Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in pediatric patients with steroid-dependent nephrotic syndrome: determination of the need for follow-up kidney biopsy

Abstract Background and Aims Steroid-dependent nephrotic syndrome (SDNS) may require a prolonged multi-drug therapy with risk of drug toxicity and renal failure. Rituximab (RTX) treatment has been found to be helpful in reducing the steroid dosage and the need for immunosuppressants (ISs), but little data are currently available regarding very long-term outcomes in adults. We herein describe a long-term, single-center experience of RTX use in a large series of adults with SDNS. Method We studied 23 adult patients with SDNS (mean age 54.2±17.1 y; 65% male; BMI 28.5±4.7), mostly consequent to membranous (47.8%) or focal glomerulonephritis (30.2 %) who were eligible to start a RTX regimen. Before entering the RTX protocol, proteinuria and eGFR were 7.06±3.87 g/24h and 65.9±28.2 ml/min/1.73 m2, respectively; albumin and CD19/CD20 ratio were 2.9±0.9 g/L and 0.99±0.01 respectively; the mean number of ISs was 2.39±0.89 and the mean annual rate of relapses was 2.2±0.9. Results Patients were followed over a mean follow-up of 64 months (range: 12-144). After RTX (mean dose: 1202.1±372.4 mg) the rate of relapses was virtually nullified (p<0.001). eGFR remained roughly stable (62.1±19.8 ml/min/1.73 m2, p=NS), while proteinuria, albumin, CD19/CD20 and BMI all significantly improved (p ranging from 0.01 to 0.001). The mean number of additional ISs was also reduced (0.44±0.12; p<0.001) and RTX enabled discontinuation of steroids in 13/23 (56.5%) patients. No major adverse events related to therapy were recorded. Conclusion Findings from this large case-series with a remarkable very long follow-up reinforce the role of RTX as an efficient and safe weapon to improve outcomes in adult patients suffering from SDNS.

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The safety and efficacy of mycophenolate mofetil in children and adolescents with steroid-dependent nephrotic syndrome: a single-centre study

Clinical Kidney Journal ◽

10.1093/ckj/sfz061 ◽

2019 ◽

Vol 13 (2) ◽

pp. 179-183

Author(s):

Saravanakumar Karunamoorthy ◽

Dineshkumar Thanigachalam ◽

Dhanapriya Jeyachandran ◽

Sakthirajan Ramanathan ◽

Gopalakrishnan Natarajan ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Mycophenolate Mofetil ◽

Median Duration ◽

Significant Risk ◽

Duration Of Treatment ◽

Minimum Period ◽

Steroid Dependent ◽

Long Term Treatment ◽

Steroid Dependent Nephrotic Syndrome

Abstract Background Steroid-dependent nephrotic syndrome (SDNS) patients experience frequent relapse or adverse effects on long-term treatment with steroids or cyclophosphamide. This study assessed the efficacy and side effect profile of mycophenolate mofetil (MMF) therapy in children with nephrotic syndrome in our population. Methods A retrospective study was performed on children with SDNS who were on MMF therapy for a minimum period of 1 year, and were on regular follow-up in the Department of Nephrology at the Institute of Child Health and hospital for children attached to Madras Medical College. Results The study included 87 patients, with a male:female ratio of 2:1. The median age at diagnosis of nephrotic syndrome was 3 years [95% confidence interval (CI): 1–8 years], which was found to be a statistically significant risk factor for MMF failure. The median duration of follow-up after initiation of MMF therapy was 3 years and 3 months (95% CI: 1 year and 3 months to 6 years and 6 months). At initial evaluation, 31 (36%) patients presented with SDNS while the remaining had frequently relapsing nephrotic syndrome progressing to SDNS. Intravenous cyclophosphamide was used as first-line therapy in 82 patients, of whom 24 patients had persistent proteinuria while the remaining 58 had attained remission for a median duration of 6 months. The median duration of treatment with MMF was 2 years and 6 months (95% CI: 1 year and 3 months to 4 years and 6 months). MMF was used at a mean dose of 28.5 mg/kg. Seventy-two (83%) patients were MMF-sensitive, and these patients had a reduction in mean prednisolone dose from 1.28 to 0.35 mg/kg (P < 0.05). Among the MMF-sensitive patients, 31 had stopped MMF after a minimum period of 2 years, following which they had a median remission period of 5 months (95% CI: 1–8 months). MMF failure occurred in 15 (17%) patients. Adverse events were documented in 19 (22%) patients. Conclusions Continuous MMF therapy achieved remission in 83% of patients. MMF was well tolerated in the study population and discontinuation of MMF resulted in 100% relapse.

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Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome

Pediatric Nephrology ◽

10.1007/s00467-011-1825-x ◽

2011 ◽

Vol 26 (6) ◽

pp. 915-920 ◽

Cited By ~ 25

Author(s):

Alberto Zagury ◽

Anne Louise de Oliveira ◽

Carlos Augusto Pinheiro de Moraes ◽

Jose Augusto de Araujo Montalvão ◽

Regina Helena Leite Lemos Novaes ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Cyclophosphamide Therapy ◽

Steroid Dependent ◽

Long Term Follow Up ◽

Steroid Dependent Nephrotic Syndrome

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Population Pharmacokinetics of Rituximab in Pediatric Patients With Frequent-Relapsing or Steroid-Dependent Nephrotic Syndrome

Frontiers in Pharmacology ◽

10.3389/fphar.2021.725665 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yewei Chen ◽

Qian Shen ◽

Min Dong ◽

Ye Xiong ◽

Hong Xu ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Pediatric Patients ◽

Volume Of Distribution ◽

Therapeutic Effects ◽

Dosing Regimen ◽

Open Label ◽

Steroid Dependent ◽

Central Volume ◽

Higher Doses ◽

Steroid Dependent Nephrotic Syndrome

Objectives: Rituximab is frequently used off-label for the treatment of frequent-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), but the relapse rate remained high and the dosing regimen varied widely. The objective of this study was to characterize rituximab pharmacokinetics (PK) in pediatric patients with FRNS/SDNS, and to investigate the differences in rituximab PK between patients with FRNS/SDNS and other disease populations.Methods: Fourteen pediatric patients received rituximab for FRNS/SDNS treatment were enrolled in a prospective, open-label, single-center PK study. A population PK model of rituximab was developed and validated, and PK parameters were derived for quantitative evaluation.Results: A two-compartment PK model best described the data. Body surface area was the most significant covariate for both central clearance (CL) and apparent central volume of distribution (V1). Patients with FRNS/SDNS exhibited a clinically relevant increase in rituximab CL compared to patient population with non-Hodgkin’s lymphoma (NHL).Conclusion: This pilot study indicated that higher doses or more frequent regimens of rituximab may be required for optimal therapeutic effects in patients with FRNS/SDNS. Further clinical studies with more patients are warranted to confirm this result.

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POS-130 EXPERIENCE WITH LEVAMISOLE IN CHILDREN WITH FREQUENTLY RELAPSING AND STEROID DEPENDENT NEPHROTIC SYNDROME HAVING FOLLOW UP AT TIKUR ANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHIOPIA

Kidney International Reports ◽

10.1016/j.ekir.2021.03.140 ◽

2021 ◽

Vol 6 (4) ◽

pp. S52-S53

Author(s):

T. Assefa ◽

B.A. BEKELE

Keyword(s):

Nephrotic Syndrome ◽

Addis Ababa ◽

Steroid Dependent ◽

Specialized Hospital ◽

Tikur Anbessa Specialized Hospital ◽

Steroid Dependent Nephrotic Syndrome

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Efficacy of Levamisole in children with Frequent Relapsing and Steroid Dependent Nephrotic Syndrome at Tertiary Care Center-Karachi

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.6.2337 ◽

2020 ◽

Vol 36 (6) ◽

Author(s):

Khemchand Netaram Moorani ◽

Aasia Mohammad Zubair ◽

Nanga Ram Veerwani ◽

Harnam Jaichand Hotchandani

Keyword(s):

Nephrotic Syndrome ◽

Care Center ◽

Tertiary Care ◽

Oral Prednisolone ◽

Steroid Resistance ◽

Tertiary Care Center ◽

Creative Commons ◽

Steroid Dependent ◽

Steroid Dependent Nephrotic Syndrome

Objectives: To determine the effectiveness of levamisole in maintaining remission of proteinuria in children with frequent relapsing and steroid dependent nephrotic syndrome (FR/SDNS). Methods: This observational study on 81 children with FR /SDNS was carried out from June 2007 - June 2017 at The Kidney Center-Postgraduate Training Institute, Karachi-Pakistan. Levamisole (leva) along with low dose prednisolone on alternate day (AD) was used after induction of remission with daily oral prednisolone in children with FR/ SDNS for 6-36 months. Patients with steroid resistance were excluded. Data was analyzed using descriptive statistics. Results: Eighty-one patients with FR (66) or SD (15) received levamisole treatment. Mean age at diagnosis was 3.72 ±2.33 years. Levamisole was used on AD in 59.25% and daily in 40.74% of cases. Twenty-four could not complete six months and were excluded, 57 patients completed treatment duration of 15.68±9.93 months and 51 post-leva follow-up of 11.70±11.23 months. Mean cumulative prednisolone dose per patient before, on-leva and post-leva was 3389.81±2785.22, 2471.97±2024.98 and 661.37± 905.37 mg respectively. Mean relapse rate per year before leva, on -leva and post -leva was 3.30 ±0.50,0.98± 1.1and 0.79±1.27 respectively. Levamisole was effective in 90% of patients. During post-leva follow up, 76.4% patients, maintained remission, whereas 23.5% behaved as FR/SD and require further immunosuppressive therapy. Conclusions: Levamisole was effective in maintaining remission in 90% while on treatment, whereas it maintained remission after discontinuation in 76.4% cases. Levamisole may be used as first steroid sparing agent before other immunosuppressive therapies in children with FR/SDNS. Further studies are required for optimal duration and dosage schedule. doi: https://doi.org/10.12669/pjms.36.6.2337 How to cite this:Moorani KN, Zubair AM, Veerwani NR, Hotchandani HJ. Efficacy of Levamisole in Children with Frequent Relapsing and Steroid Dependent Nephrotic Syndrome at Tertiary Care Center-Karachi. Pak J Med Sci. 2020;36(6):---------. doi: https://doi.org/10.12669/pjms.36.6.2337 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cyclophosphamide in frequent-relapsing or steroid-dependent nephrotic syndrome: Review of 38 patients

Paediatrica Indonesiana ◽

10.14238/pi45.1.2005.18-23 ◽

2016 ◽

Vol 45 (1) ◽

pp. 18

Author(s):

Yulia Iriani ◽

Taralan Tambunan ◽

Sudigdo Sastroasmoro

Keyword(s):

Nephrotic Syndrome ◽

Cyclophosphamide Therapy ◽

Steroid Dependent ◽

Steroid Sensitive Nephrotic Syndrome ◽

Steroid Sensitive ◽

The Mean ◽

One Year ◽

Steroid Dependent Nephrotic Syndrome ◽

Better Than

Background Steroid-sensitive nephrotic syndrome (SSNS) in chil-dren is characterized by relapsing courses in a substantial propor-tion of affected individuals. Children with frequent-relapsing neph-rotic syndrome (FRNS) or steroid-dependent nephrotic syndrome(SDNS) are at risk of severe steroid toxicity and need individual-ized treatment. Previous studies have elucidated that cyclophos-phamide (CPA) reduced the risk of relapses and increased thelength of subsequent remissions in children with relapsing SSNS.Methods This retrospective study evaluated 38 patients (26 FRNSand 12 SDNS) after cyclophosphamide therapy to elucidate theefficacy of CPA in FRNS or SDNS in the Department of Child Health,Cipto Mangunkusumo Hospital. All patients were treated with CPA(2 mg/kg per day) for 8 weeks, in combination with prednisone.Results The median (range) duration of follow up was 45 months(24-140 months) for FRNS and 29 months (24-63 months) forSDNS. The mean relapse rate one year prior to CPA therapy inFRNS and SDNS were 3.8 relapses/year (95%CI 3.4; 4.2) and 4.0relapses/year (95%CI 3.3; 4.7), which were reduced to 1.6 relapses/year (95% CI 1.1; 2.1) and 2.3 relapses/year (95%CI 1.5;3.2), re-spectively. The overall rate of cumulative sustained good response(complete remission or infrequent relapses) was 65% after 36months. Frequent relapsing versus steroid-dependent status wassignificantly correlated with rate of sustained good response after36 months (85% versus 15%) with OR=23 (95%CI 3.1;225.2).Conclusion The efficacy of cyclophosphamide therapy in themanagement of FRNS is better than in SDNS

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