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 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.