There are very few controlled trials, so recommendations are based on the evidence available. Some, but not all, reports have been able to establish a relationship between nutritional intake and growth. Growth velocity correlated positively with energy intake in 17 children with CRF [
75], and with energy but not protein intake in 15 children on CAPD [
76]. Growth velocity was inversely correlated with dietary protein intake and positively correlated with caloric intake both before the initiation of rhGH therapy and after the first year of treatment in 31 children on dialysis [
77]. The advantage of input from a dietitian has been specifically demonstrated in two studies [
11,
40], but it is likely that in all studies dietetic input was necessary.
Dietary supplements
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 m
2 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 m
2, 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 m
2 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 m
2. 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 m
2 [
91]. Three children with a GFR of 20–25 ml/min/1.73 m
2 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.
Essential aminoacid (EAA) supplements
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 m
2 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].
Amino acid-containing peritoneal dialysis solutions
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].
Intradialytic parenteral nutrition (IDPN)
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].