Possible association between an abnormal low density lipoprotein and nephropathy in lecithin: CHolesterol acyltransferase deficiency

Gjone, E; Blomhoff, J. P.; Skarbøvik, Alv J.

doi:10.1016/0009-8981(74)90037-0

Cited by 54 publications

(16 citation statements)

References 16 publications

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“…Previous extensive analyses using electron microscopy have identified 3 abnormal lipoproteins in the LDL fraction of FLD 12 : TG-rich and CE-poor particles of sizes similar to normal LDL (FLD-LDL); FC-and PL-containing particles of sizes distributing from 40 to 60 nm (LpX-like particle) 2 ; particles with a diameter of 100 nm (designated as LM-LDL) 17,30 that were later reported to be identical to LpX. 15 LpX is FCand PL-rich but TG-poor lipid particles (30%, 60%, and 2%, respectively) 22 without apolipoproteins, which range from very low density lipoprotein to large LDL fractions in fast performance liquid chromatography analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Densitygradient ultracentrifugation followed by electron microscopy revealed that the low-density lipoprotein (LDL) fraction contains 3 abnormal particles with different sizes, lipid composition, and associated apolipoproteins, 11,12 which were proposed to be important in the pathogenesis of renal manifestation in patients with FLD. [15][16][17][18] Of these, lipoprotein-X (LpX) 19,20 have been postulated to accumulate in glomeruli, potentially causing the renal damage observed in patients with FLD. [16][17][18] In 1 patient with FLD, lipid-lowering therapy led to a reduction of LpX and a concomitant reduction in proteinuria.…”

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confidence: 99%

“…[15][16][17][18] Of these, lipoprotein-X (LpX) 19,20 have been postulated to accumulate in glomeruli, potentially causing the renal damage observed in patients with FLD. [16][17][18] In 1 patient with FLD, lipid-lowering therapy led to a reduction of LpX and a concomitant reduction in proteinuria. 21 LpX is phospholipid (PL)-rich and free cholesterol (FC)-rich but triglyceride (TG)-poor particle without apolipoproteins, ranging in size between very low density lipoprotein and large LDL.…”

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confidence: 99%

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Lipoprotein Subfractions Highly Associated With Renal Damage in Familial Lecithin:Cholesterol Acyltransferase Deficiency

Kuroda

Holleboom

Stroes

et al. 2014

ATVB

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Objective-In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same LCAT gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column. Approach and Results-Lipoprotein profiles of 9 patients with LCAT deficiency were examined. Four lipoprotein fractions specific to both FLD and FED were identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to large lowdensity lipoprotein (LDL), (3) lipoproteins corresponding to small LDL to large high-density lipoprotein, and (4) to small high-density lipoprotein. Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below detection limit and 45.8±3.8%) and FED (20.7±6.4% and 28.0±6.5%) were significantly different, respectively. On in vitro incubation with recombinant LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was significantly increased (to 4.2±1.4%), whereas dysfunctional high-density lipoprotein was diminished in both FLD and FED. Conclusions-Our novel analytic approach using high-performance liquid chromatography with a gel filtration column identified large LDL and high-density lipoprotein with a composition specific to FLD, but not to FED.

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Section: Discussionmentioning

confidence: 99%

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Lipoprotein Subfractions Highly Associated With Renal Damage in Familial Lecithin:Cholesterol Acyltransferase Deficiency

Kuroda

Holleboom

Stroes

et al. 2014

ATVB

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“…The rare condition of lecithin cholesterol acyltransferase (LCAT) deficiency also represents an example in man of progressive renal injury occurring as a result of abnormal lipoprotein metabolism [1]. In this dis- ease which is characterised by an abnormal serum LDL-fraction, a link between the abnormal LDL and renal injury has been inferred [17]. The mechanism by which hypercholesterolaemia causes or aggravates glomerular injury is not known.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol-lowering therapy may retard the progression of diabetic nephropathy

et al. 1995

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SummaryThere is experimental evidence to suggest that hypercholesterolaemia may play a pathogenetic role in progressive glomerular injury. We investigated the effect of cholesterol-lowering therapy on the progression of diabetic nephropathy in 34 patients with non-insulin-dependent diabetes mellitus. Patients were randomly assigned in a single-blind fashion to treatment with either lovastatin, an HMG CoA reductase inhibitor (n = 16; mean dose 30.0 + 12.6 mg/day) or placebo (n = 18) for 2 years. Renal function was assessed by serially measuring the serum creatinine, glomerular filtration rate (using CrSl-EDTA), and 24-h urinary protein excretion. Lovastatin treatment was associated with significant reductions in total cholesterol (p < 0.001), LDL-cholesterol (p < 0.001) and apo B (p < 0.01), the reductions at 24 months being 26, 30 and 18 %, respectively. Beneficial effects on serum triglyceride, HDL-cholesterol and apo AI levels were also observed. Lp(a) showed no significant change in both groups. Glomerular filtration rate deteriorated significantly in the placebo group after 24 months (p < 0.025) but showed no significant change in the lovastatin-treated patients. The increase in serum creatinine was statistically significant (p < 0.02) in placebo-treated patients at 12 and 24 months, and in the lovastatin group after 24 months. Twenty-four hour urinary protein excretion increased in both groups (p < 0.05). Lovastatin treatment was not associated with significant elevations in liver or muscle enzymes. We conclude that effective normalisation of hypercholesterolaemia may retard the progression of diabetic nephropathy. [Diabetologia (1995) 38: 604-609]

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“…- 65 On the other hand, the prevalence of renal abnormalities in patients with the more common types of hyperlipidemias, although unknown, is probably not very high. Overt renal disease does not develop in most patients with hypercholesterolemia, which suggests that other predisposing factors (e.g., immune-mediated glomerular injury or glomerular hypertension) may have to be present for significant renal damage to occur.…”

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confidence: 99%