Review Article: Dyslipidaemia, Lipid Oxidation, And Free Radicals In Diabetic Nephropathy: An Overview
AbstractDiabetes mellitus has assumed an epidemics proportion in most parts of the world including the developing countries, and one of its ominous complications, diabetic nephropathy represents today the leading cause of end-stage renal disease in USA, Europe, and Japan. However, there is a paucity of records of the magnitude in Africa and some parts of Asia.
The pathophysiology of diabetic nephropathy can be viewed as a sequence of events evolving in a stepwise pattern starting with endothelial cell dysfunction (ECD) and end in end-stage renal failure ( Fig 1).
Majority of diabetic associated metabolic syndromes, especially dyslipidaemia predispose to ECD, and therefore diabetic nephropathy. Diabetes mellitus is frequently associated with dyslipidaemia evidenced by high prevalence rate that range from 16%-40%, and chronically elevated level of plasma lipids, low-density lipoprotein in particular, leads to modification of structures, importantly through oxidative processes. Renal tissue particularly in diabetes milieu has been suggested to accelerate oxidation of lipids and lipoproteins.
Lipids, particularly LDL oxidation are initiated by reactive oxygen species (ROS), but the rate of oxidation is usually suppressed in plasma by endogenous antioxidants. However, after ECD the lipid is sequested from the antioxidant milieu mainly in the glomerular wall intima and this accelerates its oxidation. The precise mechanism by which oxidized LDL promotes the development of ECD and diabetic nephropathy lesions remains to be elucidated. However, several lines of evidence suggest that oxidized LDL exerts many biological effects that may contribute to the initiation and progression of diabetic nephropathy. Therefore, oxidized lipids are a key early step in the pathogenesis of diabetic nephropathy.
Importantly, trials of antioxidants in diseases where free radicals play an important role in their pathogenesis reveal satisfactory results,but results of trials of antioxidants in the management of chronic diabetic complications are inconclusive.Nonetheless, most, if not all, were instituted after a long-standing hyperlipidaemia and therefore oxidative stress, with already developed complications.
This paper provides an overview on the involvement of oxidized lipids, lipoproteins and reactive oxygen species in initiation and progression of diabetic nephropathy. This will stimulate nephrologists to plan instituting the use of antioxidants as preventive measures at the diagnosis of the disease or even in those with impaired glucose tolerance. In addition, the use of lipid lowering agents in diabetics with hyperlipidaemia could become an additional cost-effective adjunct of the anti diabetic regimen.
Highland Medical Research Journal Vol.2(1) 2004: 1-7