A 58-year-old male was referred to our center by his primary care physician due to nephrotic syndrome. He had massive proteinuria (7.38 g/day) and hypoalbuminemia (1.9 g/dl). He had been treated for diabetes since the age of 50 years and had been started on insulin therapy at the age of 55 years. He had been well-managed (HbA1c, 5.3%), although a pre-proliferative retinopathy and mild renal dysfunction (sCr, 1.38 mg/dl) became evident. His renal biopsy revealed 5 of 22 glomeruli with global sclerosis. The residual glomeruli showed massive foam cell infiltration in the glomerular capillaries and severely widened mesangium (fig. ). These foam cells stained positive for CD68 (not shown). Transmission electron microscope images also revealed foam cell infiltration mainly located in the capillaries containing scattered lipid droplets and lamellar bodies in their cytoplasm (fig. ). The glomerular tufts were enlarged with hyalinosis, mesangiolysis and microaneurysmal formation, which were consistent with diabetic glomerulosclerosis. The interstitium and tubules showed moderate fibrosis and atrophy (50% of the cortical region). The foamy change was seen in some tubular epithelial cells, but no interstitial foamy cells were found. The interlobular arteries showed a moderate degree of fibrous intimal thickening, and the arterioles also showed a moderate degree of subendothelial hyalinosis. Immunofluorescence studies revealed nonspecific linear IgG deposits along the GBM; however, no significant deposit was found by electron microscopy. The patient's lipid profile showed type III HLP (table ). He had an apoE2 homozygote phenotype and the Arg158Cys genotype with no other mutations. Three years after the diagnosis, he progressed to renal failure and was started on hemodialysis.
A 51-year-old Japanese woman was admitted for evaluation of proteinuria in 2011. She had a history of appendicitis at 12 years of age, cholelithiasis at 30 years of age, myoma at 46 years of age, and at least a 5-year history of dyslipidemia. Proteinuria (1+) had been first identified during a medical checkup 3 years prior and was ignored until increasing to 3+ in 2011. Her parents and brothers suffered from dyslipidemia but had no history of renal disease.\nOn admission, her height and weight were 161 cm and 49 kg, respectively, and her blood pressure was 137/94 mm Hg. On physical examination, slight pitting edema was observed; however, there were no xanthomas. Urinary protein excretion was 4.12 g/g Cre, and the serum triglyceride level was high. She did not exhibit nephrotic syndrome. The other laboratory findings are shown in Table . A computed tomography scan showed neither atrophy nor enlargement of the kidneys.\nA renal biopsy specimen was processed in August 2011 using standard methods, and in the sections for light microscopy, the renal cortex was found to contain 11 glomeruli, 2 of which showed sclerosis. The remaining glomeruli were enlarged by distinct dilatation of the capillary lumina, which were filled with thrombus-like substances that stained slightly with periodic acid-Schiff. Some glomeruli exhibited moderate mesangial cell proliferation and increased mesangial matrix, and double contours of the capillary wall were partially observed. No crescents or adhesion in glomeruli were found (Fig. –c). A direct immunofluorescence showed no deposition of IgG, IgA, IgM, C1q, C3, or fibrinogen in glomeruli. Staining with Oil red O showed lipid droplets in the capillary lumina, which were stained positive for apoE (Fig. , e). Electron microscopic findings showed capillary dilation and occlusion with numerous lamellated lipid granules. Thin basement membranes with swollen endothelial cells were also observed. The histological findings and the results of apoE analysis (described below) satisfied the diagnostic criteria for LPG [].\nTreatment with fenofibrate and irbesartan was initiated. Two weeks later, serum triglycerides and urinary protein excretion were reduced to 200 mg/dL and 1 g/g Cre, respectively. Two months later, the former was within the normal range, and the latter was reduced to less than 0.5 g/g Cre. Eight months later, urinary protein excretion ceased and did not recur thereafter (Fig. ).\nIn a second biopsy in August 2013, the specimen contained 22 glomeruli, 4 of which were obsolescent. Two of the glomeruli were filled with thrombi, but thrombi were absent in the other glomeruli (Fig. ).