Impact of Lipoprotein Glomerulopathy on the Relationship Between Lipids and Renal Diseases

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by lipoprotein thrombi in the glomerular capillaries due to heterozygous APOE gene mutations.

“Lipoprotein glomerulopathy (LPG) is a rare disease characterized by lipoprotein thrombi in the glomerular capillaries due to heterozygous APOE gene mutations [1].”

Lipoprotein glomerulopathy (LPG) is associated with various heterozygous ApoE variants, such as ApoE Sendai and ApoE Kyoto.

“Lipoprotein glomerulopathy (LPG) was initially reported in Japan [2] and later known to be associated with various heterozygous ApoE variants, e.g., ApoE Sendai [3] and ApoE Kyoto [4].”

In LPG, ApoE variants substituted by proline or cysteine may induce severe structural changes and cause lipoprotein thrombi via charge abnormality or alternative receptor binding activity.

“Meanwhile, in LPG, there is a possibility that ApoE variants substituted by proline or cysteine induce severe structural changes and cause lipoprotein thrombi via charge abnormality or alternative receptor binding activity [4, 17, 18].”

Homozygotic E2 glomerulopathy and LPG are representative renal diseases induced by apoE mutations.

“Homozygotic E2 glomerulopathy and LPG are representative renal diseases induced by apoE mutations, e.g., homozygous E2 (Arg158Cys) [12] and various novel heterozygous apoE variants [13], respectively.”

LPG is a rare autosomal dominant renal disease with incomplete penetrance that has mainly been reported in eastern Asia.

“Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant renal disease with incomplete penetrance that has mainly been reported in eastern Asia1, 2).”

Clinically, LPG often presents as moderate to severe proteinuria and hypertriglyceridemia with elevated serum apoE levels.

“Clinically, LPG often presents as moderate to severe proteinuria and hypertriglyceridemia with elevated serum apoE levels2).”

Proteinuria in LPG may start out mild but frequently progresses to nephrotic syndrome.

“While proteinuria may start out mild, it frequently progresses to nephrotic syndrome69).”

LPG is characterized by dilated glomerular capillaries with lipoprotein clots showing lamellar formation, as seen on renal biopsy.

“LPG is characterized by dilated glomerular capillaries with lipoprotein clots showing lamellar formation, as seen on renal biopsy69).”

The apoE Sendai protein carries a missense mutation of Arg-to-Pro substitution at position 145 (R145P) within the receptor binding domain of apoE.

“The apoE Sendai protein carries a missense mutation of Arg-to-Pro substitution at position 145 (R145P) within the receptor binding domain of apoE ( 24 ).”

LPG patients present elevated apoE serum levels and often an abnormal lipid profile compared with control subjects.

“LPG patients present elevated apoE serum levels and often an abnormal lipid profi le compared with control subjects (24)(25)(26).”

LPG patients carrying apoE Sendai may show a lipoprotein profile ranging from near normal to one that resembles type III hyperlipoproteinemia.

“LPG patients carrying apoE Sendai may show a lipoprotein profi le ranging from near normal to one that resembles type III hyperlipoproteinemia (24)(25)(26).”

Proline acts as a structural disrupter in the middle of the alpha helix.

“Proline acts as a structural disrupter in the middle of the alpha helix”

Proline is commonly found as the first residue of the alpha helix or in turns in an amino acid arrangement.

“and is commonly found as the first residue of the alpha helix or in turns in an amino acid arrangement 1, 4)”

LPG is characterized by lipoprotein thrombi in glomerular capillaries.

“Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene (APOE) gene and is characterized by lipoprotein thrombi in glomerular capillaries.”

Most reports suggest that even though statins normalize patient lipid profiles, they usually do not lead to improvement in proteinuria.

“Most reports suggest that even though statins normalize patient lipid profiles, they usually do not lead to improvement in proteinuria.5”

The age of onset of LPG varies widely, ranging from 4 to 72 years, with approximately equal sex distribution and familial clustering.

“The age of onset varies widely, ranging from 4 to 72 years, with approximately equal sex distribution and familial clustering.[1,3]”

LPG is caused by mutations in the apolipoprotein E (ApoE) gene.

“Subsequently, it was discovered that LPG is caused by mutations in the apolipoprotein E (ApoE) gene.[3]”

Glucocorticoids, immunosuppressants, and anticoagulants have all demonstrated poor efficacy in LPG.

“Glucocorticoids, immunosuppressants, and anticoagulants have all demonstrated poor efficacy.[3,31]”