Lipoprotein glomerulopathy: Significance of lipoprotein and ultrastructural features

Background. Lipoprotein glomerulopathy (LPG) is a unique disease characterized by intraglomerular lipoprotein thrombi and type III hyperlipoproteinemia. Recently, we have demonstrated that LPG is associated with inherited apolipoprotein E (apoE) variants including apoE Sendai. On the other hand, electron microscopy shows that intraglomerular lipoprotein thrombi consist of lipid granules of various sizes. To elucidate the relationship between the peculiar histology and abnormal lipid metabolism related to apoE Sendai, we studied lipoprotein profiles and ultrastructural features. Methods. The subjects were 11 patients with LPG. Four patients were nephrotic, and two others became nephrotic within six months following the biopsy. Eight patients underwent apoE gene analysis and showed apoE Sendai. The other three were presumed to have apoE Sendai because this mutation was demonstrated in their kindreds. Under electron microscopy, diameters of more than 1000 lipid granules were measured in several glomeruli, and a mean value was calculated in each case. Lipoprotein profiles were analyzed by the ultracentrifugation methods. Results. The mean diameter of intraglomerular lipid granules correlated inversely with the levels of plasma triglyceride (TG; r_s = -0.73, P < 0.05), TG (r, = -0.77, P < 0.01) and cholesterol (Chol; r_s = -0.75, P < 0.05) in very low-density lipoprotein (VLDL) fraction and TG in high-density lipoprotein (HOL) fraction (r_s = -0.75, P < 0.05). The inverse correlation was also seen between the mean lipid diameter and TG/Chol ratios in whole plasma (r_s = -0.80, P < 0.01) and in HDL (r_s = -0.80, P < 0.01). In addition, the cases showing smaller lipid granules and higher TG/Chol ratios in plasma and in HDL were nephrotic or became nephrotic within six months. Conclusion. These results suggest that the size of lipid granules in LPG may become smaller under the influence of hypertriglyceridemia and particularly elevated plasma VLDL and HDL-TG, which may lead to heavy proteinuria.