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Anaemia Management
Effect of Long-term Epoetin Treatment on Serum Levels of High-density Lipoprotein
(HDL) and HDL-associated Enzymes in Patients with Chronic Kidney Disease
a report by
Alexandros D Tselepis
1
and Kostas C Siamopoulos
2
1. Professor of Biochemistry/Clinical Chemistry, Department of Biochemistry, University of Ioannina;
2. Professor of Medicine/Nephrology, Department of Internal Medicine, University of Ioannina
Lipid Abnormalities in Chronic Kidney Disease an independent risk factor for CAD and premature atherosclerosis
Patients with chronic kidney disease (CKD) are at higher risk of regardless of serum LDL cholesterol and triglyceride levels.
6
HDL is a
cardiovascular disease (CAD) than subjects in the general population. An potent antiatherogenic lipoprotein and recent observational, biological
increased prevalence of both CAD morbidity and mortality is evident at all and clinical evidence strongly suggests that HDL is a promising target
ages among patients with CKD.
1,2
Traditional risk factors (such as of therapeutic intervention.
7,8
The cardioprotective effects of HDL have
dyslipidaemia, diabetes and hypertension) as well as non-traditional risk been attributed to its role in reverse cholesterol transport, its beneficial
factors (including oxidant stress, inflammation and malnutrition, and also effects on endothelium and its antioxidant and anti-inflammatory
disturbances of serum Ca
2+
and PO
3-
4
metabolism) associated with CKD, activities.
8
Significant in the antiatherogenic effects of HDL are two
may further increase CAD risk in these patients.
1,3
Dyslipidaemia is enzymes assosciated with it: platelet-activating factor (PAF)-
common in CKD patients and alterations in serum lipid profile vary widely acetylhydrolase (PAF-AH) and paraoxonase-1 (PON1).
9,10
In this article
depending on the level of kidney function and the degree of proteinuria.
4,5
we discuss the results of recent studies regarding the effects of long-
Prior to developing severe CKD, patients frequently have elevated serum term epoetin treatment on serum levels of HDL cholesterol
total and low-density lipoprotein (LDL) cholesterol levels. As CKD advances and on the HDL-associated enzymes PAF-AH and PON1 in patients
to kidney failure, the prevalence of high LDL cholesterol levels decreases. with CKD.
The classic lipid profile of late-stage CKD includes increased triglyceride
levels, moderately elevated or normal LDL cholesterol levels and low high- Effect of Epoetin on Serum High-density
density lipoprotein (HDL) cholesterol levels.
4,5
Lipoprotein Cholesterol Levels
Recombinant human erythropoietin (epoetin) is widely used to correct
The reduction in serum levels of HDL cholesterol represents an anaemia associated with CKD.
11
Previous studies clearly document the
important lipoprotein abnormality in patients with decreased renal beneficial effects of epoetin on patients with CKD, not only in
function.
5
Low levels of HDL cholesterol have also been shown to be correcting anaemia: various other beneficial effects were also
reported.
12
Studies attempting to investigate whether long-term
epoetin administration in CKD patients has an effect on lipid profiles
Alexandros D Tselepis is a Professor of Biochemistry/
Clinical Chemistry in the Department of Biochemistry,
of patients provided inconsistent results. These studies focused on
University of Ioannina, Greece. His main scientific
haemodialysis patients and showed that epoetin treatment either does
interests are the pathophysiology of atherosclerosis,
not affect serum lipid levels
13
or significantly improves the lipid profile
especially the role of modified lipoproteins, inflammation
and oxidative stress in the development and progression by decreasing the serum levels of triglycerides, total cholesterol and
of atherosclerotic plaque. Professor Tselepis is a member
LDL cholesterol.
14,15
Importantly, it was demonstrated that the
of the Editorial Boards of four international journals,
President of the Hellenic Society for Free Radical and
beneficial effect on lipid profile may be balanced and overcome in
Oxidative Stress, a Board Member of the Hellenic Society some patients who show exaggerated increase in food intake.
15
of Atherosclerosis and a Fellow of several national and international scientific societies.
Studies on the effect of long-term epoetin administration on serum
He has participated in several European Research Networks and is a member of the Expert
Group on Structural Medicine II/Lipidomics of the European Science Foundation (ESF).
HDL cholesterol levels in CKD patients have mainly concentrated on
Professor Tselepis obtained his MD from the School of Medicine, University of Ioannina, in
dialysis patients
13,16
and have also provided inconsistent results.
1992, having obtained his PhD in biochemistry in 1986 from the University of Ioannina.
He graduated in pharmacy from the School of Pharmacy, University of Thessaloniki,
Furthermore, in a prospective, randomised, multicentre study
Greece, in 1979. performed on pre-dialysis patients, it was shown that long-term
E: atselep@uoi.gr
epoetin administration increases HDL cholesterol levels only in patient
groups treated with keto acids.
17
Kostas C Siamopoulos is a Professor of
Medicine/Nephrology in the Department of Internal
Medicine, University of Ioannina, Greece. His main recent
In a randomised controlled trial we had previously demonstrated that
scientific interests are the pathophysiology and treatment
early initiation of epoetin therapy in pre-dialysis patients with CKD stages
of chronic kidney disease with emphasis on the delay of
3 and 4 and non-severe anaemia significantly slows the progression of
renal failure. He is a member of several scientific societies
of nephrology and hypertension and several European renal disease and delays the initiation of renal replacement therapy,
18
renal research groups. Professor Siamopoulos is a
while preserving erythrocyte defence mechanisms against oxidative
reviewer in national and international journals and a
member of the Editorial Board of the American Journal of Nephrology. He also participated
stress.
19
In a nested substudy performed on the same patients we
in a number of international studies related to hypertension and diabetic nephropathy. He observed a significant increase in HDL cholesterol levels in patients
obtained his MD from the School of Medicine, University of Athens.
receiving epoetin (see Figure 1A), whereas there was no effect of epoetin
on the other lipid parameters. Consequently, there was a significant
34 © TOUCH BRIEFINGS 2007