The abnormalities of lipid metabolism in
nephrotic syndrome consist in an increase in total and
low-density lipoprotein (
LDL) cholesterol,
apolipoproteins B (
ApoB), C-II and C-III, associated in patients with heavier or marked
hypoalbuminemia with an increase in
triglycerides and
very low-density lipoprotein (
VLDL) cholesterol, while the
high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the
Apo A-I to
Apo B ratio is reduced. Both increased hepatic
lipoprotein synthesis and reduced removal capacity contribute to this
hyperlipidemia.
Proteinuria may lead to the
lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by
hypoalbuminemia, although it has been more recently suggested that urinary
protein loss is associated with the urinary loss of some important cofactor for the regulation of
lipid synthesis or catabolism. Treatment of
lipid abnormalities in patients with long-lasting heavy
proteinuria is mandatory, because they may cause or contribute to accelerated
atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial
sclerosis. Four groups of
lipid-lowering drugs have been tested: 1)
bile acid-binding resins; 2)
fibric acid; 3)
probucol; 4) inhibitors of
HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in poly- and monounsaturates
fatty acids, has been recently tested by the author, with very promising results.