Risk Factors for Cyclosporin A Nephrotoxicity in Children with Steroid-Dependant Nephrotic Syndrome

Kengne-Wafo, Severin; Massella, Laura; Diomedi-Camassei, Francesca; Gianviti, Alessandra; Vivarelli, Marina; Greco, Marcella; Stringini, Gilda; Emma, Francesco

doi:10.2215/cjn.01520209

Cited by 53 publications

(46 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, two patients (4.7%) in group A developed mild to moderate chronic cyclosporine nephrotoxicity, and zero patients in group B developed this condition. Although the reason is unclear, the prevalence of chronic cyclosporine nephrotoxicity in the present study was much lower than the prevalence in a previous study (discussed in Supplemental Appendix) (15), suggesting that the regimens used in the present study were safe with respect to the development of this condition. The two patients who developed cyclosporine nephrotoxicity both had 9-month AUC levels that seemed to be notably higher than the mean for group A (Supplemental Table 4).…”

Section: Discussioncontrasting

confidence: 75%

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 75%

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

View full text Add to dashboard Cite

show abstract

“…CsA is effective in controlling the disease over time, allowing prednisone discontinuation in many patients with steroid-dependent NS. Unfortunately, it has disadvantages, as many patients relapse after interruption and prolonged use leads to significant nephrotoxicity (50). TAC acts in a similar way but there are no studies on whether it is better than CsA (51).…”

Section: Nonsteroidal Immunosuppressive Drugsmentioning

confidence: 99%

Minimal Change Disease

Vivarelli

Massella

Ruggiero

et al. 2016

CJASN

Self Cite

417

383

View full text Add to dashboard Cite

Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%-90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.

show abstract

“…8 Importantly, prolonged CsA therapy is accompanied by time-and dose-dependent nephrotoxicity. 9 Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is a non-nephrotoxic immunosuppressive drug with inhibitory effects on T and B lymphocytes, cellsurface markers, and cytokine gene expression 10 and has proven efficacy and tolerability in renal allograft recipients. Several small studies with limited statistical power have shown that MMF has steroid-sparing effects and reduces relapse rates in patients with FR-SSNS, albeit with varying efficacy.…”

mentioning

confidence: 99%

Mycophenolate Mofetil versus Cyclosporin A in Children with Frequently Relapsing Nephrotic Syndrome

Gellermann

Weber

Pape

et al. 2013

Journal of the American Society of Nephrology

143

View full text Add to dashboard Cite

The severe side effects of long-term corticosteroid or cyclosporin A (CsA) therapy complicate the treatment of children with frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). We conducted a randomized, multicenter, open-label, crossover study comparing the efficacy and safety of a 1-year treatment with mycophenolate mofetil (MMF; target plasma mycophenolic acid trough level of 1.5-2.5 mg/ml) or CsA (target trough level of 80-100 ng/ml) in 60 pediatric patients with FR-SSNS. We assessed the frequency of relapse as the primary endpoint and evaluated pharmacokinetic profiles (area under the curve [AUC]) after 3 and 6 months of treatment. More relapses per patient per year occurred with MMF than with CsA during the first year (P=0.03), but not during the second year (P=0.14). No relapses occurred in 85% of patients during CsA therapy and in 64% of patients during MMF therapy (P=0.06). However, the time without relapse was significantly longer with CsA than with MMF during the first year (P,0.05), but not during the second year (P=0.36). In post hoc analysis, patients with low mycophenolic acid exposure (AUC ,50 mgzh/ml) experienced 1.4 relapses per year compared with 0.27 relapses per year in those with high exposure (AUC.50 mgzh/ml; P,0.05). There were no significant differences between groups with respect to BP, growth, lipid levels, or adverse events. However, cystatin clearance, estimated GFR, and hemoglobin levels increased significantly with MMF compared with CsA. These results indicate that MMF is inferior to CsA in preventing relapses in pediatric patients with FR-SSNS, but may be a less nephrotoxic treatment option.

show abstract

Risk Factors for Cyclosporin A Nephrotoxicity in Children with Steroid-Dependant Nephrotic Syndrome

Cited by 53 publications

References 32 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

Minimal Change Disease

Mycophenolate Mofetil versus Cyclosporin A in Children with Frequently Relapsing Nephrotic Syndrome

Contact Info

Product

Resources

About