Ineffectiveness of Abatacept in Steroid

and Rituximab resistant FSGS

Dr. VinothKumar Kavarthapol Jayaraman 1 , Dr. Mark Thomas 1
1 Royal Perth Hospital WA. Email: vino.kavarthapoljayaraman@health.wa.gov.au

Introduction
Focal segmental glomerular sclerosis is currently the leading cause of Nephrotic syndrome and leads to ESRD in millions of persons worldwide . In
majority of cases this was thought secondary to unknown circulating factors. However, supportive clinical data are inconsistent . Treatment is primarily
with immunosuppressive agents and primary focal segmental glomerulosclerosis (FSGS) appears to respond well to glucocorticoids . Calcinuerin inhibitors
like Cyclosporine, Tacrolimus and B cell depleting agent Rituximab has been used with varying degree of success in steroid resistant or relapsing disease.
Plasmapheresis has been shown to be beneficial in some patients with refractory primary FSGS . Recently T cell co stimulatory signal inhibition has been shown
to be beneficial in patients with recurrent FSGS .

We report a case of steroid resistant primary FSGS, who failed on cyclosporine, Rituximab and the T cell Co stimulatory inhibitor Abatacept.

Patient Information Discussion

A 62year old, Caucasian Male Abatacept (CTLA-4-Ig) is an inhibitor of the T-cell co-stimulatory molecule B7-1 (CD 80). Yu, C.C., et al has shown
presented with oedema and lethargy reversal of nephritic range proteinuria in 4 patients with rituximab resistant recurrent FSGS and one patient with
and was noted to have nephrotic range glucocorticoid resistant primary FSGS. In our patient Abatacept failed to improve proteinuria.
proteinuria and hypoalbuminemia. He
underwent renal biopsy to confirm Abatacept might not be the answer for all patients with glucocorticoid and rituximab resistant FSGS. B7-1
the diagnosis of FSGS. Secondary immunostaining has been shown to be a predictive factor for identifying the subgroup of patients who might respond
causes were excluded and patient to abatacept. We recommend performing B7-1 immunostaining prior to commencing abatacept. More trials are
was commenced on oral prednisolone necessary to find the cohort of patients who might respond to Abatacept therapy. Cost of medication should be
therapy with significant improvement considered along with risk benefit analysis prior to instituting such therapy.
in proteinuria resulting in slow
withdrawal of therapy over 3 months.
He represented 2 yrs post cessation of
prednisolone with worsening proteinuria
Lab Value Trends
Lab Value Trends
and was commenced on second
course of prednisolone therapy. In view 1600 30 Creatinine in micromol/L
of poor response, he was trialled on Urine PCR in mg/mmol
a 2 month course of Cyclosporin; he
Cr in umol/L and PCR in mg/mmol

1400 Serum Albumin in g/L

became intolerant to this with severe 25
hypertension, headaches and worsening 1200
creatinine. Renal biopsy performed at
this stage demonstrated sclerosis in 20
Albumin g/L

1000
1/16 glomeruli with mild nodular arterial
hyalinosis and <10% interstitial fibrosis
Learning Points
consistent with CNI toxicity. 800 15 1. Abatacept might not be the
answer for all patients with
Subsequently, he was converted to 600 glucocorticoid and rituximab
a six month regimen of high dose 10 resistant FSGS
alternate day prednisolone and 400 2. B7-1 immunostaining has been
cyclophosphamide therapy. With shown to be a predictive factor
5
minimal improvement in proteinuria and 200 for identifying the subgroup of
ongoing deterioration in renal function, patients who might respond to
this regimen was stopped at 5th abatacept.
0 0
month mark.
3. Cost of medication should be
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considered along with risk benefit

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Following this he was trialled on

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B cell depleting agent Rituximab analysis prior to instituting such

Date therapy.
and continued on ACE/ARB/CCB/
Statin/Diuretic therapy. Unfortunately Rituximab Abataceptt 4. Beware of literature bias
his serum albumin and proteinuria
continued to worsen leading to trial of
oral galactose therapy for 2 months.
Without much progress with any of
Before Abatacept 8 weeks post Abatacept
the above therapies patient agreed
to trail on Abatacept. He received 4 Age 62 yrs
doses of Abatacept (750mg IV) over
Sex Male
a 4 month period. Though he tolerated
this regimen, he did have noticeable Racial origin Caucasian
improvement in either proteinuria
Baseline creatinine 169 µmol/L 164 µmol/L
or creatinine.
Urine PCR 1010 mg/mmol 1050 mg/mmol
Serum albumin 16 g/L 16 g/L

Reference
1. Dragovic, D., et al., Increasing incidence of focal segmental glomerulosclerosis and an examination of demographic patterns. Clin Nephrol, 2005. 63(1): p. 1-7.
2. Haas, M., et al., Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis, 1997. 30(5): p. 621-31.
3. D’Agati, V.D., F.J. Kaskel, and R.J. Falk, Focal Segmental Glomerulosclerosis. New England Journal of Medicine, 2011. 365(25): p. 2398-2411.
4. Banfi, G., et al., The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. Clin Nephrol, 1991. 36(2): p. 53-9.
5. Mitwalli, A.H., Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit patients with focal segmental glomerulosclerosis? Nephrol Dial Transplant, 1998. 13(6): p. 1524-8.
6. Yu, C.C., et al., Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med, 2013. 369(25): p. 2416-23.

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