Kidney Week

Abstract: TH-PO155

Five Year Outcome of Steroid Resistant Focal Segmental Glomerulosclerosis (FSGS) Treated with Tacrolimus

Session Information

• Clinical Glomerular Disorders: FSGS, MN, MCD
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

• 1005 Clinical Glomerular Disorders

Authors

• Kohli, Harbir Singh, Post Graduate Institute of Medical Education and Research (PGIMER), CHANDIGARH, Haryana, India

Harbir Singh Kohli,

• Ramachandran, Raja, Nehru Hospital, Chandigarh, India

Raja Ramachandran,

• Gupta, Krishan Lal L., Postgraduate Institute of Medical Education & Research, Chandigarh, India

Krishan Lal L. Gupta,

Background

Calcineurin inhibitors (CNIs) are recommended for steroid-resistant (SR) nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) by KDIGO as the 1^st line agents. We reported earlier a remission in 52% at 1year. CNI use is limited by relapse after stopping and nephrotoxicity on prolonged use. The objective of the study was to report the 5 year outcome of patients treated initially with tacrolimus (TAC) for SR-FSGS.

Methods

Patients were treated with TAC (trough level 5–10 ng/ml) and prednisolone (0.15 mg/kg/d). TAC was discontinued in nonresponders at 24 weeks(TAC resistant). TAC was continued for 48 weeks in responders. After completing the study period, patients were managed as per treating physicians discreetion. Patients were followed up furthur for 4 years or till end stage renal disease (ESRD)/death. Primary outcomes, doubling of serum creatinine, ESRD or death and secondary outcomes remission rate (CR and PR) and persistent NS were studied.

Results

Of 44 who received TAC,at 48 weeks, CR and PR were achieved in 17 (38.6%) and 6 (13.6%) respectively, 21 (47.7%) patients were TAC resistant. At end of 5 years of starting therapy, 2 patients were lost to follow up 1 in each group. Of 22 responders14 (61%) had relapse on stopping TAC, they were restarted on TAC for another year. Four had sustained remission, while 4 became TAC dependent and 6 TAC resiatant. Of 4 Tac dependent, 3 responded to rituximab, only 2 of 6 TAC resistant received rituximab of which 1 responded. while others took ACE inhibitors or indigenous drugs. Kidney biopsy done in 8 patients after 2 years of TAC showed chronicity. Of 20 TAC resistant 2 of 3 who received rituximab responded. At the end of 5 years of starting TAC, in responders CR, PR, persistent NS, CKD, ESRD and death were seen in 3 (13.6%), 13 (59.1%), 5 (22.7%), none, 1 (4.6%) and none respectively, and amongst resistant patients1 (5%), 2 (10%), 3(15%), 3 (15%), 7 (35%) and 4 (20%). Fourteen (70%) patients with resistant disease had attained primary outcome compared to 1 (4.5%) in the remission group (p=0.0001).

Conclusion

TAC resistance portends poor prognosis with 70% having doubling of serum creatinine, ESRD or death at the end of 5 years. TAC dependency was seen in 60% of the initial TAC responders. Rituximab appears to be promising agent in both TAC dependent and resistant patients.