Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial.
BACKGROUND
To examine whether tacrolimus is more effective and safe than cyclosporine (CsA) in inducing remission in patients with steroid-resistant nephrotic syndrome (SRNS).


METHODS
Randomized controlled trial, nonblind, parallel group.


METHODS
Tertiary-care hospital; 41 consecutive patients with idiopathic SRNS, estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2), and histological characteristics showing minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis were randomly assigned to treatment with tacrolimus (n = 21) or CsA (n = 20).


METHODS
Tacrolimus (0.1 to 0.2 mg/kg/d) or CsA (5 to 6 mg/kg/d) for 1 year; cotreatment with alternate-day prednisolone and enalapril.


RESULTS
Patients achieving complete remission (urinary protein-creatinine ratio < 0.2 g/g and serum albumin > or = 2.5 g/dL) or partial remission (urinary protein-creatinine ratio, 0.2 to 2 g/g, and serum albumin > or =2.5 g/dL) at 6 and 12 months; time to remission; proportion with relapses; side effects.


RESULTS
No patient was lost to follow-up. After 6 months of therapy, remission occurred in 18 (85.7%) and 16 patients (80%) treated with tacrolimus and CsA, respectively (relative risk [RR], 1.07; 95% confidence interval [CI], 0.81 to 1.41). Rates of remission at 12 months were also similar (RR, 1.14; 95% CI, 0.84 to 1.55). The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus (RR, 4.5; 95% CI, 1.1 to 18.2; P = 0.01). The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA (difference in mean values, 45.1 mg/dL; 95% CI, 19.1 to 71.2). Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7% and 10% patients, respectively. Cosmetic side effects (hypertrichosis and gum hypertrophy) were significantly more frequent in CsA-treated patients (P < 0.001).


CONCLUSIONS
Single-center study, small sample size, and short duration of follow-up.


CONCLUSIONS
Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS. Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects.
Choudhry
Swati
S
Division of Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Bagga
Arvind
A
Hari
Pankaj
P
Sharma
Sonika
S
Kalaivani
Mani
M
Dinda
Amit
A
D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008856:Microscopy, Fluorescence; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D012074:Remission Induction; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D016559:Tacrolimus