Possible induction of renal dysfunction in patients with lecithin : cholesterol acyltransferase deficiency by oxidized phosphatidylcholine in glomeruli

To clarify the causes of renal dysfunction in familial lecithin:cholesterol acyltransferase (LCAT) deficiency, kidney samples from 4 patients with LCA T deficiency (3 homozygotes and 1 heterozygote) were examined immunohistoch emically. All of the patients exhibited corneal opacities, anemia, renal dy sfunction, deficiencies in plasma high density lipoprotein and LCAT activit y and mass, and an increase in the ratio of plasma unesterified cholesterol to esterified cholesterol. Renal lesions began with the deposition of lipi dlike structures in the glomerular basement membrane, and these structures accumulated in the mesangium and capillary subendothelium. By electron micr oscopy, 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 t hose in controls (1.30+/-0.82 versus 0.42+/-00.32 ng/5 mu g LDL, respective ly), and a significant (P<0.01) difference was observed even after adjustme nt for confounding factors by an analysis of covariance. The patient with t he highest plasma oxPC-modified LDL had the most membranelike structures in the glomeruli and showed the greatest renal deterioration from a young age . In glomerular lesions, although there was an abundance of apoB and apoE, oil red O-positive lipids, macrophages, apoA1, and malondialdehyde were sca rce. OxPC was found extracellularly in glomerular lesions, and although its distribution differed from that of apolipoproteins, it was quite similar t o that of phospholipids. In conclusion, these results indicate that oxPC in plasma and glomeruli is distinctive for patients with LCAT deficiency. The refore, oxPC may be a factor in the deterioration of kidneys in patients wi th familial LCAT deficiency.