collapsing focal segmental glomerulosclerosis ( fsgs ) , also known as collapsing glomerulopathy ( cg ) , was first described in association with hiv infection . subsequently
the clinical course of cg is characterized by rapid progression to end - stage renal disease and a dismal response to medical therapy .
a survey of observational studies reported complete and partial remission rates of 9.6 and 15.2% , respectively , despite multiple therapies that included steroids , calcineurin inhibitors ( cnis ) and cyclophosphamide .
there have been two reports suggesting a favourable response to rituximab in children with cg [ 2 , 3 ]
a 19-year - old - male presented in may 2007 with swelling of the lower limbs and periorbital puffiness of 2 months duration . evaluation at his primary health centre had revealed albuminuria on dipstick analysis , prompting referral to our institution .
he gave no history of recent infections , arthralgia , oral ulcers , cough or haemoptysis .
the blood pressure was 110/70 mmhg , pulse rate was 90 b.p.m . and respiratory rate 14/min .
mol / l ( 0.8 mg / dl ) ; serum total protein and albumin were 55 and 17
g / l ( 5.5 and 1.7 g / dl ) , respectively , and aspartate and alanine aminotransferases were 12 and 14 iu / l , respectively .
mmol / l ( 400 mg / dl ) , triglyceride 2.8 mmol / l ( 250 mg / dl ) , low - density lipoprotein 7.2 mmol / l ( 280 mg / dl ) and high - density lipoprotein 1.3 mmol / l ( 50 mg / dl ) .
he tested negative for hepatitis b surface antigen , anti - hcv antibody and human immunodeficiency virus i / ii .
kidney biopsy ( figure  1a ) revealed 10 glomeruli , which were normal on light microscopy ( lm ) , as were the tubulointerstitial and vascular compartments .
immunofluorescence did not reveal any immune deposits and electron microscopy ( em ) showed diffuse foot process effacement . 

1.photomicrograph showing ( a ) normal glomeruli by lm ( pas , 40 ) , and complete foot process effacement by em ( not shown ) , consistent with minimal - change disease ; ( b ) segmental collapse with overlying proliferation of visceral epithelial cells consistent with collapsing glomerulopathy ( masson 's trichrome , 40 ) , ( c ) electron microscrograph shows hypertrophied podocytes with vacuoles over a collapsed glomerular tuft ( uranyl acetate , 62 000 ) and ( d ) proliferating visceral epithelial cells stained with ki67 ( ihc , 40 ) photomicrograph showing ( a ) normal glomeruli by lm ( pas , 40 ) , and complete foot process effacement by em ( not shown ) , consistent with minimal - change disease ; ( b ) segmental collapse with overlying proliferation of visceral epithelial cells consistent with collapsing glomerulopathy ( masson 's trichrome , 40 ) , ( c ) electron microscrograph shows hypertrophied podocytes with vacuoles over a collapsed glomerular tuft ( uranyl acetate , 62 000 ) and ( d ) proliferating visceral epithelial cells stained with ki67 ( ihc , 40 ) a diagnosis of minimal - change disease ( mcd ) was made and the patient was started on oral prednisolone at 1 mg / kg / day .
however , the proteinuria did not show any reduction . at the end of 4 months
, the daily urinary protein excretion remained at 5 g. he was deemed to be steroid resistant and treated first with oral cyclophosphamide at 2 mg / kg for 3 months , followed by oral cyclosporine ( 4 mg / kg / day , average c0 120 ng / ml ) and oral prednisolone ( 0.1 mg / kg / day ) for 6 months , mycophenolate mofetil 2 g / day for 6 months and finally a combination of tacrolimus ( 0.1 mg / kg / day , average tac c0 7 ng / ml ) and oral prednisolone ( 0.1 mg / kg / day ) .
< 20 g / l ( 2.0 g / dl ) and the serum creatinine 6280 mol / l ( 0.70.9 mg / dl ) ( figure  2 ) . during the entire course of his illness
, he was continued on supportive therapy with torsemide 1020 mg twice daily , atorvastatin 20 mg / day and losartan 150 mg / day . 

temporal evolution of the clinical and laboratory parameters . at this time , the kidney biopsy was repeated .
lm revealed 13 glomeruli , 2 of which showed segmental collapse of the capillary tuft with an overlying crown of podocytes along with synechiae formation , 2 showed segmental endocapillary cellularity with foam cells , 2 were globally sclerosed and the remaining 7 did not show any significant abnormality ( figure  1b ) .
tubules showed abundant protein absorption droplets along with patchy tubular atrophy occupying 20% of the biopsy area .
tubules close to the medulla showed marked nucleomegaly along with nuclear smudging associated with tubular necrosis , interstitial oedema and mild - to - moderate patchy plasma cell - rich interstitial inflammation occupying 10% of the biopsy area .
there was diffuse and extensive foot process effacement , and no reticular aggregates were seen .
ki 67 immunostain showed nuclear positivity in the podocytes of glomeruli showing collapse ( figure  1d ) .
the patient 's serum tested negative by polymerase chain reaction for cytomegalovirus and parvovirus b-19 . in view of his resistance to the above therapies and a persistently severe nephrotic state with the biopsy showing many plasma cells , the patient was treated with 4 weekly injections of rituximab ( 375 mg / m / dose ) .
his oedema subsided and he stopped requiring the diuretic 3 months after the last dose .
six months after the last dose of rituximab , the 24-h urine protein was 1.8 g with a serum albumin of 37
the patient has now been followed up for 18 months and remains asymptomatic . on his last follow - up ,
his 24-h urine protein is 1.2 g , serum creatinine 80 mol / l ( 0.9 mg / dl ) and serum albumin 47
figure  2 shows the evolution of his clinical and laboratory parameters during the course of the treatment .
we report the first case of adult - onset collapsing fsgs successfully treated with rituximab .
the prognosis of cg not associated with hiv infection has been uniformly dismal [ 68 ] .
based upon a survey of the observational studies that have reported the response to treatment of collapsing fsgs , the rates of durable complete and partial remission were 9.6 and 15.2% , respectively .
valeri et al . had reported steroid resistance in all of the 26 ( 100% ) cg patients treated with steroids .
one out of six ( 17% ) of the patients with steroid - resistant cg treated with cyclophosphamide achieved partial remission and two out three patients with steroid - resistant cg treated with cyclosporine achieved remission ( one complete and one partial ) . even though the evidence base is weak , aggressive treatment seems to be associated with higher remission rates , especially in patients with serum creatinine < 177 mol / l ( < 2 mg / dl ) and < 20% interstitial fibrosis on kidney biopsy [ 9 , 10 ] .
rituximab has been successfully used in the management of several glomerular diseases including idiopathic membranous glomerulonephritis , steroid - dependent and -resistant childhood nephrotic syndrome ( mcd and fsgs ) and vasculitides .
the efficacy of rituximab in idiopathic cg was shown in two case reports in the paediatric age group .
described a 2-year - old boy with steroid- and cyclosporine - resistant cg who went into complete remission with four doses of rituximab .
however , the child had a relapse after 4 months and required re - treatment with methyl prednisolone to achieve remission .
reported a favourable response to rituximab in a young patient with cg with dominant c1q containing mesangial immune deposits and cd 20 + interstitial infiltrates , who was initially resistant to steroids .
other interesting aspects of our case were that the initial kidney biopsy showed features of mcd , failure to respond to steroids , cyclophosphamide , cnis and mycophenolate mofetil , and the disease being found to have evolved into cg .
he tested negative for parvovirus b19 , which has been implicated in some cases of cg .
the lack of response suggests the possibility of fsgs . in a series of 11 patients with steroid - resistant mcd in whom
another possibility is of unsampled fsgs reported as mcd in the first biopsy , which had 10 glomeruli , whereas ideally 25 glomeruli should be evaluated to avoid missing this focal disease .
rituximab , tried in view of a persistent severe nephrotic state , led to partial remission , which has now been sustained for 18 months .
a less than complete response is not surprising in view of the histological changes on biopsy .
compared with the report of the successful use of rituximab in c1q nephropathy with cg by bitzan et al .
, our patient lacked cd 20 + infiltrates in the interstitium , but still responded to rituximab .
recently , it has become clear that b cells display a variety of functions other than antibody production , which could contribute to autoimmunity .
rituximab depletes b - lymphocytes and blocks t - cell activation by b - lymphocytes and other b - cell - derived factors .
our case is unique by the fact that it is the first case of adult - onset collapsing fsgs that has responded favourably to rituximab after failing all other treatments . in conclusion ,
we show a favourable effect of rituximab in an adult with cg , a difficult - to - treat condition .
we declare that the results presented in this paper have not been published previously in whole or in part , except in abstract format .
 collapsing focal segmental glomerulosclerosis ( fsgs ) , or collapsing glomerulopathy ( cg ) , responds poorly to commonly employed therapies , with a high proportion of patients progressing to end - stage renal disease . 
 we report an adult in a nephrotic state , diagnosed with minimal - change disease on biopsy , who failed to respond to steroids , calcineurin inhibitors ( cnis ) , mycophenolate mofetil and cyclophosphamide . 
 repeat biopsy showed cg . 
 treatment with 4 weekly doses of rituximab led to sustained remission of his nephrotic state . 
 this is the first report of adult - onset cg that has responded favourably to rituximab . 
 rituximab could be a treatment option for patients with this difficult - to - treat condition . 
Background
Case report
Discussion