Impact of the cyclosporine-ketoconazole interaction in children with steroid-dependent idiopathic nephrotic syndrome.
BACKGROUND
Children with steroid-dependent nephrotic syndrome experience serious side effects from steroid therapy. Cyclosporine A (CsA), which is an effective agent in the treatment of steroid-dependent nephrotic syndrome, is expensive and, consequently, often unaffordable in developing countries. Many studies have documented the benefit of ketoconazole administration in transplant adults treated with CsA. We have conducted a retrospective study with the objective of addressing cost-savings, safety, and the efficacy of the co-administration of ketoconazole and CsA to children with steroid-dependent nephrotic syndrome.


METHODS
This study included 102 nephrotic patients who were steroid-dependent and who received cyclosporine therapy. The commonest pathologic lesions were focal segmental glomerulosclerosis (64 patients) and minimal change disease (36 patients). Among the patients participating in the study, 78 received daily ketoconazole therapy (ketoconazole group) in the form of a 50-mg dose accompanied by an initial one-third decrease in the CsA dose, while 24 received CsA alone (non- ketoconazole group). All of the patients were children (below 18 years), and the male-to-female ratio was 3:1. The mean duration of treatment was 22.9 months. The characteristics of both groups were comparable.


RESULTS
Co-administration of ketoconazole significantly reduced mean doses of CsA by 48% with a net cost savings of 38%. It also resulted in a significant improvement in the CsA response and a more successful steroid withdrawal as well as a decrease in the frequency of renal impairment. Liver function tests remained normal in both groups up to and including the final follow-up (mean of 33.6 months).


CONCLUSIONS
The co-administration of ketoconazole to CsA in children with idiopathic steroid-dependent nephrotic syndrome safely results in a significant reduction in CsA cost, which causes great concern in developing countries. It may also improve CsA response.
El-Husseini
Amr
A
Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. amr_2000_2002@yahoo.com
El-Basuony
Fathy
F
Mahmoud
Ihab
I
Donia
Ahmed
A
Sheashaa
Hussein
H
Sabry
Alaa
A
Hassan
Nabil
N
Sayed-Ahmad
Nagy
N
Sobh
Mohamed
M
D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D007654:Ketoconazole / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced* / Q000188:drug therapy* / Q000191:economics; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D002216:Captopril; D007654:Ketoconazole