Objective: To observe the effects of long-term cyclosporine A (CsA) treatment in 20 children with steroid-resistant idiopathic nephrotic syndrome (SRNS) and analyse the relevant influencing factors of CsA therapy.
Methods: Twenty children with SRNS received CsA therapy for 2 years between February 2001 and October 2006 in the Department of Nephrology. The mean age of children at initiation of CsA therapy was 5.5 years (30 months to 12 years). The initial renal histology showed minimal change (MCNS) in 15 patients, focal segmental glomerulosclerosis (FSGS) in 4 patients and mesangial proliferative glomerulonephritis (MsPGN) in one. The starting dose of CsA was 3 - 5 mg/(kg.d), adjusted to maintain a trough level of 100- 200 microg/L during the first 6 months. After one year, a low dose of CsA 1 - 3 mg/(kg.d) with a trough level of 40 - 70 microg/L was applied to maintain remission for 1 year. Liver function, serum albumin, serum cholesterol, serum creatinine, urinary NAG/Cr, 24 h urinary protein excretion and CsA whole blood trough level of the patients were monitored every one or three months.
Results: (1) Complete remission (proteinuria < or = 0.1 g/d or negative by dipstick for 3 consecutive days), partial remission (proteinuria between 0.1 g/d and 50 mg/(kg.d), serum albumin > or = 30 g/L) and resistance to CsA (proteinuria > or = 50 mg/(kg.d), or > or = 3+ by dipstick, after 6 months of CsA treatment over a trough level of 100 microg/L) were observed in 65%, 20% and 15%, respectively. Eleven patients who had complete remission discontinued CsA, in 5 (45%) patients the disease relapsed, and resumption of CsA therapy was followed by remission in three of them. (2) MCNS showed a 93% response to CsA therapy while non-MCNS showed a 60% response, but the difference was not significant (P > 0.05). (3) Hypertrichosis, gingival hyperplasia and hypertension occurred in 75%, 25% and 10% of the patients, respectively. Two patients were found to have renal impairment (> 30% rise of serum creatinine) and recovered in 2 weeks. Four patients showed a rise of urinary NAG/Cr. The central nervous system adverse event occurred in 2 cases. Post-therapy biopsies performed in 3 patients (2 with FSGS and one with MCNS) did not show any relevant tubulointerstitial fibrosis. Two patients with FSGS of the twenty cases progressed into end-stage renal failure.
Conclusions: CsA treatment was confirmed to be effective in children with SRNS. Renal fibrosis was rare in patients treated with a low dose of CsA for 2 years.