Abstract
Lipoprotein glomerulopathy (LPG) is a rare hereditary disease characterized by intraglomerular lipoprotein thrombi and increased serum apolipoprotein E (APOE) concentrations. Several types of APOE mutations are known to associate with LPG. We have previously reported a 4-year-old girl with LPG who was a heterozygote of APOE-Sendai (Arg145Pro) mutation. This time, we present another 7-year-old girl with LPG carrying heterozygous APOE-Sendai (Arg145Pro) mutation. She was found to have proteinuria and hematuria by a routine school urinalysis at the age of 6 years. At the age of 7 years, the patient was referred to our hospital for evaluation of heavy proteinuria. There were no obvious abnormalities on physical examination at the first visit. Laboratory data showed she had no hypoproteinemia, hyperlipidemia and renal dysfunction. However, urinalysis showed positive for occult blood and protein test, and her urine protein/creatinine ratio was 3.8 g/g•cre. Then renal biopsy was performed due to the persistent urinary abnormality. Light microscopic examination showed marked dilatation of the capillary lumen in glomeruli by a pale-stained substance by periodic acid Schiff. Electron microscopy showed that thrombus-like substances in glomerular capillaries were composed of granules and vacuoles of various sizes, forming concentric lamellate. Gel electrophoresis analysis revealed the presence of a mid-band and VLDL fraction was elevated. Her serum APOE level was elevated to 12.2 mg/dl (reference range 2.8-4.6 mg/dl). Direct DNA sequencing revealed a heterozygote of APOE-Sendai mutation (Arg145Pro). These results led to diagnosis of LPG. Her mother and elder brother also had the same mutation, however, they had no signs of renal disease. We started to treat her with lipid-lowering agents, especially fibrates, triglycerides-lowering agent. At present, her urinary protein decreased and hematuria disappeared. Her APOE level decreased to 6.7 mg/dl.
It is known that LPG patients initially show mild proteinuria and a half of the LPG patients progress to chronic renal failure. Recently, however, intensive therapy using lipid-lowering agents, including fibrates, were reported to improve patient's clinical condition with histological resolution. Early treatment with lipid-lowering agents is important to prevent the development of renal failure.
Unlike other APOE variants, APOE-Sendai was detected in only north-east part of Japan, especially in Yamagata and Miyagi prefectures, suggesting a founder effect. There are many healthy carriers of APOE variants in the families with LPG, which suggests that additional factors also are involved in the onset of LPG. To elucidate the precise mechanism for LPG, we started the prevalence survey of APOE-Sendai among general population and hemodialysis patients in Yamagata prefecture. And we will determine the haplotype of APOE in the patients to see the founder effect of APOE-Sendai. Based on these data, we would like to elucidate the pathogenesis of LPG.
