| Abstract|| |
The use of Cyclosporin-A (CsA) has been well described and is currently recommended for use in patients with steroid dependent nephrotic syndrome (SDNS), especially when they start having steroid side effects. Over a three-year period, a total of 10 patients diagnosed as having SNDS at the King Hussein Medical Center, Amman, Jordan were retrospectively studied. Their mean age was 9.53 ± 4.9 years. All patients included in the study failed to maintain long-term remission following cyclophosphamide therapy and had all manifested at least one steroid side effect prior to the introduction of CsA. Kidney biopsy was performed on all patients and all had normal renal functions prior to the introduction of CsA. After inducing remission with conventional steroid therapy, CsA was given in a dose of 4-6 mg/Kg/day orally in two divided doses and adjusted to maintain a mean blood trough level between 100 and 150 ng/ml. Total duration of therapy ranged between six and 24 months with a mean of 17 ± 7.7. Steroid therapy was stopped in all patients within two months of starting CsA. Four patients relapsed after 4-6 months of stopping steroids. However, remission was re-induced when low dose alternate day prednisolone therapy was added. Two patients relapsed four months after stopping CsA, which was given for 24 months. Our study suggests that CsA is effective in maintaining long-term remission and decreasing steroid requirements in patients with SDNS.
Keywords: Cyclosporin-A, Nephrotic syndrome, Steroids
|How to cite this article:|
Saca E, Hazza I. Cyclosporine-A Therapy in Steroid Dependent Nephrotic Syndrome: Experience in Amman, Jordan. Saudi J Kidney Dis Transpl 2002;13:520-3
|How to cite this URL:|
Saca E, Hazza I. Cyclosporine-A Therapy in Steroid Dependent Nephrotic Syndrome: Experience in Amman, Jordan. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2014 Jul 31];13:520-3. Available from: http://www.sjkdt.org/text.asp?2002/13/4/520/33111
| Introduction|| |
Children with steroid dependent nephrotic syndrome (SDNS) usually experience steroid toxicity as they need to be maintained on steroids for a long time.  Cyclosporine-A (CsA) therapy is well recognized as having a steroid sparing effect in such patients and complete remission with discontinuation of steroids can be achieved in more than 75% of patients with SDNS. ,, This study was conducted prospectively at the King Hussein Medical Center describing our experience with the use of CsA in such children.
| Patients and Methods|| |
A total of 10 patients diagnosed as having SDNS were included in the study. Their age ranged between 4 and 14 years with a mean of 9.53 ± 4.9 years. All patients included failed to maintain long-term remission following steroid and cyclophosphamide therapy and had all manifested at least one steroid side effect prior to the introduction of CsA. The relevant data of the study patients are given in [Table - 1]. Kidney biopsy was performed on all the study patients. The definitions and criteria for the nephrotic syndrome (NS), remission, and relapse were those used by the International Study of Kidney Disease in Children. The NS was defined as urinary protein excretion >40 mg/m 2 per hour with hypoalbuminemia <25 g/l. Remission was defined as reduction of urinary protein excretion to <4 mg/m 2 per hour (Albustix, 0 to trace) for three consecutive days. Relapse was defined as the reappearance of proteinuria >40 mg/m 2 per hour for three consecutive days. Steroid dependency was defined as a remission within four weeks of prednisolone therapy with relapse occurring when the dose of prednisolone was reduced to below a critical level or within two weeks of discontinuation of therapy. 
Nine of the study patients had minimal change nephrotic syndrome (MCNS) and one patient had focal segmental glomerulosclerosis (FSGS). Remission was induced in all patients with traditional steroid therapy, 2 mg/kg/day. Once remission was achieved, CsA was introduced and the steroids were tapered by 0.5 mg/kg every two weeks. CsA was given in a dose of 4-6 mg/kg/day orally in two divided doses and adjusted to maintain a target trough blood level between 100 and 150 ng/ml all through the duration of therapy. Total duration of CsA therapy ranged between 6 and 24 months with a mean of 17 ± 77 months. Kidney function tests were normal in all study patients. Patients were monitored weekly for the first four weeks and monthly thereafter for hepatotoxicity, nephrotoxicity, and hypertension. The nephrotic state was evaluated with serial biochemical blood tests and urine analysis.
| Results|| |
All patients responded well to CsA and achieved complete remission and steroid therapy could be tapered and stopped within two months of starting CsA therapy. Four patients relapsed after six months; however, remission was re-induced when low dose alternate day steroid therapy was added using doses less than previously required. Two patients relapsed four months after stopping CsA treatment, which was given for a total duration of 24 months.
Hirsutism and gingival hyperplasia were the commonest side effects encountered (in 8 and 7 of the 10 patients respectively), but were not severe enough to warrant discontinuation of CsA therapy. [Table - 2] summarises all the side effects seen.
| Discussion|| |
There is consistent evidence that CsA decreases proteinuria by two different mechanisms. The first is its immunosuppressive action, which is directed toward secretion of a glomerular permeability factor. The second appears to be a non-immunologic effect on glomerular permselectivity, explaining reduced proteinuria in various etiologies of the nephrotic syndrome with no immunological background.
Ninety-five percent of children with MCNS respond to steroid therapy. However, more than 40% of responders have subsequent relapses.  The major concern in the therapy of SDNS is steroid side effects. The efficacy of CsA in the treatment of steroid responsive MCNS has been well demonstrated and the drug is proposed for use in patients with SDNS, especially when they have steroid side effects and have failed to achieve longterm sustained remission following cyclo phosphamide therapy. ,, For such patients the use of CsA becomes necessary to overcome, or at least decrease, steroid dependency and side effects. ,,
The main concern regarding CsA therapy is its nephrotoxicity characterized by tubulointerstitial lesions, focal glomerulosclerosis and arteriolar lesions, reported to occur in more than 15% of patients taking long-term low dose CsA. ,, Our study shows that all patients with MCNS had good response as we were able to stop steroids within one month of starting CsA therapy. Even patients who relapsed while on CsA therapy (40%) re-achieved remission when combined with alternate day prednisolone at doses lower than previously used and continued to be in remission without relapsing. This correlates well with the literature regarding the favorable response of MCNS to CsA.
The side effects encountered were all mild and on no occasion were we obliged to discontinue CsA.
Although there was no significant deterioration in the mean serum creatinine following CsA therapy, it is known that this does not rule out chronic CsA nephrotoxicity as this can only be documented by kidney biopsy. 
| Conclusion|| |
Treatment with CsA in children with SDNS is effective in maintaining long-term remission and minimizing steroid side effects. However, because of its potential nephrotoxicity it should not be used as a first line drug and its use should be limited to patients who failed other treatment modalities and/or have severe steroid side effects.
| References|| |
|1.||Inoue Y, Iijima K, Nakamura H, Yoshikawa N. Two-year cyclosporine treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 1999;13:33-8. [PUBMED] [FULLTEXT]|
|2.||Singh A, Tejani C, Tejani A. One-center experience with cyclosporine in refractory nephrotic syndrome in children. Pediatr Nephrol 1999;13(1):26-32. |
|3.||Mowry JA, McCarthy ET. Cyclosporine in glomerular disease. Semin Nephrol 1996; 16(6):548-54. |
|4.||International Study of Kidney Disease in Children. Early identification of frequent relapsers among children with minimal change nephrotic syndrome. J Pediatr 1982; 101:514-8. [PUBMED] |
|5.||Ragazzoni E, Agliata S, Airoldi G, et al. Nephrotic syndrome refractory to conventional therapy. Minerva Urol Nefrol 1999; 51(2):89-94. |
|6.||Hino S, Takemura T, Okada M, et al. Follow-up study of children with nephrotic syndrome treated with a long-term moderate dose of cyclosporine. Am J Kidney Dis 1998;31(6):932-9. |
|7.||Gregory MJ, Smoyer WE, Sedman A, et al. Long-term cyclosporine therapy for pediatric nephrotic syndrome: a clinical and histologic analysis. J Am Soc Nephrol 1996;7(4):543-9. |
Department of Pediatrics, King Hussein Medical Center, P.O. Box 143924, Amman 11814
[Table - 1], [Table - 2]