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Nutrition
The Role of Growth Hormone in the Treatment of Malnutrition in
Adult Patients on Chronic Haemodialysis
a report by
Anne-Marie Kappelgaard,
1
Martin Lange
2
and Meguid El Nahas
3
1. Novo Nordisk A/S, Copenhagen; 2. Novo Nordisk Inc., Princeton, New Jersey; 3. Sheffield Kidney Institute, Northern General Hospital, Sheffield
Magnitude of the Epidemiological Problem
Figure 1: Kaplan-Meier Survival Curves for Patients
Malnutrition in chronic haemodialysis patients is estimated to occur in
1.0
12–40% of patients.
1,2
Various surveys among chronic haemodialysis
Normal
or peritoneal dialysis patients suggest that the overall prevalence of
0.8
malnutrition is 25–50%.
2–9
Chronic kidney disease (CKD) is an
emerging significant public health problem. In the UK, the incidence of
al
0.6
end-stage renal disease (ESRD) requiring dialysis or transplantation
Mild
Surviv
increased from 67 per million people in the early 1990s to 108 per
0.4
million by 2005.
10
Indeed, the increasing incidence and prevalence of
CKD and ESRD is a global trend. For example, the number of patients
p<0.001
Moderate
0.2
undergoing renal replacement therapy (RRT) during the last 10 years in
the US has doubled, with in excess of 450,000 patients currently
0.0
receiving treatment.
11
0 6 12 18 24 30 36
Months
Outlook for Patients on Maintenance Haemodialysis
The annual mortality rate for maintenance haemodialysis (MHD) patients
Normal (n=46), mild malnutrition (n=65) and moderate to severe malnutrition (n=17)
assessed by subjective global nutritional assessment.
is excessively high, estimated at 21% in the US in 1998, despite marked
Source: Qureshi et al.
19
advances in management strategies.
12
Five-year survival data indicate that
fewer than 33% of MHD patients are still alive five years after initiating malnutrition evaluated by SGNA in non-survivors (85%) compared
chronic dialysis treatment.
11,12
Overall, the US mortality rate exceeds that with survivors (44%), more marked anthropometric signs of
of EU countries; this may reflect the case mix with a much higher malnutrition, e.g. lower bodyweight and less muscle mass, were
prevalence of patients with diabetic nephropathy on dialysis in the US; evident in the non-survivors. Indeed, evidence of malnutrition,
these patients are known to have higher morbidity and mortality rates. evaluated by SGNA, was a significant predictor of mortality (p<0.001)
(see Figure 1).
19
The major cause of morbidity in patients on haemodialysis is
cardiovascular disease (CVD), which accounts for nearly 50% of all Moreover, in an analysis of 12,000 patients receiving haemodialysis
deaths and 30% of all hospitalisations.
13
Indeed, the annual mortality therapy, Lowrie et al.
20
demonstrated a progressive increase in the
rate due to CVD is 10–20-fold higher for patients on haemodialysis adjusted risk ratio for mortality as serum albumin levels decreased.
than for the general population, even after adjustment for age, gender, Further evidence of the close association between malnutrition in MHD
race and presence of other co-morbid conditions such as diabetes.
14
patients and increased risk of mortality was recently borne out in a
five-year retrospective observational study, which found that low body
How Does Malnutrition Impact on the Prognosis of mass index (BMI) (<19kg/m
2
) and hypoalbuminaemia were strong
Haemodialysis Patients? predictors of death in 187 haemodialysis patients.
21
In recent years, the link among malnutrition, inflammation, CVD and
increased mortality in MHD patients has been recognised.
15
Numerous Therefore, it is evident from this discussion that malnutrition in
reports focus on the association between hypoalbuminaemia and poor haemodialysis patients acts an independent causative factor for mortality,
nutritional status assessed by means of anthropometry, subjective and that timely correction of malnutrition may improve prognosis in this
global nutritional assessment (SNGA) or total body nitrogen and clinical patient population. Malnutrition may also act in a multiplier fashion to
outcome. These reports support the hypothesis that malnutrition may increase cardiovascular morbidity and mortality in this population.
cause or contribute to the high rates of morbidity and mortality, as well
as decreased health-related quality of life (HRQoL).
16–18
Pathogenesis of Malnutrition in Haemodialysis Patients
The pathogenesis of malnutrition in MHD patients is multifactorial. Of
In a cross-sectional study of 128 haemodialysis patients (mean age 61 the factors that appear to contribute to the net body protein
years), malnutrition – as assessed by SNGA and anthropometric and catabolism in this clinical population, inadequate dietary intake of
biochemical measurements – was more prevalent at the start of the energy and/or protein, uraemic milieu with resistance to anabolic
study in patients who subsequently died during the 36-month follow- hormones such as insulin and growth hormone, intercurrent illness
up period than in survivors.
19
As well as a higher prevalence of and amino acid loss through the dialysis membrane are likely to be
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