Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome

Background and objectivesThere is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial.Design, setting, participants, & measurementsParticipants aged 2–20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects.ResultsThe trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9–32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14–51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids.ConclusionsACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

Download Full-text

The Efficacy and Safety of Rituximab for Childhood Steroid-Dependent Nephrotic Syndrome: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2021.728010 ◽

2021 ◽

Vol 9 ◽

Author(s):

Sidi Liu ◽

Chuying Gui ◽

Zhenzhen Lu ◽

Huijie Li ◽

Zhike Fu ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Randomized Clinical Trials ◽

Remission Rate ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Steroid Dependent ◽

Alternative Treatment Option ◽

Control Study ◽

Steroid Dependent Nephrotic Syndrome

Objectives: Rituximab (RTX), a possible alternative treatment option, is recognized as a new therapeutic hope for the treatment of steroid-dependent nephrotic syndrome (SDNS) in children. However, the efficacy and safety of RTX in the treatment of childhood SDNS are still controversial. The objective of this study was to evaluate the efficacy and safety of RTX treatment in children with SDNS.Study Design: Six randomized controlled trials (RCTs) and one retrospective comparative control study data from studies, performed before January 2021 were collected, from PubMed, Cochrane Library, Embase, and Web of Science. The studies evaluating the efficacy and safety of RTX in childhood SDNS were included.Results: Six RCTs and one retrospective comparative control study were included in our analysis. Compared with the control group, the RTX treatment group achieved a higher complete remission rate (OR = 5.21; 95% CI, 3.18–8.54; p < 0.00001), and we found significant differences between the two groups on serum albumin level (MD = 0.88; 95% CI, 0.43–1.33; p = 0.0001) and estimated glomerular filtration rate (MD = 6.43; 95% CI, 2.68–10.19; p = 0.0008). However, RTX treatment did not significantly lower serum creatinine levels nor did it significantly reduce the occurrence of proteinuria. In addition, we found no advantages with RTX on treatment safety.Conclusions: RTX has shown satisfactory characteristics in terms of efficacy and may be a promising treatment method for SDNS in children. However, the long-term effects have not been fully evaluated and should be further studied through randomized clinical trials.

Download Full-text

Therapeutic Effect of Chai-Ling-Tang (Sairei-to) on the Steroid-dependent Nephrotic Syndrome in Children

The American Journal of Chinese Medicine ◽

10.1142/s0192415x95000304 ◽

1995 ◽

Vol 23 (03n04) ◽

pp. 255-260 ◽

Cited By ~ 21

Author(s):

Xiao-Yun Liu

Keyword(s):

Nephrotic Syndrome ◽

Side Effects ◽

Toxic Effect ◽

Cytotoxic Agents ◽

Short Term ◽

Prednisone Dosage ◽

Steroid Dependent ◽

Steroid Dependent Nephrotic Syndrome ◽

Negative Conversion

37 children with steroid-dependent nephrotic syndrome (SDNS) were administered with Chai-Ling-Tang (Sairei-to) under corticosteroid. After treatment with Chai-Ling-Tang, relapse was markedly improved, time for negative conversion of proteinuria shortened, prednisone dosage significantly reduced, and side effects eased. 32 children with SDNS treated with prednisone and cyclophosphamide served as control. Results showed that short-term and long-term relapse and average prednisone dosage were similar between these two groups. It is considered that Chai-Ling-Tang may be a useful substitute for patients with SDNS who fail to respond to or manifest severe toxic effect from cytotoxic agents.

Download Full-text

Relapse of Nephrotic Syndrome after Adrenocorticotropic Hormone-Induced Remission: Implications of Adrenocorticotropic Hormone Antibodies

American Journal of Nephrology ◽

10.1159/000506854 ◽

2020 ◽

Vol 51 (5) ◽

pp. 390-394 ◽

Cited By ~ 1

Author(s):

Snehal Shrivastava ◽

Bohan Chen ◽

Lance D. Dworkin ◽

Deepak K. Malhotra ◽

Rujun Gong

Keyword(s):

Nephrotic Syndrome ◽

Side Effects ◽

Adrenocorticotropic Hormone ◽

De Novo ◽

Glycogen Synthase ◽

Therapeutic Modality ◽

Glomerular Diseases ◽

Steroid Dependent ◽

Number Of Patients ◽

Acth Therapy

Background: Prolonged use of corticosteroids continues to be the mainstay in the management of most proteinuric glomerulopathies, but is limited by extensive side effects. Alternative medications such as adrenocorticotropic hormone (ACTH) have been recently used to treat refractory glomerulopathies and have shown superior outcomes when compared with steroids. However, the clinical responsiveness to ACTH therapy varies considerably with a number of patients exhibiting de novo or acquired resistance. The underlying mechanism remains unknown. Methods: A patient with steroid-dependent focal segmental glomerulosclerosis (FSGS) developed severe steroid side effects impacting quality of life and was converted to repository porcine ACTH therapy. Immediate response in the form of remission of nephrotic syndrome was noted followed by relapse in 10 weeks. Suspecting the role of some ACTH-antagonizing factors, the patient’s serum was examined. Results: Immunoblot-based antibody assay revealed high titers of de novo IgG antibodies in the patient’s serum that were reactive to the porcine corticotropin with negligible cross-reactivity to human corticotropin. In vitro, in cultured B16 melanoma cells that express abundant melanocortin receptors, addition of the patient’s serum substantially abrogated the porcine corticotropin triggered signaling activity of the melanocortinergic pathway, marked by phosphorylation of glycogen synthase kinase 3β, thus suggesting a mitigating effect on the biological functionality of porcine corticotropin. Conclusion: ACTH is a useful alternative therapeutic modality for refractory proteinuric glomerulopathies like FSGS. However, as quintessential therapeutic biologics, natural ACTH, regardless of purity and origin, is inevitably antigenic and may cause the formation of neutralizing antibodies in some sensitive patients, followed by resistance to ACTH therapy. It is imperative to develop ACTH analogues with less immunogenicity for improving its responsiveness in patients with glomerular diseases.

Download Full-text

Efficacy and side effects of mycophenolate mofetil therapy in children with steroid dependent nephrotic syndrome in a tertiary paediatric nephrology centre in Sri Lanka

Sri Lanka Journal of Child Health ◽

10.4038/sljch.v48i1.8652 ◽

2019 ◽

Vol 48 (1) ◽

pp. 53 ◽

Cited By ~ 1

Author(s):

H N S Hettiarachchi ◽

M Raja ◽

U I Karunadasa ◽

R S Thalgahagoda

Keyword(s):

Nephrotic Syndrome ◽

Mycophenolate Mofetil ◽

Side Effects ◽

Sri Lanka ◽

Paediatric Nephrology ◽

Steroid Dependent ◽

Steroid Dependent Nephrotic Syndrome

Download Full-text

Rituximab Use in Nephrotic Syndrome

Journal of Clinical Review & Case Reports ◽

10.33140/jcrc/03/01/00001 ◽

2018 ◽

Vol 3 (1) ◽

Keyword(s):

Nephrotic Syndrome ◽

Mycophenolate Mofetil ◽

Side Effects ◽

Calcineurin Inhibitor ◽

Minimal Change ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Steroid Dependent ◽

Minimal Change Glomerulonephritis ◽

Steroid Dependent Nephrotic Syndrome

Background: Nephrotic syndrome may be caused by primary (idiopathic) renal disease or by a variety of secondary causes. Patients present with marked edema, proteinuria, hypoalbuminemia, and often hyperlipidemia. Treatment of most patients should include fluid and sodium restriction, oral or intravenous diuretics, and angiotensin-converting enzyme inhibitors. Adults with nephrotic syndrome may benefit from corticosteroid treatment. The treatment of patients with the steroid-resistant nephrotic syndrome (SRNS) and steroid-dependent nephrotic syndrome (SDNS) is challenging. On the basis of suggestions that B lymphocytes are crucial in the pathogenesis of the nephrotic syndrome, rituximab (a monoclonal antibody against CD20 antigen) is used in treatment of these patients. Aim of study: To evaluate the role of rituximaband mycophenolic acid in treatment of patientswith steroid-resistant (SRNS) and steroid-dependent nephrotic syndrome (SDNS), whom not respond or relapse after calcineurin inhibitor (CNI) (tacrolimus or cyclosporine) had been used. Patients and methods: Case series study was done between 2012 - 2015 in AL-Sadder Teaching Hospital Nephrology Center and record 40 patients with different age groups, males and females with different histopathological types (Minimal Change Glomerulonephritis, Focal Segmental Glomerulosclerosis, Mesengeo Prolifrative Glomerulonephritis). These patients were taking prednisilone and\or calcineurin inhibitor (tacrolimus “prograf”) or (cyclosporine “sandimmune”), and they get either Steroid Dependent Nephrotic Syndrome or Steroid Resistant Nephrotic Syndrome with frequent admission more than four time per year. To these patients we start rituximab intravenous infusion monthly for at least six months with the use of steroid and mycophenolate mofetil during these six months. The patients followed up for 3-12 months after initiation of rituximab by different investigations and the patients were classified according to their response into complete, partial and no response. After one year stop rituximab treatment, follow the patients clinically and by investigations for (1-2) years to determine which patients get relapse. Results: Majority (80%) of patients with nephrotic syndrome who had good response to rituximab were younger age group < 15 years. Better response to rituximab associated with Minimal Change Glomerulonephritis. There was significant reduction in blood urea, serum creatinine, urine (protein/creatinine) ratio and serum cholesterol. Serum albumin was significant elevated. Response to rituximab was not significantly associated with gender or steroid response. Majority of patients with good response not relapse and need more time for follow up. Relapsing after stopping rituximab not significantly associated with age, gender, histopathological type and steroid response. Conclusion: Rituximab and mycophenolate mofetil used in steroid-resistant nephrotic syndrome to get ride from side effects of calcineurine inhibitor (tacrolimus or cyclosporine). Rituximab and mycophenolate mofetil used in steroid-dependent nephrotic syndrome after calcineurine inhibitorto get ride from side effects of steroid. Improvement in renal function is result from stopping of calcineurine inhibitor (nephrotoxic drugs) and/or from rituximab and mycophenolate mofetil. Cost of rituximab is less than the cost that needed if the patients had frequent admissions to the hospital or developed renal failure and ended with dialysis.

Download Full-text

Corticosteroid Sparing Agents in Frequent Relapsing and Steroid Dependent Nephrotic Syndrome in Children: A Single Center Retrospective Study

10.21203/rs.3.rs-763201/v1 ◽

2021 ◽

Author(s):

Bashair Alabbasi ◽

Naif Abdulmajeed ◽

Abdulmonem Alghamdi ◽

Saeed Alzahrani ◽

Saeed Alghwery ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Retrospective Study ◽

Side Effects ◽

Immunosuppressive Agents ◽

Small Sample ◽

Second Line ◽

Overall Response ◽

Steroid Dependent ◽

Steroid Sparing ◽

Steroid Dependent Nephrotic Syndrome

Abstract Background: Children with frequently relapsing nephrotic syndrome (FRNS) or Steroid-dependent nephrotic syndrome (SDNS) may be prescribed non-corticosteroid immunosuppressive agents whenever there is a failure to maintain remission with low-dose alternate-day prednisone and/or signiﬁcant adverse effects of prednisone develop. A wide variety of immunosuppressive agents have been used in these patients to reduce the number of relapses and maintain remission. Objective: to evaluate the outcome of Steroid sparing agents in the management of FRNS and SDNS in children with nephrotic syndrome. Patients and methods: A retrospective study was conducted on all steroid-sensitive nephrotic syndrome (SSNS) children (1-11 years) who received any type of second line agents (e.g. CNI, MMF, cyclophosphamide, and Rituximab) over a period of 9 years from January 2010 to January 2019 in pediatric nephrology unit in Prince Sultan Military Medical City, Riyadh. Results: The study included 24 patients. Their age at diagnosis ranged between 1 and 11 years with a mean of 3.8 years and standard deviation of (±) 2.6 years. During the first year of steroid therapy, relapse occurred among 87% of patients; of them, the number of relapses being 4 or more in 21.7%. Regarding indication for the second line of treatment, SDNS was the most frequent reported (60.9%), followed by FRNS (30.4%). Concerning agents used in the second line, MMF ranked first (58.4%), followed by Cyclophosphamide (33.3%). Number of relapses after starting steroid sparing agent was more than once among 41.7% of patients. Duration of remission after starting steroid sparing agent ranged between 2 and 72 months (14±14.1). Overall response to the second line of treatment was observed among majority of patients (91.7%). Renal biopsy was performed in 45.8% of patients. Concerning side effects of steroid sparing agents, electrolytes disturbances and hypertension were reported by two (8.3%) and one (4.2%) patients respectively. Duration of remission was significantly longer among patients treated with cyclosporine (48±33.9 months) compared to other lines of treatment, p<0.001. On the other hand, hypertension was only reported among patients treated with cyclosporine, p=0.003. Conclusion: The overall response of children with SDNS and FRNS to the second line agents was significant, with favorable longer remission free period with Cyclosporine use with no major side effects. Our results affected by the retrospective design of the study, as well as the small sample size. Therefore larger scale study with prospective design is highly encouraged.

Download Full-text