podocytic infolding glomerulopathy ( pig ) has recently been proposed as a possible new pathological entity . in pig , microspheres or microtubular structures , or both , are associated with the infolding of cytoplasmic processes of podocytes into the glomerular basement membrane ( gbm ) . it is not known whether this lesion indicates a new disease entity or a transient morphological finding of a well - known disease . however , several cases with an apparently unique microstructure showing podocytic infolding have been reported as pig . although most cases were diagnosed as lupus nephritis or another primary glomerulonephritis , based on light microscopic findings , 4 cases were diagnosed as a minor glomerular abnormality ( mga ) . we report a case of pig with microspheres in the gbm that were diagnosed as mga based on light microscopic findings . after 3 years , the patient had a nephrotic - range proteinuria and was diagnosed by a second renal biopsy as having focal segmental glomerulosclerosis ( fsgs ) with pig . this is the first report of a case of pig that was diagnosed as mga based on the first light microscopic findings and , 3 years later , as complicated with fsgs . 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 m. no cytopenia , hypocomplementemia , or elevated liver enzymes were found ( table 1 ) . 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 . 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 . 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 m. 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 1 ) . 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 . the microspheres observed in the gbm were sparser than in the first biopsy ( fig . prednisolone 40 mg / day ( 0.7 mg / kg ) was prescribed , and the up level gradually decreased . this case exhibited microspheres in the gbm on the electron microscopic findings at the first renal biopsy , although light microscopy showed only mga . joh et al .   reported 25 cases with microspheres and microtubular structures in the gbm as pig . the light microscopic findings of pig reveal a bubbling or stipple formation in association with an occasional spike formation on pam staining . on electron microscopy , cytoplasmic processes of podocytes infold into the gbm , which involves thickening of the lamina densa . these microspheres or microtubular structures have a unit membrane and may be equivalent to a cytoplasmic membrane . on the first biopsy , this case showed mga in the light microscopic findings . in previous reports , of which 2 were diagnosed as rheumatoid arthritis and mixed connective tissue disease , and 1 exhibited lupus - like characteristics , immunofluorescent staining revealed immunoglobulin deposition . the other case was diagnosed as minimal change nephrotic syndrome and pig complicated by sjgren 's syndrome ; immunoglobulin and complement were negative on immunofluorescent staining , and podocytic infolding and foot process effacement were found on electron microscopy . our case was different from the former 3 cases because immunoglobulin and complement were both negative , and from the latter case because of the clinical findings and scattered foot process effacement . the second biopsy in our case showed pig complicated by fsgs with fewer findings of podocytic infolding . previous reports include 4 cases of pig complicated by fsgs [ 4 , 5 , 6 , 7 ] . one of them , who had serial biopsies , was diagnosed after the first biopsy as having pig and fsgs associated with vesico - ureteral reflux ( vur ) . after a urethral catheter had been in place for a year , the second biopsy revealed findings indicative of fsgs and the disappearance of almost all podocytic infolding . there is the possibility that on the initial biopsy our patient had fsgs that could not be detected by renal biopsy because of the small number of lesions . the fact that the first biopsy revealed scattered foot process effacement and one global sclerosis has indicated the possibility of fsgs at the initial biopsy . therefore , our case might have been diagnosed as pig and fsgs at the first biopsy . however , in the pig case with fsgs due to vur , the second biopsy showed less podocytic infolding than the first , as the up decreased with improving vur . therefore , in pig complicated with fsgs , the amount of podocytic infolding would be in proportion to up level . on the other hand , our case showed less podocytic infolding at the second biopsy even though the up increased . this would be compatible with our case having had pig without fsgs , rather than complicated with fsgs at the first biopsy . moreover , it is more important to make clear whether podocyte infolding is a morphological phenomenon or a finding of a new disease entity . especially in fsgs in which podocyte injury is evaluated as fundamental damage , podocyte infolding may be caused by a morphological phenomenon of fsgs . however , because of a decrease of these lesions despite an increased up level at the second biopsy , the podocyte infolding may be a new disease entity such as pig which trends to associate with fsgs and collagen disease . if the podocytic infolding is a morphological phenomenon of fsgs , the podocytic infolding would be increased in proportion to increased up . some of the cases with podocyte infoldings , which until now have been believed to be a morphological phenomenon with other glomerulonephritis , would be a new disease entity . to discuss whether this lesion is pig or a morphological phenomenon , however , in collagen disease - associated pig , the mechanism might involve antibody complement - mediated factors , which might be related to the role of special types of complement activation in situ on the microstructures , as developed on immune electron microscopic analysis [ 9 , 10 ] . however , some of these cases were negative for immunoglobulin and complement in the immunofluorescence findings . further cases of pig need to be analyzed in order to determine whether pig is a new disease entity or a transient morphological finding of a well - known disease .
podocytic infolding glomerulopathy ( pig ) has been proposed as a new disease entity . 
 a 14-year - old girl underwent renal biopsy at our institution because of a chance finding of proteinuria . 
 light microscopic findings revealed a minor glomerular abnormality , but under a higher magnification , after periodic acid methenamine silver staining , a bubbling appearance in the glomerular basement membrane ( gbm ) was observed . 
 an electron microscopic examination revealed microspheres in the gbm , which were sparse but global . 
 the patient was diagnosed as having pig . 
 after 3 years , her urinary protein had increased and a second biopsy was performed , showing focal segmental glomerulosclerosis in addition to a lesser degree of podocytic infolding than at the first biopsy . 
 this is the first report of a case complicated by a different type of glomerulonephritis after being diagnosed as pig . 
 a few cases of pig are complicated by focal segmental glomerulosclerosis , suggesting several mechanisms for the disorder .