Increasing evidence points to the fact that plasma
HDL cholesterol levels do not always accurately predict HDL function including reverse
cholesterol transport and modulation of
inflammation. These functions appear to have evolved as part of our innate immune system. HDL is anti inflammatory in healthy individuals in the absence of systemic oxidative stress and
inflammation. In those with
chronic illnesses such as
renal failure however, HDL may become dysfunctional and actually promote
inflammation. HDL may be thought of as a shuttle whose size can be estimated by
HDL cholesterol levels. The content of the shuttle however, is what determines the anti inflammatory potential of HDL and can change from one, supporting reverse
cholesterol transport to one that is less efficient in carrying out this function.
Chronic kidney disease (CKD), and inflammatory disorder, is associated with development of accelerated
atherosclerosis and premature death from
coronary artery disease (CAD). Patients with CKD present with
dyslipidemia, oxidative stress and systemic
inflammation. Among the abnormalities in lipid metabolism in these patients is reduced levels and protective capacity of HDL. Recent studies have shown that HDL from patients with
end stage renal disease is not capable of preventing
LDL oxidation and that it induces monocyte migration in artery wall model systems. Treatment of plasma from these patients, with an HDL mimetic
peptide improved the anti inflammatory properties of patient's HDL and made
LDL more resistant to oxidative modification. Animal models of
kidney disease also had proinflammatory HDL and treatment with the
peptide mimetic improved markers of
inflammation and anti inflammatory capacity of HDL. Whether HDL mimetic
peptides will have therapeutic benefit in patients with
renal failure will have to be determined in clinical studies.