Efficacy and safety of cyclosporine versus tacrolimus in steroid and cyclophosphamide resistant nephrotic syndrome: A prospective study

Abstract

Calcineurin inhibitors (CNIs) are the preferred drugs for treatment of childhood steroid-resistant nephrotic syndrome (SRNS) who are also resistant to cyclophosphamide (CYC). Although few studies have shown a benefit of one over the other, efficacy and safety of either CNIs (tacrolimus [TAC] or cyclosporine [CSA]) in this special population remained to be assessed in long-term studies. Forty-five children with SRNS who were also resistant to CYC (CYC-SRNS) from January 2006 to June 2011, were included in the study. Patients were treated with CNI either TAC or CSA based on 1:1 allocations and were prospectively observed. Patients who were nonresponsive to CNIs had been treated with mycophenolate mofetil. Outcomes were measured in terms of remission of NS, adverse effects of drugs, and progression of disease. After 6 months of treatment, 16/23 (69.5%) patients on CSA achieved remission and 18/22 (81.8%) on TAC achieved remission (P = 0.3). The side effects hypertrichosis, and gum hyperplasia were significantly less in TAC group as compared to CSA group (P < 0.001). The 1-, 2-, 3-, 4-, and 5-year estimated renal survival (doubling of serum creatinine as event) in CSA group was 96%, 91%, 85%, 54%, and 33% and in TAC group was 96%, 95%, 90%, 89%, and 79%, respectively (P = 0.02). Although TAC and CSA are equally efficacious, TAC has significantly less side effects. The long-term outcome of renal function was significantly better in patients who were treated with TAC as compared to CSA.

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

“…Several studies have shown the effectiveness of PDN in relapsing SRNS at 2 mg/kg/day to induce remission [52,53] with a change to QOD PDN, followed by tapering until the end of month 6 [185,186]. Intravenous MPDN was also effective in inducing remission in relapsing patients [71,74,187].…”

Current understandings in treating children with steroid-resistant nephrotic syndrome

“…While other CNIs like voclosporin are currently being tested in clinical trials, CSA and TAC are the two major agents which are commonly used in the treatment of nephrotic syndrome. TAC and CSA are generally accepted to have similar therapeutic effects [ 7 ], showing similarly superior efficacy over CPM [ 29 ] and no significant difference in the numbers of SRNS patients achieving remission [ 30 , 33 ]. Prasad et al studied 45 children with SRNS who were resistant to CPM, in which they treated the patients with either CSA or TAC and compared treatment outcome at 6 months [ 33 ].…”

“…TAC and CSA are generally accepted to have similar therapeutic effects [ 7 ], showing similarly superior efficacy over CPM [ 29 ] and no significant difference in the numbers of SRNS patients achieving remission [ 30 , 33 ]. Prasad et al studied 45 children with SRNS who were resistant to CPM, in which they treated the patients with either CSA or TAC and compared treatment outcome at 6 months [ 33 ]. They showed that CNIs were effective in CPM-resistant nephrotic syndrome and reported comparable results of TAC and CSA in inducing remission in 70% and 82% of patients, respectively ( P = 0.3) [ 33 ].…”

“…Prasad et al studied 45 children with SRNS who were resistant to CPM, in which they treated the patients with either CSA or TAC and compared treatment outcome at 6 months [ 33 ]. They showed that CNIs were effective in CPM-resistant nephrotic syndrome and reported comparable results of TAC and CSA in inducing remission in 70% and 82% of patients, respectively ( P = 0.3) [ 33 ]. However, Choudhry et al showed that significantly fewer children relapsed in the TAC-treated group compared to the CSA-treated group [ 34 ], suggesting superior efficacy of TAC over CSA.…”

Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults

“…1 However, tacrolimus is a more potent immunosuppressant than cyclosporin 15 with a more favorable renal safety profile. [16][17][18] It also compares favorably with cyclophosphamide for inducing remission in steroiddependent/steroid-resistant adults with MCNS, [19][20][21] and is effective as rescue therapy for patients who have failed treatment with other immunosuppressants. [21][22][23] In addition to its immunosuppressive action, tacrolimus acts directly on podocytes 24,25 to stabilize the actin cytoskeleton and reduce levels of angiopoietin-like protein 4, a protein associated with podocyte injury and the pathogenesis of proteinuria in MCNS.…”