Apolipoprotein E Mutation and Double Filtration Plasmapheresis Therapy on a New Chinese Patient with Lipoprotein Glomerulopathy

Abstract

Background/Aims: Lipoprotein glomerulopathy (LPG) is a rare hereditary disease. In this study, we investigated the apoE mutation and the role of double filtration plasmapheresis therapy (DFPP) on a new Chinese patient with LPG. Methods: Renal biopsy was performed on this patient to allow a definitive diagnosis. The mutations in the coding sequence of apoE and the hereditary pedigree of this patient were investigated by DNA sequencing. The patient was treated with DFPP, and clinical parameters before and after DFPP were compared. Results: Two missense mutations were found in this patient: Cys112Arg and Arg25Cys. Arg25Cys was previously designated as APOE Kyoto. Family genotyping showed that Cys112Arg and Arg25Cys mutation were transmitted through his father and his mother, respectively. The patient's parents are healthy so far to date. Possibly there was a dose effect on apoE mutation induced LPG. Furthermore, DFPP treatment was first used on this patient and led to dramatic changes: Proteinuria and apo E values declined, and hemoglobin level increased significantly. Conclusion: APOE Kyoto mutation was found in a new Chinese patient with LPG, accompanied by Cys112Arg. More cases and further functional experiments are needed to investigate the role of these two mutations together in LPG. DFPP is an effective therapeutic modality for improving NS in patients with LPG.

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review

“…Steroid-resistant nephrotic syndrome associated to severe proteinuria is the clinical hallmark of LPG. The disease progresses slowly to kidney failure in approximately 50% of the affected patients, and recurrence in renal allografts can also be found 1 , 4 , 5 , 7 , 12 , 13 , 14 , 15 , 16…”

“…Among the missense mutations, four are proline, four are arginine substitutions (at position 145, 147, 150, and 158 of the mature protein), and three are cysteine for arginine substitutions (at position 25, 114, and 150 of the mature protein) 4 , 7 , 8 , 19 , 25 , 26 , 27 , 28. Deletions involve the region encompassing the amino acid residues 141-146 (141-143, 142-144, and 144-146 in the central region of the binding domain) or the region encompassing the amino acid residues 156-173 (which includes the Arg172 residue involved in the binding to LDL receptor) 13 , 15 , 17 , 19 , 20 , 23 , 29 , 30. One amino acid duplication that has been recently reported involves the residue Asp151 31…”

“…It is possible that there was a dose effect on apoE mutation induced by LPG. That is, co-occurrence of two mutations (two chromosomes respectively carrying a mutation) induces the relatively obvious clinical manifestations 35…”

“…E4 isoform is associated to an increased risk of Alzheimer's disease. ApoE2 displays less than 1% binding affinity for the hepatic LDL receptor 3 , 8 , 13 , 14 , 15 , 17 , 21 , 28 , 38. ApoE Kyoto facilitates lipoprotein deposition in glomerular capillaries due to increased endothelial cell binding 19 , 21 , 34 , 41 , 42…”

“…Many reports describe various therapies such as LDL aphaeresis, plasma exchange, renal transplantation, steroids, antiplatelets, anticoagulants, ACEI, ARB, urokinase, and antilipidemic drugs 4 , 8 , 18 , 21 , 32 , 35 , 39. Leiri et al 39.…”