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Nutrition and Hypoalbuminuria
The Ability of Albumin to Predict Outcome in Haemodialysis Patients
a report by
Kamyar Kalantar-Zadeh
Associate Professor of Medicine and Paediatrics and Epidemiology, David Geffen School of Medicine, University of California at Los Angeles (UCLA), and
Director of Off-Campus Dialysis Expansion and Epidemiology, Division of Nephrology and Hypertension, Harbor-UCLA
Among haemodialysis (HD) patients in the US, mortality rates exceed interstitial space. The main functions of albumin include maintenance
20% per year,
1
with the age-adjusted death rate estimated at five- to of colloid osmotic pressure, binding and transport, free radical
10-fold higher than that of the general population.
2
Indeed, during the scavenging, inhibition of platelet function and antithrombotic effects
first few months after the initiation of HD mortality rates may even and effects on vascular permeability. As albumin has a relatively low
exceed this figure, and it is reported that 6% of all new patients die molecular weight compared with other major intravascular proteins, it
within the first 90 days of the initiation of HD treatment.
3
comprises approximately 75–80% of the colloid osmotic pressure.
Cardiovascular disease (CVD) is the leading cause of morbidity among Does Hypoalbuminuria Have a Role in the
dialysis patients, accounting for approximately 50% of deaths and Increased Morbidity and Mortality Observed in
30% of hospitalisations.
4
Annual CVD mortality is 10- to 20-fold Haemodialysis Patients?
higher for patients with end-stage renal disease (ESRD) than for the Among markers of the malnutrition–inflammation complex, there has
general population, even after adjustment for age, ethnicity, gender been extensive interest in the role of hypoalbuminuria. Low albumin
and the presence of diabetes mellitus.
5
Furthermore, the rates of CVD levels are more prevalent among HD patients than in the general
in patients undergoing HD aged between 45 and 64 years are more population,
19–23
and the prevalence of reduced albumin levels increases
than three times greater, at 181 per 1,000 patient-years compared in patients with chronic kidney disease (CKD) during the progression
with 50 per 1,000 patient-years in the general population.
2
The to ESRD.
24
increased CVD morbidity and mortality are attributed to the presence
of accelerated atherosclerosis leading to peripheral and cerebral Several studies have implicated hypoalbuminuria as a powerful
vascular and cardiac ischaemic disease.
6
Observational studies among predictor of mortality.
25
In other studies, reduced serum albumin
prevalent HD patients have identified a number of patient levels and inflammation were found to predict protein–energy
characteristics that are associated with greater mortality risk, including malnutrition, CVD and poor clinical outcome in patients with
traditional risk factors such as older age and non-traditional risk ESRD.
26–29
In 176 patients with ESRD, multivariate analysis showed
factors such as anaemia,
7
low serum albumin levels
8–12
and increased that mortality was predicted by serum albumin levels (relative risk
C-reactive protein (CRP) and interleukin-6 levels.
13–15
[RR] 2.9, 95% confidence interval [CI] 1.5–5.3; p<0.01).
14
The results
also showed that the RR associated with the lowest quartiles of
A large multicentre clinical trial failed to show any survival advantage serum albumin was greater than for the upper quartile. Similar to
of increasing the dialysis dose or the use of different dialysis these findings, Lowrie et al.
25
showed that serum albumin
membranes in HD patients.
16
Another large randomised controlled trial concentrations between 3.5 and 4.0g/dl increased the relative risk of
failed to show any survival improvement of statins in diabetic HD death two-fold, and albumin concentrations between 3.0 and
patients.
17
Furthermore, despite ongoing efforts at treating 3.5g/dl increased the mortality risk by a factor of five compared with
conventional CVD risk factors in HD patients, including obesity,
hypertension, hypercholesterolaemia and hyperhomocysteinaemia, no
substantial improvement in survival in these individuals has been
Kamyar Kalantar-Zadeh is an Associate Professor of Medicine
and Paediatrics and Epidemiology at the David Geffen School of
reported. Indeed, epidemiological studies have indicated paradoxically
Medicine, University of California at Los Angeles (UCLA), and
inverse associations between classic CVD risk factors and death in HD Director of the Dialysis Expansion Program and Epidemiology at
patients, a phenomenon that has been referred to as ‘reverse
Harbor-UCLA Medical Center in Southern California. He has
received many awards, including the 2007 annual National
epidemiology’.
18
The malnutrition–inflammation complex syndrome,
Kidney Foundation (NKF) Joel D Kopple award in renal
comprising both protein–energy malnutrition and inflammation, has
nutrition, and grants from organisations such as the National
been implicated as the most powerful indicator of death in HD patients
Institutes of Health (NIH), the NKF and the American Heart
Association (AHA). He has been a Council or Committee Member of numerous associations,
and a key factor in the reverse epidemiology.
18
including the American Society of Nephrology (ASN), the NKF and the International Society of
Renal Nutrition and Metabolism (ISRNM), and has served as a member of the Editorial Board of
several journals. Dr Kalantar has authored or co-authored more than 100 original research papers,
Albumin
reviews and editorials and close to 200 abstracts. He lectures frequently on non-traditional
Albumin is the most abundant circulating plasma protein in the body cardiovascular risk factors in patients with chronic kidney disease, including malnutrition–
and has a half-life in serum of approximately 20 days. It is synthesised
inflammation syndrome, obesity, mineral and bone disorders, anaemia and acid-base homeostasis.
Dr Kalantar received his MD from the University of Bonn in Germany, and a Master’s degree in
by the liver and predominantly catabolised by the vascular
Public Health and a PhD in epidemiology from the University of California in Berkeley.
endothelium. Of the total albumin pool of 4–5g/kg bodyweight,
E: kamkal@ucla.edu
40–45% is in the intravascular space and the other 55–60% is in the
© TOUCH BRIEFINGS 2007 37
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