Nutrition in children with CRF and on dialysis

It is unlikely that energy requirements for children with CRF are different from those of normal children, and energy intakes below the EAR will contribute to growth failure. Restoration of normal energy requirements to 100% EAR allows for catch-up growth in children under 2 years and shows some benefit in older children (see section on Dietary supplements). If recurrent vomiting resulting from abnormal gastric motility and delayed gastric emptying is not treated, energy intake may need to be increased by up to 30% daily to replace lost feed and food in order to preserve growth; once vomiting is controlled growth is maintained on normal energy requirements [21]. To ensure an adequate energy intake it is advisable to use the EAR for height age if the child is below the 2nd centile for height.

There is no evidence that intakes for children on dialysis should exceed those for normal children [10], though dietary energy intake may need to be reduced for children on PD to compensate for the energy derived from dialysate glucose, estimated at 8–12 kcal/kg/day if there is excessive weight gain [7, 22].

Post-transplant energy requirements should match those of normal children, though care needs to be taken with increased appetite in response to steroid administration. Up to 13% of transplanted chidren become obese [23, 24]. A reduction in energy intake is indicated where there is excessive weight gain and will help correct any dyslipidaemia.

Protein intakes in CRF must provide at least 100% RNI if protein is not to become the limiting factor for growth. Inadequate protein will impact on body composition with a preponderance of fat rather than lean tissue. Adequate energy must be given to promote deposition of protein [25]. To ensure an adequate protein intake, it is advisable to use the RNI for height age if the child is below the 2nd centile for height.

In children undergoing PD, protein intake must provide at least 100% RNI plus an allowance for both replacement of transperitoneal losses and replacement of daily nitrogen losses in order to achieve positive nitrogen balance [7, 18, 22]. There are few studies describing the optimal amount of protein for children on PD and the existing data does not include all age groups. Taking this into account, and the wide variability in transperitoneal losses of protein, recommended intakes for protein for populations of children on PD may be considered generous. Routine assessment of growth, albumin and urea levels will determine the required intake for the individual child. For chronic haemodialysis, the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommends the RDA for age plus an increment of 0.4 g/kg/day to achieve positive nitrogen balance [10]. This recommendation is based on work done in adults on HD who failed to maintain nitrogen balance on 1.1 g protein/kg/day [26]. Published recommended intakes for the US and the UK shown in Tables 2 and 3 are for populations and may need adjustment for the individual.

Post-transplant protein requirements should match those of normal children.

Little is known about the requirements of children with CRF. It would be reasonable to give the RNI for vitamins, minerals and micronutrients as for normal children, with the exception of calcium, phosphate, magnesium, sodium and potassium, which may be deranged and must be determined for the individual child. UK RNIs are shown in Table 4.

*Vitamin A - care should be taken not to give excessive amounts of vitamin A, as the resultant high serum levels can lead to hypercalcaemia, anaemia and hyperlipidaemia [29]. A common practice guideline is not to exceed 200% of the RNI from the diet and/or supplements.

*Folic acid - hyperhomocysteinaemia is an independent risk factor for cardiovascular disease [30, 31]. Additional folic acid may be given to effectively lower plasma homocysteine levels. A common practice guideline is to supplement when the glomerular filtration rate (GFR) is <40 ml/min/1.73 m², but the doses used are arbitrary.

Infants: 250 μg/kg to maximum of 2.5 mg daily

Children 1–5 years: 2.5 mg daily

Children >5 years: 5 mg daily

In adults on PD, blood concentrations of some water soluble vitamins (C, B6 and folic acid) are reported to be low. This is due to a combination of inadequate intake, increased transperitoneal losses and increased needs. In children supplements of these vitamins have been given with the result that blood concentrations have met or exceeded normal values [32, 33]. Accordingly, based on these authors’ recommendations and the RNIs above, the following intakes are suggested [27]:

Vitamin C: 15 mg (infants)-60 mg (children) daily

Vitamin B6: 0.2 mg (infants)-1.5 mg (children) daily

Folate: 60 μg (infants)-400 μg (children) daily

These amounts may well be met from food, feeds and nutritional supplements so it is important to assess the dietary contribution before routinely giving medicinal supplements. Whilst adequate vitamin C needs to be given to offset dialysate losses excessive intakes should be avoided, as the resulting elevated oxalate levels may lead to cardiovascular complications [34]. If folic acid is given to lower plasma homocysteine this will more than compensate for dialysate losses of folate. The K/DOQI recommends that supplementation should be considered if dietary intake alone does not meet or exceed the dietary reference intake, if blood vitamin levels are below normal values, or if there is clinical evidence of deficiency [10].

There are no reported specific micronutrient requirements for children on HD and post transplant and 100% of the RNIs can be considered the goal for these children.

Control of phosphate, calcium and parathyroid hormone (PTH) levels is necessary to prevent renal bone disease. Dietary phosphate may need to be restricted when the GFR falls below the normal range, and almost always when below 50 ml/min/1.73 m². The following common practice guidelines will help maintain serum phosphate within acceptable reference ranges, although phosphate binders may also be necessary.

Infants <10 kg: <400 mg daily

Children 10–20 kg: <600 mg daily

Children 20–40 kg: <800 mg daily

Children >40 kg: <1,000 mg daily

Anaemia can be prevented by the prescription of iron supplements and erythropoietin (rhuEPO). Advice to increase dietary haem iron and reduce the inhibition of non-haem iron absorption by: phytates in wholegrains and legumes; polyphenols in tea, coffee and cocoa; calcium in dairy products; and simultaneous administration of phosphate binders and antacids should be given. It may be necesary to give intravenous iron if stores are low. Low dietary intakes of copper and zinc are reported [35] in children on PD. The K/DOQI recommends the intake of these to be monitored every 4–6 months and supplements given if necessary [10].

It is during the infantile phase of growth that the most significant loss of height potential can occur, but also it is the phase during which there is the greatest potential for catch-up with nutritional intervention. Many infants with CRF are already growth-retarded by the time they are first seen in a paediatric nephrology service: a loss of HtSDS from birth of −1.68 SD (up to −5 SD/year) has been reported [43]. Approximately one-third of the reduction in height occurs during foetal life and one-third during the first 3 months, accompanied by a similar decline in head circumference [44‐46]. Mean HtSDS below the lower limit of normal has been reported in most studies [43‐46]. However, catch-up can occur, even on dialysis [47‐49]. Poor nutritional status is associated with starting PD at a younger age [50]. Interestingly, infants who grew well continued with catch-up in early childhood [43, 47].

During the childhood phase, growth in CRF usually parallels the centiles but without catch-up [43, 46]. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) CRF database (<20 years of age, GFR <75 ml/min/1.73 m²) has shown a mean HtSDS that has changed little since 1996 when it was −1.5 in 1,725 patients, to −1.4 (one third >−1.88) in 3,863 patients in 1998 and −1.4 in 4,666 patients in 2001 [51‐53]. European study group data on 321 children aged 1–10 years with congenital CRF reported a mean HtSDS of −2.37. Increasing severity of CRF adversely affects growth: when the patients were divided into those with a GFR greater or less than 25 ml/min/1.73 m², the HtSDS was −1.65 and −2.79, respectively [44]. Reports of growth on dialysis vary from improvement [54], to no change [55] to declining HtSDS [56], with a worsening of nutritional status in children dialysed for more than a year [50].

The pubertal phase of rapid growth is another period when loss of height potential can occur. Early studies demonstrated that puberty was delayed, with an irreversible decline in height SDS, particularly in patients on dialysis [57, 58]. However, others have reported normal pubertal progression and growth [43, 46, 59].

Children with CRF and short stature are significantly protein-depleted for age, although not for height: 17 patients, mean age 12.9 years had total body nitrogen (TBN) and TBN/height of 54% and 63%, respectively, when predicted from age, but 100% when predicted from height. Energy and protein intakes were 65% and 172% of RDA, respectively. This suggests that chronic energy deficiency may contribute to impaired protein deposition which, in turn, may be important in the pathogenesis of growth failure in CRF [25].

It has been suggested that the ratio of the length of trunk to limb is low in CRF, suggesting a disproportionately greater effect of disease and/or treatment on spinal growth [60] although not all have found this [61].

BIA in children starting PD showed an improvement of hydration and nutrition after 6 months, although levels remained below normal, suggesting that introduction of dialysis should not be left until malnutrition has developed [62, 63]. DEXA studies of 20 PD patients receiving the RDA for energy and a daily protein intake of 144.3% and 129.9% RI at months one and six showed an increase in BMD, bone mineral content (BMC) and FFM. However, the daily protein intake showed a negative correlation with these parameters and also plasma bicarbonate, suggesting that a high protein intake may negatively affect bone mineralization and FFM by its effect on acid-base status [64].

Disturbances in plasma and intracellular AAs have been found in CRF. Muscle isoleucine and valine levels and the valine/glycine ratio were low in children with CRF who were short but had no other signs of malnutrition (normal skinfold thickness, MAC and serum proteins) [65]. Levels have been studied in ten children on CAPD. Although plasma levels of essential AAs (EAAs) were low, only muscle intracellular leucine and valine were low, whereas both plasma and intracellular levels of some non-essential AAs were high. No correlations were found between plasma and muscle AAs and indicators of nutritional status, except muscle branched-chain AA levels with BMI [66].

Because of the importance of nutrition in the first two years of life it might be expected that enteral nutrition would be most effective at this age. Most studies have therefore concentrated on this age group, and there is evidence to show that nutritional supplementation is of benefit. Eight studies have demonstrated an improvement in growth [21, 47, 78‐83], three showed an initial decline followed by stabilisation [84‐86], three showed no effect on growth [11, 87, 88] and one showed a decline in HtSDS [89]. All but one study [86] used feeds administered by nasogastric or gastrostomy tubes and aim for at least the EAR for energy and RNI for protein, with a protein supplement for dialysis.

An early study of nasogastric feeding in 14 children weighing <10 kg demonstrated a benefit on HtSDS and WtSDS in 11 [78]. Twenty-six children aged <2 years with a GFR <26 ml/min/1.73 m² were treated with a whey-based infant formula (supplemented with fat and/or carbohydrate) which provided 100% of the RNI for protein for Ht age and 100% of the EAR for energy for chronological age. HtSDS increased from −2.9 to −2.1 over 2 years [21]. A similar feed resulted in improvement in HtSDS from −2.34 at 6 months of age to −1.93 at 2 years in 24 infants with a GFR <20 ml/min/1.73 m², and from −2.17 to −1.24 in 13 infants on dialysis over a similar time-frame, although a protein supplement for dialysis was included [47]. A further study from the same centre showed an increase in HtSDS from −1.8 to −0.8 at 2 years in 20 infants on PD [79]. Three studies, each reporting the results of nasogastric feeding in three young children with CRF, have shown benefit in eight out of the nine children [80‐82]. It is important not to restrict the salt and water content of the diet in the salt-wasting polyuric infant: a feed providing just over the RDA for calories and protein diluted to 0.3–0.5 kcal/ml with additional 2–4 mEq of sodium/100 ml in 24 infants resulted in improvement of HtSDS by 1.37 SD at 1 year and 1.82 SD at 2 years [83].

Three studies have shown an initial decline followed by normalisation of growth. Twelve infants with CRF dropped to a HtSDS of −2 by 12 months of age and then stabilised at that level [84]. Decline in HtSDS was arrested in eight children <2.5 years of age after starting gastrostomy feeds [85] and stabilised after 3 months in the only study using supplementation without nasogastric or gastrostomy feeds [86]. In three studies, enteral feeds made no impact on growth: there was no change in infants with CRF [87], HD [88] or PD [11]. In one study, a decline in HtSDS occurred in 82 children <2 years of age at the start of dialysis [89].

Whether supplemental feeds benefit children over 2 years of age has been challenged [90]. Six studies have included older children [21, 80, 81, 85, 89, 91]. Of these there was an improvement in growth in three [80, 81, 91]. Dietary advice and supplements of glucose polymer and vitamins (as Ketovite) were given to 65 children aged 2–16 years with a GFR <75 ml/min/1.73 m² if their EAR and RNI, respectively, fell below 80% as assessed by annual 3-day dietary diaries. Mean HtSDS was maintained in those with a GFR of 25–75 and significantly increased in children with a GFR <25 ml/min/1.73 m². There was an increase in HtSDS and/or BMI SDS in all the patients on supplements, and change in energy intake correlated with change in HtSDS in those with a GFR <25 ml/min/1.73 m² [91]. Three children with a GFR of 20–25 ml/min/1.73 m² fed overnight by nasogastric tube for 11–16 months with increasing amounts until weight gain occurred improved their HtSDS [81], as did three children with CRF over the course of a year [80]. Two studies have shown no change in HtSDS. Nine children aged 2–5 years, treated with a whole protein enteral feed supplemented with fat and/or carbohydrate showed no change in HtSDS (−2.3 to −2.0) [21], as did seven children in given gastrostomy feeds [85]. One study has demonstrated an ongoing decline in HtSDS in children aged 2–5 years at the start of dialysis, 14 of whom were given supplements and 20 not [89].

Complications of gastrostomy are uncommon, but include gastro-colic fistulae, paraoesophageal herniae and, in children on PD, post-surgical peritonitis and an increased risk of exit site infection and dialysis catheter removal from infection, a risk that might be reduced if open rather than percutaneous surgery is used [92, 93]. After removal the track usually closes spontaneously [94]. There have been concerns that enteral tube feeding precludes the development of normal feeding behaviour [95]. However, other studies have shown that, despite long term nasogastric or gastrostomy feeding, oral feeding is resumed in the majority of children after successful transplantation [21, 96]. Positive reinforcement at feeding times using behavioural therapy techniques allowed five infants who had PD and nasogastric tube feeding initiated in the first month of life, and who showed persistent food refusal, to convert to oral feeding [97]. Our impression is that spontaneous oral intake increases with long-term tube feeding; indeed, over a period of 31 months energy intake from the feed did not increase, implying that oral intake had improved over this time to support the demonstrated growth [21]. Reports of the use of Nissen fundoplication are principally from one group [21, 47, 54, 79, 88, 92], making assessment of its effect difficult, although results of growth from this centre are good.

Serum EAAs, carnitine and total protein levels have been demonstrated to be low in CRF, particularly in patients on PD [98]. It has been suggested, therefore, that a low protein diet supplemented with EAAs might benefit growth by ensuring adequate AA intake without protein toxicity. However, results have been inconclusive. No improvement in growth was seen in seven children with severe CRF who were given half the protein RDA for height age as EAAs for 6–8 months [99]. Ten children with CRF managed for 3 years using a strict low protein diet supplemented by a mixture of the keto and amino forms of the EAAs and histidine showed a significant increase in height and weight velocity [100]. HtSDS improved from −1.93 to −1.37 over 30 months in 20 patients with a GFR <50 ml/min/1.73 m² on a diet of 0.6 g/kg of protein supplemented with ketoacids [101]. Ten children on HD given AA supplementation (0.25 g/kg body weight i.v.) with and without carnitine (25 mg/kg body weight i.v.) had no overall improvement in AA levels [102].

Excessive glucose absorption and dialysate AA and protein losses contribute to malnutrition in children on PD. It has been suggested, therefore, that using an AA dialysate might both decrease glucose load and replace AA losses. AAs are absorbed in proportion to the concentration difference between dialysate and plasma; after a 1% AA exchange in seven children on CAPD, the rise in plasma levels of AAs correlated with the ratio of the amount of AA in the bag to the basal plasma concentration. The amount of AA absorbed was 66% after 1 h, and 86% after 4 h and 6 h [103, 104].

However, there is no evidence for any long-term nutritional benefit: eight children on CAPD who had a first morning exchange of 1% AA dialysate instead of dextrose for 12–18 months had no improvement in any plasma or anthropometric parameter of nutrition; plasma urea increased. Plasma EAAs, which had been low, improved but the intracellular pool of free AAs, measured in polymorphonuclear leucocytes did not improve [105]. Two randomised prospective cross-over studies of 3 months AA or dextrose dialysate for three months have been performed, both in seven growth-retarded children either on CAPD [106] or continuous cycling PD (CCPD) [107]. In the children on CAPD there was no nutritional benefit from the AA dialysis [106]. The children on CCPD received dextrose dialysate overnight, plus a single daytime dwell of either AA dialysate or dextrose dialysate. Appetite, calorie and protein intake improved and total body nitrogen increased in half the children during AA dialysis. However, total plasma protein and albumin did not change and fasting AAs after 3 months of AA dialysis were comparable to baseline; plasma urea concentrations were higher [107]. High plasma urea may be due to inadequate protein synthesis in the absence of glucose. Ten children underwent overnight CCPD using a 3:1 ratio of glucose to AA solutions simultaneously during the night. Glucose absorption was 33.7% and AA absorption was 55.2% of the infused amount, and although plasma AA levels were high for the entire ambulatory PD (APD) treatment the plasma urea levels did not increase suggesting that the AAs were being used for protein synthesis with this regimen [108].

Disadvantages compared with glucose include cost, and reports of fluid removal are variable. However, equal amounts of urea and creatinine are removed, normoglycaemia is maintained and there are no reported adverse clinical or biochemical effects, other than a slight increase in plasma urea [106, 107, 109].

There are only four studies of IDPN during HD in children so it is difficult to draw conclusions about its effectiveness. Losses of AAs occur into the dialysate during HD and depend on their plasma concentrations and molecular weights. AAs were added to the dialysate of three children in increasing concentrations. Plasma nonessential AAs were not affected, but EAAs improved [110]. Four malnourished children on HD were given IDPN as AAs (8.5% solution), glucose (10% to 15% dextrose), and 20% fat emulsion at every dialysis session (three times a week) for 7–12 weeks. Oral intake improved and, although weight did not improve during treatment, it did so subsequently. Albumin did not change [111]. The weights of three children improved after 6 weeks of IDPN; again, albumin did not improve [112]. Nine patients who on HD had a >10% weight loss and were <90th percentile of ideal body weight received thrice weekly IDPN. In six, BMI increased in the first 5 months and PCR increased, whereas serum albumin did not change; those who did not gain weight were considered to have psychosocial causes for their malnutrition [113].

There may be cases when, despite at least 6 months of adequate nutrition, growth continues to be poor. GH may be offered in these circumstances.