Preprandial C2 monitoring of cyclosporine treatment in children with nephrotic syndrome

Fujinaga, Shuichiro; Kaneko, Kazunari; Takada, Moriatsu; Ohtomo, Yoshiyuki; Akashi, Shunji; Yamashiro, Yuichiro

doi:10.1007/s00467-005-1932-7

Cited by 12 publications

(9 citation statements)

References 6 publications

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“…In the previous studies of mCyA treatment by C 2 monitoring for childhood FRNS, the mean relapse rates varied from 0.2 to 1.5 per year under the mean C 2 levels, which ranged from 497.8 to 729.0 ng/ml (13,16,18,20). The relapse rate in group A in the present study (0.41/person-year) was not inferior to the relapse rates in previous studies.…”

Section: Discussioncontrasting

confidence: 53%

“…One of the clinical benefits of C 2 monitoring, shown in the majority of studies on transplantation, is a reduction in mean cyclosporine dose, which may reduce the rate of adverse effects of cyclosporine, including chronic cyclosporine nephrotoxicity (12). Several reports described the efficacy and/or safety of mCyA treatment with C 2 monitoring, mainly with single daily dose, in children with FRNS (13)(14)(15)(16)(17)(18)(19)(20). However, there were few prospective studies to determine appropriate C 2 target with two divided oral doses of mCyA in children with FRNS.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclosporine C2 Monitoring for the Treatment of Frequently Relapsing Nephrotic Syndrome in Children

Iijima¹,

Sako²,

Oba³

et al. 2014

Clinical Journal of the American Society of Nephrology

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to compare two protocols for treating children with frequently relapsing nephrotic syndrome using microemulsified cyclosporine.Design, setting, participants, & measurements Ninety-three children with frequently relapsing nephrotic syndrome were randomly assigned to group A (n=46) or group B (n=47). In both groups, the 2-hour postdose cyclosporine level was monitored. For group A, the cyclosporine target was set to 600-700 ng/ml for the first 6 months and 450-550 ng/ml for the next 18 months; for group B, it was set to 450-550 ng/ml for the first 6 months and 300-400 ng/ml for the next 18 months. The primary end point was the sustained remission rate. At the end of the study, if there was no difference in safety profile between the two groups and the sustained remission rate in group A was superior to group B with a decision threshold of 8%, then the regimen for group A would be determined the better treatment.Results Eight children from an ineligible institution, where cyclosporine levels were not measured, were excluded from all analyses. At 24 months, the sustained remission rate was nonsignificantly higher in group A (n=43) than group B (n=42; 64.4% versus 50.0%; hazard ratio, 0.57; 95% confidence interval, 0.29 to 1.11; P=0.09), and the progression-free survival rate was significantly higher (88.1% versus 68.4%; hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.94; P=0.03). The relapse rate was significantly lower in group A than group B (0.41 versus 0.95 times/person-year; hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.84; P=0.02). The rate and severity of adverse events were similar in both treatment groups. ConclusionThe sustained remission rate was not significantly different between the two treatment groups, but the regimen with the higher 2-hour postdose cyclosporine level target improved progression-free survival and reduced the relapse rate.

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Section: Discussioncontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Cyclosporine C2 Monitoring for the Treatment of Frequently Relapsing Nephrotic Syndrome in Children

Iijima¹,

Sako²,

Oba³

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…26 Therefore, converting from C0 monitoring to a single measurement of blood concentration two hours after CsA administration (C2) may reduce the incidence of CsAN, as C2 monitoring has been reported to be a more accurate predictor of drug exposure than C0 27 and results in a reduction of CsA dose. 28 Alternatively, genetic screening for mutations of podocin could be useful in order to reduce the possibility of unnecessary administration of steroids or CsA; as it has recently been postulated that children with SRNS and homozygous or compound heterozygous mutations in the gene encoding podocin do not respond to standard steroid or CsA treatment but have a reduced risk for recurrence in a renal transplant, early renal transplantation might be an alternative strategy in such patients. 29 In conclusion, alternative treatment involving cessation, tapering, or replacement should be seriously considered before 36 months of administration of CsA and the use of CsA in children younger than 5 years should be avoided if possible.…”

Section: Discussionmentioning

confidence: 99%

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome

Fujinaga

Kaneko²,

Muto³

et al. 2006

Archives of Disease in Childhood

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Background: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. Aims and Methods: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. Results: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. Conclusion: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.

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“…The reason why [14]. Some recent studies also demonstrated that preprandial administration of CyA provided a more stable absorption profile [9,18,23]. With administration preprandially or just before meal, the drug reaches the digestive tract prior to food, and subsequent entry of food into the digestive tract promotes bile secretion; this may be connected with the good absorption of CyA [14].…”

Section: Discussionmentioning

confidence: 88%

“…Even though Neoral® was administered, some patients showed a delay in absorption [20]. Recently, however, some reports indicated that preprandial administration of CyA provided a stable absorption profile [9,14,18,23]. Trough levels (C0) have traditionally been used to monitor CyA whole blood concentration in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

Ushijima¹,

Uemura²,

Yamada³

2011

Eur J Pediatr

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The aim of this study was to investigate age-related pharmacokinetic differences of cyclosporine (CyA) in children with nephrotic syndrome. Whole blood concentrations of CyA were monitored for a total of 96 times in 36 cases. The 25 male and 11 female patients ranged in age from 1.9 to 19.7 years with a mean age of 9.1 years. Renal biopsy showed minimal change in 33 patients and focal segmental glomerulosclerosis in three patients. CyA was orally administered in two divided doses just before meals. The doses of CyA administered were adjusted such that the target value for blood concentration at 2 h post-dose (C2) was 400-450 ng/ml. The 96 subjects were divided into three groups according to age: group I, 1-5 years (n = 30); group II, 6-10 years (n = 34); and group III, ≥ 11 years (n = 32). In all subjects, peak levels (Cmax) of CyA were reached at C1 or C2. There was no significant difference between the groups for C2, area under the whole blood concentration-time curve up to 4 h post-dose (AUC0-4), and Cmax. The mean CyA doses of groups I, II, and III were 4.8 ± 1.0 mg/kg/day, 3.8 ± 0.9 mg/kg/day, and 3.0 ± 0.6 mg/kg/day, respectively, and there were significant differences between every two groups. In addition, the dose-normalized Cmax (Cmax/dose) and AUC0-4 (AUC0-4/dose) values were significantly lower in the younger group than in the older group. These findings suggested that in children, when the same concentration is targeted, the required CyA dose would vary according to age but would be significantly higher for the younger children.

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Preprandial C2 monitoring of cyclosporine treatment in children with nephrotic syndrome

Cited by 12 publications

References 6 publications

Cyclosporine C2 Monitoring for the Treatment of Frequently Relapsing Nephrotic Syndrome in Children

Cyclosporine C2 Monitoring for the Treatment of Frequently Relapsing Nephrotic Syndrome in Children

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome

Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

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