nephrotic syndrome with the deposition of non - amyloidal fibril structures in the glomeruli was first reported in 1977 by rosenmann et al . , and the term  fibrillary glomerulonephritis  ( fgn ) has been used since 1987 .
fgn is a rare glomerular deposition disease and accounts for approximately 0.51.0% of all adult glomerulonephritis cases on renal biopsy [ 3 , 4 , 5 , 6 ] .
it is characterized by the deposition of microfibrils  1030 nm in diameter  in the mesangial and/or glomerular capillary walls .
congo red stain shows a negative reaction [ 3 , 4 , 5 , 6 ] . on immunofluorescent study , immunoglobulin g ( igg ) and c3
igg4 is predominantly positive in the staining for subclasses of igg [ 1 , 3 , 4 , 5 , 6 ] .
fgn usually develops at middle or older age [ 5 , 6 ] , and the typical clinical findings are proteinuria , which often reaches the nephrotic range .
treatment with steroids and immunosuppressive agents is not effective , and the renal outcome is generally poor [ 3 , 4 , 5 , 6 , 7 ] .
although a few familial cases have been reported in the past [ 8 , 9 ] , the clinical and pathological features were not fully evaluated .
herein , we report a patient with fgn and a family history of renal disease , and we compare the histological and clinical features with those of previous familial fgn .
their father ( case 3 ) had already died of nephrotic syndrome but did not undergo renal biopsy . in the pedigree analysis ( fig .
1 ) , case 1 's children had no medical history on routine school medical checkup .
the brothers paternal uncle was diagnosed with rheumatoid arthritis , and their paternal grandfather had a history of cerebral infarction .
case 1 was originally healthy , and there was no abnormality in urinalysis at a young age .
proteinuria ( 1 + on dipstick test ) was detected annually thereafter , but the patient was not referred to the hospital for specialist evaluation at that time .
he was referred to a nearby hospital at 40 years of age and underwent a more detailed examination by renal biopsy at our department .
his urine protein excretion was 1.33 g / g cr without microscopic hematuria , and serum creatinine was 66.3
serological tests for hepatitis b or c virus were both negative . on light microscopy , 90 glomeruli were observed , and no global or segmental sclerosis was detected .
all glomeruli showed mild mesangial expansion and segmental thickening of the glomerular capillary wall ( fig .
2 ) . elastofibrosis in the interlobular arterial tissue was observed , whereas arteriolar hyalinosis was not observed .
congo red staining was negative , and positive apple green color was not detected under polarized light .
immunofluorescence showed igg and c3 depositions in the mesangium and glomerular capillary walls ; additionally , the vessel walls showed strong igg and c3 depositions and mild igm and c1q depositions .
iga and lambda were negative , and kappa was very slightly positive in the glomeruli .
electron microscopy revealed electron - dense deposits with randomly arranged nonbranching fibrils , measuring approximately 20 nm in diameter in the mesangial lesion and glomerular basement membranes ( fig .
the patient was diagnosed with fgn , and treatment with 50 mg of oral losartan potassium once daily was initiated .
serum creatinine was stable , and the excretion of urine protein was decreased to 0.53 g / g cr 7 months after the start of therapy .
case 2 had no significant medical history in his annual medical checks . at 34 years of age
the dipstick test for occult blood was also positive at a later annual urinalysis ; thus , he was admitted to a nearby hospital for renal biopsy .
he had no hypertension or edema at the time of admission and urine protein excretion was 2.0 g / day without microscopic hematuria .
immunological tests including antinuclear antibody , complements , and immunoglobulins were not specific , and hepatitis b or c viral tests were also negative . on light microscopy ,
49 glomeruli were observed but no global or segmental sclerosis was observed , and there was diffuse mesangial matrix expansion , along with partial double contour of the glomerular basement membranes ( fig .
tubular atrophy and interlobular arterial sclerosis were very mild , whereas arteriolar hyalinosis was negative .
on immunofluorescence , mild igg and igm , and strong c3 depositions were observed in the mesangium and capillary walls .
he was diagnosed with membranoproliferative glomerulonephritis ( mpgn ) and treated with prednisolone and cyclophosphamide .
two years later , this combination therapy was discontinued because the treatment was ineffective , and imidapril 5 mg / day was prescribed after that .
five years after his biopsy , his urine protein excretion was 1.68 g / day , and serum creatinine was 70.7
he did not undergo renal biopsy , and , unfortunately , the medical records have been lost .
case 1 was originally healthy , and there was no abnormality in urinalysis at a young age .
proteinuria ( 1 + on dipstick test ) was detected annually thereafter , but the patient was not referred to the hospital for specialist evaluation at that time .
he was referred to a nearby hospital at 40 years of age and underwent a more detailed examination by renal biopsy at our department .
his urine protein excretion was 1.33 g / g cr without microscopic hematuria , and serum creatinine was 66.3
serological tests for hepatitis b or c virus were both negative . on light microscopy , 90 glomeruli were observed , and no global or segmental sclerosis was detected .
all glomeruli showed mild mesangial expansion and segmental thickening of the glomerular capillary wall ( fig .
2 ) . elastofibrosis in the interlobular arterial tissue was observed , whereas arteriolar hyalinosis was not observed .
congo red staining was negative , and positive apple green color was not detected under polarized light .
immunofluorescence showed igg and c3 depositions in the mesangium and glomerular capillary walls ; additionally , the vessel walls showed strong igg and c3 depositions and mild igm and c1q depositions .
iga and lambda were negative , and kappa was very slightly positive in the glomeruli .
electron microscopy revealed electron - dense deposits with randomly arranged nonbranching fibrils , measuring approximately 20 nm in diameter in the mesangial lesion and glomerular basement membranes ( fig .
the patient was diagnosed with fgn , and treatment with 50 mg of oral losartan potassium once daily was initiated .
serum creatinine was stable , and the excretion of urine protein was decreased to 0.53 g / g cr 7 months after the start of therapy .
case 2 had no significant medical history in his annual medical checks . at 34 years of age
the dipstick test for occult blood was also positive at a later annual urinalysis ; thus , he was admitted to a nearby hospital for renal biopsy .
he had no hypertension or edema at the time of admission and urine protein excretion was 2.0 g / day without microscopic hematuria .
immunological tests including antinuclear antibody , complements , and immunoglobulins were not specific , and hepatitis b or c viral tests were also negative . on light microscopy ,
49 glomeruli were observed but no global or segmental sclerosis was observed , and there was diffuse mesangial matrix expansion , along with partial double contour of the glomerular basement membranes ( fig .
tubular atrophy and interlobular arterial sclerosis were very mild , whereas arteriolar hyalinosis was negative .
on immunofluorescence , mild igg and igm , and strong c3 depositions were observed in the mesangium and capillary walls .
he was diagnosed with membranoproliferative glomerulonephritis ( mpgn ) and treated with prednisolone and cyclophosphamide .
two years later , this combination therapy was discontinued because the treatment was ineffective , and imidapril 5 mg / day was prescribed after that .
five years after his biopsy , his urine protein excretion was 1.68 g / day , and serum creatinine was 70.7
he did not undergo renal biopsy , and , unfortunately , the medical records have been lost .
the unique point was the deposition of microfibrils with 20 nm in diameter in the basement membranes of the arteriolar wall .
fibrils of fgn are typically found in the mesangium and glomerular basement membranes with or without subepithelial and subendothelial electron - dense deposits [ 4 , 5 , 6 , 10 , 11 , 12 ] . in a few previous reports
, fibril structures were noticed in the tubular basement membranes by electron microscopy , whereas arteriolar deposition was not confirmed [ 4 , 5 , 6 , 10 , 11 , 12 ] .
although the pathophysiology of the fibrillary deposition is still unknown , the histopathological features suggest that the fibrils might be derived from immunoglobulins and have an affinity to the extracellular matrix [ 4 , 5 , 9 , 13 ]
. it may be natural that fibrils deposit in the basement membrane of the arteriolar wall in fgn .
fgn exhibits various glomerular changes , including mpgn , mesangial proliferative glomerulonephritis ( mespgn ) , and membranous glomerulonephritis [ 34 , 5 , 6 ] .
some individuals with fgn have background diseases such as hepatitis c virus infection , polyclonal gammopathy , and lymphoproliferative disorders [ 5 , 6 , 14 , 15 ] . from the above
table 1 shows previously published familial cases [ 8 , 9 ] . in this summary ,
the histological patterns comprised mgpn , mespgn , and membranous glomerulonephritis . in our cases as well as in previous familial cases , there were no comorbidities such as infectious , autoimmune , or malignant diseases in their history .
the glomerular changes of case 1 and case 2 were thought to be more comparable to mespgn than mpgn , and there were no secondary causes that would induce mespgn .
therefore , fgn was presumed to be the clinical diagnosis in the case of the elder brother ( case 2 ) , although electron microscopy was not performed and this is a limitation in our report .
the variety of inherited pathways , including father to son , father to daughter , and mother to son , was confirmed in the previous reports [ 8 , 9 ] ; therefore , an autosomal dominant genetic form is suspected .
fgn develops at 4060 years of age ; thus , patients with fgn could procreate in their reproductive years .
herein , we reported a very rare case of fgn with fibril deposition in the arteriolar wall and possible cases of familial incidence . to clarify the etiology and effective therapy for fgn
 herein , we report a case of fibrillary glomerulonephritis ( fgn ) . 
 fgn usually shows non - amyloidal fibrils in the mesangium and glomerular capillary walls on electron microscopy . 
 inherited cases of fgn have been reported in only 3 families , and the suspected genetic form was autosomal dominant . in the present case , 
 the deposition of microfibrils in the arteriolar wall as well as the glomerulus is unique . 
 our patient 's father died of nephrotic syndrome , and his elder brother had a biopsy - proven glomerulopathy . 
 the histological findings of the brothers are similar to mesangial proliferative glomerulonephritis and resemble each other . 
 therefore , our case is presumed to be familial fgn 
 . additionally , herein , we review the literature and reconsider the histological and clinical characters of fgn . 