- Takao Saito, MD, PhD
Takao Saito, MD, PhD
- Professor Emeritus, Fukuoka University
- Director, Sanko Clinic
- Specified Medical Corporation Sanko Group
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Brad H Rovin, MD
Brad H Rovin, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine and Pathology
- The Ohio State University College of Medicine
Lipoprotein glomerulopathy (LPG) is a unique and rare disorder of renal lipidosis that was first reported in a Japanese patient in 1989 . It is characterized by lipoprotein thrombi in glomeruli, an abnormal plasma lipoprotein profile that resembles type III hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (apo E) concentrations. LPG was subsequently found to be due to mutations of the APOE gene . However, intrinsic renal factors are also involved in the pathogenesis of LPG because of the incomplete penetrance based upon many asymptomatic carriers of APOE variants [3-5].
A review of the clinical features of LPG is presented in this topic review.
Initial reports of familial cases as well as recurrence in transplanted kidneys suggested that a systemically acting genetic factor may underlie lipoprotein glomerulopathy (LPG). It was also observed that the serum apo E isoform was inconsistent with the APOE genotype among affected individuals.
These findings predicted that an uncharacterized variant(s) of the APOE gene may underlie the pathogenesis of this disorder . This was subsequently confirmed as mutations in the APOE gene have been found in all reported cases of LPG in which DNA sequencing has been performed (algorithm 1).
APOE variants — Apolipoprotein E (apo E), an essential apolipoprotein, is a major constituent of various plasma lipoproteins. Plasma lipoprotein levels are determined in part by the binding activities of apo E to the LDL receptor, LDL receptor-related protein, and VLDL receptor. Apo E is composed of 299 amino acids and has a relative molecular mass of 34kDa.
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- APOE variants
- Role of other factors
- CLINICAL FEATURES
- Renal findings
- Non-renal manifestations
- Lipid and lipoprotein profiles
- Histopathologic findings
- - Light microscopy
- - Electron microscopy
- - Confirmation of lipoprotein deposits
- DIFFERENTIAL DIAGNOSIS
- Specific therapies
- Nonspecific therapy
- SUMMARY AND RECOMMENDATIONS