scholarly journals Recent Update in The Management of Childhood Nephrotic Syndrome

2016 ◽  
Vol 34 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Mohammad Imrul Kayes
Keyword(s):  
Nephrotic Syndrome ◽  
Calcineurin Inhibitors ◽  
Clinical Problem ◽  
Developed Countries ◽  
Optimal Care ◽  
Steroid Dependency ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sensitive

Nephrotic Syndrome (NS) is a common renal disease seen in children. Children who go into complete remission following treatment with corticosteroids are classified as having steroid sensitive NS. In developed countries over 80% of children with idiopathic NS have steroid sensitive disease. The exact pathogenesis of this condition remains elusive. Podocyte injury and proteinuria are the two main issues in the pathogenesis. Recent studies suggest release of cytokines by T-cells as well as a strong contribution of Bcell immunity. Genetic studies have reported human leucocyte antigen (HLA) class II antigens DR and DQ associations linked to steroid sensitive NS. Most children with steroid sensitive NS have multiple relapses and a significant percentage also develop steroid dependent NS. Diuretic- resistant edema also a clinical problem to manage these patients. These children receive multiple courses of steroids and are at high risk of developing steroid toxicity. Patient with frequent relapses who develop steroid dependency thus require alternative treatment. Steroid resistant NS considers when failure to response within 8 weeks of steroid therapy. Steroids sparing agents used include levamisole, cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors (cyclosporine and tacrolimus), rituximab and vincristine; these agents have greatly reduced the adverse effects seen with long-term use of steroids; so therapy needs to be individualized to achieve optimal care of each child.J Bangladesh Coll Phys Surg 2016; 34(1): 26-32

scholarly journals Levamisole in Children with Idiopathic Nephrotic Syndrome: Clinical Efficacy and Pathophysiological Aspects

2019 ◽  
Vol 8 (6) ◽  
pp. 860 ◽  
Author(s):  
Anne K. Mühlig ◽  
Jun Young Lee ◽  
Markus J. Kemper ◽  
Andreas Kronbichler ◽  
Jae Won Yang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Low Frequency ◽  
Glomerular Diseases ◽  
Steroid Dependency ◽  
Randomized Controlled ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Steroid sensitive nephrotic syndrome is one of the most common pediatric glomerular diseases. Unfortunately, it follows a relapsing and remitting course in the majority of cases, with 50% of all cases relapsing once or even more often. Most children with idiopathic nephrotic syndrome respond initially to steroid therapy, nevertheless repeated courses for patients with relapses induce significant steroid toxicity. Patients with frequent relapses or steroid dependency thus require alternative treatment, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, levamisole, or rituximab. To reduce the relapse rate, several drugs have been used. Among these, levamisole has been considered the least toxic and least expensive therapy. Several randomized controlled trials (RCT) showed that levamisole is effective in reducing the relapse risk in steroid sensitive forms of nephrotic syndrome with a low frequency of side effects. Levamisole is a synthetic imidazothiazole derivative with immune-modulatory properties. In this article, we review recent data from randomized trials and observational studies to assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.

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

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.

scholarly journals Management of idiopathic nephrotic syndrome in childhood

2004 ◽  
Vol 132 (9-10) ◽  
pp. 352-359 ◽  
Author(s):  
Amira Peco-Antic
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Alkylating Agents ◽  
Oral Prednisone ◽  
Symptomatic Treatment ◽  
Dietary Regimen ◽  
Steroid Resistant ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sensitive

The management of idiopathic nephrotic syndrome (INS) in children includes immunosuppressive and symptomatic treatment. The response to corticosteroid therapy is the best prognostic marker of the disease. The majority of children with INS (about 85%) are steroid-sensitive as they normalize proteinuria within 4 weeks of daily, oral prednisone administration. The most of steroid-sensitive patients (94%) has minimal change of nephrotic syndrome, while the majority (80.5%-94.4%) of those who are steroid-resistant has focal segmental glomerulosderosis or mesangioproliferative glomerulonephritis. Initial therapy of INS consists of 60 mg/m2/day prednisone daily for 4 weeks followed by 40 mg/m2 on alternate days for 4 weeks, thereafter decreasing alternate day therapy every month by 25% over the next 4 months. Thus, the overall duration of the initial cortico-steroids course is 6 months that may be significantly protective against the future development of frequent relapses. Approximately 30% of patients experience only one attack and are cured after the first course of therapy; 10-20% have only 3 or 4 steroid-responsive episodes before permanent cure; the remaining 40-50% of patients are frequent relapsers, or steroid-dependent. Standard relapse therapy consists of 60 mg/m2/ day prednisone until urine is protein free for at least 3 days, followed by 40 mg/m2 on alternate days for 4 weeks. The treatment of frequent-relapses and steroid-dependent INS includes several different regimens: maintenance (6 months) alternate steroid therapy just above steroid threshold (0.1-0.5 mg/kg/ 48h), levamisole, alkylating agents (cyclophosphamide or chlorambucil) or cyclosporine. The worse prognosis is expected in steroid-resistant patients who are the most difficult to treat. Renal biopsy should be performed in them. At present, there is no consensus on therapeutic regimen for steroid-resistant patients. The following immunosuppressive drugs have been used with varying success: cyclosporine, intravenous methyl prednisone pulses alone or combined with or followed by alkylating agents, plasma-exchange, and angiotensin-converting enzyme (ACE) inhibitors. Symptomatic treatment includes: 1) dietary regimen with normal protein intake and salt restriction, 2) calcium and vitamin D are prescribed with steroids, 3) diuretics should be used in case of severe edema, 4) infusion of albumin in case of severe hypovolemia, 5) treatment of hypertension, 6) anticoagulant therapy, and 7) prophylactic antibiotics in high-risk patients.

scholarly journals Therapies for Glomerular Diseases in Children

2018 ◽  
Vol 54 (01) ◽  
pp. 043-053
Author(s):  
Arvind Bagga
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Steroid Resistance ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Dependence ◽  
Frequent Relapses ◽  
Steroid Sensitive

AbstractNephrotic syndrome is an important chronic disease of childhood, with a steroid sensitive course in most patients. Research on pathogenesis has emphasized the importance of T-lymphocyte dysregulation and vascular permeability factors that alter podocyte function and glomerular permselectivity. Mutations in genes that encode important podocyte proteins and therapeutic targets within podocytes have been identified. A hypothesis unifying available evidence on pathogenesis is yet to be proposed. An important proportion of patients have difficult disease course, characterized by frequent relapses, steroid dependence or steroid resistance, requiring therapy with alternative immunosuppressive agents. Clinical studies support the use of levamisole, cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNIs) and rituximab in patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult and patients failing to achieve remission show progressive renal damage. Prospective studies in patients with steroid sensitive and steroid resistant nephrotic syndrome are the basis of current guidelines while ongoing studies will help identify and formulate effective and safe therapies.

Patterns of Childhood Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome in Saudi Children

2016 ◽  
Vol 56 (2) ◽  
pp. 177-183
Author(s):  
Abdulla A. Alharthi
Keyword(s):  
Chronic Kidney Disease ◽  
Saudi Arabia ◽  
Nephrotic Syndrome ◽  
Kidney Disease ◽  
Steroid Resistant ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sensitive ◽  
Stage Renal Disease ◽  
End Stage

Nephrotic syndrome (NS) is one of the most common causes of chronic kidney disease in children. Mostly, NS is controlled by steroids. In spite of this, 10% to 20% of the patients have steroid resistant NS (SRNS), and the rest have steroid sensitive NS (SSNS). Eighty-seven children with NS (66 SSNS; 21SRNS) were retrospectively studied within the past 10 years in Taif region of Saudi Arabia. Regarding outcome, 66 (76%) patient responded to the steroid therapy, while 21 (24%) patients characterize as SRNS. Out of 66 SSNS, 25 children revealed complete remission, 26 were diagnosed as steroid dependent, and 15 were identified as frequent relapses. Among 21 SRNS biopsied patients, focal segmental glomerulosclerosis was the most common histological patterns of NS followed by the membranoproliferative glomerulonephritis pattern, which is significantly different from other studies performed in the Kingdom of Saudi Arabia. Out of 21 SRNS patients, 13 developed chronic kidney disease, 4 got end-stage renal disease, and 4 patients died.

scholarly journals P0401RITUXIMAB VESUS CYCLOPHOSPHAMIDE AS FIRST STEROID SPARING AGENT IN CHILDHOOD FREQUENTLY RELAPSING OR STEROID DEPENDENT NEPHROTIC SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jameela Kari ◽  
Amr Albanna ◽  
Khalid Alhassan ◽  
Osama Safdar ◽  
Mohamed Shalaby ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Randomized Study ◽  
Immunosuppressive Agents ◽  
Oral Cyclophosphamide ◽  
First Line ◽  
Open Label ◽  
Steroid Dependency ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sparing

Abstract Background and Aims Approximately 50% of children with steroid sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications Method A prospective open label randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia or active infection. The recruited children were allocated either to the oral cyclophosphamide (3mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months Results 46 subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR: 0.36; 95% CI: 0.09 – 1.45; p=0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N=10) and 6.3 months in the rituximab group (N=3). Both treatments were associated with a significant (p=?) reduction in prescribed dose of oral alternate days steroid from 1.02 to 0.36mg/kg (Cyclophoshamide) and 0.86 to 0.08mg/kg (Rituximab). Importantly, a significantly (P = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity beside severe leucopenia and neutropenia on the 7th week of treatment although she showed complete recovery with withdrawal of cyclophosphamide and maintained remission. A minor infusion related reaction was observed in 1 patient (5%) in the rituximab group. Conclusion Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide

Rituximab in childhood steroid-sensitive nephrotic syndrome: are multiple subsequent courses safe and effective?

2020 ◽  
pp. archdischild-2020-319609
Author(s):  
Chantida Subun ◽  
Picha Suwannahitatorn ◽  
Hazel Webb ◽  
Kjell Tullus
Keyword(s):  
Nephrotic Syndrome ◽  
Side Effects ◽  
Age Groups ◽  
Term Treatment ◽  
Street Hospital ◽  
Steroid Dependency ◽  
Great Ormond Street Hospital ◽  
Steroid Dependent ◽  
Long Term Treatment

IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in children. The majority of patients respond well to steroids. However, the relapse rate is high and many develop steroid dependency. Although other immunosuppressive medicines are successfully used as steroid-sparing agents, some children still have frequent relapsing episodes. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in treating difficult frequently relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). Data on the effectiveness and long-term treatment outcomes of repeated courses of RTX are, however, scarce.Material and methodsChildren and young people with FR/SDNS, aged 1–18 years, who received RTX at Great Ormond Street Hospital (GOSH) from 2006 to 2018 were reviewed.ResultsDuring these 12 years, 103 children with FR/SDNS received RTX infusions at GOSH. Among these, 58 cases needed repeated courses of RTX: 2, 3, 4, 5, 6 and 7 repeated courses were given to 21, 21, 7, 5, 1 and 3 patients, respectively. The overall median time to relapse post-RTX was 11 months (range 1–53 months). There was no change in relapse-free interval with subsequent courses of RTX. No difference was found between age groups, genders and ethnicities. No severe side effects were noted.ConclusionsRTX seems to be safe even after several repeated courses. However, long-term follow-up and further studies are needed, with a focus on side-effects in particular.

MO1027EFFICACY OF CALCINEURIN INHIBITORS IN CHILDREN WITH MONOGENIC STEROID-RESISTANT NEPHROTIC SYNDROME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Larisa Prikhodina ◽  
Svetlana Papizh ◽  
Inna Povolotskaya
Keyword(s):  
Nephrotic Syndrome ◽  
Calcineurin Inhibitors ◽  
Compound Heterozygous ◽  
Target Level ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Pathogenic Variants ◽  
Nail Patella Syndrome

Abstract Background and Aims Monogenic causes of steroid-resistant nephrotic syndrome (SRNS) have been reported for up to one-third of children depending on age of the disease onset. Immunosuppressive treatment of genetic SRNS with calcineurin inhibitors (CNIs) is still controversial. The aim of the study was to investigate the efficacy of CNIs with focus on inducing remission and long-term kidney function in children with monogenic SRNS. Method Retrospective analysis of efficacy CNIs in five children (2M/3F) with monogenic SRNS was performed. Kidney biopsy prior CNIs revealed FSGS (n=4) and MCD (n=1). The initial cyclosporine (CsA) dose was 5 mg/kg/24h to keep a target level of 80-150 ng/ml and tacrolimus (TAC) - 0.1 mg/kg/24h to achieve a target level of 5-10 ng/ml. CsA took all 5 patients with subsequent switching to TAC in 2 children due to cosmetic side effects. The median follow-up period was 165.0 (IQR: 59.0; 185.5) months. Next generation sequencing (NGS) was used for identification of pathogenic variants in all patients. Results The median age at onset of monogenic SRNS was 33.0 (IQR: 16.5; 63.0) months. 2/5 (40%) patients presented with acute SRNS, 1/5 (20%) child with infantile NS, 1/5 (20%) - with isolated nephrotic range proteinuria with hypoalbuminemia and 1/5 (20%) - with NS and extrarenal features of Nail-Patella syndrome. NGS identified previously described pathogenic variants in all 5 children, including NPHS2 homozygous c.28dup (p.Glu87Ter) (n=1), NPHS2 compound heterozygous c.868G&gt;A (p.Val290Met) in combination with c.686G&gt;A (p.Arg229Gln) (n=1), LMX1B heterozygous c.788T&gt;G (p.Val263Gly) (n=1), LMX1B heterozygous c.737G&gt;A (p.Arg246Gln) (n=1), and COL4A3 heterozygous c.2962G&gt;A (p.Gly988Arg) variant (n=1). The median time from diagnosis to initiation of CNIs treatment was 72.0 (IQR: 33.0; 93.0) months. CNIs induced complete remission in 2/5 (40%) patients, presented with acute SRNS, including one girl with MCD due to NPHS2 compound heterozygous variants with mutation-dependent pathogenicity of one (p.R229Q) of them and one boy with FSGS due to COL4A3 heterozygous variant (n=1). Partial remission was induced by CNIs in 2/5 (40%) girls with FSGS due to LMX1B heterozygous variants with isolated SRNS (n=1) and Nail-Patella syndrome (n=1). The median duration of CNIs treatment to obtain complete or partial remission was 13.5 (IQR: 6.8; 15.8) months. Acute CNIs-associated nephrotoxicity had 2 patients with LMX1B variants. At the last follow up full and partial responders to CNIs treatment aged of 16.5 (IQR: 11.8; 17.5) years had CKD-1 (n=3) and CKD-2 (n=1). 1/5 (20%) boy with NPHS2-associated infantile NS was CNI resistant and developed CKD-5 at the age of 6.5 years with subsequent living related kidney transplantation. Conclusion We found that 4/5 (80%) children with monogenic SRNS demonstrated partial or full response to CNIs treatment with stable long-term kidney function. We assume that CNIs might improve podocyte function by stabilization of their cytoskeleton disrupted in patients with monogenic SRNS.

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

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&lt;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&lt;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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