The number of transplants continues to grow with continued medical advances in the area of solid organ transplantation and immunosuppressive therapy. Prolonged waiting times for transplant candidates—even up to 1-2 years (as long as 5-7 y for kidney transplantation)—have led to rising concerns regarding the nutritional management of these patients in combination with required medical therapy.
The following conditions require early assessment of the individual's nutritional status with aggressive intervention in anticipation of positive clinical outcomes:
End-stage liver disease
End-stage renal failure
End-stage heart failure
End-stage pulmonary failure
Irreversible intestinal failure
The goals of nutrition therapy during the wait for transplantation are (1) to replenish malnourished individuals, (2) to maintain the status of those with adequate muscle and energy reserve, (3) to promote weight loss in candidates with excessive weight based on body mass index (BMI), and (4) to manage patients' symptoms to maximize quality of life.
For further information on renal transplantation, see Mayo Clinic - Kidney Transplant Information.
Subjective global assessment
Standard parameters of nutritional assessment are often invalid in end-stage organ failure, which leads to difficulty in identifying and assessing nutritional status. The combination of objective and subjective parameters has been established as the best approach in the nutritional assessment of these individuals and is an excellent independent predictor of outcomes in patients undergoing liver transplantation.
Subjective global assessment (SGA) is a clinical evaluation of protein-energy malnutrition (PEM) based on evidence of edema, ascites, muscle wasting, subcutaneous fat loss, decreased functional capacity, and gastrointestinal symptoms of diarrhea, nausea, and vomiting. This tool has also been studied for use in assessing patients on dialysis and candidates for lung transplantation. 
Based on the results of this history and physical assessment, patients can be placed in nutritional risk categories of well nourished, mildly to moderately malnourished, or severely malnourished. Patients in moderately to severely malnourished states who have progressive weight loss or muscle wasting (especially with excessive fluid retention in kidney, heart, or liver disease with ascites and decreased functional capacity) are considered high risk and require aggressive nutrition intervention.
Despite the widespread use of SGA, some studies have found it to be imprecise, with a sensitivity of 22% and a specificity of 96% when evaluating patients with alcoholic cirrhosis. This problem has led to the development of other parameters for measuring nutritional status in patients awaiting transplantation. In a study by Alvares and colleagues, handgrip strength was shown to be an easy and effective tool in assessing nutritional risk in patients with end-stage liver disease. Patients with cirrhosis were assessed over a 1-year period. A lower handgrip measurement and increased rates of complications were found in those who were undernourished. 
Anthropometrics and laboratory values
The more traditional nutritional assessment parameters of anthropometrics, including triceps skinfold (TSF) and arm muscle circumference (AMC), can be used to assess the degree of fat or muscle store loss and are useful in monitoring changes in a patient's status over time. These measurements can be affected by hydration status, edema, or fluid overload.
Assessment of lean body mass by dual-energy x-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA) are also affected by hydration status, which limits their usefulness. Laboratory values for hemoglobin, hematocrit, serum iron, transferrin, glucose, blood urea nitrogen, creatinine, lipid profile, and protein stores of albumin and transthyretin (prealbumin) should be evaluated and monitored. Albumin synthesis is reduced with decreased hepatic synthesis. Electrolyte balance requires close monitoring for transplant candidates on diuretics or dialysis and for those with malabsorption induced by lactulose to treat hepatic encephalopathy.
Other methodologies used in assessing nutritional status
BIA is a recently described method used for assessing PEM in patients with chronic liver disease. Many studies have reported that BIA is an inaccurate estimate of PEM in cirrhotic persons with ascites or edema. Imprecision has also been reported in evaluating persons with cirrhosis but without fluid retention, particularly when extrapolating from population studies.
Sophisticated measurements of body cell mass show that this central, expanding mass of working tissue and most important metabolically active component in the body is decreased in cirrhotic patients, irrespective of etiology. Three different measurements, ie, total body potassium, intracellular water, and total body protein, are decreased in individuals with cirrhosis.
In patients with cirrhosis, accurate nutritional status is not easy to assess; this leads to difficulty in identifying patients at risk for malnutrition and evaluating the effectiveness of nutritional intervention. As an enhancement to subjective global assessment, researchers have devised a global assessment scheme incorporating both subjective and objective variables for use in patients with cirrhosis. The tools of body mass index (BMI) and mid-arm muscle circumference (MAMC) are used in combination with a detailed dietary intake in a semistructured, algorithmic system to provide a nutritional assessment scheme. Initial reports of this global assessment scheme indicate that it provides a simple, reproducible, valid, and predictive method of assessing nutritional status in patients with cirrhosis. 
Clinicians must remember that all methods commonly used for nutritional assessment, particularly in patients with cirrhosis, are influenced by the presence of liver disease per se or are influenced in combination with renal failure, alcohol ingestion, and expansion of the extracellular water compartment. Nevertheless, nutritional assessment is beneficial in all patients awaiting organ transplantation, particularly when a composite score emphasizing anthropometry is combined with overall clinical judgment. [4, 5]
Nutritional goals for patients with end-stage organ failure awaiting transplantation depend on the individual's weight history and current status. The ultimate goal is to maintain muscle and fat stores in those with adequate stores, to replete those who are moderately to severely malnourished based on SGA rating, and to promote weight loss in candidates who are obese. In liver disease, a poor nutritional state and hypermetabolism adversely affect survival after liver transplantation. On the other hand, severe obesity with BMI greater than 35 kg/m2 is associated with wound infection, multisystem organ failure, and increased transplantation costs. In heart transplant recipients, a reduction of weight-to-BMI ratio to less than 27 kg/m2 is suggested. [6, 7, 8]
With the increased incidence of weight gain globally in the United States, the focus on weight requirements and recommendations in recipients of solid organ transplant has increased. Current recommendations following an extensive review of obesity on morbidity and mortality in organ transplantation by Hasse in 2007 led to challenging each transplant center to determine guidelines of weight restrictions for each individual center. Focus should be placed on the specific characteristics of their potential recipients, donor pool, and risks of restricting transplantation in those who are obese.  When weight restrictions of upper limits have been established for each solid organ transplant individual, patients can successfully lose weight with the commitment of the patient and support of the family and transplant center. 
Table 1. Nutritional Requirements (Open Table in a new window)
Calories (kcals/kg estimated dry
Liver: 25-30 kcals/kg
Kidney: 30-45 kcals/kg
Lung: 30 kcals/kg
Liver: 35-40 kcals/kg
Lung: 35-40 kcals/kg
estimated dry body weight)
Liver: 1.0-1.5 g/kg
Kidney: 1.2-1.4 g/kg (on dialysis in Stage 5)
Kidney: 1.2-1.5 g/kg (on CAPD)
Lung: 1.0-1.5 g/kg
Liver: 1.5-2.0 g/kg
Kidney: 1.5-2.5 g/kg (on CVVH/CVVHD)
Lung: 1.5-2.0 g/kg
|Liver: 0.8-1 g/kg|
|Fat||30% of energy intake||Increase for total energy intake||< 30% of energy intake|
|Sodium||2000 mg/d||2000 mg/d||2000 mg/d|
Liver: 1-1.5 L/d (if
Kidney: Urine + 1 L/d
Heart: 1-1.5 L/d
Causes and Incidence of Malnutrition
Malnutrition in cirrhosis is multifactorial. Inadequate diets and unnecessary dietary restrictions of protein, fluid, and salt can lead to less palatable diets and a suboptimal oral intake. Malabsorption may occur because of bile salt or exocrine pancreatic insufficiency and decreased fat absorption, which can occur in cholestatic and noncholestatic patients. Anorexia and early satiety, especially in the presence of ascites, is common because pressure exerted on the stomach, diaphragm, and intestinal tract reduces the gastric capacity for a meal of normal size. Altered protein and energy metabolism can also occur with accelerated protein breakdown and amino acid oxidation for energy and an increased rate of gluconeogenesis.
The incidence of protein and energy malnutrition is high in patients with end-stage liver disease who have cirrhosis with resultant weight loss. Quantitative disturbances in energy metabolism in cirrhosis are heterogeneous. Malnutrition may occur in 34-82% of patients with alcoholic cirrhosis and in 27-87% of patients with nonalcoholic cirrhosis, based on anthropometric data in these patient populations. 
No pattern has been consistently identified when absolute energy expenditures of control and cirrhotic patients have been compared; however, when measured energy is expressed in comparison to calculated energy expenditure, energy expenditure is normal in most patients with cirrhosis, although 16-34% are hypermetabolic. The type and stage of liver disease may account for some of these variables in energy expenditure. Indirect calorimetry is often useful in the hospitalized patient to assess actual energy requirements.
Protein requirements in liver disease are difficult to assess when prescribing nutrition recommendations. In most stable patients with cirrhosis, 0.8 grams of protein per kg is the minimum daily requirement. To promote positive nitrogen balance and to prevent endogenous protein breakdown, 1.2-1.5 grams of protein per kg are recommended. Avoid unnecessary protein restrictions, which may exacerbate malnutrition in some patients. If the patient appears to be protein sensitive with an increased incidence of encephalopathy on the higher level of protein intake, branched-chain enteral formulas with restricted aromatic amino acids can be used to assure a continued level of protein intake.
In decompensated cirrhosis with ascites and encephalopathy, where patients may display behavioral changes, reversal of sleep patterns, disorientation, and coma, the role of branched-chain amino acids (BCAA) remains controversial. In a 15-center randomized trial, 174 patients with cirrhosis were given BCAA supplements, lactoalbumin, or maltodextrins and were observed for 1 year.  The goal was to determine if a nutritional approach might prevent progressive liver failure and improve the nutritional status and quality of life for these patients.
Conclusions showed stable or improved nutritional status and liver enzymes in the patients treated with BCAA supplements. Those on BCAA had decreased Child-Pugh scores. Anorexia and health-related quality of life surveys improved with BCAA. Long-term compliance with BCAA supplements, however, was poor because of decreased palatability. Further studies are needed to more clearly define the role of BCAA in the prevention of liver failure in patients with end-stage liver disease awaiting transplantation. 
In cholestatic liver disease of primary biliary cirrhosis and primary sclerosing cholangitis, attention should also be given to the possible need for fat-soluble vitamin supplementation. Vitamins A, D, E, and K may be deficient if steatorrhea is higher than 10 grams per day. Caution should be used when considering vitamin A supplementation in patients with cirrhosis as serum retinol levels may not reflect the true level of vitamin storage in the liver and may lead to detrimental side effects according to Ukleja et al.  Calcium supplementation may be required to slow the progression of osteodystrophy.  Zinc deficiency is also common in patients with cirrhosis and is a cofactor in hepatic synthesis of urea from ammonia. Serum levels have been found to be lower in patients with cirrhosis; with supplementation, this may lead to an increased uptake of ammonia and release of glutamine from leg skeletal muscle. 
Appropriate weight for height based on body mass index (BMI) has been an issue of concern among liver transplant centers with regard to the impact of obesity on patient and graft survival. A recent report by Rodriquez et al of a large, multicenter cohort of US adults who underwent liver transplantation between 1987 and 2005 indicates that malnutrition (BMI < 20) and morbid obesity (BMI >40) are associated with significant decreases in patient and graft survival as well as 30-day mortality increase (for high BMI). Cardiovascular mortality and infection-related allograft failure were also associated with BMI >35. Many transplant centers have taken steps to achieve weight loss in patients evaluated for liver transplantation and delay transplantation until this BMI is achieved. 
Up to 40% of patients with chronic renal failure who require hemodialysis or long-term peritoneal dialysis reportedly have protein-energy malnutrition (PEM) and are associated with increased morbidity and mortality rates. [17, 18, 19] Decreased levels of nitrogen stores and body weight and depleted visceral protein stores of albumin and transferrin are observed. Vitamin and mineral deficiencies of vitamin B-6, folic acid, vitamin C, 1,25-dihydroxycholecalciferol, and iron are common. Vitamin D status of renal transplant recipients has lead to a focus on further appropriate repletion of vitamin D in the transplant candidate. Further studies are needed to determine adequate dosing. 
Causes for malnutrition are multifactorial and include blood loss; protein and other nutrient loss during dialysis; catabolism due to chronic illness; and anorexia due to altered taste sensation, suboptimal oral intake, and depression.
Chronic kidney disease is defined in 5 stages. Stage 5 is a glomerular filtration rate (GFR) of < 15 mL/min/1.73 m2, with the requirement of dialysis or renal replacement therapy. Patients on hemodialysis may lose 2-8 grams of free amino acids per treatment day and 5-12 grams of free amino acids in peritoneal dialysis. Protein recommendations for these patients should be 1.2-1.4 grams protein per kg per day for hemodialysis and up to 1.5 grams protein per kg per day in peritoneal dialysis.  Current recommendations for fluid are to limit to 1 liter daily, with a maximum of 2 liters. 
Because many patients in stage 5 kidney failure have poor appetites and higher requirements than those with less severe failure, steps should be taken to prevent malnutrition and increase nutrition intervention for improved patient outcomes.
BMI has been extensively studied in kidney transplant candidates for variables of patient and graft survival, rate of delayed graft function, incidence of acute cellular rejection, and occurrence of wound infections. Results from the available literature are mixed; however, the consensus appears to be to achieve a BMI of 35 or less for improved transplant outcomes and graft survival. [9, 23, 24]
Pancreas transplants are usually performed in combination with kidney transplants to treat diabetic nephropathy and to improve metabolic processes and quality of life. 
Nutritional management of candidates for pancreas transplantation often varies, requiring management of renal function to prevent further nutritional decline. Even though obesity with BMI >27 kg/m2 is not a contraindication to pancreas transplantation, it is thought to be a factor in delayed wound healing in the early posttransplant period. Recipients with a BMI >30 have the most significant risk factor for posttransplant technical failures. [26, 27] Greater weight gains following transplantation have been reported. Such weight gain in women may lead to poorer graft function and survival rates.
Malnutrition has been reported in 45% of patients awaiting heart transplant; these patients are at risk for developing cardiac cachexia. [28, 29, 30] The specific form of PEM is thought to be caused by anorexia and hypermetabolism attributable to increased cardiac and respiratory workload. These patients display depleted visceral protein stores in addition to loss of fatty tissue and lean body mass. Adequate nutrition to achieve and maintain optimal nutritional status before transplantation is essential to reduce the postoperative length of stay and morbidity and mortality rates.
When nutritional repletion is required, 35-40 calories per kg and 1.5-2 grams of protein per kg may be needed. Diet recommendations must be individualized to the specific patient to provide energy-dense nutritional supplements as needed to meet energy requirements and to restrict fluid or sodium only when necessary. If weight loss is required to attain a BMI of less than 27 kg/m2, calories should be restricted by 500 per day to promote 1 pound of weight loss per week.  Encourage exercise as tolerated to promote loss of fatty tissue while maintaining lean muscle mass. The encouragement of exercise applies to all adults awaiting transplantation, particularly those who need to lose weight because of an excessive BMI.
The incidence of malnutrition among patients with lung disease varies depending upon the etiology of their disease. Those with increased breathing work (eg, those with emphysema, cystic fibrosis, and other types of bronchiectasis) appear to be the most hypermetabolic and have the greatest incidence of malnutrition.  In patients with cystic fibrosis, malnutrition may also be due to chronic lung infections and malabsorption. Poor oral intake due to early satiety, edema, and ascites from intra-abdominal pressure, in addition to hypoxia contributing to anorexia, lead to an increased incidence of malnutrition. 
When nutrition repletion is required, 35-40 calories per kg and 1.5-2.0 grams of protein per kg may be required. Frequent ingestion of small portions of energy-dense foods and supplements can help patients achieve optimal oral nutrition. If patients cannot consistently meet increased nutritional demands, they may benefit from enteral nutrition supplementation. BMI in lung transplant candidates appears to be a more accurate predictor of risk for short-term complications than percent ideal body weight. The most appropriate BMI in this patient population has yet to be determined. [23, 34]
The main goal of small bowel transplantation (SBT) is to offer patients who were previously dependent on total parenteral nutrition (TPN) an equal or better chance of survival than that offered by dependency on TPN. Other goals of SBT include reducing TPN-related complications such as metabolic bone disease, cholestasis, and liver failure. Metabolic bone disease, which occurs in up to 15% of patients within a few months after beginning TPN, can lead to osteomalacia, causing debilitating bone disease, joint pain, vertebral compression, and pathologic fractures. Chronic cholestasis occurs in 15-85% of patients on home TPN.  This problem may be due to the length of time on TPN, the TPN prescription, and the possibility of intestinal or systemic conditions associated with intestinal failure. 
Chronic and end-stage liver disease continues to occur in patients on long-term TPN even though development of new TPN formulations has been pursued to reduce the incidence of hepatobiliary dysfunction, especially steatosis. In patients receiving long-term TPN, liver failure and death can ensue. Intestinal transplantation is now a possible option for patients who are dependent on TPN for the long term. Intestinal transplantation can help achieve nutritional autonomy and allow the patient to remain well nourished and free from TPN within 3 months posttransplant, barring any unforeseen complications that necessitate TPN therapy (eg, chylous ascites, increased intestinal transit time). The incidence of chylous ascites following intestinal transplant appears to be low, but may in part be due to prophylactic modalities in feeding regimens for these solid organ recipients according to Weseman. 
Intestinal rehabilitation refers to the process of optimizing bowel function to reduce the dependence of TPN. Although outcomes for TPN weaning despite short bowel syndrome are highly patient-specific and based on functional and structural changes of the remaining bowel, all attempts at storing nutritional autonomy should be investigated. In adults with some healthy small bowel remaining, nutritional autonomy may be achievable with 50-70 cm of healthy small bowel (if some colon remains intact) or 110-150 cm of healthy small bowel (if the small bowel ends in a terminal ostomy). Comprehensive management with diet modification, patient education, growth factors, and surgical intervention for intestinal lengthening, when indicated, may potentially lead to the reduction on TPN dependence and decreased requirement for intestinal transplantation.
When intestinal rehabilitation fails, patients with loss of line access, life-threatening central catheter infections, nonreconstructible GI tract, and progressive liver disease should be referred early for potential intestinal transplant candidacy. During the transplant evaluation process, the nutritional status of the potential transplant recipient should be thoroughly assessed and monitored periodically until the time of transplantation. 
Restoration of nutrient deficiencies, maintenance of an appropriate weight for height, treatment of osteomalacia, and assurance of mobility and functional capacity potentially benefit the patient in the posttransplant recover phase.  During the transplant evaluation process, patients should be assessed for the appropriateness of the composition of PN prescription for the individual’s requirements in macronutrients as well as potential nutrient deficiencies or toxicities. A complete assessment of fat-soluble and water-soluble vitamins should be conducted during the transplant evaluation process, along with essential fatty acid profile for triene:tetraene ratio, zinc, selenium, carnitine, and copper.
In patients with short bowel syndrome (SBS) with high ostomy outputs, zinc deficiency is common and can be easily treated with supplementation in the parenteral nutrition (PN) prescription. Metabolic bone disease, cholestasis, and liver failure can be complications of PN failure. Metabolic bone disease, which occurs in as many as 15% of patients within a few months after becoming PN-dependent, can lead to osteomalacia. This can cause debilitating bone disease, joint pain, vertebral compression, and pathologic fractures. Chronic cholestasis varies in frequency from 15-85% of patients on home PN. This may be due to the length of time on PN, the nutrition prescription, and a lack of adequate calcium and vitamin D absorption due to SBS. 
Osteoporosis has been reported in 67% of patients with intestinal failure who are dependent on PN and may also be linked to BMI and duration of the SBS. Intravenous bisphosphonates are now commonly used to maintain bone mass in patients with SBS. Monitoring for bone density and appropriate therapy prior to transplant benefits patients because the posttransplant course with steroid therapy as part of the dual immunosuppressive regimen leads to increased calcium loss. Patients should be assessed for bone mineral density with dual energy x-ray absorptiometry (DEXA) during the evaluation process if they have not had a recent baseline measurement.
Chronic and end-stage liver disease continues to occur in patients on long-term PN even though development of new PN formulations have been pursued to reduce the incidence of hepatobiliary dysfunction, especially steatosis. As in liver transplantation, nutritionally malnourished patients who undergo combined liver/small bowel transplantation may exhibit poorer graft function and an increase in the incidence of bacterial infections. Efforts should be made to nutritionally replete patients prior to transplantation.
Nutrition Care Guidelines
Since the incidence of malnutrition among patients with end-stage organ failure is high, intensive nutritional assessment and development of an individualized nutrition care plan is required. Patients requiring intensive intervention include those determined to be in moderately to severely malnourished states (based on subjective global assessment [SGA]) or potential transplant candidates with excessive body weight (based on BMI). The first line of nutrition intervention is optimizing the oral intake of patients with depleted muscle and fat stores. Small, frequent meals and snacks of energy dense foods are suggested. Commercially available liquid nutritional supplements help achieve optimal energy and protein intake based on assessed requirements. Self-recorded food logs can assist in serial monitoring of nutritional progress on routine clinic visits.
More aggressive intervention should be considered only if the patient cannot maintain an adequate level of oral intake to sustain his or her weight or to promote nutritional repletion. Enteral nutrition supplementation can be implemented and managed well in the home setting with the support of today's home health care agencies. These agencies educate the patient and family and provide monitoring and troubleshooting assistance.
Nutrition studies assessing outcomes of improvement in nutritional status, immune function, infection rates, length of stay, and posttransplant morbidity and mortality rates have shown positive benefits with aggressive pretransplant nutrition intervention. The skill and direction of the primary care physician in identifying and treating reversible causes of organ failure, in optimizing the patient's health and nutrition, and in anticipating ongoing potential problems the patient may incur lead to improved quality of life and lengthen the bridge to transplantation despite prolonged waiting periods for organs to become available.
In today's healthcare environment, more patients are including dietary supplements in their own health care practices with the intention of optimizing their energy, health, and sense of well-being. Many products are readily available, including botanicals, vitamins, and minerals. Healthcare professionals must routinely inquire about the use of dietary supplements and other products, some of which may lead to adverse health effects.
The literature identifies some herbal therapies as potentially helpful in protecting the liver from oxidative injury, in promoting virus elimination, and in blocking fibrogenesis.  Herbal therapies include glycyrrhizin, phyllanthin, silibinin, picroside, and baicalein, which are derivatives of licorice root, milk thistle, and sho-saiko-to.
Other herbal preparations that have proven hepatotoxicity include comfrey, greater celandine, chaparral, germander, and Chinese herbal mixtures. Issues of herbal therapy in perioperative care have recently raised concern as having a negative impact in this presurgical population. Worrisome herbs include echinacea, ephedra, garlic, ginkgo, ginseng, kava, St John's wort, and valerian. Issues of bleeding from the use of garlic, ginkgo, and ginseng; cardiovascular instability from ephedra; and hypoglycemia from ginseng have been reported. Increased sedative effects of anesthetics by kava and valerian and increased metabolism of drugs used in the perioperative period are reportedly associated with St John's wort.
Many patients with end-stage organ failure attempt to find over-the-counter medications to help care for themselves without full knowledge of potential adverse effects. As many studies to assess the potential benefits of herbal therapies have yet to be performed, healthcare professionals must stay familiar with the commonly used herbal medications and must recognize when such use should be discontinued. 
Patients living with a chronic disease may show, upon subjective global assessment (SGA), not only signs of malnutrition (eg, muscle wasting and weight loss) but also osteopenia, partly because of the lack of physical activity.
The exact cause of low bone mineral density in patients with cholestasis is not fully understood.  Bone mineral density is best measured by dual-energy x-ray absorptiometry (DEXA). Optimizing the patient's nutritional status, assuring a calcium intake of 1-1.5 grams per day, and monitoring vitamin D levels can aid in supportive therapy to reduce this loss of bone density.
Heart and kidney transplant candidates may also exhibit bone loss due to long-term use of loop diuretics or abnormalities in the metabolism of vitamin D, phosphorus, and calcium. The assurance of optimal medical management and reduction of further bone loss is essential because of the effects of posttransplant immunosuppressive therapy on bone mass. 
Appropriate nutritional assessment and identification of specific nutrition requirements—whether maintenance, repletion, or the need for weight reduction prior to transplantation—require individualized assessment and, in some cases, aggressive nutrition intervention. The goals are to maintain the patient with end-stage organ failure prior to transplantation and to reduce postoperative complications after transplantation.