Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

Tellier, Stéphanie; Dallocchio, A.; Guigonis, Vincent; Saint-Marcoux, F.; Llanas, Brigitte; Ichay, L.; Bandı́n, Isabel; Godron, A.; Morin, Denis; Brochard, Karine; Gandia, Peggy; Bouchet, Stéphane; Marquet, Pierre; Decramer, Stéphane; Harambat, Jérôme

doi:10.2215/cjn.00320116

Cited by 37 publications

(37 citation statements)

References 41 publications

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“…Studies in patients with frequent relapses show that targeting higher levels of 12-hour area under the curve of mycophenolic acid, ranging from 30 to 45 mg$h/ml, were associated with sustained remission and lower corticosteroid requirement. [46][47][48][49] Similarly, an area under the curve >60 mg$h/ml and a trough concentration >3 mg/ml were associated with remission of proteinuria in children with nephrotic syndrome or lupus nephritis. 50 However, the dose of MMF in the current study was comparable to those reported previously (i.e., 25-35 mg/kg or 800-1200 mg/m 2 20,26,29 including studies that demonstrate pharmacokinetic adequacy.…”

Section: Discussionmentioning

confidence: 97%

Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome

Sinha

Gupta

Kalaivani

et al. 2017

Kidney International

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Studies of nephrotic syndrome show that substitution of calcineurin inhibitors by mycophenolate mofetil (MMF) enables sustained remission and corticosteroid sparing and avoids therapy associated adverse effects. However, controlled studies in patients with steroid resistance are lacking. Here we examined the effect of switching from therapy with tacrolimus to MMF on disease course in an open-label, one-to-one randomized, controlled trial on children (one to 18 years old), recently diagnosed with steroid-resistant nephrotic syndrome, at a referral center in India. Following six months of therapy with tacrolimus, patients with complete or partial remission were randomly assigned such that 29 received MMF while 31 received tacrolimus along with tapering prednisolone on alternate days for 12 months. On intention-to-treat analyses, the proportion of patients with a favorable outcome (sustained remission, infrequent relapses) at one year was significantly lower (44.8%) in the MMF group than in the tacrolimus group (90.3%). The incidence of relapses was significantly higher for patients treated with MMF than tacrolimus (mean difference: 1.05 relapses per person-year). While there was no difference in the proportion of patients with sustained remission, the risk of recurrence of steroid resistance was significantly higher for patients receiving MMF compared to tacrolimus (mean difference: 20.7%). Compared to tacrolimus, patients receiving MMF had a significantly (71%) lower likelihood of a favorable outcome and significantly increased risk of treatment failure (frequent relapses, steroid resistance). Thus, replacing tacrolimus with MMF after six months of tacrolimus therapy for steroid-resistant nephrotic syndrome in children is associated with significant risk of frequent relapses or recurrence of resistance. These findings have implications for guiding the duration of therapy with tacrolimus for steroid-resistant nephrotic syndrome.

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Section: Discussionmentioning

confidence: 97%

Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome

Sinha

Gupta

Kalaivani

et al. 2017

Kidney International

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“…The MPA pharmacokinetic parameters are highly variable, and there are numerous factors which may contribute to this variability, e.g., treatment duration, therapeutic indication, drugs co-administered, genetic, physiologic, and environmental factors, as well as kidney or liver dysfunction [8]. For TDM, MPA AUC 0-12 is the most useful parameter; however, obtaining full pharmacokinetic profile is time-consuming and inconvenient for patients, especially for children [25], and there is still a need to establish target values for children with nephrotic syndrome [8]. In our previous study [22], we suggested that for those children, MPA AUC 0-12 > 60 μg h/mL may be considered efficient to avoid proteinuria recurrence and ensure the safe and effective treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we did not observe any toxicity in those children. Other studies showed that MPA AUC 0-12 above 30 μg h/mL is recommended for children with nephrotic syndrome [26] or described fewer relapses in children with MPA AUC 0-12 above 45 μg h/mL [8]. However, there are some cases where MMF is ineffective when standard doses are administered.…”

Section: Discussionmentioning

confidence: 99%

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Limited sampling strategy to predict mycophenolic acid area under the curve in pediatric patients with nephrotic syndrome: a retrospective cohort study

Sobiak

Resztak

Pawiński

et al. 2019

Eur J Clin Pharmacol

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Purpose Limited sampling strategy (LSS) is a precise and relatively convenient therapeutic drug monitoring method. We evaluated LSSs for mycophenolic acid (MPA) in children with nephrotic syndrome treated with mycophenolic mofetil (MMF) and validated the LSSs using two different approaches. Methods We measured MPA plasma concentrations in 31 children using HPLC-UV method and received 37 MPA pharmacokinetic profiles (0-12 h). For six children, MPA profiles were estimated twice after two MMF doses. LSSs were developed using multilinear regression with STATISTICA and R software and validated using validation group and bootstrap method, respectively. Results The best three time point equations included C 1 , C 3 , C 6 (good guess 83%, bias − 2.78%; 95% confidence interval (CI) − 9.85-0.46); C 1 , C 2 , C 6 (good guess 72%, bias 0.72%; 95% CI − 5.33-7.69); and C 1 , C 2 , C 4 (good guess 72%, bias 2.05%; 95% CI − 4.92-13.01) for STATISTICA software. For R software, the best equations consisted of C 1 , C 3 , C 6 (good guess 92%, bias − 2.69%; 95% CI − 27.18-33.75); C 0 , C 1 , C 3 (good guess 84%, bias − 2.11%; 95% CI − 24.19-22.29); and C 0 , C 1 , C 2 (good guess 84%, bias − 0.48%; 95% CI − 30.77-54.07). During validation, better results were obtained for R evaluations, i.e., bootstrap method. Conclusions The most useful equations included C 0 , C 1 , C 3 and C 0 , C 1 , C 2 time points; however, the most precise included C 1 , C 3 , C 6 time points because of MPA enterohepatic recirculation. Better results were obtained for bootstrap validation due to greater number of patients. Validated LSS should be used only in the population for which it was developed. As there is growing evidence that underexposure of MPA is associated with insufficient treatment response, we recommend the introduction of therapeutic drug monitoring for MPA in children with nephrotic syndrome.

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“…Применяется в трансплантологии для профилактики и лечения отторжения органов. В литературе описаны случаи использования микофенолата мофетила при стероидзависимом идиопатическом нефротическом синдроме [83], системной красной волчанке [84] и других заболеваниях. В литературе имеются единичные указания на применение микофенолата мофетила при PANS.…”

Section: микофенолата мофетилunclassified

Current Approaches to PANS/PANDAS Diagnostics and Management

Костик

2020

Vopr. sovr. pediatr.

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PANS, or Pediatric Acute-onset Neuropsychiatric Syndrome, is characterized by the sudden onset of obsessive-compulsive syndrome and accompanied by anxiety, emotional lability and other symptoms. PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections, is a subtype of PANS. Modern data on PANS/PANDAS etiology, pathogenesis, diagnostics and management is presented in this article. Therapeutic decisions on using anti-inflammatory and immunotropic therapy including non-steroidal anti-inflammatory drugs, glucocorticoids, intravenous immunoglobulin, plasmapheresis, rituximab and mycophenolate mofetil are analysed.

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Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

Cited by 37 publications

References 41 publications

Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome

Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome

Limited sampling strategy to predict mycophenolic acid area under the curve in pediatric patients with nephrotic syndrome: a retrospective cohort study

Current Approaches to PANS/PANDAS Diagnostics and Management

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