A 78-year-old male with nephrotic syndrome was referred to our center by his primary care physician. The patient had a history of hypertension since the age of 45 years, hypothyroidism since the age of 68 years and diabetes mellitus since the age of 70 years. He also had a history of percutaneous coronary intervention for coronary artery disease and femoropopliteal bypass surgery for peripheral arterial disease at the age of 74 years, and a history of Wallenberg syndrome since the age of 77 years. He was being treated with an angiotensin II receptor blocker, a calcium-channel blocker, pitavastatin, aspirin and levothyroxine sodium hydrate. Diabetic control by diet and an oral α-glucosidase inhibitor were sufficient. There was no evidence of retinopathy or albuminuria before the episode of nephrosis. His urinalysis on admission was positive for proteinuria (2.5 g/day) and red blood cells (1–4/hpf). His blood chemistry findings were as follows: albumin 3.2 g/dl, creatinine 1.11 mg/dl and HbA1c 6.1%. A kidney biopsy revealed 21 glomeruli, of which 2 were globally sclerotic. The glomeruli showed increased mesangial matrices and mild GBM thickening. Massive foam cells had infiltrated into the glomerular capillaries and mesangial region (fig. ). These foam cells stained positive with Oil Red O (fig. ) and immunohistochemically stained positive for CD68 (fig. ). Transmission electron microscope images also revealed foam cell infiltration mainly located in the capillaries, and some mesangial cells showed scattered lipid droplets in their cytoplasm (fig. ). Mild interstitial fibrosis and tubular atrophy (20% of the cortical region) as well as moderate arteriosclerosis and arteriolar hyalinosis were found. The foamy change was seen in some tubular epithelial cells but no interstitial foamy cells were found. Immunofluorescence studies revealed segmental deposits of IgM and C3 in the mesangial area and slightly peripheral IgG deposits in the glomeruli; however, no significant deposit was found by electron microscopy. He had an apoE2 homozygote phenotype and the Arg158Cys genotype with no other mutations. After the diagnosis, ezetimibe was added to his statin therapy. The patient's most recent serum creatinine was increased to 2.1 mg/dl after 2 years.
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. ).