Feldt-Rasmussen_edit.qxp 13/2/08 10:51 Page 47
Nutrition and Hypoalbuminuria
Figure 1: End-stage Renal Disease, US 1980–2004 –
Short-term GH treatment also increased EPO synthesis. These findings
Prevalence Counts and Adjusted Rates by Primary Diagnosis
1
indicate a potential beneficial effect of GH treatment on mortality and
morbidity in these patients. However, the studies were performed on
Counts Rates
200 600 small patient numbers (11 patients in each treatment arm), most were
Diabetes carried out over short periods of time and only four were randomised
150
Hypertension
450
Glomerulonephritis
controlled trials.
34,36,37,45
Cystic kidney
100 300
A phase II dose-finding, clinical, proof-of-concept trial was conducted in
the period 2003–2005.
51
The trial was a 26-week, randomised, double-
50 150
Rate per million population
blind, parallel-group, placebo-controlled, multicentre trial investigating
Number of patients (in thousands)
the effects of three different doses (20, 35 and 50µg/kg/day) of
0 0
Norditropin (rhGH Novo Nordisk A/S) on nutritional status in adult
80 84 88 92 96 00 04 80 84 88 92 96 00 04
patients on chronic dialysis with serum albumin and LBM as primary end-
Year Year
points. A total of 139 subjects without diabetes were randomised and the
Figure 2: Risk of Death Is Increasing with Decreasing Albumin
trial resulted in the following conclusions:
Levels in 20,000 patients – Normal Reference >3.8g/dl
10
• GH treatment appears to be a safe and effective treatment to improve
20
nutritional status in adult patients on chronic dialysis.
18
• Six months of treatment with GH led to statistically significant gains in
16
LBM compared with placebo. This positive treatment effect was
14
observed for all three GH dose groups evaluated in the trial and
12 remained consistent on the per protocol (PP) analysis set and other
10 exploratory analyses.
8 •A positive trend towards increasing albumin levels was observed
Relative risk of death (%) 6 compared with placebo (p=0.06).
4 • Significant beneficial changes in other (cardiovascular) biomarkers of
2 mortality – homocysteine, transferrin, high-density lipoprotein (HDL) –
0
as well as HRQoL were observed.
>4.5 4.0–4.5 3.5–4.0 3.0–3.4 2.5–3.0 <2.5
• GH treatment was well tolerated and safe.
Serum albumin (g/dl)
• Based on these observations, as well as on the well-known correlation
of albumin and LBM with mortality and morbidity, GH treatment in
stature in children with chronic renal insufficiency. In these patient groups, malnourished adult patients on chronic dialysis is likely also to
GH has proved to be both a safe and efficacious treatment. decrease mortality and morbidity and to increase HRQoL.
Apart from its obvious effect on linear growth in children, GH exerts Safety Aspects of Treatment with Growth Hormone
physiological effects on systemic and organ-specific metabolism and Treatment with rhGH has been proved to be safe in both children and
maintenance. GH has important metabolic effects as it directs protein adults. Side effects are typically related to fluid retention and are
homeostasis towards anabolism, and has also been proved to inhibit reversible upon dose reduction. In the initial studies in adults
protein degradation and to stimulate de novo protein synthesis.
22–24
GH performed in the early 1990s, supra-physiological doses of GH were
has further been demonstrated to modify inflammation, improve used in GH-deficient patients without marked side effects,
52
most
cardiovascular status and lipid profile and increase erythropoietin (EPO) being related to fluid retention. Studies in children with chronic renal
synthesis and erythropoiesis in diverse patient populations.
25–29
insufficiency, aiming at improving stature, have also shown that
treatment with GH is safe.
53,54
Growth Hormone Effects in Adult Patients on
Chronic Dialysis Clinical trials do not support the use of GH in the treatment of seriously
Patients on chronic dialysis are considered to be GH-resistant with low ill intensive care unit (ICU) patients. Indeed, in a large trial of acute ICU
or normal insulin-like growth factor-I (IGF-I) levels despite rather high patients (n=532) treated with GH at a dose of 100g/kg/day, a higher
endogenous GH levels. In addition, these patients seem to have low mortality of 40% (n=108) was found in the GH-treated group
free (bio-active) IGF-I levels due to high levels of IGF-binding proteins. compared with 20% (n=51) in the placebo-treated group (p=0.001).
55
From animal models it is suggested that uraemic patients also suffer However, previous trials with smaller numbers of subjects but
from actual IGF-I resistance.
30,31
Based on these observations, as well comparable doses have demonstrated beneficial or no effects of GH
as on the above-mentioned abundant – in particular anabolic – effects treatment in ICU patients.
56,57
of GH, the effect of GH treatment in adult patients on chronic dialysis
has been investigated in a number of small studies.
32–50
Overall, GH GH has both direct and indirect effects on glucose homeostasis, and
was shown to reduce protein catabolism, increase muscle mass and treatment with GH may have an impact on glucose metabolism that can
strength and improve HRQoL. Furthermore, GH treatment in these be measured clinically. One trial with four weeks of treatment with GH in
patients improved nutritional markers that are inversely related to dialysis patients resulted in an initial increase in blood glucose, reaching
mortality in dialysis patients – i.e. serum albumin, transferrin or urea. steady state after two weeks.
45
Another trial of six months duration
47 EUROPEAN RENAL DISEASE 2007
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