Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys)

Area of Science:

• Nephrology
• Cardiovascular Genetics
• Metabolic Disorders

Background:

• Apolipoprotein E5 (apoE5) is a rare isoform of apoE.
• The apoE5 (Glu3Lys) variant, characterized by a glutamic acid substitution at codon 3, is found in 0.1% of the Japanese population.
• Previous research links apoE5 (Glu3Lys) to hyperlipidemia and cardiovascular issues, noting its enhanced LDL receptor-binding activity compared to apoE3.

Observation:

• A 51-year-old male presented with nephrotic syndrome.
• Renal biopsy revealed segmental sclerosis, podocyte hypertrophy, and foam cell infiltration, consistent with focal segmental glomerulosclerosis (FSGS).
• The patient had mild diabetes mellitus and monoclonal gammopathy of undetermined significance, but no specific nephropathy related to these conditions was identified.

Findings:

• This is the first reported case of nephropathy solely associated with the apoE5 (Glu3Lys) variant.
• The observed FSGS suggests a potential role for abnormal lipid metabolism driven by apoE5 (Glu3Lys).
• The findings indicate that dyslipidemia and apoE activity are critical factors in FSGS pathogenesis.

Implications:

• Abnormal lipid metabolism due to the apoE5 (Glu3Lys) variant may be a contributing factor in the development of FSGS.
• This case underscores the importance of considering genetic lipid metabolism variations in unexplained nephrotic syndrome.
• Further research is warranted to elucidate the precise mechanisms linking apoE5 (Glu3Lys) to renal pathology.