Renal Lesions in Familial Lecithin-Cholesterol Acyltransferase Deficiency

Abstract

Renal lesions of a new case of lecithin-cholesterol acyltransferase deficiency in an 18-year-old male are described. Large mesangial deposits and a sieve-like transformation of the peripheral basement membrane were the main glomerular lesions. Immunofluorescence identified C3 deposits in the mesangium. A heterogeneous pattern of ultrastructural findings was observed by electron microscopy. Thread-like structures with faint cross-striation and irregular tubular structures embedded in an amorphous material were found in mesangial and subepithelial sites. Mesangial areas and peripheral basement membranes showed irregular holes sometimes containing highly osmiophilic lamellar bodies. It is suggested that many mechanisms may be involved in the production of renal lesions induced by the lipoprotein abnormalities characteristic of the disease.

A Novel in Vivo Lecithin-Cholesterol Acyltransferase (LCAT)-Deficient Mouse Expressing Predominantly LpX Is Associated with Spontaneous Glomerulopathy

“…Although there are no in vitro studies of the effect of LpX on podocytes, LpX does have direct effects on cultured glomerular mesangial cells. 12 Dense inclusions in podocytes were associated with focal areas of foot process effacement, and this finding is similar to changes that have been described in kidney biopsies from patients with LCAT deficiency 10,11 It has long been of great interest to understand the origin of LpX particles. To date, spontaneous production of LpX has been described in cholestatic liver disease, complete LCAT deficiency, and a murine model of ferrochelatase deficiency.…”

“…This mouse model and the nephropathy seen in human LCATdeficiency both show light microscopic mesangial matrix expansion, glomerular hilar foam cell infiltrates, and lipid deposits in the glomeruli and tubulointerstitium. 10 Ultrastructural features are also similar in both, showing lamellar osmiophilic deposits in the mesangium, in proximity to the glomerular basement membrane, and in the interstitium. 10,11 The SϩlcatϪ/Ϫ mice show evidence of mesangial injury, mesangial matrix expansion, and glomerulosclerosis progressing from 6 to 10 months of age.…”

“…10 Ultrastructural features are also similar in both, showing lamellar osmiophilic deposits in the mesangium, in proximity to the glomerular basement membrane, and in the interstitium. 10,11 The SϩlcatϪ/Ϫ mice show evidence of mesangial injury, mesangial matrix expansion, and glomerulosclerosis progressing from 6 to 10 months of age. This is also similar to that seen in human LCAT-deficiency nephropathy, where the lesions chronically are associated with progressive mesangial and glomerular sclerosis.…”

“…9 Renal biopsy in patients with familial LCAT deficiency has shown mesangial expansion, lipid accumulation, and foam cell infiltrates in the capillary walls and in the mesangium. 10 Electron microscopy has shown membranelike lamellar osmiophilic deposits in the glomerular basement membrane, subepithelially, subendothelially, and in the mesangium. 10,11 The underlying etiology of the glomerulopathy remains unclear and animal models emulating the spontaneous nephropathy seen in familial human LCAT deficiency have not been available.…”

“…10 Electron microscopy has shown membranelike lamellar osmiophilic deposits in the glomerular basement membrane, subepithelially, subendothelially, and in the mesangium. 10,11 The underlying etiology of the glomerulopathy remains unclear and animal models emulating the spontaneous nephropathy seen in familial human LCAT deficiency have not been available. Anecdotal evidence in clinical observations implicated an association between the presence of LpX and the development of glomerulopathy.…”