Effect of enteral feeding on lipid subfractions
in children with chronic renal failureJameela A. Kari1, Vanessa Shaw1, David T. Vallance2, and Lesley Rees11 Nephrourology Unit, Great Ormond Street NHS Trust, London WC1N 1EH, UK
2 Department of Biochemistry, Royal Free Hospital and School of Medicine, Hampstead, London NW3, UK
Received August 19, 1997; received in revised form December 19, 1997; accepted January 2, 1998
Abstract. The anorexia of chronic renal failure (CRF) is
(LDL), apoprotein B (apo B) and lipoprotein(a) [Lp(a)],
frequently managed with enteral feeds using combinations
and reduced high-density lipoprotein (HDL), apo A1 and
of commercial preparations, glucose polymers and fat
apo A2 [2], all of which are believed to predispose to
emulsions. Such feeds might predispose to atherogenic
atherosclerosis. Studies in children have demonstrated
blood lipid profiles. Our aim, therefore, was to compare the
similar findings, but with a higher incidence of hypercho-
blood lipid profiles of enterally fed and non-enterally fed
children. Plasma lipid subfractions were measured in
As well as the metabolic effects of CRF, the blood lipid
37 children with CRF managed conservatively and 10
profiles of patients may be influenced by their diet. High
managed with peritoneal dialysis (PD); 10 of the children
intakes of saturated fatty acids (FAs) increase serum LDL
were tube fed, 5 of whom were on PD. Results were
and TGs. Polyunsaturated FAs reduce LDL, but at the same
compared between these groups. Overall, triglycerides
time also reduce HDL [4], which is protective against
(TGs, mean + SD) were high (2.3+1.4 mmol/l) and total
coronary heart disease [5]. Monounsaturated FAs lower
cholesterol (TC) was at the upper limit of normal
both LDL and TGs, and are associated with higher levels of
(5.2+1.5 mmol/l). Low-density lipoprotein (LDL), high-
HDL. High intakes of refined carbohydrate (CHO) increase
density lipoprotein (HDL), apoprotein A1 (apo A1), A2
(apo A2) and B (apo B), and lipoprotein (a) [Lp(a)] were
It is our policy to institute early enteral feeding in
within the normal range. There was an inverse correlation
children with CRF with a declining growth velocity. Such
between TGs and glomerular filtration rate (P = 0.0001).
feeds are based on whole-protein (and occasionally protein
There were no differences in the levels of TC, TG, LDL,
hydrolysate) complete feeds and are supplemented with
HDL, apo A1, apo A2 or Lp(a) between tube-fed and non-
glucose polymers and/or peanut oil emulsions as additional
tube-fed children. We conclude that enteral feeding does
energy sources. The children eat little or no complex CHO
or non-starch polysaccharides (fibre), so most of their in-
take of CHO is refined. We were concerned, therefore, that
Key words: Chronic renal failure ± Lipids ± Lipoproteins ±
while providing adequate nutrition for growth, tube feeding
regimens might have an adverse effect on the blood lipid
Our purpose was to study the lipid profiles of children
attending our CRF clinic who were eating a high-energy,
low-phosphate, but otherwise unrestricted diet and to
compare the results with those of a group of children who
were receiving at least 50% of their energy as an enteral
Hyperlipidaemia is one of the factors believed to be re-
sponsible for the high incidence of atherosclerosis in
chronic renal failure (CRF) [1]. Abnormalities of lipids and
lipoproteins reported in CRF include: increased triglycer-
ides (TGs), total cholesterol (TC), low-density lipoprotein
Patients. Forty-seven children (32 boys) aged 1±17 years [mean
9.3+5.2 (SD)] with CRF [defined for the purposes of this study as a
Correspondence to: J. A. Kari, Nephrourology Unit, Institute of Child
plasma creatinine concentration 4150 mmol/l (1.7 mg/dl)] were
Health and Great Ormond Street Hospital for Children, 30 Guildford
studied. Thirty-seven were managed medically, 5 of whom were ent-
erally fed. The other 10 were receiving peritoneal dialysis (PD), 5 of
ANOVA, Analysis of variance; SDS, standard deviation score; TG,
* Insignificant when adjusted for age and creatinine by analysis of
triglyceride; TC, total cholesterol; LDL, low-density lipoprotein; HDL,
high-density lipoprotein; apo A1, apoprotein A1; Lp(a), lipoprotein (a)
assessed formally: they were recommended to eat the family diet but
with an emphasis on high-energy, low-phosphate foods.
Older children were fasted overnight prior to blood sampling, but
younger children were fasted for at least 4 h (although they were
allowed water). This length of time has been used in other large studies
[6]. Serum TC, TG, LDL, HDL, apo A1, apo A2, apo B and Lp(a) and
Lipid subfractions were compared between the four patient groups
(Table 2) using analysis of variance. Analysis of covariance (AN-
COVA) was used to adjust for age and creatinine when a significant
difference was found between groups. A significant P value was
defined as 50.05. Each subject and/or their parents gave informed
consent to the study, which was approved by the local committee on
Methods. TC was measured using the cholesterol C system high-per-
formance cholesterol oxidase 4-aminophenazone method and TG by
FA, Fatty acid; trans, transpolyunsaturated FA
glyceryl phosphate oxidase 4-aminophenazone high-performance en-
zymatic colorimetric test (both Boehringer Mannheim Diagnostica)
b Dietary reference values for food energy and nutrients for the United
[7]. HDL was measured following precipitation of apo B-containing
lipoproteins and LDL was calculated using the Friedewald formula [8].
c The Dietary and Nutritional Survey of British Adults [18]
apo A1 and apo B were measured using immunoturbidimetry (Im-
d Maximum recommended 10% of total energy intake
muno, Sevenoaks, Kent, UK) [9], and Lp(a) by enzyme-linked im-
munosorbent assay (Immuno) [10]. GFR was estimated from the
clearance of 51chromium EDTA [11] or by the Schwartz formula [12].
whom were enterally fed (Table 1). The mean (range) glomerular fil-
tration rate (GFR) of the medically managed children was 15 (5±35)
ml/min per 1.73 m2. Children with nephrotic syndrome were excluded
because of its effect on lipid metabolism [5].
The mean (range) length of time on enteral feeds was 18.2 (6±32)
months. The feeds were prepared from whey-based infant formulae or
Children who were managed medically and on PD without
cows' milk protein-based adult enteral feeds, and were delivered by
enteral feeds (groups 1 and 2) were older than the enterally
pump overnight. One child received a soya-based feed because of
fed children. Medically managed children were taller, but
parental suspicion of cows' milk protein intolerance. One received a
there was no difference in body mass index among the four
whey hydrolysate to enhance stomach emptying. All feeds included a
comprehensive range of vitamins and minerals. The aim was to offer
adequate nutrition for growth, while maintaining blood chemistry
The results of the lipid subfractions are shown in Table 1.
within acceptable parameters by the provision of at least the estimated
TGs were elevated in all groups. Figure 1 illustrates the
average requirement for energy for chronological age using additional
relationship between serum TGs and method of feeding,
glucose polymers and peanut oil emulsions, and reference nutrient
plasma creatinine and treatment modality. There was an
intake for protein for height age (dietary reference values, Table 2).
overall positive correlation between TGs and creatinine
Table 2 shows the tube feed composition for protein, CHO and
FAs, and the corresponding United Kingdom recommended dietary
(r = 0.63, P 50.0001). However, there was no difference
intakes for a healthy population. Also shown are the observed dietary
among the patient groups when the results were corrected
intakes of British adults (comparable figures are not available for
for age and creatinine (ANCOVA P = 0.07). There was also
children). The dietary intake of the non-tube-fed children was not
a negative correlation between TGs and GFR in children in
However, we achieved a balanced energy intake with
our enteral formula composition, which did not differ sig-
nificantly from published recommendations for dietary in-
take for a normal population. Indeed, the total fat intake,
and particularly the saturated fat intake, was less in the
tube-fed children than in a normal adult population eating
an unrestricted diet (Table 2). Despite a CHO intake
comprised mainly of refined sugars rather than a mixture of
sugars, starch and fibre, there was no adverse effect on
Although the children were under regular dietary re-
view, we were not able to fully analyse the intakes of those
who were not tube fed because there are only a few foods
that have been analysed for their FA composition. As these
children were eating a relatively free diet rather than re-
ceiving a precisely prescribed enteral feed, it is possible
that their diet was less balanced than that of the tube-fed
It might be expected that the glucose load during PD
Fig. 1. Effect of method of feeding, plasma creatinine and treatment
would have an adverse effect on plasma lipids, resulting in
modality on serum triglycerides. EF, Enteral feeding; PD, peritoneal
hypertriglyceridaemia and decreased HDL [15]. Although
the patients on PD were the only group to have levels of
atherogenic lipids above the normal range, those on PD
group 1 (P = 0.0001), even when age was taken into con-
who were enterally fed did not. One possible explanation is
that the enteral feed was beneficial to the plasma lipids, but
Children managed by PD (group 3) were the only group
the numbers are too small to draw any conclusions.
with levels of the atherogenic lipids TC, LDL and apo B
All the children had high TG levels. The importance of
that were above the normal range, although TC levels were
TGs in atherogenesis is controversial, but recently it has
at the upper limit of normal in the other groups. However,
been found that hypertriglyceridaemia is associated with a
only apo B was significantly higher in children on PD when
high proportion of small, dense LDL, which is now rec-
adjusted for age and creatinine (ANCOVA P = 0.01). No
ognised to be particularly atherogenic. Although overall the
other lipid subfractions were abnormal in any other group.
lipid fractions that we measured were at acceptable levels,
There was no correlation between GFR and any lipid
we did not study those subfractions that are now recognised
In conclusion, this small study would suggest that an
enteral feeding regimen providing an appropriate energy
intake with a balanced profile of fat and CHO can be ad-
ministered to children with CRF who are both con-
servatively managed and on PD, without detrimentally af-
In this study we have confirmed previous reports that hy-
pertriglyceridaemia correlates inversely with GFR in CRF,
and that TC is at the upper limit of the normal range [2, 3].
Acknowledgements. We acknowledge Dr. Sarah E. Lederman and Dr.
Our patients did not, however, have abnormalities of
Judith Taylor for their help in recruiting patients from their clinics, and
apo A1, apo A2, apo B and Lp(a), which have been found
Dr. Richard Morris for his help with the statistics.
in some, although not all, previous studies [2, 3]. Angio-
graphic studies have shown that low apo A and high apo B
(or their ratio) may be better indicators of future coronary
heart disease than HDL levels [5]. HDL, high levels of
which protect against vascular disease, was reduced in
previous studies [2, 3], but was also normal in our patients.
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Literature abstractsNephrol Dial Transplant (1997) 12: 1668±1671
Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants
G. Filler, R. Grygas, I. Mai, H. J. Stolpe, C. Greiner, S. Bauer, and J. H. H. Ehrich
Background. Only few data exist on pharmacokinetics of tacrolimus
At the time of switch, median serum creatinine was 234+82 mmol/l
and 6 months after switch 201+99 mmol/l. All grafts are still func-
Patients. In 1995 and 1996, 14 children (mean age 13 years, range
tioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range
5±23 years) received tacrolimus after renal transplantation; 10 of these
0.036 ±0.30 mg/kg). Mean trough level was 7.1+2.6 ng/ml in the
after biopsy-proven steroid-resistant rejection (2 with vascular rejec-
morning and 6.5+2.0 ng/ml in the evening. Median time of maximum
tion), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one
concentration (tmax) was 120 min after application, and the mean
for untreatable gingival hyperplasia on CsA, and one child was treated
maximum concentration (Cmax) was 15.2+6.7 ng/ml. Mean area under
primarily after transplantation because of severe liver involvement in
the curve (AUC) was 104+33 ng * h/ml, with a range from 65 to
nephronophthisis. Pharmacokinetic investigations were performed
169 ng * h/ml. No patient had unsatisfactorily low trough levels during
after establishing a stable maintenance dose with trough levels in the
the study. There was only a weak but significant (P 50.05) correlation
between dose per kg body weight and AUC and, as expected, an ex-
Results. Mean follow-up time was 6 months (range 3±25 months).
cellent correlation (r = 0.73, P 50.001) between AUC and trough
Eleven patients are still on tacrolimus. Two were discontinued because
of severe aggravation of chronic persistent hepatitis C (one of them
Conclusion. Because of interindividual variation between patients,
also developed diabetes mellitus), and one patient was subsequently
therapeutic drug monitoring of tacrolimus is mandatory. In this study, a
switched to conventional immunosuppression because of tacrolimus-
daily dose of 0.15 mg/kg was sufficient in most patients. We rec-
associated nephrotoxicity. All tacrolimus levels were measured by a
ommend the performance of at least one pharmacokinetic study after
modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity.
establishing stable FK 506 trough levels to ascertain a safe profile.
Immunity of diphtheria and tetanus in a young population on a dialysis regimen
Luciana Ghio, Chiara Pedrazzi, Baroukh M. Assael, Alfonso Panuccio, Marina Foti, and Alberto Edefonti
In 54 transplant recipients diphtheria and tetanus immunity after pri-
bodies developed in the transplant recipients and dialysis patients but
mary vaccination was significantly lower than in 57 control subject
no diphtheria antibodies developed in two transplant recipients. No
and 35 patients on a dialysis regimen. After a booster, tetanus anti-
adverse reactions, including acute graft rejection episodes, occurred.
DEPRESSION DURING THE TRANSITION TO MENOPAUSE: A Guide for Patients and Families David A. Kahn, MD, Margaret L. Moline, PhD, Ruth W. Ross, MA, Lori L. Altshuler, MD, and Lee S. Cohen, MD www.womensmentalhealth.org It is a common myth that as women enter the menopausal years, it is “normal” to feel depressed. Serious depression, however, should never be viewed as a “normal
Secretary: Joy Woodward P O Box 53219, Kenilworth 7745, South Africa. Editorial Team: Mick Dower with Coen Calitz, Johan Schoombee and John Winter (The views expressed in this publication do not necessarily reflect the views of the Cape Cliivia Club) The year end meeting was held at Kirstenbosch, followed by the traditional braai. Over a 100 members attended and enjoyed Johan Scho