Possible Induction of Renal Dysfunction in Patients With Lecithin:Cholesterol Acyltransferase Deficiency by Oxidized Phosphatidylcholine in Glomeruli

Abstract—To clarify the causes of renal dysfunction in familial lecithin:cholesterol acyltransferase (LCAT) deficiency, kidney samples from 4 patients with LCAT deficiency (3 homozygotes and 1 heterozygote) were examined immunohistochemically. All of the patients exhibited corneal opacities, anemia, renal dysfunction, deficiencies in plasma high density lipoprotein and LCAT activity and mass, and an increase in the ratio of plasma unesterified cholesterol to esterified cholesterol. Renal lesions began with the deposition of lipidlike structures in the glomerular basement membrane, and these structures accumulated in the mesangium and capillary subendothelium. By electron microscopy, 2 types of distinctive structure were found in glomerular lesions: vacuole structures and cross-striated, membranelike structures. The plasma oxidized phosphatidylcholine (oxPC) –modified low density lipoprotein (LDL) levels in LCAT-deficient subjects were significantly (P<0.01) higher than those in controls (1.30±0.82 versus ...