A Case of Podocytic Infolding Glomerulopathy with Focal Segmental Glomerulosclerosis
A 14-year-old girl was referred to our institution as an inpatient because of proteinuria. When she was 9 years old, she had urinary protein (UP) detected during a school physical examination and she was followed in the Pediatrics Department of our hospital. Her UP gradually increased to a level of 1.9 g/day, and at 14 years, she was referred to our division. Laboratory tests showed a UP level of 2.35 g/day, negative results for urinary sedimentation, and creatinine clearance of 111.9 ml/min/1.73 m2. No cytopenia, hypocomplementemia, or elevated liver enzymes were found (table ). Her physical findings were normal. Light microscopy of her first renal biopsy specimens showed a total of 14 glomeruli, 1 of which had global sclerosis; the others were MGAs. However, under light microscopy at a higher magnification under periodic acid methenamine silver (PAM) staining, the glomeruli had a bubbling appearance of diffuse glomerular loops (fig. ). Immunofluorescent staining was negative for immunoglobulin, complement, and fibrinogen. Electron microscopy revealed microspheres in the GBM, which were sparse but global (fig. ). The microstructures took various forms, and almost all of them were encircled with a unit membrane. There was no direct consecutive podocytic infolding in the GBM, nor any mesangial interposition. The endothelial cells were not swollen. Foot process effacement was scattered and there was no thickening of the GBM. This finding suggested the possibility of PIG. The patient was started on telmisartan 10 mg/day. However, her UP level gradually increased to the nephrotic range by 16 years, and at 17 years of age, she underwent a second renal biopsy. Laboratory tests showed a UP level of 3.06 g/day, negative results for urinary sedimentation, and creatinine clearance of 156.5 ml/min/1.73 m2. Antinuclear antibodies had changed to positive and the double-stranded deoxyribonucleic acid (dsDNA) level was elevated at 14 IU/ml. Serum total protein level was 5.5 g/dl and serum albumin level was 3.4 g/dl. No cytopenia, hypocomplementemia, or physical findings indicative of collagen disease were found (table ). Light microscopy of the second renal biopsy specimens revealed 31 glomeruli, of which 4 had global sclerosis, 2 had segmental sclerosis with cellular variant, while the remainder were MGA. The bubbling appearance of glomerular loops was detected at higher magnification on PAM staining, as in the first biopsy, although their number had markedly decreased. Immunofluorescent staining was positive for IgM, C3, and C1q in the segmental sclerosis lesions, whereas all were negative in the other lesions. Electron microscopy revealed endothelial cell swelling and endocapillary cell proliferation in the segmental sclerotic lesions. Foot process effacement was global. The microspheres observed in the GBM were sparser than in the first biopsy (fig. ). We diagnosed PIG complicated by FSGS. Prednisolone 40 mg/day (0.7 mg/kg) was prescribed, and the UP level gradually decreased. After 9 months, the UP was less than 0.5 g/day.