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. ).
A 66-year-old male was referred to our center by his primary care physician because of the increase of proteinuria. He was diagnosed with diabetes at the age of 50 years but remained untreated. At the age of 60 years, he started voglibose at the diabetes center of our hospital. At the age of 66 years, urinary abnormality of protein 3+ and occult blood 1+ was pointed out, combined with simple diabetic retinopathy and a serum creatinine level of 0.96 mg/dl. He was referred to our center for further investigation, and a renal biopsy was performed. One of 11 glomeruli showed global sclerosis, and the other glomeruli showed massive foam cell infiltration in the glomerular capillaries and mildly expanded mesangium (fig. ). These foam cells immunohistochemically stained positive for cluster differentiation 68 (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 basement membrane (GBM) showed mild thickening, and nodular lesions were formed in some glomeruli. The interstitium and tubules showed mild fibrosis and atrophy (25% of the cortical region), and a moderate degree of arteriolar hyalinosis was also found. No interstitial foamy cells or foamy tubular degeneration was found. Immunofluorescence study revealed no significant glomerular deposits. The patient's lipid profile showed type III HLP (table ). Apolipoprotein phenotype analysis showed a homozygosity of apoE2. A further DNA sequence analysis was performed as described previously [] and showed a nucleotide substitution of cysteine for arginine at codon 158 (Arg158Cys) of the apoE gene and no other mutations. Eicosapentaenoic acid was added to his statin therapy, but he progressed to end-stage renal failure and was started on dialysis 8 years after the diagnosis.