Preprandial C2 monitoring of cyclosporine treatment in children with nephrotic syndrome

Abstract

Sirs, We read with great interest the article by Rinaldi et al. [1] regarding cyclosporin (CsA) monitoring by use of abbreviated area under the curve (AUC) in nephrotic syndrome (NS). Although dose monitoring based on CsA trough levels (C0) has been widely used, it has been reported to be poor predictor of clinical outcome [2]. Recently, monitoring of 2-h post-dose CsA levels (C2) has been reported to be useful in adult transplant recipients [3], although the best way to monitor the blood levels remains unclear in children. Rinaldi et al. stated that mean CsA blood levels correlate with AUC better than C0 or C2 levels [1]. Though abbreviated AUC using this measure may be helpful in children with long-lasting NS and result in a low incidence and less toxicity, it is impractical to collect several blood samples and is more expensive. We are currently investigating the usefulness of single measurement of blood concentration 2 h after preprandial CsA (Neoral oral formulation, Novartis) administration. So far, 12 children (mean age 9.6 years) with steroiddependent (N=8) or steroid-resistant NS (N=4) in remission were enrolled in the study. Renal biopsy was performed on all patients before commencement of CsA treatment; this revealed minimal change disease in 11, focal segmental glomerulosclerosis in 1. CsA level had been initially monitored by C0 level for 6 months (C0 period) and subsequently converted to C2 level (6 months: C2 period). Oral dose of CsA was started from 2.5–5 mg kg 1 daily in two divided doses and was adjusted to target levels: C0 of 50–100 ng mL 1 by postprandial administration and C2 of 400–600 ng mL 1 by preprandial administration. It is postulated that high variability of intra-individual or inter-individual CsA blood level during the absorption phase [4] results in low reproducibility. Therefore, we used preprandial C2 level for monitoring because this may improve the variability [5]. With regard to steroids during the study period, predonisone (PSL) was used only until achieving remission when patients relapsed: then it was tapered off over 3 to 6 months. Clinical and laboratory data during the study period are summarized in Table 1: whereas the average number of relapses was not significantly different between the C0 period and the C2 period, the mean dose of CsA in the C2 period was significantly lower than that in C0 period (P<0.01) and the mean dose of PSL in the C2 period was nearly two-thirds that in C0 period. Because clearance of CsA is more rapid in children than in adults [6], C0 might be lower than the corresponding AUC, resulting in a larger dose of CsA. Taken together, we believe that CsA monitoring using the preprandial C2 level is closer to the AUC than that using C0, and is more simple and less expensive than that of mean concentrations. S. Fujinaga ()) · M. Takada · Y. Ohtomo · S. Akashi Division of Nephrology, Saitama Children’s Medical Center, Shuichiro 2100, Magome Iwatsuki City, Saitama 339, 8551 Iwatsuki, Japan e-mail: f_shuich@d2.dion.ne.jp Tel.: +81-48-758-1811 Fax: +81-48-758-1818