A 45-year-old man presented with occult blood in urine since 24 years old. He began to treat hypertension at the age of 37, when he had microscopic hematuria and proteinuria of 0.4 g/g creatinine. Since proteinuria was gradually increased to 1.16 g/g creatinine, he was admitted to our hospital to evaluate urinary abnormalities. He did not experience macroscopic hematuria. He was full-term birth, but birth weight information could not be obtained. He had no family history of renal diseases. On admission, height and body weight were 177 cm and 98.7 kg, respectively. Body mass index (BMI) was 31.5 kg/m2. He had over 80 kg (BMI >25.5 kg/m2) since 15 years old. Blood pressure was 140/78 mmHg. He was treated with the dosage of 25 mg/day of losartan potassium, 5 mg/day of amlodipine OD and 20 mg/day of febuxostat. Physical examination was not remarkable. Urinary examination showed proteinuria of 0.7 g/g creatinine, red blood cell of 10-19/high power filed and positive red cell casts. Blood chemistry showed serum creatinine of 0.69 mg/dL, cystatin C of 0.74 mg/L, albumin of 4.1 g/dL, uric acid of 6.3 mg/dL, LDL-cholesterol of 144 mg/dL and HbA1c of 5.5%. The estimated glomerular filtration rate calculated by the revised serum creatinine-based Japanese equation was 97.6 mL/min/1.73 m2. Immunological examination indicated no abnormal results including C-reactive protein, IgG, IgA, complement and anti-nuclear antibody. The electrocardiogram and chest X-ray were normal. Abdominal ultrasound detected normal shape and size in the kidneys.
With a clinical suspicion of IgA nephropathy, kidney biopsy was performed. Kidney biopsy revealed 1 global sclerosis out of 16 obtained glomeruli. Nonsclerotic glomeruli exhibited slight enlargement (glomerular diameter from 180 mum to 200 mum) without significant proliferative changes. One glomerulus showed segmental sclerosis at the perihilar region, diagnostic of FSGS (Figures 1(a)-1(c)). There were mild degree of tubular atrophy and interstitial fibrosis accompanied by mononuclear cell infiltration. Mild intimal thickening in small arteries and arteriolar hyalinosis were found. Immunofluorescent study showed no deposition of immnoreactants and a preserved linear alpha-5 of type IV collagen staining (Figure 1(d)), supportive for TBMN rather than AS. Electron microscopy showed thinning of the glomerular basement membrane (GBM) (GBM width between 140 nm and 250 nm) without splitting or lamellation, fulfilling the diagnostic criteria of TBMN (Figure 2). Foot process effacement was partial, and glomerular epithelial detachment was not seen (Figure 2). Hypertension can be a cause of FSGS. However, it is less likely that FSGS lesion in our patient was caused by hypertension because that his hypertension was less severe degree and that kidney biopsy did not include ischemic glomerular lesions, which are a common feature in hypertensive nephrosclerosis. As our patient has significant obesity, the presence of glomerulomegaly and perihilar segmental glomerulosclerosis, and the absence of diffuse foot process effacement collectively supported the diagnosis of obesity-associated FSGS.
We further examined possible additional lesions consistent with obesity-related glomerulopathy (ORG). The glomerular density (the number of nonsclerotic glomeruli per renal cortical area) measured using an image analysis program (Aperio ImageScope, Leica, Buffalo Grove, IL, USA) was 1.7 mm2, which was low compared with that in nonobese kidney donors and comparable to the reported glomerular density in patients with ORG. GBM width of the nonsclerotic area of the glomerulus with perihilar sclerosis was expected to be thick or normal in ORG, however, electron microscopic specimen including the glomerulus was not obtained. Since there was no detachment of podocytes from GBM, the expected reduction of the coating area of podocyte on the glomerular surface in ORG was not evident. Other characteristics of ORG, such as tubular hypertrophy and the presence of the lipid droplets in the mesangial cells, podocytes and proximal tubular cells were not found.
Reduction of body weight by diet therapy from 98.7 kg to 92.0 kg, and increasing a dose of angiotensin-receptor blocker, losartan potassium to 100 mg/day successfully reduced blood pressure to 125/75 mmHg and proteinuria from 1.16 to 0.16 g/g creatinine 9 months after the kidney biopsy. However, subsequently re-increase in body weight brought about increasing proteinuria up to 1.2 g/g creatinine. Microscopic hematuria persisted, and renal function was stable during the clinical course.