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The Role of Growth Hormone in the Treatment of Malnutrition in Adult Patients on Chronic Haemodialysis
Figure 2: Urea Kinetics
30 9 1.4
8
25
1.2
7
1
20 6
U
N (mmol/l)
5
0.8
15
c
rate (g/kg/24h)
4
0.6
10 3
c
ataboli
0.4
Pre-dialysis B
Urea generation (g/24h)
2
5
1
Protein
0.2
0 0 0
Control Week 1 Week 2 Control Week 1 Week 2 Control Week 1 Week 2
Blood urea nitrogen Urea generation Protein catabolic rate
Blood urea nitrogen (BUN), urea generation and protein catabolic rate during an initial one-week control period and a subsequent two-week period of growth hormone (5 or 10mg)
administration. Growth hormone was administered immediately after haemodialysis three times weekly. Patients served as their own controls. Data are mean ± standard error (SE).
Source: Ziegler et al.
52
among the most important.
22,23
Crucially, the presence and extent of Of the factors that have been identified as predictors of poor outcome in
chronic inflammation is a potential catabolic factor that worsens the patients with ESRD, protein catabolism leading to uraemic malnutrition is
nutritional status of ESRD patients.
24,25
important because it is potentially reversibile.
Can Improvements in Nutrition Lead to a Decrease in Role of Growth Hormone
Mortality and Morbidity? In addition to the well-documented effects of growth hormone (GH) on
In a retrospective evaluation of 58,000 patients on chronic linear growth in children, GH promotes nitrogen retention and increases
haemodialysis, improvements in serum albumin levels of 2g/l over a six- lean body mass (LBM) in normal subjects and in GH-deficient
month period were associated with improved survival rates during the patients.
30–33
GH also has clinically relevant beneficial effects on
inflammation, cardiovascular status, lipid profile, erythropoietin (EPO)
synthesis and erythropoieses, as well as on bone turnover in a number
of patient populations.
34–37
Despite the range of available
Despite the fact that MHD patients have normal or even slightly
elevated GH levels, and sometimes even normal insulin-like growth
therapies, most are of limited efficacy
factor (IGF-I) levels, resistance to the anabolic actions of GH and
and are not without side effects or
IGF-I have been described.
38
Low free serum levels of IGF-I are
suggested to result from high levels of IGF-I binding proteins. Low IGF-
matters concerning compliance.
I levels in the HD population have also been linked to malnutrition.
39
Data from animal models indicate that uraemia may cause resistance to
IGF-I.
40,41
Therefore, the rationale for treating MHD patients with GH
was the use of pharmacological GH doses in an attempt to overcome
GH resistance and promote protein anabolism.
following 18 months.
26,27
Likewise, in a large cohort study involving
15,287 patients receiving long-term haemodialysis, those achieving In uraemic animal models, recombinant human GH administered at
clinical measure targets – including serum albumin values of 40g/l or pharmacological doses induced a net anabolic action and improved
higher – were associated with a decrease in hospitalisation and food utilisation.
42,43
Recombinant human GH administered to healthy
mortality rates.
28
In this context, changes in serum albumin may have subjects and in hospital patients with normal renal function over a
reflected improved nutrition and/or reduction in its inflammatory drive. wide range of nutrient intakes is associated with improved nitrogen
balance and other protein anabolic effects.
39,44,45
Options for Treating Malnutrition
Several therapeutic options are available to improve malnutrition in Clinical Studies on the Use of Growth Hormone in Adult
MHD patients. They include dialytic, nutritional and drug interventions Patients on Chronic Haemodialysis
such as treatment of reversible causes of anorexia, increased nutrient Several small-scale, short-term clinical studies have demonstrated a net
supply, correction of metabolic acidosis, use of anabolic hormones, anabolic action of pharmacological dose of GH inducing a positive
anti-inflammatory therapies and treatment of co-morbid illnesses.
29
protein balance in MHD patients.
46–52
Ziegler et al.
52
reported a
significant reduction (20–25%; p<0.01) in blood urea nitrogen (BUN)
Despite the range of available therapies, most are of limited efficacy values from control values during a two-week GH (5 and 10mg)
and are not without side effects or matters concerning compliance. treatment period. Similarly urea kinetic modelling showed that urea
Consequently, malnutrition and a high mortality rate remain a generation and the protein catabolic rate were significantly lower
challenge in the management of this patient population. during GH administration than during the control week (see Figure 2).
EUROPEAN RENAL DISEASE 2007 71
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