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

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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MO291RITUXIMAB IS EFFECTIVE AND SAFE IN ADULTS WITH STEROID-DEPENDENT NEPHROTIC SYNDROME: A LONG-TERM, SINGLE-CENTER EXPERIENCE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0049 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Gemma Patella ◽

Alessandro Comi ◽

Giuseppe Coppolino ◽

Nicolino Comi ◽

Giorgio Fuiano ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Case Series ◽

Adult Patients ◽

Single Center ◽

Single Center Experience ◽

Steroid Dependent ◽

The Mean ◽

Steroid Dependent Nephrotic Syndrome

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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Assessment of Behavior Abnormalities of Corticosteroids in Children with Nephrotic Syndrome

ISRN Psychiatry ◽

10.1155/2013/921253 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Doaa Mohammed Youssef ◽

Mohamed Mohamed Abdelsalam ◽

Ali Mohamed Abozeid ◽

Usama Mahmoud Youssef

Keyword(s):

Nephrotic Syndrome ◽

High Dose ◽

Mean Values ◽

Pediatric Anxiety ◽

Steroid Sensitive Nephrotic Syndrome ◽

Steroid Sensitive ◽

The Mean ◽

Anxiety Depression

Introduction. The objective of this work was to define the frequency and severity of steroid related behavioral side effects in children with steroid sensitive idiopathic nephrotic syndrome (SSNS) during Treatment for relapse. Methods. 30 pediatric patients with steroid sensitive nephrotic syndrome were studied; known as SSNS at complete remission or low dose of Prednisolone and have relapse on follow up. All children in this study were subjected to full history taking, thorough clinical examination, assessment socioeconomic standard, and assessment of pediatric quality of life, a battery of psychometric tests included pediatric anxiety, depression, and aggression scores. Results. Our results revealed that there are highly significant increase in the mean values of anxiety, depression and aggression among cases starts to appear on week one and extends to three, five and seven weeks compared to baseline. In the seventh week of follow up cases show significant positive correlation between prednisone doses and mean values of anxiety and depression scores and aggression. Conclusion. we concluded that all studied children with SSNS often experience significant problems with anxiety, depression, and increased aggression during high dose steroid therapy.

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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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Lipoprotein (a) as a Predictor of Steroid Dependence in Paediatric Steroid Sensitive Nephrotic Syndrome

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/46262.14409 ◽

2021 ◽

Author(s):

Surupa Basu ◽

Sushmita Banerjee ◽

Pranab Roy ◽

Apurba Ghosh

Keyword(s):

Nephrotic Syndrome ◽

First Episode ◽

Urine Protein ◽

Lipoprotein A ◽

Steroid Dependence ◽

Steroid Dependency ◽

Steroid Dependent ◽

Steroid Sensitive ◽

One Year ◽

Lipid Parameters

Introduction: Lipoprotein a {Lp(a)} increases in Nephrotic Syndrome (NS). Although the majority of paediatric NS are steroid sensitive, relpase and steroid dependence are commonly seen in this cases. Lp(a) is an LDL-like lipoprotein that consists of an LDL particle to which the glycoprotein apolipoprotein(a) {apo(a)} is attached. Aim: To evaluate the potential of Lp(a), measured on admission, for the prediction of relapse/steroid dependency. Materials and Methods: Children (n=36) with first episode NS were recruited in this prospective observational case-control study and followed up for one year. They were tested at presentation for Lp(a) (mg/dL) and standard tests such as haemoglobin, albumin, protein, cholesterol, triglyceride, and urine protein. Children received standard therapy for NS, and were followed for a period of one year from diagnosis to record days to initial remission, relapse episodes, steroid dependence etc. Patients were categorised as: no relapse (NR), Infrequent Relapse (IFR), frequent relapse (FR) and Steroid Dependent (SD) as per standard definitions. Fifteen healthy volunteers were also tested for lipid profile and Lp(a) levels. Results: Of 36 cases (median age 3 years, 19 males), there were 15NR, 7IFR, 2FR and 12SD. The mean Lp(a) of the NS group (165.2±120.4 mg/dL) was higher than controls (30.52±21.9 mg/dL) (p<0.0001). All the lipid parameters except HDL-cholesterol were significantly higher in the NS group. Within the NS group, Lp(a) showed significant correlation (Spearman-rho) with albumin (p=0.0062,r=0.47), but no correlation with lipid parameters or urine protein. Comparison of Lp(a)levels in the NS groups revealed that the SD patients had a high Lp(a)(222.0±115.7 mg/dL) compared to NR (129.7±120.1 mg/dL) (p=0.02). Conclusion: Concentration of plasma Lp(a) in patients with SDNS was higher compared to patients who did not suffer any relapse, and this concentration may serve as a marker for prediction of SDNS.

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Is tacrolimus for childhood steroid-dependent nephrotic syndrome better than ciclosporin A?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfl222 ◽

2006 ◽

Vol 21 (7) ◽

pp. 1761-1763 ◽

Cited By ~ 24

Author(s):

Jörg Dötsch ◽

Katalin Dittrich ◽

Christian Plank ◽

Wolfgang Rascher

Keyword(s):

Nephrotic Syndrome ◽

Steroid Dependent ◽

Ciclosporin A ◽

Steroid Dependent Nephrotic Syndrome ◽

Better Than

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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 tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation

BMJ ◽

10.1136/bmj.l1800 ◽

2019 ◽

pp. l1800 ◽

Cited By ~ 10

Author(s):

Nicholas J A Webb ◽

Rebecca L Woolley ◽

Tosin Lambe ◽

Emma Frew ◽

Elizabeth A Brettell ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Confidence Interval ◽

Immunosuppressive Treatment ◽

Phase Iii ◽

Prednisolone Treatment ◽

Steroid Dependent ◽

Life Years ◽

Steroid Sensitive Nephrotic Syndrome ◽

Steroid Sensitive ◽

Extended Course

Abstract Objective To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m 2 ) or a standard eight week course of prednisolone (total dose 2240 mg/m 2 ). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). Main outcome measures The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval −0.005 to 0.037) and cost savings (difference −£1673 ($2160; €1930), 95% confidence interval −£3455 to £109). Conclusions Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration ISRCTN16645249; EudraCT 2010-022489-29.

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