INTRODUCTION	Section 2 of 9
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Background: Growth and development are important challenges to physicians caring for children with end-stage organ (ie, kidney, heart, liver) failure. Transplantation may successfully reverse the growth impairment in these children, for whom it remains the most physiologic treatment for growth retardation. Nutritional status improves after transplantation, and most children have the potential to experience accelerated growth, to obtain normal height, and to improve cognitive and developmental skills, including behavioral, motor, and social functions. Appropriate neurologic development can be expected after transplantation, and children have the potential to perform at levels that are adequate for their ages.

Many neuropsychological deficits, as well as physical impairments and growth failure, however, may still occur and persist. In one study, pediatric recipients of liver transplants, when compared with other groups of chronically ill children, scored lower in many motor and psychological tests and obtained fewer academic achievements. A mild functional impairment was present in 79% of children after liver transplantation, when the children were compared with a reference population.

This article discusses general principles of growth and development in children after transplantation, with a special focus on recipients of kidney and liver transplants.

Pathophysiology:

Pathophysiology of growth failure in children with chronic disease

Linear growth is one of the most important differences between adults and children. A multitude of factors affect somatic growth, such as the hypothalamic-pituitary axis, growth hormones, insulinlike growth factors, and binding proteins. Thyroid and adrenal hormones, the sex steroid hormones released during puberty, are also under the central control of the hypothalamic-pituitary axis and play an important role in achieving optimal growth potential.

Growth retardation is a hallmark of chronic illnesses such as chronic kidney disease (CKD) in children, and it is associated with increased morbidity and mortality. Growth retardation is assessed by the standard-deviation score (SDS) or height-deficit score (Z-score). These scores measure the patient's height in relation to that of unaffected children of similar age. Children with congenital CKD exhibit a relative loss in the nutrient-dependent infant phase and the gonadal hormone–dependent pubertal phase, as well as reduced percentile-parallel growth in the mainly growth hormone–dependent growth period in mid-childhood.

Classification of the stages of CKD (as per the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative [NKF-K/DOQI]) using glomerular filtration rate (GFR) measurements (mL/min/1.73 m²) are provided:

• ≥90 GFR - Kidney damage with normal or increased GFR

• 60-89 GFR - Kidney damage with mild reduction of GFR

• 30-59 GFR - Kidney damage with moderate reduction of GFR

• 15-29 GFR - Kidney damage with severe reduction of GFR

• <15 GFR - Kidney failure

The severity of growth retardation is directly related to the age of onset of renal failure—the earlier the onset, the more severe the growth disturbance. Because one third of a child's growth occurs during the first 2 years of life, any disturbance of the rapid growth during infancy reduces height potential more than a growth disturbance in later childhood. CKD results in marked height deficit in this age group. The main contributing factor to growth retardation in infants is inadequate nutritional intake and water and electrolyte losses. Additional factors include metabolic acidosis, renal osteodystrophy, and catabolic states associated with infections.

The mid-childhood period of growth is characterized by a relative constant growth rate of 5-7 cm/y and is mainly regulated by growth hormone, thyroid hormone, and adequate nutrition. The growth pattern of a child with congenital CKD often follows the percentile achieved at the end of infancy. In children who develop CKD after age 2 years, growth usually follows the percentile achieved after stabilization of the disease. Growth retardation in this age group is mainly determined by the degree of renal insufficiency. Relative height tends to decrease in patients with GFR below 25 ml/min/1.73m²; growth is usually stable when the GFR is above that threshold.

Growth failure in patients with CKD is largely caused by perturbations in the growth hormone–insulinlike growth factor–I (GH-IGF-I) axis. The IGF system plays a critical role in all phases of mammalian growth. The prenatal contribution of the IGFs is independent of GH. Shortly after birth, GH-dependent IGF-I production becomes the critical regulator of skeletal growth. The relatively stable growth in childhood is principally under the control of the GH-IGF-I axis and thyrotropin. Twenty percent of adult height is attained during puberty, which is modulated both by the GH-IGF-I axis and sex hormones. GH is the most potent secretagogue for IGF-I, which mediates most of the action of GH. GH levels are reported to be high normal or elevated in children with CKD. Despite the GH levels, somatic growth is not stimulated, because the bioactivity of IGF-I is decreased in uremia.

IGF-I is transported in plasma bound to IGF-binding proteins (IGFBPs), mostly to IGFBP-3. Only about 1% of plasma IGF-I occurs in the free bioactive form. There are 6 main IGFBPs in the circulation, two of which, IGFBP-1 and IGFBP-2, have inhibitory effects on IGF action. Children with CKD have normal levels of intact IGFBP-3 but elevated levels of other IGFBPs in proportion to the degree of renal failure, leading to an inhibition of IGF activity and a GH-resistant state. CKD also reduces the expression of IGF-I by reducing postreceptor signaling. Treatment with supraphysiologic doses of recombinant human GH (rhGH) increases the bioactivity of serum IGF-I, thus overcoming the inhibitory effects of excess IGFBPs. Children who have the lowest growth velocity before treatment benefit the most from rhGH.

The effects of chronic metabolic acidosis on growth may be partially mediated by the GH-IGF-I axis. Animal studies have shown an anti-anabolic effect of acidosis in bone growth centers, which is partly related to a state of resistance to GH and IGF. This may be a contributing factor in the development of delayed longitudinal growth and may contribute to renal osteodystrophy in patients with CKD.

The onset of puberty is delayed in adolescents with CKD, with an average delay of about 2 years for the appearance of clinical signs of puberty. Thus, children with chronic renal insufficiency enter puberty with growth retardation. The pubertal growth spurt is delayed, shortened, and associated with a reduced growth velocity. The mean pubertal height gain is only 50% that of normal late-maturing children, and the loss of growth potential may be irreversible.

Growth retardation is preventable and can be reversed in patients who develop CKD in infancy and in mid-childhood. Measures include correction of the metabolic acidosis, optimization of nutrition and water and electrolyte balance, correction of renal osteodystrophy, and treatment with rhGH.

Growth failure in end-stage liver disease (ESLD) is a significant problem, especially in patients younger than 5 years. Multiple factors are involved, such as anorexia, deficiencies of fat-soluble vitamins and trace elements, fat malabsorption, decreased hepatic protein synthesis, and increased energy requirements. One must consider psychological factors and acquired dietary behavior, particularly in patients with a history of prolonged tube feeding and long hospitalization.

Imbalance of growth-promoting hormones also plays an important role. The endocrinologic network of GH, IGF (somatomedins), and IGFBP is altered in patients with ESLD, as well as in liver transplant patients. Children with cirrhosis have normal or elevated hormone levels but develop resistance to the hormone's biologic activities, which is reversed by liver transplantation.

Most pediatric heart transplant recipients have suboptimal growth parameters before transplantation. Some of the contributing factors are poor intestinal perfusion leading to nutrient malabsorption, inadequate renal perfusion, and hemodynamic instability leading to ischemic injury to the hypothalamic-pituitary axis. Poor feeding, which may be mandated or caused by poor appetite, coupled with increased energy expenditure, may lead to negative nitrogen balance and growth deceleration.

Growth and development after kidney transplantation

The optimal goal of renal transplantation is attainment of target final adult height. Even though growth velocity improves after renal transplantation, most children do not have catch-up growth; height deficit is not compensated, so the standard-deviation score does not improve. Englund et al have shown that the growth increment following transplantation is maximal for the most growth-retarded children and that the growth is most marked in the first 3 years after transplantation. Thus, growth after transplantation is affected by the degree of stunting at transplantation and by renal function after transplantation.

The greatest growth retardation is seen in younger children; therefore, age of onset of disease and duration of disease are important determinants. Recipients who receive an allograft before age 6 years may manifest acceleration in growth velocity (catch-up growth). The majority of allograft recipients who are older than 6 years at the time of transplantation fail to demonstrate catch-up growth and manifest a negative change (delta) in standardized height (Z-score) following transplantation. Both allograft dysfunction and steroid use may impair growth after transplantation. Renal transplantation in the most growth-retarded children younger than 6 years has the greatest beneficial effect on growth potential. A large number of patients may still not achieve ideal adult height. This is likely related to renal osteodystrophy, which is exclusive to patients with CKD.

Chronic renal failure is known to have adverse effects on neurodevelopment. The two critical periods of brain development occur at 15-20 weeks of gestation, involving neuronal proliferation, and at 25-30 weeks after birth, with focus on glial proliferation. Thus, any developmental problem during the first year of life may result in irreversible brain damage. Studies have suggested that developmental delay of 60-85% occurs in infants with renal insufficiency, related to the early onset and longer duration of the renal disease. Tube feedings have become an important component in the care of these children because malnutrition has repeatedly been implicated as a detrimental influence on development.

A study by Valanne et al (2004) of 33 renal transplant patients younger than 5 years revealed that 54% (18 patients) had ischemic lesions in the vascular border zones, with good correlation to pretransplant hemodynamic crises. Those patients with border-zone infarcts were older at time of transplantation and had received dialysis for a longer period, suggesting that most of the lesions in these patients could have been prevented by careful monitoring and early transplantation.

Successful renal transplantation during infancy is associated with improvement of developmental outcome. Children with renal transplants have been shown to achieve a level of cognitive function similar to that of healthy children. In recent studies of pretransplantation and posttransplantation development, up to 80% of children attended normal school and had normal motor skills, providing additional benefit of early transplantation (Qvist et al, 2002).

Growth and development after liver transplantation

Approximately 20% of pediatric liver transplant recipients are estimated to experience growth impairment at some point after transplantation. A recent suggestion was that a pretransplantation growth defect may not be completely corrected in liver transplant recipients, although an increasing percentage of children are demonstrating catch-up growth. Growth may initially worsen after transplantation (during the initial 6 months), but catch-up growth begins afterward.

The SPLIT 2000 (Studies of Pediatric Liver Transplantation) annual report demonstrated that growth failure was more significant in patients younger than 5 years but that these same patients also manifested the greatest improvement 18 months after transplantation. According to the report, some important pretransplantation factors affecting posttransplantation growth are age at transplantation (patients younger than 2 years had the greatest catch-up growth), Z-score at transplantation, and primary diagnosis (patients with biliary atresia seem to have the most catch-up growth). A proper recognition of children with nutritional and growth deficits before solid-organ transplantation is therefore fundamental.

Posttransplantation factors that may impact growth include graft function and the need for retransplantation, steroid use, and occurrence of posttransplant lymphoproliferative disease (PTLD). Corticosteroids influence the GH-IGF axis by suppression of pituitary GH production, inducing IGF inhibitors in serum and increasing IGFBPs. Steroids also cause direct inhibition of skeletal matrix production by decreasing synthesis of type1 collagen, chondrocyte proliferation, and bone matrix production. GH counteracts the catabolic activity through increased protein and collagen synthesis. Endogenous cortisol levels appear to be reduced in liver transplant patients and correlate with growth impairment. An increase in the percentage of liver transplant patients who demonstrate catch-up growth has been attributed to steroid withdrawal and supplemental use of growth hormone. Liver transplant recipients have been shown to have more catch-up growth than kidney transplant recipients, especially after steroid withdrawal. A careful multispecialty approach is therefore necessary to decrease the incidence of growth failure after solid-organ transplantation in children. Pretransplantation nutritional therapy can be optimized; the most appropriate timing of surgery can be selected; and the best immunosuppressive regimen can be determined.

Cognitive and emotional difficulties have been shown to occur more often in liver transplant patients than in age-matched controls. Visual spatial deficits seem to occur in children with liver transplants, but motor abilities are generally not affected. Studies have shown that infants who undergo liver transplantation in the first year of life can achieve healthy neurodevelopment. In the first year after transplantation, however, language skills may be blunted, probably because of nasogastric tube feeding. Psychoneurologic scores were maintained during 4 years of follow-up observation, although a transient reduction in social skills and eye-hand coordination occurred during the same period, when the children spent longer times in the hospital. In older children, neurologic deficits that are established at the time of transplantation are more difficult to overcome. Liver transplant recipients seem to experience greater psychosocial problems than kidney transplant recipients, which is likely related to body image, especially in the adolescent age group.

Growth and development after small bowel transplantation

Small bowel transplantation poses specific nutritional problems. Small bowel transplant patients may commonly have macronutrient and micronutrient deficiencies because of high stomal output and diarrhea. Decreased intestinal motility and malabsorption may also be present. Chronic dependence on parenteral nutrition may lead to food aversion; however, preliminary data demonstrate that growth is normal in 50% of recipients, and 15% may experience catch-up growth. Studies have shown that most patients continue to experience cognitive delays several years after small bowel transplantation. Children who receive small bowel transplants when they are infants may also demonstrate motor delays.

Growth and development after heart transplantation

Growth outcomes in pediatric heart transplantation patients have been encouraging. Some reports have suggested that growth delay may be less of a problem for heart transplant recipients than for liver and kidney transplant recipients. This difference may be due to the fact that children with congenital heart disease receive heart transplants at a very young age and those with acquired conditions are much older when they receive transplants, thus bypassing the critical periods of growth.

Studies of growth after heart transplantation reveal varied results:

• Chinnock and Baum (1998) reported on 66 infants younger than 6 months who received heart transplants and did not receive maintenance steroid therapy. Catch-up growth for these patients was almost universal in the first year after heart transplantation.

• Cohen et al performed a retrospective analysis of the effects of cardiac transplantation on skeletal maturation and linear growth. Bone age delays as great as 3-4 years were seen in the years before transplantation. Bone age delay greater than 12 months was seen in 38.5% of patients at the time of transplantation. Children who received heart transplants before age 7 years and those with a pretransplantation diagnosis of cardiomyopathy experienced the greatest decrease in skeletal growth.

• The seventh pediatric report of the Registry for the International Society for Heart and Lung Transplantation (Boucek, 2004) reveals that adolescent heart transplant recipients had no major changes in growth Z-score after transplantation and no dramatic changes when stratified for steroid use. The patients did have an increase in weight Z-scores, again with no stratification for steroid use.

Important factors that affect growth after transplantation include age at transplantation, etiology of cardiac failure, graft function, chronic renal dysfunction after heart transplantation, and steroid use. Children initiated on a steroid-free protocol almost universally demonstrate catch-up growth. Evidence suggests that the growth-suppressive effects of steroids can be overcome by exogenously administered growth hormone. Recent data suggest that growth hormone modulates cardiac growth independent of somatic growth. Children who have growth hormone deficiencies have subnormal left ventricular mass.

Very few studies have been performed on neurocognitive development after heart transplantation in pediatric patients, but the data suggest that patients do not suffer major deficits in mental or psychomotor development. Wray et al demonstrated that though the overall mean developmental score of infants and young children was within normal range after heart transplantation, scores were significantly lower than those of healthy children. Patients with congenital heart disease had a significantly lower developmental quotient and lower scores in locomotor ability, speech and hearing, eye-hand coordination, and performance than those patients with cardiomyopathy.

Researchers at Loma Linda University Medical Center found that infants with hypoplastic left heart syndrome who received heart transplants before age 6 months had ultimately normal growth and developmental outcomes within normal limits.

Growth and development after lung transplantation

Few lung transplants are performed in the pediatric population, with cystic fibrosis being the primary indication for lung transplantation in children. Malnutrition in pediatric patients with cystic fibrosis is multifactorial (eg, pancreatic insufficiency causing fat malabsorption, diabetes mellitus, anorexia, poor appetite, and intestinal obstruction). Some of these patients are severely malnourished before transplantation. Decreased bone density due to vitamin D deficiency and long-term steroid use can further erode bone mass. At some adult transplant centers, patients who are below 80% of ideal body weight are not considered good candidates for lung transplantation. Body mass index is an important indicator of good nutritional status before and after transplantation.

Osteoporosis is another important risk factor, especially because bone mineral density may worsen after transplantation as a result of long-term steroid use. Daily administration of steroids, which is the rule in pediatric lung transplantation, unlike in other solid-organ transplantations, further decreases bone growth. Long-term survival after lung transplantation is not as encouraging as that seen after heart transplantation; graft half-life in lung transplantation is approximately 3.5 years.

Frequency:

• In the US: A review of the 2005 North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) database of kidney recipients demonstrated that at time of transplantation, the mean height deficits for all patients is -1.85; that is, the average patient is nearly 2 standard deviations below the appropriate age- and sex-adjusted height level, or is shorter than the third percentile of their peers. At the time of transplantation, linear growth is impaired more often in recipients of livers than in those who receive kidneys. However, the frequency of catch-up growth in liver recipients can be greater than that in kidney recipients, probably because of decreased administration of corticosteroids.

  Exact incidence of catch-up growth varies according to different groups and immunosuppressive regimens. In 294 unselected candidates for liver transplants, Bartosh et al (1999) reported the mean height Z-score at the time of transplantation to be -1.6 ± 1.8, with 39% of patients below 2.0. As many as 47% of patients demonstrated catch-up growth after transplantation. In infants who receive heart transplants, 88% reach a normal height after 5 years, mainly because of good catch-up growth.

• Internationally: Sarna et al from Finland reported 79% of liver recipients as being below the reference range for height at 3 years after transplantation. In the same series, the catch-up growth after transplantation was reported to be 26% in the first year, 47% in the second year, and 56% in the third year. In 1999, Viner et al from England reported severe growth retardation in 20% of patients at the time of liver transplantation.

Mortality/Morbidity: Nutritional status and growth failure are directly correlated with overall mortality and morbidity after liver and renal transplantation. Children with weight less than -1 standard-deviation score have a lower survival rate at 2 years after transplantation (57%) than those with weight greater than -1 standard-deviation score (95%). The same is true for height.

Race: Growth impairment after renal transplantation appears to be greater in black and Hispanics than in whites.

Sex: In the NAPRTCS 2005 report of kidney transplant patients, mean height deficits is greater for males (-1.90) than females (-1.77). Most studies do not report an association between sex and growth retardation after transplantation.

Age: Age is usually correlated directly with growth retardation at the time of transplantation; however, age is inversely correlated with the rate of growth after transplantation.

• Of pediatric patients receiving kidney transplants, only those patients younger than 6 years demonstrate significant recovery, with catch-up growth of 47% in patients younger than 2 years and 43% in those aged 2-5 years. Children older than 5 years have, as a group, not been shown to experience catch-up growth.

• Although liver transplantation in persons younger than 2 years was initially associated with poor height outcome, later results did not confirm such findings. The current view is that transplantation in infancy better preserves the height potential of the patient and prevents growth retardation before transplantation. The greatest catch-up growth has been seen in patients younger than 2 years.

• Patients with early onset of liver disease but older age at the time of transplantation have an increased incidence of neuropsychological impairment because of the prolonged neurotoxic effect of liver toxins on brain development. Infants who receive transplants before any damage is established may be expected to experience healthy neuropsychological development.

	CLINICAL	Section 3 of 9
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History:

• Determine specific etiologies of liver disease because some etiologies are associated with worsened growth impairment.

• Patients with Alagille syndrome and familial cirrhosis do not demonstrate growth improvement after liver transplantation, suggesting the presence of congenital anomalies or other genetic defects as limiting factors.

• Severe malnutrition can be present in children with extrahepatic biliary atresia. These children can be particularly malnourished before transplantation. However, they are expected to have satisfactory catch-up growth in the postoperative period.

• Patients with Byler syndrome and other cholestatic conditions can also present with growth failure.

• Specific etiologies of renal disease associated with worsened growth impairment are seen in children with prenatal conditions and kidney disease that develops in infancy and childhood.

• Congenital nephrotic syndrome is associated with massive urinary protein loss.

• Nephrotic syndrome in infancy and childhood presents as significant albuminuria and may result in growth retardation because of long-term steroid use.

• Nephrogenic diabetes insipidus is associated with fluid and electrolyte imbalance, polyuria, polydipsia, and growth retardation.

• Genetic defects include neonatal Bartter syndrome, polycystic kidney disease, and cystinosis.

• Developmental anomalies include obstructive uropathies such as prune-belly syndrome, posterior urethral valves, and renal dysplasia or hypoplasia, all of which are associated with polyuria and natriuresis that lead to growth impairment.

• A comprehensive nutritional history is very important.

• Children with ESLD often develop behavioral feeding problems that should be recognized and corrected promptly. These problems may continue after transplantation and may lead to decreased oral intake.

• Anorexia, hospitalization-related depression, unpalatable diet, tense ascites, vomiting and diarrhea, cholestasis, and encephalopathy are some pretransplantation factors that lead to growth retardation.

• The presence of night blindness may be an indicator of vitamin A deficiency.

• Anemia may be caused by iron deficiency or vitamin B-12 and folate deficiencies.

• In the presence of cholestasis, a history of bleeding is suspicious of a vitamin K deficit.

• Failure to thrive (in infants), anorexia, hypogeusia, mood swings, and diarrhea may indicate zinc deficiency.

• A delay in pubertal development and menarche is common after transplantation. However, pubertal progress usually resumes within 3-5 years after liver transplantation.

• Anorexia, caloric deficits, hyposthenuria, salt wasting, anemia, metabolic acidosis, electrolyte depletion, renal osteodystrophy, and growth hormone resistance can lead to nutritional deprivation in CKD. Management should be age specific and should be tailored to the underlying condition.

• Renal dysplasia and obstructive uropathy are the 2 most common causes of renal failure in childhood. These children have a congenital polyuric, salt-wasting form of renal failure and have growth retardation because of chronic intravascular depletion and a negative sodium balance. These patients require nutritional support with water and salt supplementation.

• Infant enteral formulas: low phosphorus; breast milk is encouraged. However, formulas are low in protein for infants on peritoneal dialysis and need to be supplemented with iron and vitamin D. Nasogastric or gastrostomy tube feedings may be necessary.

• In older children, a high-calorie, low-phosphorus diet is important.

• Patients with end-stage renal disease who have no residual renal function (anuric) need a low-sodium, low-potassium, low-phosphorus diet and fluid restriction.

• Among the factors that may cause growth retardation in the posttransplant period in liver recipients are the following:
  • Preoperative stunting

  • Prolonged hospitalization

  • Medications

  • Corticosteroids

• Determinants of posttransplantation growth in renal transplant patients:
  • Age at transplantation

  • Corticosteroid use

  • Growth hormone level

  • Allograft function

  • Posttransplantation sexual maturation

Physical:

• To assess nutritional status in patients after transplantation, perform anthropometric measurements, which include height, weight, skinfold thickness (triceps and subscapular), and mid-arm circumference.

• Weight is not an accurate indicator of nutritional status in patients with liver cirrhosis, because of the possibility of fluid retention and ascites, or in kidney recipients with nephrotic syndrome and peripheral edema.

• Height is a more accurate indicator of nutritional status in liver recipients and kidney recipients.

• Peripheral edema may make assessing skinfold thickness and mid-arm circumference more difficult.

• Assess ophthalmoplegia, hemolysis, hyporeflexia, and ataxia for vitamin E deficiency.

• Assess acrodermatitis and alopecia for zinc deficiency.

• Assess ecchymosis and easy bruisability for vitamin K deficiency.

• Assess follicular hyperkeratosis, Bitot spots, and xerophthalmia for vitamin A deficiency.

• Assess for iron deficiency (blood loss or poor dietary intake), especially in those with renal allograft dysfunction and CKD.

• Assess lipid profile. Monitor for obesity in patients with chronic glucocorticoid use.

• Assess albumin loss in malnourished patients, patients with nephrotic syndrome, and those on peritoneal dialysis before transplantation.

	WORKUP	Section 4 of 9
Author Information Introduction Clinical Workup Treatment Medication Follow-up Miscellaneous Bibliography

Lab Studies:

• Albumin, prealbumin, and retinol-binding protein levels are classic nutritional markers. However, assessment of malnutrition in patients with liver cirrhosis before transplantation cannot rely completely on these tests because the proteins are produced in the liver.

• Obtain levels of fat-soluble vitamins (eg, vitamins A, D, and E) and eventually correct deficiencies.

• Obtain prothrombin time (PT) and activated partial thromboplastin time (aPTT).

• Obtain cholesterol and triglyceride levels.

• Important mineral elements that can be deficient in these patients include zinc, calcium, and iron.

• Total lymphocyte count is also a nutritional marker.

• Patients with CKD: assess for anemia caused by iron, folate, and erythropoietin deficiency.

• Monitor calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone for secondary hyperparathyroidism (HPTH) or renal osteodystrophy (ROD). These patients may need vitamin D replacement in the pretransplantation and posttransplantation periods.

Imaging Studies:

• Bone radiograph to assess for renal ROD.

• It is important to obtain bone densitometry before transplantation to assess the presence of metabolic bone disease.

• Patients with end-stage renal disease and uncontrollable secondary HPTH or ROD: Parathyroid scan to rule out parathyroid gland hyperplasia. These patients may need parathyroidectomy before transplantation.

Other Tests:

• Body composition measurements have been used to assess nutritional status in pediatric patients before and after liver transplantation. These include total body potassium measurement, neutron activation, total body electrical conductivity, and dual-energy x-ray absorptiometry (DEXA) scanning. Unfortunately, only a few centers have these methodologies available. Delayed skin hypersensitivity has been used to assess nutritional status. However, the test is not very accurate in patients with liver transplants.