for Adults with Chronic Kidney Disease

Diet^*
Emphasize reduced saturated fat:
	Saturated fat: <7% of total calories
	Polyunsaturated fat: up to 10% of total calories
	Monounsaturated fat: up to 20% of total calories
	Total fat: 25% to 35% of total calories
	Cholesterol: <200 mg per day
	Carbohydrate: 50% to 60% of total calories
Emphasize components that reduce dyslipidemia
	Fiber: 20 to 30 g per day; emphasize 5 to 10 g per day viscous (soluble) fiber
	Consider plant stanols/sterols 2 g per day
	Improve glycemic control
Emphasize total calories to attain/maintain standard NHANES body weight
	Match intake of overall energy (calories) to overall energy needs
	Body mass index 25 to 28 kg/m²
	Waist circumference
		Men <40 inches (102 cm)
		Women <35 inches (88 cm)
		Waist-to-hip ratio (men <1; women <8)
Physical Activity
Moderate daily lifestyle activities
	Use pedometer to attain/maintain 10,000 steps per day
	Emphasize regular daily motion and distance (within ability)
Moderate planned physical activity
	Three to 4 times per week, 20- to 30-minute periods of activity
	Include 5-minute warm-up and cool-down
	Choose walking, swimming, supervised exercise (within ability)
	Include resistance exercise training
	Emphasize lean muscle mass and reducing excess body fat
Habits
Alchohol in moderation: limit one drink per day with approval of physician
Smoking cessation
^*Consult a dietitian with expertise in chronic kidney disease.
NHANES, National Health and Nutrition Examination Survey.
From the National Kidney Foundation. KDOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease. Am J Kidney Dis 2003;41(Suppl 3):S1-S92, with permission.

Potassium

Hyperkalemia, often seen in the post-transplantation period in the presence of the calcineurin inhibitors or impaired graft function, may be exaggerated with the use of β-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, acidosis, and potassium-containing phosphorus supplements. Treatment of hyperkalemia may require dietary potassium restriction or more aggressive measures. If potassium restriction is warranted, about 1 mEq of potassium should be allowed per gram of protein in the diet, so as not to interfere with adequate protein intake.

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