A Case of Lipoprotein Glomerulopathy with apoE Chicago and apoE (Glu3Lys) Treated with Fenofibrate

Abstract

Lipoprotein glomerulopathy (LPG) is characterized by the accumulation of lipoprotein thrombi within glomerular capillaries. This rare disorder is associated with various types of mutations in the apolipoprotein E gene (apoE). Herein, we present a case of LPG with a combination of apoE Chicago (Arg147Pro) and apoE (Glu3Lys) mutations. A 51-year-old Japanese woman presented with severe (3+) proteinuria. The initial renal biopsy showed glomerular capillary dilation and occlusion with lipid granules, a specific characteristic of LPG. Phenotype, genotype, and apoE DNA sequence analyses detected 2 mutations as described above within the same allele. Although both mutations had already been reported in 1 case of LPG each, this is the first time that the combination of the 2 mutations was identified in the same case. Familial analysis detected the same mutations in the patient’s mother. However, she has not suffered LPG thus far. In addition, a re-analysis of the previous LPG case with apoE (Glu3Lys) also identified the apoE Chicago mutation, as was observed in our case. Treatment with fenofibrate and irbesartan was initiated, and urinary protein excretion ceased within 1 year; recurrence was not observed after an additional 2 years of follow-up. A second biopsy after 2 years showed great improvement, with lipoprotein thrombi identified only in 2 of 18 glomeruli.

A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I

“…To the best of our knowledge, only two cases of LPG with apoE5 (Glu3Lys) have been reported [5,6] and these are confirmed to have apoEChicago by Kodera [5] (Table 1). Accordingly, this is the first report to describe a case of LPG with the combination of apoE-Sendai and apoE5 (Glu3Lys).…”

“…Accordingly, this is the first report to describe a case of LPG with the combination of apoE-Sendai and apoE5 (Glu3Lys). Although apoEChicago [7] and apoE-Sendai [2] are the representative mutations in LPG indicating phenotype E2 on IEF, apoEChicago, if apoE5 (Glu3Lys) exists on the same allele, seems to be expressed as phenotype E4, probably by the offset of electrical charge [5]. Few reports have described apoE5, so its prevalence, lipid profile, and associations with disease remain poorly understood.…”

“…Sam et al [7] demonstrated enhanced binding of apoE-Chicago to glomerular capillaries in a patient with LPG. On the basis of these findings, Kodera et al [5] speculated that the binding capacity of apoE to glomerular capillaries was altered by the coexistence of apoE-Chicago and apoE5 (Glu3Lys) on the same allele (Case 1 and 3 in Table 1). In the present case, however, apoE-Sendai and ing that the substituted mutation is heterozygous.…”

Apolipoprotein E–related glomerular disorders

“…Miyata et al 87 identified heterozygous apoE mutations with apoE2 and apoE5 (Glu3Lys) in this patient. In contrast, Kodera et al 88 recently reported another case of LPG that possessed apoE Chicago and apoE5 (Glu3Lys), and they clarified, by gene analysis of the family of the patient, that both mutations were expressed within the same allele. Additonally, apoE Chicago was also identified in a re-analysis 88 of the case previously analyzed by Miyata et al.…”

“…In contrast, Kodera et al 88 recently reported another case of LPG that possessed apoE Chicago and apoE5 (Glu3Lys), and they clarified, by gene analysis of the family of the patient, that both mutations were expressed within the same allele. Additonally, apoE Chicago was also identified in a re-analysis 88 of the case previously analyzed by Miyata et al. 87 Takasaki et al 89 also reported a case of LPG with a combination of apoE Sendai and apoE5 (Glu3Lys).…”