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 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.