Hyperlipidemia and
lipoprotein abnormalities are often encountered in patients with
nephrotic syndrome or
chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of
lipid deposition in renal tissue and the role of
lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular
lipid deposition is observed in
genetic diseases such as
Fabry's disease,
lecithin:cholesterol acyltransferase activity (
LCAT) deficiency and
arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as
nephrotic syndrome and cholestatic
liver disease. Studies on animals with
lupus nephritis,
aminonucleoside nephrosis, reduced renal mass,
diabetes mellitus or systemic
hypertension have shown that
cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different
lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of
lipid induced glomerular damage.
Apo E-containing
lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix.
Lipoproteins are able to stimulate
DNA synthesis in these cells, and increase the synthesis of
mitogens and
extracellular matrix protein. The pathogenic role of oxidized
lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified
lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified
lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects
hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that
lipoproteins may play a critical role in mediating the development of glomerulosclerosis.