Nutritional Management of the Child with Kidney Disease

C H A P T E R

35 Nutritional Management of the Child with Kidney Disease Vimal Chadha, Bradley A. Warady Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

INTRODUCTION Protein energy malnutrition (PEM) is a common problem in children with chronic kidney disease (CKD). While the exact prevalence of PEM in children with CKD is not known, an indirect estimate can be gauged from the prevalence of growth failure in these patients, especially during the first few years of life. While several factors such as metabolic acidosis, calcitriol deficiency, renal osteodystrophy, and most importantly tissue resistance to the actions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) contribute to the impaired skeletal growth of children with CKD, malnutrition plays a critical role. Clinical experience suggests that inadequate nutrition may also contribute to an impaired neurodevelopmental outcome in the youngest patients with renal insufficiency [1e4]. Most importantly, physical manifestations of poor growth, such as short stature and low body mass index (BMI), have been associated with an increased risk of mortality in children with CKD [5]. On the other hand, the growing epidemic of obesity has raised concern about over-nutrition and its longterm implications in patients with CKD. Recent data from the International Pediatric Peritoneal Dialysis Network (IPPN) has revealed that being overweight is emerging as a greater problem than under-nutrition among children receiving peritoneal dialysis (PD) in developed countries [6]. In addition, the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) database and other reports have shown an increasing prevalence of obesity in pediatric CKD patients awaiting transplantation, as well as in those with earlier stages of CKD [7,8]. Multivariate analysis of BMI Standard Deviation Score (SDS) has shown a U-shaped association between BMI and the risk of death, with extremes in BMI associated with increased

Nutritional Management of Renal Disease http://dx.doi.org/10.1016/B978-0-12-391934-2.00035-7

risk of mortality in children with stage 5 CKD [5,9]. Interestingly, this finding contrasts with the data from adults on maintenance dialysis, in whom increased weight seems to be associated with an improved outcome [10]. The goal of this chapter is to provide a comprehensive review of the many factors that impact the nutritional status of infants, children and adolescents with CKD or receiving maintenance dialysis and to provide treatment recommendations. Since the last publication of this chapter in 2004, the National Kidney Foundation e Kidney Disease Outcome Quality Initiative (KDOQI) Clinical Practice Guidelines for Nutrition in Children with CKD: 2008 Update was published in 2009 and included a comprehensive review of the literature and the input of experts in the field [11]. Where appropriate, information derived from those guidelines will be incorporated into this text.

ETIOLOGY OF PROTEIN-ENERGY WASTING The accumulation of new evidence and novel thinking in the field of nutrition in CKD has resulted in a recent redefinition of the commonly used term “malnutrition”. The new term, protein-energy wasting (PEW), has been proposed by The International Society of Renal Nutrition and Metabolism (ISRNM) to describe a “state of decreased body stores of protein and energy”. In contrast to simple “malnutrition” that is caused by decreased intake alone, PEW is defined as a complex metabolic syndrome associated with an underlying chronic illness and characterized by a loss of muscle, with or without the loss of fat. While inadequate intake may contribute to PEW, recent evidence indicates that other factors such as systemic inflammation, endocrine perturbations, and abnormal neuropeptide signaling

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Copyright Ó 2013 Elsevier Inc. All rights reserved.

582 TABLE 35.1

NUTRITIONAL MANAGEMENT OF RENAL DISEASE

Causes of Protein-Energy Wasting (PEW) in Children with Chronic Kidney Disease

• Inadequate food intake secondary to: • anorexia • altered taste sensation • nausea/vomiting • emotional distress • intercurrent illness • unpalatable prescribed diets • imposed dietary restriction • impaired ability to procure food because of socioeconomic situation • Chronic inflammatory state • Catabolic response to superimposed illnesses • Possible accumulation of endogenously formed uremic toxins and/ or the ingestion of exogenous toxins • Removal of nutrients during dialysis procedure • Endocrine causes such as: • resistance to the actions of insulin and IGF-I • hyperglucagonemia • hyperparathyroidism

play important roles in wasting in the context of CKD. This topic is discussed in detail in Chapters 5, 11 and 12. A good perspective of PEW in children with CKD is provided in a recent review article by Mak et al. [12]. This section provides a brief overview of the causes of PEW as it pertains to children with CKD. The origin of PEW in children with CKD is multifactorial (Table 35.1); however, an inadequate dietary intake is considered a major contributing factor, especially in infants [13]. Nausea and vomiting are common in infants and children with CKD, with delayed gastric emptying and gastroesophageal reflux being detected in as many as 73% of patients with renal insufficiency [14]. Whereas the etiology of these gastrointestinal abnormalities is unclear, factors such as autonomic dysfunction and the actions of uremic toxins on gastric smooth muscle activity have been implicated [15]. The taste sensation of patients with CKD is frequently altered and likely also influences the voluntary nutrient intake. Although zinc depletion has been linked to anorexia, and a low dietary intake of zinc and low serum zinc concentrations have been reported in children with decreased taste acuity undergoing maintenance dialysis [16,17], a benefit of supplementation with zinc in terms of improving taste acuity and appetite has not been clearly demonstrated. Serum levels of a small peptide hormone “leptin” have been shown to be elevated in patients with CKD and those undergoing maintenance dialysis. Produced mainly in adipose tissue and primarily cleared by the kidney, it is speculated that hyperleptinemia might also contribute to uremic anorexia and malnutrition [18e20]. Finally, patients with CKD usually receive multiple medications, and drugs such as angiotensin converting enzyme (ACE)

inhibitors or antihistamines may adversely influence taste perception and, in turn, nutrient intake [21,22]. Adolescents are a unique patient group who appear to be particularly vulnerable to malnutrition due to their poor eating habits. They skip meals, favor fast foods, and in the presence of imposed dietary restrictions, find it difficult to meet the nutritional requirements of normal pubertal growth and development. Finally, the diagnosis/presence of advanced CKD may result in substantial emotional distress in many patients and their families, which may adversely affect nutritional intake. The socioeconomic status of the family might also, on occasion, prevent the patient and family from procuring appropriate food items.

ASSESSMENT OF NUTRITIONAL STATUS Assessment of the nutritional status of children with CKD requires the evaluation of multiple indices, as there is no single measure that by itself can accurately reflect a patient’s nutritional status. A variety of physical measurements and anthropometric data plotted on appropriate growth charts, along with an evaluation of the dietary intake, are required to provide a complete picture. The recommended frequency of the nutritional evaluation depends on both the age of the child and the severity of CKD (Table 35.2).

Evaluation of Nutrient Intake Dietary recall and food intake records kept in a diary are the two most common methods used for estimating nutrient intake [23,24]. The dietary recall (usually obtained for the previous 24 hours) is a simple, rapid method of obtaining a crude assessment of dietary intake. Since it relies on the patient’s (or their parents) memory, the responses may not always be valid. However, the advantages to the recall method are that respondents usually will not be able to modify their eating behavior in anticipation of this dietary evaluation, and they do not have to be literate to provide the information. The most important limitation of the 24hour recall method is its poor ability to capture the day-to-day variability in dietary intake. Children may be even more susceptible to this limitation than adults because they tend to exhibit more day-to-day variability [25]. Therefore, it may be useful to obtain three 24-hour recalls (preferably including one weekend day) to more completely evaluate the food-intake pattern. A trained dietitian can obtain useful information from patients by using various models of foods and measuring devices to estimate food portion sizes. Dietary diaries are prospective written reports of foods eaten during a specified length of time,

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TABLE 35.2

Recommended Parameters and Frequency of Nutritional Assessment for Children with CKD Stages 2 to 5 and 5D [Ref. 11] Minimum Interval in Months Age up to <1 Year

Age >3 Years

Age 1e3 Years

Measure

CKD 2-3

CKD 4-5

CKD 5D

CKD 2-3

CKD 4-5

CKD 5D

CKD 2

CKD 3

CKD 4-5

CKD 5D

Dietary intake

0.5e3

0.5e3

0.5e2

1e3

1e3

1e3

6e12

6

3e4

3e4

Height or length-for-age percentile or SDS

0.5e1.5

0.5e1.5

0.5e1

1e3

1e2

1

3e6

3e6

1e3

1e3

Height or length velocityfor-age percentile or SDS

0.5e2

0.5e2

0.5e1

1e6

1e3

1e2

6

6

6

6

Estimated dry weight and weight-for-age percentile or SDS

0.5e1.5

0.5e1.5

0.25e1

1e3

1e2

0.5e1

3e6

3e6

1e3

1e3

BMI-for-height-age percentile or SDS

0.5e1.5

0.5e1.5

0.5e1

1e3

1e2

1

3e6

3e6

1e3

1e3

Head circumference-for-age percentile or SDS

0.5e1.5

0.5e1.5

0.5e1

1e3

1e2

1e2

N/A

N/A

N/A

N/A

nPCR

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

1*

* Only applies to adolescents receiving HD. N/A, not applicable.

characteristically 3 to 4 days, including a weekend day. A food intake diary provides a more reliable estimate of an individual’s nutrient intake than do single day records. The actual number of days chosen to collect food records should depend upon the degree of accuracy needed, the day-to-day variability in the intake of the nutrient being measured, and the cooperation of the patient. Records kept for more than 3 days increase the likelihood of inaccurate reporting because an individual’s motivation will typically decrease with an increasing number of days of dietary data collection, especially if the days are consecutive [26]. Food records must be maintained meticulously to maximize the accuracy of the diary. Food intake should be recorded at the time the food is eaten to minimize any reliance on memory. Recording errors can be minimized if proper directions on how to approximate portion sizes and servings of fluid are provided. The dietitian should carefully review the food record with the patient for accuracy and completeness shortly after it is completed. While dietary diaries have been shown to give unbiased estimates of energy intake in normal-weight children younger than 10 years, underreporting is common in adolescents [27,28]. Accordingly, 24-hour recalls may be better suited to adolescents. The intake of calories, macronutrients (carbohydrate, protein and fat), vitamins and minerals derived from interviews or diaries is typically calculated using computer-based programs.

Physical Measurements (Anthropometry) The evaluation of anthropometric parameters is a fundamental component of the nutritional assessment

in pediatrics, and must be accurately measured using calibrated equipment according to standardized techniques, and ideally, by the same person on each occasion [11,29,30]. Recumbent length, height, weight, and head circumference are measured directly, and BMI is calculated as weight (in kg) divided by height (in meters) squared; reference values are available for children older than 2 years of age [31,32]. It is important to note that serial measurements are necessary for the assessment of growth. Once measured, weight, length/height, head circumference, and BMI should be plotted on the appropriate growth chart, specific for the patient’s age and sex. For premature infants, the growth parameters should be plotted after correcting for their gestational age until they are 2 years old. In 2000, the Center for Disease Control (CDC) published revised North American growth reference charts for infants and children up to 20 years of age [33] and in 2006, the World Health Organization (WHO) released new growth standards for children from birth to 5 years of age [34]. The WHO growth standards are distinguished from the CDC reference charts in two important ways. First, the children contributing to the WHO Growth Standards were specifically selected to represent children growing under ideal conditions, i.e., they had nonsmoking mothers, were from areas of high socioeconomic status, and received regular pediatric health care, including immunizations. In addition, a subset of 882 infants, all breastfed for at least 4 months, provided longitudinal data for 24 months. Second, the study population was of broad ethnic diversity. In turn, an important observation made was that ethnicity had very little impact on growth, indicating that the growth

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NUTRITIONAL MANAGEMENT OF RENAL DISEASE

standards reflect a reasonable expectation for growth regardless of ethnicity; only 3% of the variability in growth within the population could be attributed to country of origin [34]. Because the WHO Growth Standards represent ideal growth and ideal growth should be the goal for children with CKD as well, the WHO Growth Standards should be used as the reference for children from birth to 2 years. Thereafter, the differences between the CDC reference curves and the WHO Growth Standards are minimal. For this reason and because the switch is made from length to height measurement at 2 years, this appears to be a reasonable age to make the transition from the WHO Growth Standards to the CDC reference curves [11]. In the general population, undernutrition is defined as weight-for-age, height-for-age, and weight-for-height more negative than e2.0 SD from the reference median [35]. It is important to recognize that the weight-forage SDS is not particularly useful in isolation as weight-for-age will be low in growth retarded children. Therefore, it should be interpreted in the context of the height-for-age SDS. Accordingly, BMI is an accepted and standard method of assessing weight relative to height [36]. However, BMI is not completely independent of either age or height because of age related changes in body proportions. For this reason, BMI is expressed relative to age in developing children [37], where age functions as a surrogate for both height and maturation. In children with CKD, in whom growth retardation and delayed maturation are common, this approach has limitations. Expressing BMI relative to chronological age in a child with growth and/or maturational delay will result in inappropriate underestimation of his or her BMI compared with peers of similar height and developmental age. To avoid this problem, it may be preferable to express BMI relative to heightage (the age at which the child’s height would be on the 50th percentile) in children with CKD [38]. This approach ensures that children with CKD are compared with the most appropriate reference group: those of similar height and maturation. However, caution must be used in applying this approach to children outside the pubertal or peripubertal period, for whom the correlation between height-age and maturation is less clear. BMI relative to chronological age may be more logical in some cases, particularly when sexual maturation is complete. In addition to absolute values, all anthropometric measurements should be expressed in terms of SDS, (also known as z score) which can be calculated by using data from tables of L, M and S values [39] for each measure and entering them into the following equation: SDS ¼ ½ðobserved measureOMÞ  1OðL  SÞ

The 2000 Growth Charts LMS tables from the US National Center for Health Statistics, and WHO Growth Standards LMS tables are available on-line [34,40e42]. An SDS within two standard deviations of the mean encompasses 95% of healthy children; an SDS greater than þ2.0 or more negative than e2.0 is abnormal and mandates further evaluation. Recumbent length is measured in children up to approximately 2 years of age or in older children who are unable to stand without assistance. Height is measured when the child is able to stand unassisted. The timing of when the length measurement is changed to height measurement should be noted on the growth chart because of the discrepancy between the two measurements that commonly exist [43]. Weight should be measured while the child is nude (young infants) or with very light clothing. Special attention should be devoted to patients with edema or who are undergoing maintenance dialysis, since changes in weight are more reflective of shifts in fluid balance than true weight gain or loss. It is important to determine the patient’s “dry weight,” which can be challenging as growing children are expected to gain weight. Five parameters are helpful for this estimate: measured weight, presence of edema, blood pressure, laboratory data, and the dietary interview. The mid-week, postdialysis weight is used for evaluation purposes in the hemodialysis (HD) patient, and the weight at a monthly visit (minus dialysis fluid in the peritoneal cavity) is used for the child receiving PD. A careful physical examination should be conducted to look for edema in the periorbital, pedal, and other regions of the body. Hypertension that resolves with dialysis is generally indicative of excess fluid weight. Decreased serum sodium and albumin levels may be markers of over-hydration. Likewise, a rapid weight gain in the absence of a significant increase in reported energy intake or decrease in physical activity must be critically evaluated before it is assumed to be dry weight gain. The head circumference is measured in children up to 36 months of age with a firm, non-stretchable tape. The tape is placed just above the supra-orbital ridges and over the most prominent point on the occiput as the maximum head circumference to the nearest 0.1 cm is recorded. Some of the previously recommended anthropometric measurements such as triceps skinfold thickness (TSF) and mid-arm circumference (MAC) used to calculate mid-arm muscle circumference and mid-arm muscle area are not recommended by the current K/ DOQI Pediatric Nutrition Guidelines [11] as skinfold thickness measurement is extremely operator dependent and lacks precision [44] and in the presence of fluid overload, both MAC and TSF are also likely to be overestimated [38].

NUTRITIONAL MANAGEMENT OF THE CHILD WITH KIDNEY DISEASE

Special Studies of Protein Catabolism Protein equivalent of total nitrogen appearance (PNA), which is sometimes inappropriately referred to as protein catabolic rate (PCR), is a useful tool for the indirect estimation of dietary protein intake. It is based on the simple principle that during steady-state conditions, total nitrogen losses are equal to or slightly less than the total nitrogen intake [45]. The majority of nitrogen losses (approximately 65%) occur as urea excretion in urine and/or dialysate [46]. Nitrogen is also lost as non-urea nitrogen in creatinine, uric acid, feces, skin and hair. Protein loss in urine and/or dialysate is an additional source of nitrogen loss. The total nitrogen losses from the body are represented as total nitrogen appearance (TNA). The PNA can, in turn, be estimated by multiplying the TNA by 6.25 based on the fact that the nitrogen content of protein is relatively constant at 16%. Recognizing the practical difficulties associated with the measurement of all sources of nitrogen loss, in addition to the fact that a portion of these losses (e.g., hair and skin) are small and fixed, several researchers have attempted to derive quantitative relationships between TNA and the easily measurable and most abundant source of nitrogen loss, urea nitrogen [46e50]. The most commonly used formula to estimate dietary protein intake by urinary urea-nitrogen excretion in adults, and published by Maroni et al. [47] is as follows: Protein intake ðg=kg=dayÞ ¼ ½urea-N excretion ðg=kg=dayÞ þ 0:031  6:25 Maroni et al. proposed that the non-urea-N excretion (0.031 g/kg/day) was constant. In contrast, Wingen et al. [48] documented that in children (2 to 18 years of age) the non-urea-N excretion was higher (0.085  0.061 g/kg/day) and was highly correlated to dietary protein intake (r ¼ 0.839). This relationship did not appear to be influenced by the age of the patient. They derived the formula: Protein intake ðg=kg=dayÞ ¼ ½urea-N excretionðg=kg=dayÞ  15:39  0:8 Mendley and Majkowski [46] initially defined the relationship between urea-N and TNA in children undergoing PD as: TNA (g/day) ¼ 1.26 (urea-N appearance) þ 0.83. Their data suggested that the non-urea nitrogen appearance in children was greater than that reported by Maroni et al. [47], and supported the observations of Wingen et al. [48]. However, in contrast to Wingen et al.’s observation in children with CKD, the non-urea nitrogen excretion in patients undergoing PD varied by age, being significantly greater in the youngest

585

patients. This is likely due to the relatively greater dialysate protein losses that occur in younger patients. Their formula was subsequently revised to reflect the impact of age as follows: TNA ¼ 1:03 ðurea-N appearanceÞ þ 0:02 ðweight in kgÞ þ 0:56 ðfor subjects age 0 to 5 yrsÞ or 0:98 ðfor subjects age 6 to 15 yrsÞ Edefonti et al. [50] later reported that incorporating the dialysate protein-nitrogen and BSA in the formula yielded the best prediction of TNA in children undergoing PD. He recommended that the TNA be calculated in the following manner: TNAðg=dayÞ ¼ 0:03 þ 1:138 Urea-Nurine þ 0:99 Urea-Ndialysate þ 1:18 BSA þ 0:965 Protein-Ndialysate As protein requirements are primarily determined from fat-free, edema-free body mass, PNA is usually normalized (nPNA) to some function of body weight. The usual weight used to normalize PNA is derived from the urea distribution space ( Vurea /0.58), as this idealized weight does not include the body fat weight. Several important limitations of PNA should be recognized with respect to its usage in pediatrics. PNA is known to approximate protein intake only when the patient is in nitrogen equilibrium. However, because of growth, children are in an anabolic state and the PNA will therefore typically underestimate the actual dietary protein intake. It has also been demonstrated that children treated with recombinant human growth (rhGH) hormone may have a significantly increased DPI without exhibiting greater nitrogen excretion, reflective of an anabolic state [46]. On the other hand, in the catabolic patient, child or adult, PNA will exceed protein intake to the extent that there is net degradation and metabolism of endogenous protein pools to form urea. Therefore, PNA can fluctuate from day-to-day and a single measurement of PNA may not reflect the usual protein intake. Additionally, PNA estimates have been found to be inaccurate at extremes of protein intake [51,52]. In patients undergoing maintenance HD, the normalized protein catabolic rate (nPCR), which is equivalent to nPNA, is measured and it is dependent upon the urea generation rate (G) during the inter-dialytic period [53]. While the nPCR can be calculated simultaneously during formal Kt/V estimations by urea kinetic modeling, a simple algebraic formula used in pediatric HD patients [54] has been shown to yield nearly identical nPCR results: nPCR ¼ 5:43  est G=V1 þ 0:17

586

NUTRITIONAL MANAGEMENT OF RENAL DISEASE

where V1 is total body water ( in L ¼ 0:58post-dialysis weight in kg), and estG is calculated as: est Gðmg=minÞ

¼ ½ ðC2  V2 Þ  ðC1  V1 Þ=t

where C1 and V1 are post-dialysis BUN (mg/dL) and total body water (in dL ¼ 5.8  post-dialysis weight in kg), respectively, from the previous HD treatment; C2 and V2 are pre-dialysis BUN (mg/dL) and total body water (in dL ¼ 5.8  pre-dialysis weight in kg), respectively, from the current HD treatment, and t is time (minutes) from the end of one dialysis treatment to the beginning of the next treatment. Recent pediatric data demonstrated that nPCR <1 g/kg/d of protein predicted a sustained weight loss of at least 2% per month for three consecutive months in adolescent and young adult-aged patients [55], whereas serum albumin levels could not. However, in younger pediatric HD patients, neither nPCR nor serum albumin level was effective in predicting weight loss.

Other Measures Serum albumin: Serum albumin was recommended in the 2000 K/DOQI Nutrition Guidelines [56] as a marker of nutritional status because PEM may lead to hypoalbuminemia. Many studies have shown that hypoalbuminemia present at the time of dialysis initiation, as well as during the course of chronic dialysis is a strong independent predictor of patient morbidity and mortality [57e64]. However, despite its clinical utility, serum albumin levels may be insensitive to short-term changes in nutritional status, do not necessarily correlate with changes in other nutritional parameters, and can be influenced by non-nutritional factors such as infection/inflammation, hydration status, peritoneal or urinary albumin losses, and acidemia [65e69]. Therefore, while hypoalbuminemia remains an important component of the general evaluation of patients with CKD, its value as an exclusive marker of nutritional status is questionable. Bioelectrical impedance analysis (BIA): BIA is an attractive tool for the nutritional assessment of individuals undergoing dialysis because it is noninvasive, painless, relatively inexpensive to perform, and requires minimal operator training. Whereas BIA allows for an accurate assessment of fat free mass in healthy children [70], the estimate of fat free mass of dialysis patients may be confounded by variations in hydration. Dual energy X-ray absorptiometry (DEXA): Whole body dual energy X-ray absorptiometry (DEXA) is a reliable, noninvasive method to assess the three main components of body composition: fat mass, fat-free mass, and bone mineral mass/density. The accuracy of DEXA is minimally influenced by the variations in

hydration that commonly occur in patients on dialysis. Studies of DEXA in this patient population have demonstrated its superior precision and accuracy when compared to anthropometry, total body potassium counting, creatinine index, and bioelectrical impedance [71e74]. The main limitations to DEXA in pediatrics are its substantial cost and the lack of reliable normal values in children on dialysis. Subjective Global Assessment (SGA): The Subjective Global Assessment (SGA), a method of nutritional assessment using clinical judgment rather than objective measures, has been widely used to assess the nutritional status of adults with CKD. An SGA specific for the pediatric population has recently been developed and validated in children undergoing major surgery [75], and its applicability in children with CKD is currently being studied. In 2001, the malnutritioneinflammation score (MIS) was introduced as one of the CKD-specific nutritional scoring systems which incorporates seven components of the original SGA plus body-mass index (BMI), serum albumin level, and total iron binding capacity (TIBC) or transferrin level. In adult patients receiving HD, the MIS is strongly associated with inflammation, nutritional status, quality of life, and 5-year prospective mortality [76]. Nutritional physical examination: Finally, the socalled nutritional physical examination can be used as an adjunct to other nutritional assessment and monitoring techniques. The nutritional physical examination involves the assessment of a patient for the presence or absence of physical signs suggestive of nutrient deficiency or excess. A careful examination of the tongue, skin, teeth, breath, and hair may provide important clues to the nutritional status [77].

NUTRITIONAL REQUIREMENTS The nutritional requirements for children with CKD and those undergoing maintenance dialysis are generally based on the published recommended dietary allowances (RDA) for healthy children [78]. However, it is important to recognize that the RDAs are estimates of the average needs of the normal population, are meant to be applied to children as a group and do not take into account the specific requirements of an individual patient. The American Academy of Pediatrics’ Committee on Nutrition states that RDAs cannot be used as a measure of nutritional adequacy in children [79]. The basis for the RDA values vary for different nutrients. While the RDA for energy reflects the average energy intake needed to maintain body weight and activity of well-nourished normal-sized individuals (with an additional provision for infants and children to ensure normal growth), the RDAs for protein are

587

NUTRITIONAL MANAGEMENT OF THE CHILD WITH KIDNEY DISEASE

based on protein nitrogen loss (mean þ 2SD), and are further adjusted to account for poor protein quality and individual variability [80]. The RDAs for a number of nutrients have been replaced by Dietary Reference Intakes (DRIs) [81]. The new DRIs are comprised of a set of four reference values: Estimated Average Requirement (EAR), Recommended Daily Allowance (RDA), Adequate Intake (AI), and Tolerable Upper Intake Level (UL). The EAR is the median usual intake value that is estimated to meet the requirements of half of the healthy individuals in a specific age and gender group, while the other half of individuals are at risk for nutritional deficiency and/or chronic disease. EARs are used to assess the prevalence of nutrient inadequacy in a group of individuals. RDAs are intake levels that, according to the available scientific evidence, meet the nutrient requirement of almost all (>97%) healthy individuals in a specific age and gender group. Adequate Intake values are used when the scientific TABLE 35.3

Equations to Estimate Energy Requirements for Children at Healthy Weights

Age

Estimated Energy Requirement (EER) (kcal/d) [ Total Energy Expenditure D Energy Deposition

0e3 mo

EER ¼ [89  weight (kg) e 100] þ 175

4e6 mo

EER ¼ [89  weight (kg) e 100] þ 56

7e12 mo

EER ¼ [89  weight (kg) e 100] þ 22

13e35 mo

EER ¼ [89  weight (kg) e 100] þ 20

3e8 y Boys:

EER ¼ 88.5 e 61.9  age (y) þ PA  [26.7  weight (kg) þ 903  height (m)] þ 20

Girls:

EER ¼ 135.3 e 30.8  age (y) þ PA  [10  weight (kg) þ 934  height (m)] þ 20

9e18 y Boys:

EER ¼ 88.5 e 61.9  age (y) þ PA  [26.7  weight (kg) þ 903  height (m)] þ 25

Girls:

EER ¼ 135.3 e 30.8  age (y) þ PA  [10  weight (kg) þ 934  height (m)] þ 25

Reproduced with permission from Ref: [95].

TABLE 35.4

evidence is lacking to establish an EAR or an RDA. Adequate Intakes are derived either from experimental data or are approximated from the observed mean nutrient intakes of apparently healthy people. The Tolerable Upper Intake Level is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects in almost all individuals in a specified group. The UL is not intended to be a recommended intake level and the potential risk for adverse effects increases if the intake exceeds the UL.

Energy Requirements A variety of studies have shown that the majority of pediatric patients with CKD exhibit an inadequate dietary energy intake [82e86]. Furthermore, the energy intake progressively decreases with worsening renal failure [86]. A number of studies in infants and children on PD have documented mean energy intakes of less than 75% of RDA [87e89], which corresponds to approximately 100% of the estimated energy requirement (EER or EAR) in children older than 3 months. In a large, prospective study of growth failure in children with CKD, caloric intakes were <80% of the RDA for age in more than one-half of food records obtained [90]. While inadequate voluntary energy intake has been clearly demonstrated in infants with CKD [91,92], energy intakes for older children are generally normal relative to their body size [90]. Since energy intake is the principle determinate of growth during infancy, malnutrition has the most marked negative effect on growth in children with congenital disorders leading to CKD [93]. More than half (58.3%) of infants with CKD in the 2008 NAPRTCS report had a height SDS worse than e1.88 (mean for all infants: e2.34) [94]. Energy requirements for children with CKD should be considered to be 100% of the EER for chronological age, that is individually adjusted for the Physical Activity Level (PAL) and BMI [11,95] (Tables 35.3 and 35.4). It is

Physical Activity Coefficients for Determination of Energy Requirements in Children Ages 3e18 Years Level of Physical Activity

Gender

Sedentary

Low Active

Active

Very Active

Typical activities of daily living (ADL) only

ADL þ 30e60 min of daily moderate activity (e.g., walking at 5e7 km/h)

ADL þ  60 min of daily moderate activity

ADL þ  60 min of daily moderate activity þ an additional 60 min of vigorous activity or 120 min of moderate activity

Boys

1.0

1.13

1.26

1.42

Girls

1.0

1.16

1.31

1.56

Health Canada: www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Reproduced with permission of the Minister of Public Works and Government Services Canada 2008.

588

NUTRITIONAL MANAGEMENT OF RENAL DISEASE

important to note that calculated energy requirements are estimates, and some children will require more or less for normal growth; therefore, all dietary prescriptions should be individualized. Energy requirements for patients treated with maintenance HD or PD are similar to those of pre-dialysis patients. In children receiving maintenance PD therapy, variable glucose absorption takes place from the dialysis fluid depending on the PD modality, dialysate glucose concentration, and peritoneal membrane solute transport capacity. In a study of 31 children older than 3 years on ambulatory PD therapy, the mean energy intake derived from peritoneal glucose absorption was 9 kcal/ kg/day [96]. Since many children who receive chronic PD are underweight, the prescribed energy intake in them should exclude the estimated calorie absorption from the dialysate as failure to do so may compromise the nutritional quality of the diet. However, some children e and particularly infants receiving PD therapy e gain weight at a faster rate than normal despite oral and/or enteral energy intakes that are lower than the average requirements. Reduced physical activity and increased exposure to high dialysate glucose concentrations for fluid removal may be explanations; in these cases, the calorie contribution from dialysate should be taken into account when estimating energy requirements. Maximizing caloric intake has been noted to be particularly effective in improving height velocity only in infants with CKD or receiving dialysis [91e93,97,98]. As children older than 2 years of age with CKD do not generally experience catch-up growth [99], the provision of adequate energy intake early in life is crucial. Rizzoni et al. [13] demonstrated that the growth of infants with CKD receiving 100% of the RDA averaged 53% (range 10 to 72%) of expected, whereas it averaged 97% (range 61% to 130%) of expected during periods when the energy intake was 100% of the RDA. In a study of 35 children younger than 5 years with CKD stages 4 to 5, significant weight gain and accelerated linear growth was demonstrated in those starting enteral feeding at <2 years of age, while improved weight gain and maintenance of growth velocity was observed in those starting enteral feeds at age 2 to 5 years, in each case without exceeding normal energy requirements [91]. If children younger than 3 years with a length (or height) for age < e1.88 SDS fail to achieve expected weight gain and growth when receiving an intake based on chronological age, estimated requirements may be increased by using height-age related recommendations. Finally, while energy supplementation resulting in a total energy intake exceeding the RDA for age has been administered to children treated with long-term dialysis, there are no data that demonstrate a resultant and consistent improvement in growth velocity [100e102]. On the other hand, prevention and treatment of obesity in

patients with CKD is important and energy requirements for overweight or obese children are lower and can be estimated by using equations specific for children heavier than a healthy weight [95].

Protein Requirements Low-protein diets reduce the generation of nitrogenous wastes and inorganic ions, both of which might be responsible for many of the clinical and metabolic disturbances characteristic of uremia. In addition, there is a nearly linear relationship between protein and phosphorus intake [103] which results in the frequent association between hyperphosphatemia and a high protein diet [104]. Accordingly, low-protein diets decrease the development of hyperphosphatemia, metabolic acidosis, hyperkalemia, and other electrolyte disorders. Pediatricians, on the other hand, are rightly concerned about the potential for harmful effects of severe dietary protein restriction, particularly as it pertains to the growth of infants and young children with CKD. Experimental studies in young animals have shown that a decrease in dietary protein intake during the normally rapid period of growth to a level that is sufficient to slow the deterioration of kidney function, does adversely affect growth [105]. As a result, very few studies of dietary protein restriction have been conducted in children with CKD [106,107]. In the largest and most significant pediatric trial, 191 children with CKD stages 3 to 4 were randomized to a reduced dietary protein intake of 100% RDA (0.8 to 1.1 g/kg ideal body weight) or to continue ad libitum intake (mean intake 181% RDA). This modest reduction in protein intake, with maintenance of energy intake greater than 80% RDA in both groups, did not adversely affect growth, serum albumin or the rate of CKD progression within the observation period of 2e3 years [107]. Hence, although there is no evidence for a nephroprotective effect of dietary protein restriction, this study did provide evidence that dietary protein intake can be safely restricted to 0.8 to 1.1 g/kg/d in children with CKD. As in adults, the “restriction” of protein intake is recommended as a means of decreasing the dietary phosphorus intake and the risk for hyperphosphatemia because of its frequent association with cardiovascular disease (CVD) in patients with CKD. While the spontaneous DPI is reduced in progressive CKD in a manner similar to that of energy intake, the DPI typically remains far in excess of the average requirements, ranging from 150% to 200% of the RDA [84,90,107]. Current K/DOQI Pediatric Nutrition guidelines recommend maintaining the DPI at 100% to 140% of the DRI for ideal body weight in children with CKD stage 3 and at 100% to 120% of the DRI in children with CKD stages 4 to 5 (Table 35.5) [11]. It is

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NUTRITIONAL MANAGEMENT OF THE CHILD WITH KIDNEY DISEASE

TABLE 35.5

Recommended Dietary Protein Intake in Children with CKD Stages 3e5 and 5D

Age

DRI (g/kg/d)

Recommended for CKD Stage 3(g/kg/d) (100e140% DRI)

Recommended for CKD Stages 4e5 (g/kg/d) (100e120% DRI)

Recommended for HD (g/kg/d)

Recommended for PD (g/kg/d)

0e6 months

1.5

1.5e2.1

1.5e1.8

1.6

1.8

7e12 months

1.2

1.2e1.7

1.2e1.5

1.3

1.5

1e3 years

1.05

1.05e1.5

1.05e1.25

1.15

1.3

4e13 years

0.95

0.95e1.35

0.95e1.15

1.05

1.1

14e18 years

0.85

0.85e1.2

0.85e1.05

0.95

1.0

DRI þ 0.1 g/kg/d to compensate for dialysis losses. DRI þ 0.15e0.3 g/kg/d depending on patient age to compensate for peritoneal losses.

important to note that the protein DRI values are lower than the RDA across all age groups [95]. These dietary protein recommendations refer to the needs for a stable child and assume that energy intake is adequate (i.e., it meets 100% of EER). Inadequate caloric intake results in the inefficient use of dietary protein as a calorie source, with a resultant increased generation of urea. Ensuring that caloric needs are met is an important step in assessing protein requirements and modifying protein intake. It is advised that at least 50% of the total protein intake consist of protein of high biologic value such as the protein from milk, eggs, meat, fish, and poultry. Protein requirements may be increased in patients with proteinuria and during recovery from intercurrent illness and may be adjusted to height age instead of chronological age if evidence of protein deficiency exists. Modification of protein recommendations may also be necessary in obese children. Obese individuals have a greater percentage of body fat, which is much less metabolically active than lean body mass. Therefore, it is believed that basing protein (and energy) requirements of obese individuals on their actual weight may overestimate requirements. Conversely, using ideal body weight for an obese person does not take into account the increase in body protein needed for structural support of extra fat tissue. Therefore, a common practice is to estimate protein requirements of obese individuals based on an “adjusted” weight (i.e., adjusted weight ¼ ideal weight for height þ 25%  [actual weight  ideal weight], where 25% represents the percentage of body fat tissue that is metabolically active) rather than their actual body weight [108]. The optimal protein intake for pediatric patients on maintenance dialysis has not yet been well defined. Reviews of nitrogen-balance studies performed in adult dialysis patients with different protein intakes [109e114] conclude that HD patients are in neutral nitrogen balance with a protein intake as low as 0.75 to 0.87 g/kg/d, and PD patients, with 0.9 to 1.0 g/kg/d.

A single nitrogen-balance study has been performed in dialyzed children [96]. In 31 pediatric patients receiving automated PD, the investigators observed a positive correlation between nitrogen balance and DPI and concluded that the DPI should be at least 144% of RDA. However, nitrogen balance also positively correlated with total energy intake, and no multivariate analysis was performed to address whether energy intake, protein intake, or both were independent effectors of nitrogen balance. A single randomized prospective study in adults [115] and several trials in children have addressed the effect of selectively increasing the amino acid supply in patients on PD therapy. Despite increases in amino acid and dietary protein intake, no significant beneficial effects on nutritional status and longitudinal growth were achieved by this intervention in children, whereas the urea concentration frequently increased [116e120]. These results are compatible with the interpretation that it is not possible to induce tissue anabolism by selectively increasing protein and amino acid ingestion, except in subjects with subnormal baseline protein intake. If more protein is ingested than needed for metabolic purposes, all the excess is oxidized and results in accumulation of nitrogenous-containing end products. There is some concern that a high DPI may even be harmful to dialyzed children. In a DXA study of body composition in 20 children on long-term PD therapy and with a mean DPI of 144% RDA, protein intake inversely correlated with bone mineral density, bone mineral content, fat-free mass, and plasma bicarbonate level, suggesting that a high protein intake may cause tissue catabolism and bone loss by worsening metabolic acidosis [121]. Finally, the most convincing argument for limiting DPI in dialyzed children is derived from the solid evidence for a key etiologic role of dietary phosphorus load in the pathogenesis of dialysis-associated calcifying arteriopathy. There is a nearly linear relationship between protein and phosphorus intake [103], which results in the frequent association between high

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NUTRITIONAL MANAGEMENT OF RENAL DISEASE

quantities of protein in the diet and hyperphosphatemia [122]. Hence, it appears most appropriate to limit protein intake in children on dialysis to the safe levels known to ensure adequate growth and nutrition in healthy children. Although dialyzed children require larger amounts of protein per unit of body weight compared to adults in order to grow in size and lean body mass, this demand is fully accounted for by the age-adjusted pediatric DRI. Hence, the only additional dietary protein requirement justified by evidence is the replacement of dialytic nitrogen losses. In those on long-term PD therapy, daily peritoneal protein losses decrease with age across childhood from an average of 0.28 g/kg in the first year of life to less than 0.1 g/kg in adolescents [123]. Peritoneal amino acid losses add approximately one-third to the nitrogen lost with protein, resulting in a total additional dietary protein requirement ranging from 0.15 to 0.35 g/kg, depending on patient age (Table 35.5). Patients with high-peritoneal transport characteristics tend to have low serum albumin levels likely due to increased peritoneal protein losses; these patients may have slightly greater protein requirements. Because dialytic protein concentrations can be measured easily, consideration should be given to regular monitoring of peritoneal protein excretion and individual adaptation of the dietary protein prescription according to actual peritoneal losses. Amino acid and protein losses during HD vary according to dialyzer membrane characteristics and reuse. Whereas losses have not been quantified in children, an average of 8 to 10 g of amino acids and less than 1 to 3 g of protein are lost per HD session in adults [124e127]. On the basis of three HD sessions per week for a 70 kg adult, this equates to 0.08 g/kg/day. Assuming that dialytic amino acid losses are linearly related to urea kinetics, children can be expected to have similar or slightly higher amino acid losses than adults and an added DPI of 0.1 g/kg/d should be appropriate to compensate for pediatric HD losses. Under all conditions, at least 50% of dietary protein intake should be of high biological value to protect body protein and minimize urea generation.

Lipid Requirements Dyslipidemia is a frequently recognized complication of CKD in children [128], occurs relatively early in the course of CKD (i.e., Stage 3 CKD) and increases in prevalence with decreasing kidney function [129]. Hypercholesterolemia and hypertriglyceridemia have been reported in 69% and 90% of children with CKD stage 5, respectively [130]. Recent data from the CKiD study reported the presence of dyslipidemia in 44% of 250 children with mild to moderate CKD; the most common

abnormality was hypertriglyceridemia in 75% [131]. The dyslipidemia seen in children with CKD has complex underlying metabolic alterations and is characterized by increased levels of serum triglycerides in combination with high levels of VLDL and intermediate-density lipoproteins (IDLs), low levels of HDL particles, and normal or modestly increased levels of total and low density lipoprotein (LDL) cholesterol [128,132,133]. This pattern of dyslipidemia has been labeled “atherogenic”. In addition, hypertriglyceridemia has been shown to be an independent contributor to the development of CVD [134,135] and may also accelerate the progression of CKD [136]. The optimal management of dyslipidemia in children with CKD is not clearly defined. Treatment of malnutrition related to impaired kidney function is essential and should supersede any potential rise in lipid levels that might result from it. On the contrary, prevention and treatment of obesity in patients with CKD is an important strategy to reduce the risk of hyperlipidemia [137]. Correction of metabolic acidosis, vitamin D therapy, and correction of anemia with erythropoietin each also seem to have some normalizing effect on dyslipidemia in children with CKD [138e140]. The K/ DOQI Dyslipidemia Guidelines’ recommendations [141], endorsed by the KDOQI Cardiovascular Guidelines [142], recommend that the dietary and lifestyle recommendations made for adults are also appropriate for post-pubertal children and adolescents with CKD. In 1992, the National Cholesterol Education Program (NCEP) Pediatric Panel Report [143] provided dietary recommendations for all children. These guidelines were recently endorsed by the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents [144]. The latter publication recommends that in children with identified hypercholesterolemia, less than 25% to 30% of calories should come from dietary fat, of which 7% should be from saturated fatty acids; the daily cholesterol intake should be <200 mg. For serum triglyceride >150 mg/ dL, therapeutic lifestyle changes (TLC) are recommended along with a low fat diet and a low intake of simple carbohydrates. The child should be encouraged to ingest complex carbohydrates in lieu of simple sugars and concentrated sweets and to use unsaturated fats such as oils and margarines from corn, safflower, and soy. Plant stanol esters in the form of dietary supplements reduce intestinal cholesterol absorption and may provide a safe and effective means of reducing serum cholesterol. High intakes of n-3 polyunsaturated fatty acids (omega-3 fatty acids [n-3 FA], docosahexanoic acid [DHA], and eicosapentanoic acid [EPA]) are associated with decreasing TG levels and a decreased risk of heart disease [145,146]. Therefore, EPA and DHA, found

NUTRITIONAL MANAGEMENT OF THE CHILD WITH KIDNEY DISEASE

almost exclusively in fish and marine sources, must be provided in the diet; the highest sources are fatty fish (e.g., tuna, mackerel, trout, salmon, herring, sardines, and anchovies) [147]. Although n-3 FAs have been found to be extremely safe by both Health Canada and the US Food and Drug Administration, there is insufficient evidence at this time to recommend routine use of n-3 FAs to treat hypertriglyceridemia in children with CKD. Dietary fiber, particularly naturally occurring viscous fiber, reduces total and LDL cholesterol levels and high intakes have been associated with reduced rates of CVD. The AI for total fiber is based on daily caloric intake, and for all children 1 year and older is 14 g/ 1000 kcal/d. Dietary fiber is found in most fruits, vegetables, legumes, and whole grains, which are foods restricted in low-potassium and low-phosphorus diets; therefore, meeting normal daily fiber recommendations is challenging for children with CKD. Tasteless mineraland electrolyte-free powdered forms of fiber (e.g., UnifiberÒ, BenefiberÒ ) are available to add to meals or drinks if children are unable to meet their fiber intake by diet. High-fiber diets require additional fluid intake, which may not be possible for oliguric or anuric patients with strict fluid restriction.

BONE MINERAL METABOLISM Calcium Adequate dietary calcium intake during childhood is necessary for skeletal development and acquisition of optimal peak bone mass [148]. The current recommendation is that patients with CKD should achieve a calcium intake of 100% of the DRI [149] (Table 35.6). Infants and young children usually meet the DRI for calcium with the consumption of adequate volumes of breast milk/formula. Unfortunately, the largest sources

TABLE 35.6

Recommended Calcium Intake for Children with CKD Stages 2e5 and 5D Upper Limit for CKD Stages 2e5, 5D (Dietary D Phosphate Binders)

Age

DRI

Upper Limit (for Healthy Children)

0e6 months

210

ND

420

7e12 months

270

ND

540

1e3 years

500

2500

1000

4e8 years

800

2500

1600

9e18 years

1300

2500

2500

ND, not determined. Determined as 200% of the DRI, to a maximum of 2500 mg elemental calcium.

591

of dietary calcium for most persons are dairy products which are also rich in phosphorus; in turn, phosphorus restriction universally leads to a decreased calcium intake. In these situations, calcium supplementation may be required as low phosphorus, high calcium containing foods such as collards, dandelion greens, kale, rhubarb, and spinach usually do not make up a substantial part of a child’s diet. Several products fortified with calcium such as fruit juices and breakfast foods are commercially available and limited studies have suggested that the bioavailability of calcium from these products is at least comparable to that of milk [150]. Calcium can also be supplemented in medicinal forms such as carbonate (40% elemental calcium), acetate (25% elemental calcium), and gluconate (9% elemental calcium) salts of calcium that are commonly used as phosphate binders. When used for calcium supplementation alone, ingesting these products between meals maximizes calcium absorption. Chloride and citrate salts of calcium should be avoided as the former may lead to acidosis in patients with CKD and the latter may enhance aluminum absorption. On the other hand, excessive calcium intake in conjunction with activated vitamin D analogs can lead to (i) hypercalcemia; (ii) adynamic bone disease; and (iii) systemic calcification. Accordingly, the K/DOQI guidelines recommend that the combined elemental calcium intake from nutritional sources and phosphate binders should not exceed two times the DRI for age, except for ages 9e18 years (both genders) where two times the DRI (2600 mg) exceeds the Tolerable Upper Intake Level (UL) of 2500 mg [149] (Table 35.6). The serum level of total corrected calcium should be maintained within the normal range (8.8e9.5 mg/dL), preferably towards the lower end and definitely not more than 10.2 mg/dL, while the serum calcium and phosphorus product should be kept below 55 mg/dL in adolescents >12 years, and <65 mg/dL in younger children [151]. The calcium balance in patients undergoing maintenance dialysis is also affected by the dialysate calcium concentration. The calcium balance during PD is usually negative with use of a 2.5 mEq/L calcium dialysate and positive with a dialysate calcium concentration of 3.0e3.5 mEq/L [152]. As a result, it may be wise to use a low calcium dialysate (2.5 mEq/L) in children undergoing dialysis who are receiving calcium-containing phosphate binders along with activated vitamin D sterols. On the contrary, a 3.0e3.5 mEq/L calcium dialysate should be used if hypocalcemia is present in a child with elevated PTH (>300 pg/mL) as part of the treatment of secondary hyperparathyroidism (SHPT) and may be needed in children restricted to non-calcium containing phosphate binders only.

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NUTRITIONAL MANAGEMENT OF RENAL DISEASE

Phosphorus

TABLE 35.8 Recommended Maximum Oral and/or Enteral Phosphorus (mg/d) Intake for Children with CKD

In an effort to prevent/control CKD-associated bone disease and CVD, serum phosphorus concentrations above the normal reference range for age (Table 35.7), should be avoided in patients with advanced CKD. However, even during the earlier stages of CKD when the serum phosphorus levels are typically within normal range, the dietary phosphorus load is an important determinant of the severity of hyperparathyroidism. Dietary phosphorus restriction decreases PTH levels and increases 1,25(OH)2D, whereas dietary phosphorus intakes approximately twice the DRI for age aggravate hyperparathyroidism despite little or no change in serum phosphorus levels (likely the result of elevated FGF-23 levels and enhanced phosphorus excretion) [153]. It is important to note that the higher physiological serum concentrations of calcium and phosphorus that are observed in healthy infants and young children, presumably reflect the increased requirements for these minerals by the rapidly growing skeleton. Rickets due to phosphorus deficiency can occur in preterm infants whose diet provides insufficient quantities of phosphorus, as well as in infants and children with hypophosphatemia due to inherited disorders of renal phosphate transport. Hence, when dietary phosphorus is restricted to control hyperphosphatemia and SHPT in children with CKD, subnormal serum phosphorus values are equally important to avoid. Recently published recommendations suggest that in children with CKD whose serum PTH concentration exceeds the target range (Table 35.7) but whose serum phosphorus concentration remains normal, the dietary phosphorus intake should be restricted to 100% of the DRI; in contrast, the intake should be restricted to 80% of the DRI when the serum phosphorus concentration exceeds the normal reference range for age (Table 35.8) [11]. Despite the need to restrict dietary phosphorus, most clinicians recognize that an overly strict dietary phosphorus restriction is not only often impractical, but it TABLE 35.7

Age-Specific Normal Ranges of Blood Ionized Calcium, Total Calcium and Phosphorus

Age

DRI (mg/d)

High PTH and Normal Phosphorus

High PTH and High Phosphorus

0e6 months

100

100

80

7e12 months

275

275

220

1e3 years

460

460

370

4e8 years

500

500

400

9e18 years

1250

1250

1000

Health Canada: www.hc-sc.gc.ca/fn-an/alt_ formats/hpfb-dgpsa/pdf/nutrition/dri_ tables-eng.pdg. Reproduced with the Permission of the Minister of Public Works and Government Services Canada, 2008. 100% of the DRI; 80% of the DRI.

can be ill advised as it may lead to an inadvertent poor dietary protein intake with a possible increase in mortality [53]. In addition, extremely low phosphorus diets are typically unpalatable. While young infants are characteristically managed with a low-phosphorus containing milk formula such as Similac PM 60/40 (Abbott Nutrition), or Renastart (Vitaflo Nutrition), or by pretreatment of breast milk, infant formula and cow’s milk with sevelamer carbonate (RenvelaÒ ) which can effectively reduce the phosphorus content in the supernatant by 80e90% [154,155], it is important to note that some infants may require phosphorus supplementation in the form of sodium phosphate (Neutra Phos) because of their higher physiological needs, as mentioned previously. Most other patients with CKD require oral intestinal phosphate binders to control hyperphosphatemia. Phosphorus control is particularly difficult in vegetarians since for the same total quantity of dietary protein delivered, the phosphorus content is greater in protein derived from vegetable sources (average 20 mg of phosphorus per gm of protein) vs. animal protein (average 11 mg of phosphorus per gram of protein). However, the bioavailability of phosphorus from plant-derived food is very low; therefore, despite their higher specific phosphorus content, some plant sources of protein may actually result in a lower rate of phosphorus uptake per mass of protein than meat based foods [11]. Whereas food labels rarely state the phosphorus content, chocolates, nuts, dried beans, and cola soft drinks are rich in phosphorus and should be avoided; nondairy creamers and certain frozen nondairy desserts may be used in place of milk and ice cream.

Age

Ionized Calcium (mmol/L)

Calcium (mg/dL)

Phosphorus (mg/dL)

0e5 months

1.22e1.40

8.7e11.3

5.2e8.4

6e12 months

1.20e1.40

8.7e11.0

5.0e7.8

1e5 years

1.22e1.32

9.4e10.8

4.5e6.5

6e12 years

1.15e1.32

9.4e10.3

3.6e5.8

Vitamin D

13e20 years

1.12e1.30

8.8e10.2

2.3e4.5

Recent clinical evidence suggests a high prevalence (typically 80% to 90%) of nutritional vitamin D insufficiency in both children and adults with CKD [156]. In

Conversion factor for calcium and ionized calcium: mg/dL  0.25 ¼ mmol/L. Conversion factor for phosphorus: mg/dL  0.323 ¼ mmol/L.

NUTRITIONAL MANAGEMENT OF THE CHILD WITH KIDNEY DISEASE

TABLE 35.9 Serum 25(OH)D (ng/mL)

Recommended Supplementation for Vitamin D Deficiency/Insufficiency in Children with CKD

Definition

Ergocaliferol (Vitamin D2) or Cholecalciferol (Vitamin D3) Dosing

Duration (months)

<5

Severe vitamin D deficiency

8000 IU/d orally or enterally  4 wk or (50,000 IU/wk  4 wk); then 4000 IU/d or (50,000 IU twice per mo for 2 mo)  2 mo

3

5e15

Mild vitamin D deficiency

4000 IU/d orally or enterally  12 wk or (50,000 IU every other wk, for 12 wk)

3

16e30

Vitamin D insufficiency

2000 IU daily or (50,000 IU every 4 wk)

3

a recent publication, Ali et al reported a 20e75% prevalence of vitamin D deficiency (25(OH)D <15 ng/mL) in children with CKD stages 1e5, with higher prevalence rates in Hispanics and African-Americans, likely due to increased melanin content in their skin [156]. This insufficiency may aggravate SHPT in patients with CKD as the availability of 25(OH)2 D becomes a rate limiting step for the synthesis of 1,25(OH)2 D. Accordingly, the latest KDOQI Pediatric Nutrition Guidelines suggest checking serum 25(OH)2 D levels once per year in children with CKD stages 2e5 [11]. If the serum level of 25(OH)2 D is <30 ng/mL, supplementation with vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) is suggested, with the specific dosing regimen dependent on the severity of the deficiency (Table 35.9). Cholecalciferol appears to have higher bioefficacy than ergocalciferol, although long-term comparative trials are lacking in humans [157,158]. During the repletion phase, serum levels of calcium and phosphorus should be measured 1 month following the initiation or a change in the dose of vitamin D and at least every 3 months thereafter. Once patients are replete with vitamin D, supplemental vitamin D should be continued and 25(OH)2 D levels checked yearly [11,151].

ACIDeBASE AND ELECTROLYTES AcideBase Status Infants and children normally have a relatively larger endogenous hydrogen ion load (2e3 mEq/kg) than do adults (1 mEq/kg); in turn, metabolic acidosis is a common manifestation of CKD in children and an important negative influence on growth through a number of growth factor specific mechanisms, including reduction in thyroid hormone levels and blunting of IGF response to growth

593

hormone [159]. Furthermore, studies performed in adults and children have shown that chronic acidosis is associated with increased oxidation of branched-chain amino acids, increased protein degradation [160], and decreased albumin synthesis [161]. Persistent acidosis also has detrimental effects on bone because it alters the normal accretion of hydroxyapatite into bone matrix and causes bone demineralization as bone buffers are increasingly used for neutralizing the excess acid load. Thus, it is recommended that the serum bicarbonate level should be maintained at or above 22 mEq/L in children with CKD by supplementing with oral bicarbonate as needed [11].

Sodium Sodium requirements in children with CKD are dependent on the underlying kidney disease and the degree of renal insufficiency. Children who have CKD as a result of obstructive uropathy or renal dysplasia are most often polyuric and may experience substantial urinary sodium losses despite advanced degrees of CKD. Sodium depletion adversely affects growth and nitrogen retention [162], and its intake supports normal expansion of the ECF volume needed for muscle development and mineralization of bone [163]. Fine et al. demonstrated poor weight gain in animals deprived of salt with a resultant decreased extracellular volume, bone mass and fat mass [164]. Parekh et al. reported the beneficial effect of a dilute, sodium supplemented (2e4 mEq sodium per 100 mL formula), high-volume (180 to 240 mL/kg per 24 hours, depending on urine output) feeding regimen on the linear growth of 24 young children with severe polyuric CKD. The treated group of patients was able to maintain a nearly normal height SDS despite the presence of significant renal insufficiency [165]. Therefore, infants and children with polyuric saltwasting forms of CKD who do not have their sodium and water losses corrected may experience vomiting, constipation, and significant growth retardation associated with chronic intravascular volume depletion and a negative sodium balance [165]. It is important to note that normal serum sodium levels do not rule out sodium depletion and the need for supplementation. Sodium supplementation can be given as chloride or bicarbonate, depending upon the patient’s acidebase status. In contrast, children with CKD resulting from a primary glomerular disease, or those who are oliguric or anuric, typically require a sodium and fluid restriction to minimize fluid gain, edema formation, and hypertension. The prescribed fluid intake is usually a fraction of the calculated maintenance volume adjusted for the degree of oliguria. According to the most recent 2005 Dietary Guidelines, the sodium intake for children older than 2 years should be restricted to <1500 mg (65 mmol) [166], which corresponds to

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NUTRITIONAL MANAGEMENT OF RENAL DISEASE

sodium intake of 1 to 2 mmol/kg/day for those younger than 2 years. These patients should be advised to avoid processed foods and snacks from fast-food restaurants as the majority (75%) of sodium in the diet comes from salt added during food processing. Infants receiving PD are predisposed to substantial sodium losses, even when anuric. High ultrafiltration requirements per kilogram of body weight result in removal of significant amounts of sodium chloride. These losses are not adequately replaced through the low sodium content of breast milk (160 mg/L or 7 mmol/L) or standard commercial infant formulas (160 to 185 mg/L or 7 to 8 mmol/L) [167]. Therefore, infants on PD are at risk of developing hyponatremia that can result in cerebral edema and blindness and must be maintained in neutral sodium balance. Sodium supplementation should be individualized based on clinical symptoms, including hypotension, hyponatremia, and/or abnormal serum chloride levels.

Potassium Potassium homeostasis in children with CKD is usually unaffected until the glomerular filtration rate (GFR) falls to <10% of normal. However, children with renal dysplasia, post-obstructive kidney damage, severe reflux nephropathy, and renal insufficiency secondary to interstitial nephritis often demonstrate renal tubular resistance to aldosterone and may manifest hyperkalemia, even when their GFR is relatively well preserved. The hyperkalemia experienced by these children is exacerbated by volume contraction (and can be particularly common in salt losers) and the majority of the patients respond to salt and water repletion. In patients who are persistently hyperkalemic, dietary potassium intake should be limited. As potassium content is infrequently listed on food labels and cannot be tasted, a list of foods rich in potassium such as chocolates, French fries, potato chips, bananas, green leafy vegetables, dried fruits, and orange juice should be provided to patients and their families. Altering the methods of food preparation, such as soaking vegetables before cooking, helps decrease potassium content. Moderate to severe hyperkalemia may require treatment with a potassium binder such as sodium polystyrene sulfonate (Kayexalate); in hypertensive children, calcium polystyrene sulfonate can be used instead to decrease the sodium load. In the case of infants and young children being fed milk formula, the potassium content of the formula can be reduced by pretreating it with a potassium binder [168]. If constipated, the patient should be treated aggressively as significant quantities of potassium are eliminated through the gastrointestinal route in patients with CKD. In children undergoing HD, dietary potassium intake should be distributed throughout the day, as high serum

concentrations of potassium can develop when a large quantity of potassium is ingested at one time, regardless of the total daily dietary content. On the other hand, some patients receiving PD may become hypokalemic due to potassium losses in the dialysate and will require potassium supplementation.

VITAMINS AND MICRONUTRIENTS Vitamins and minerals are essential for normal growth and development and either a deficiency or an excess can prove harmful. Unfortunately, the vitamin and mineral needs of pediatric patients with CKD are not clearly defined (other than for Vitamin D), and the limited data that is available is derived from patients undergoing maintenance dialysis. Children with CKD are prone to develop vitamin deficiencies because of anorexia and dietary restrictions, while they are also at risk to develop toxic levels of vitamins when the renal clearance is significantly impaired. All of the water-soluble vitamins except pyridoxine are eliminated by the kidneys and their clearance in patients with CKD is not known. However, most watersoluble vitamins are lost during maintenance dialysis and, in turn, are routinely supplemented by special vitamin formulations that do not contain vitamin A and D, such as Nephronex (L Lorens Pharmaceuticals), and Nephro-Vite (R & D Laboratories, Inc., Marina Del Rey, CA). Studies conducted in the adult dialysis population have provided evidence of low blood concentrations of water-soluble vitamins and minerals because of inadequate intake, increased losses, and increased needs [169,170]. Deficiency of vitamin B6 can result from poor dietary intake as well as impaired formation and/or increased clearance of pyridoxal phosphate in the dialysis fluid [171]. Vitamin B12 and folic acid, both of which are important for effective erythropoiesis, differ in their peritoneal clearance; while there can be significant losses of folic acid, only small quantities of vitamin B12 are lost by this route [172]. Accordingly, supplementation with 0.8 to 1.0 mg folic acid is routinely recommended, while the necessity of vitamin B12 supplementation remains unsettled. A higher dose of folic acid (2.5 mg per day) has been suggested for children with CKD as supplemental folic acid has been shown to decrease the elevated homocysteine level that is commonly seen in patients with renal failure and is a potential risk factor for cardiovascular morbidity and mortality [173,174]. In contrast, serum thiamine and riboflavin levels have been reported to be normal in PD patients, with or without supplementation, in association with negligible losses during dialysis [175]. Supplementation with vitamin C is occasionally recommended because of the significant quantity that can

NUTRITIONAL MANAGEMENT OF THE CHILD WITH KIDNEY DISEASE

be lost during PD [176]. It is important to recognize however, that while adequate levels of vitamin C are necessary for the formation of collagen, an excessive intake of vitamin C in the dialysis population may result in elevated oxalate levels as an end-product of vitamin C metabolism and lead to the development of significant vascular complications [177]. Accordingly, vitamin C intake should not exceed 100 mg/day. Vitamin K deficiency is likely in patients who receive frequent antibiotics and has been reported in a small number of adults [178]. Vitamin A levels are usually elevated in patients undergoing PD despite the lack of vitamin A in the vitamin supplement formulation. The elevated levels are a result of the loss of the kidneys normal ability to excrete vitamin A metabolites [179]. Since elevated levels of vitamin A can be associated with the development of hypercalcemia and complications related to a high calcium-phosphorus product, it is critically important to avoid the use of vitamin supplements that include vitamin A. In children older than 6 years of age undergoing PD, vitamin supplementation has been associated with normal or greater than normal serum levels of the water-soluble vitamins [176]. However, no published studies have assessed the blood vitamin levels of children undergoing maintenance dialysis in the absence of the use of a vitamin supplement. As most infant milk formulas including Similac PM 60/40 are fortified with both water-soluble and fat-soluble vitamins, most infants with CKD/ESRD receive the DRI/RDA for all vitamins (including vitamin A) by dietary intake alone. Warady et al. [180] reported on the vitamin status of a group of seven infants undergoing PD; their main nutrient intake was infant milk formula (Similac PM 60/40) and they received a water-soluble vitamin supplement (Iberet; Abbott Laboratories, Abbott Park, IL). The combined dietary and supplement intake exceeded the RDA for the water-soluble vitamins in all but one patient who received only 79% of the RDA for vitamin B6 because of inadequate formula intake. In all cases, the patient’s serum concentrations of the water-soluble vitamins were comparable to or greater than the values reported in normal infants. In addition, the serum vitamin A levels were significantly greater than normal values, despite the lack of supplemental vitamin A. Aluminum, copper, chromium, lead, strontium, tin, and silicon levels have all been noted to be elevated in patients with CKD, reflecting the fact that their clearance is dependent on an adequate GFR [181,182]. Other trace elements have not been well studied in children; however, zinc levels have been shown to be low in malnourished children and should be monitored and supplemented as necessary [181]. Based on the limited data referred to above, the current KDOQI Pediatric Nutrition Guidelines [11]

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recommend the intake of at least 100% of the DRI for thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B8), cobalamin (B12), ascorbic acid (C), retinol (A), a-tocopherol (E), vitamin K, folic acid, copper, and zinc for children with CKD stages 2 to 5, and those receiving maintenance dialysis. They suggest supplementation of vitamins and trace elements if dietary intake alone does not meet 100% of the DRI or if clinical evidence of a deficiency, possibly confirmed by low blood levels of the vitamin or trace element, is present [11]. As most infant milk formulas including Similac PM 60/40 are fortified with both water-soluble and fat-soluble vitamins, the majority of infants with CKD (and not yet on dialysis) receive the dietary reference intakes (DRI) for all vitamins (including vitamin A) by dietary intake alone and do not require vitamin supplementation.

Carnitine Carnitine is an essential compound in the oxidative process of fatty acids and adenosine triphosphate formation [183], and the kidney is the major site for its synthesis in humans. While there is evidence of carnitine deficiency in patients undergoing HD [184], and far less information regarding its status in those receiving PD, there is little information on the carnitine status of children with CKD. Carnitine deficiency can result in the development of anemia, cardiomyopathy, and muscle weakness [184]. However, most, but not all of the few pediatric studies that have been conducted on the subject of carnitine deficiency in dialysis patients have provided evidence for an increase in the plasma carnitine level after carnitine supplementation with no associated change in any symptoms [185]. As such, there currently is insufficient evidence to support the routine use of carnitine in either the pediatric CKD or dialysis patient populations. However, a trial of carnitine may be indicated when all other causes for the symptoms in question have been excluded, carnitine deficiency has been confirmed, and the patient has been unresponsive to standard therapies [186]. Carnitine deficiency is confirmed by measurements of plasma free and total carnitine with an acyl:free carnitine ratio greater than 0.4 (i.e., [total e free carnitine] O free carnitine) or a total serum carnitine value less than 40 mmol/L [184].

NUTRITION MANAGEMENT A registered dietitian with experience in pediatric renal diseases should play the central role in the dietary management of children with CKD/ESRD. In addition to possessing knowledge related to nutritional

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requirements, this person should also be skilled in the evaluation of physical growth, developmental assessment, and the educational and social needs of this special population. The dietitian must be able to establish a positive rapport with both the child and the primary caretakers in order to enhance compliance with the recommended nutritional regimen. The focus of the dietitian’s treatment plan is determined by the patient’s age. In the case of infants, the parents or primary caretaker who is responsible for feeding the child has the greatest interaction with the dietician; in contrast, adolescents must receive the majority of information directly, as they often eat independently. For children between these two extremes, both the parents and the child are typically involved in different aspects of the dietary management. It is noteworthy that the two most vulnerable groups of patients in terms of the risk for malnutrition are infants and adolescents. While infants are at special risk because of the frequent occurrence of anorexia and emesis, many adolescents have poor eating habits, as mentioned previously. An individualized nutrition plan taking into account a variety of factors should be developed for each patient by the dietician in consultation with the physician, patient (when appropriate) and family, with clearly defined short and long-term objectives. As cultural food preferences play an important role in the family’s ability to adhere to dietary changes, dietary instructions should be tailored to help families modify, but not eliminate cultural food preferences. Background information on cultural diets and translated versions of renal diets and food lists are available for reference [187]. The plan should be modified as necessary according to changes in the child’s nutritional status, renal function, dialytic therapy, medication regimen, and psychosocial situation. Dietary restrictions should be limited as much as possible with a goal of enhancing nutrient intake. Restrictions of nutrients should ideally be imposed only when there is a clear indication, rather than an anticipated need. It is also important to find substitutes for restricted foods so as to maintain an adequate caloric intake. A simple explanation of the role of the nutrient in the body, the rationale for the diet modification, and the desired outcomes to be achieved (e.g. normalization of biochemical parameter, specific amount of weight gain) is helpful in obtaining cooperation of the patient and caretakers, thereby increasing the likelihood of success. Adopting and maintaining changes in eating habits is also easier for a child if family members make similar changes, or at least avoid eating restricted foods in the child’s presence. In addition, caregivers outside of the immediate family (e.g. grandparents, school staff, babysitters) should be aware of the diet restrictions and be asked to provide consistency of care in helping

the child follow his/her diet. While the ideal goal is full compliance with the prescribed regimen, it is not always a realistic expectation and “partial compliance” is often acceptable. Being very rigid with the dietary prescription adds to parental stress and increases the risk for behavioral eating problems in the young child such as food refusal, gagging, and vomiting.

Oral Supplementation Infants with CKD requiring fluid restriction or those who have a poor oral intake may require a greater caloric density of their milk formula than the standard 20 kcal/oz. The increase in caloric density should not be achieved by concentrating the milk formula, as this approach will also increase the protein and mineral content. The provision of extra calories can be achieved by adding carbohydrate and/or fat modules to the formula. A glucose polymer such as Polycose (Abbott Nutrition) has a low osmolality and is generally the initial supplement added to infant formulas. Additional calories can be added in the form of corn oil. Oils containing medium chain triglyceride (MCT) are generally not necessary unless there is coexistent malabsorption. However, usage of corn and other oils as additives is not common as they do not mix well with formula and cause problems with tube-feedings. Microlipid (Nestle Nutrition), a 50% fat emulsion from safflower oil with 4.5 kcal/mL and DuocalÒ (Nutrica North America), a fat and carbohydrate combo modular with 5 kcal per gram of powder (59% calories from carbohydrate and 41% from fat), are common commercially available products for energy supplementation. The latter is not approved for infants younger than 1 year. Older infants may tolerate the addition of corn syrup or sugar, which are readily available and inexpensive. The quantity of both carbohydrate and fat modules can gradually be increased to raise the caloric density to as much as 60 kcal/oz [188]. It is important to wait at least 24 hours following each 2- to 4-kcal/oz incremental increase in concentration to enhance patient tolerance of the formula. Nutritional therapy, irrespective of the route of administration or caloric density of the formula, should provide a balance of calories from carbohydrate and unsaturated fats within the physiological ranges recommended as the Acceptable Macronutrient Distribution Ranges (AMDR) of the DRI. Recommended AMDR for children older than 4 years are 45e65% from carbohydrate, 25e35% from fat (polyunsaturated/saturated ratio of 1), and 10e30% from protein; children younger than 3 years need a somewhat greater proportion of fat (30e40%) in their diets to meet energy needs. An adequate amount of non-protein calories should be provided for protein-sparing effects. It should, however,

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be noted that during the advanced stages of uremia, the protein-sparing effect of added fat calories may be inferior to the effect of added concentrated carbohydrate calories [29]. Children beyond infancy characteristically refuse the high-calorie carbohydrate supplements. For them, it is often easier to encourage common foods that have a high caloric content, but a relatively low mineral and protein content. Powdered fruit drinks, frozen fruit flavored desserts, candy, jelly, honey, and other concentrated sweets can be used for this purpose. However, the altered taste acuity associated with uremia may limit the acceptability of these foods. In addition, one may need to avoid high carbohydrate foods in the presence of hypertriglyceridemia. Under these circumstances, unsaturated fats may be the preferred choice of high calorie food sources. Children and adolescents should also be encouraged to use margarine on popcorn, bread, vegetables, rice, and noodles for added calories. A variety of calorie-dense (1.8 kcal/mL) preparations such as Nepro and Suplena (Abbott Nutrition) have been formulated specifically for renal patients and are commercially available. Suplena has a lower protein content than Nepro (30g/L vs. 70 g/L), and is preferable for pre-dialysis patients. These preparations are characterized by a low renal osmolar load and a low vitamin A and D content. Although initially produced for patients older than 10 years, they have been successfully used in children as young as 3 years; however, it is advisable to dilute them to half to two-thirds strength when used in young children. Recently, Hobbs et al. reported the successful use of these adult renal formulas in seven hyperkalemic infants with improved growth and normalization of the serum potassium level [189]. In contrast to energy intake, the protein requirements of children with CKD are usually met by voluntary, unsupplemented consumption. If the protein intake is insufficient due to concomitant phosphorus restriction in the patient with severely impaired renal function, the protein module, Beneprotein (Nestle Nutrition), a whey protein concentrate, can be added to the formula to increase the protein content. As much as 1 g of Beneprotein , which is equivalent to 0.86 g protein, can be added to each ounce of formula. Semi-synthetic diets supplemented with either amino or keto forms of essential amino acid (EAA) have also been tried to ensure an adequate protein intake. However, the lack of sufficient data in children precludes making any firm recommendation regarding their possible clinical application.

Enteral Nutritional Support Aggressive enteral feeding should be considered if the nutritional intake by the oral route is sub optimal despite all attempts at oral supplementation. The use of enteral support has resulted in maintenance or

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improvement of SD scores for weight and/or height in infants and young children with moderate to severe CKD and those undergoing maintenance dialysis [4,13,23,190e193]. In fact, several investigators, including Kari et al. [92] have advocated early enteral feeding at the first sign of growth failure during infancy. Nasogastric (NG) tubes [191,193e195], gastrostomy catheters [196], gastrostomy buttons [197,198], and gastrojejunostomy tubes [199], have been used to provide supplemental enteral feeding to children with renal disease with encouraging results. The feeding can be given as an intermittent bolus, or more commonly by continuous infusion during the night. Continuous overnight feeds are generally preferred to allow time during the day for regular oral intake. Historically, the NG tube has been used most frequently in infants and young children, as it is easily inserted and is generally well tolerated [193,200]. Ellis et al. reported usage of NG tube by 78% and 68% of children who initiated dialysis at <3 months and 3e20 months of age, respectively [201]. However, this route of therapy is often complicated by recurrent emesis and the need for frequent tube replacement, in addition to the risk of pulmonary aspiration, nasoseptal erosion, and psychological distress of the caretaker because of the cosmetic appearance. Persistent emesis can be addressed by slowing the rate of formula delivery and by the addition of antiemetic agents such as metoclopramide or domperidol. Additionally, whey predominant formulas can be used as they have been shown to stimulate gastric emptying [202,203]. The gastrostomy tube or button has been used as the enteral route of choice by many clinicians, and has the cosmetic advantage of being hidden beneath clothing. Once placed, it can be used within several days. Many, but not all clinicians recommend that the patient should be investigated for gastroesophageal reflux prior to undertaking gastrostomy placement so that a Nissen fundoplication can be created at the same sitting, if required. The reported complications of gastrostomy tubes/buttons include exit-site infection, leakage, obstruction, gastrocutaneous fistula, and peritonitis [204,205]. Peritonitis is potentially the most serious complication and is a likely factor inhibiting the more widespread adoption of gastrostomy as opposed to NG feeding in the PD population [206]. Warady et al. reported that 11 (24%) of 45 episodes of fungal peritonitis were associated with the presence of a gastrostomy tube or button, but there was no statistically significant correlation between the presence of a gastrostomy and the development of fungal peritonitis [207]. To decrease the risk of peritonitis, the gastrostomy should be placed either before or simultaneously during PD catheter placement. In addition, it may be better to avoid combining gastrostomy placement and peritoneal dialysis catheter placement in a severely malnourished

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patient until the nutritional status and general immunity of the patient can be improved by other means, such as NG tube feeds [205]. A recent report by Rees et al. [208], demonstrated the effectiveness of NG tube and gastrostomy feeding in improving the nutritional status of young (<2 years) children receiving chronic PD. However, the report also revealed marked global variation in feeding strategies and the complex relationship between enteral feeding and growth. A common and serious complication of using any form of enteral tube feeding is a prolonged and potentially difficult transition from tube to oral feeding [209,210]. Regular non-nutritive sucking and repetitive oral stimulation are recommended for all tube-fed infants. A multidisciplinary feeding team consisting of a dietitian, occupational therapist, and behavioral psychologist can help facilitate the transition from tube to oral feeding.

Alternative Routes of Nutritional Support The substitution of amino acids for dextrose in the peritoneal dialysis fluid and the provision of parenteral nutrition during hemodialysis sessions (intradialytic parenteral nutrition; IDPN) are two additional aggressive approaches to nutritional supplementation that have had limited pediatric application. Intraperitoneal nutrition has been evaluated in only a small number of children receiving PD and for a limited period of time [211e214]. The quantity of amino acids absorbed from the dialysate routinely exceeded the protein lost in the dialysate. Very little experience with IDPN has been reported in the pediatric population. A short-term study of 10 chronic hemodialysis patients, ages 10 to 18 years, conducted in the Netherlands documented weight gain in nine patients with no significant change in plasma amino acid profile [215]. Similarly, Goldstein et al. [216], demonstrated reversal of weight loss and initiation of weight gain within 6 weeks of IDPN initiation in three malnourished adolescents undergoing hemodialysis. Future studies may prove these routes of nutritional supplementation to be valuable adjuncts to the oral and enteral routes of therapy.

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