Management of idiopathic nephrotic syndrome in childhood

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.

Download Full-text

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

Clinical Pediatrics ◽

10.1177/0009922816645521 ◽

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.

Download Full-text

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

Journal of Clinical Medicine ◽

10.3390/jcm8060860 ◽

2019 ◽

Vol 8 (6) ◽

pp. 860 ◽

Cited By ~ 7

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.

Download Full-text

Bacterial meningitis in a known case of steroid-resistant nephrotic syndrome

Indian Journal of Child Health ◽

10.32677/ijch.v8i9.3039 ◽

2021 ◽

Vol 8 (9) ◽

pp. 338-339

Author(s):

Saili Vishwanath Bunde ◽

Mumtaz Sharif ◽

Amit Saxena

Keyword(s):

Nephrotic Syndrome ◽

Idiopathic Nephrotic Syndrome ◽

Treatment Options ◽

Immunosuppressive Drugs ◽

Significant Side Effect ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Steroid Dependent ◽

Appropriate Treatment ◽

Frequent Relapses

Nephrotic syndrome (NS) is a kidney disorder in which, excess protein is being excreted through urine. While most cases of idiopathic nephrotic syndrome respond to steroid therapy and experience a limited number of relapses prior to complete remission, some cases suffer from frequent relapses and become steroid-dependent or are primarily steroid-resistant. Treatment options are limited to immunosuppressive drugs with significant side effect profiles. Infections in nephrotic syndrome are common and can be severe. Meningitis is one of the complications associated with nephrotic syndrome. Here, we report a child with steroid-resistant nephrotic syndrome (SRNS) with meningitis. Early detection and appropriate treatment of these complications can be lifesaving.

Download Full-text

A Case of Nephrotic Syndrome, Showing Evidence of Response to Saquinavir

Case Reports in Nephrology ◽

10.1155/2015/512549 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Giles Walters ◽

Faisal A. Choudhury ◽

Budhima Nanayakkara

Keyword(s):

Nephrotic Syndrome ◽

Focal Segmental Glomerulosclerosis ◽

Idiopathic Nephrotic Syndrome ◽

Treatment Options ◽

Immunosuppressive Drugs ◽

Significant Side Effect ◽

Steroid Resistant ◽

Segmental Glomerulosclerosis ◽

Steroid Dependent ◽

Frequent Relapses

The treatment of primary nephrotic syndrome such as minimal change nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis nephropathy remains challenging. Whilst most cases of idiopathic nephrotic syndrome respond to steroid therapy and experience a limited number of relapses prior to complete remission, some cases suffer from frequent relapses and become steroid dependent or are primarily steroid resistant. Treatment options are limited to immunosuppressive drugs with significant side effect profiles. New modalities targeting novel pathways in the pathogenesis of nephrotic syndrome are actively sought. Here we report the case of a patient with steroid dependent focal segmental glomerulosclerosis (FSGS) nephrotic syndrome with a favourable response to a novel proteasome inhibitor saquinavir.

Download Full-text

Immunosuppressive therapy in children with steroid-resistant, frequently-relapsing, and steroid-dependent idiopathic nephrotic syndrome: a single center experience

Electronic physician ◽

10.19082/2039 ◽

2016 ◽

Vol 8 (2) ◽

pp. 2039-2047 ◽

Cited By ~ 1

Author(s):

Bahia Hassan Moustafa ◽

Omar Atef Tolba

Keyword(s):

Nephrotic Syndrome ◽

Immunosuppressive Therapy ◽

Idiopathic Nephrotic Syndrome ◽

Single Center ◽

Steroid Resistant ◽

Single Center Experience ◽

Steroid Dependent

Download Full-text

Urinary Proteome of Steroid-Sensitive and Steroid-Resistant Idiopathic Nephrotic Syndrome of Childhood

American Journal of Nephrology ◽

10.1159/000093814 ◽

2006 ◽

Vol 26 (3) ◽

pp. 258-267 ◽

Cited By ~ 46

Author(s):

Robert P. Woroniecki ◽

Tatyana N. Orlova ◽

Natasha Mendelev ◽

Ibrahim F. Shatat ◽

Susan M. Hailpern ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Idiopathic Nephrotic Syndrome ◽

Steroid Resistant ◽

Urinary Proteome ◽

Steroid Sensitive

Download Full-text

Recent Update in The Management of Childhood Nephrotic Syndrome

Journal of Bangladesh College of Physicians and Surgeons ◽

10.3329/jbcps.v34i1.29119 ◽

2016 ◽

Vol 34 (1) ◽

pp. 26-32 ◽

Cited By ~ 1

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

Download Full-text

Difference of Vitamin D and Interleukin-6 Levels in Children with Steroid- Resistant, Steroid-Sensitive and Idiopathic Nephrotic Syndrome

Journal of Tropical Life Science ◽

10.11594/jtls.09.02.07 ◽

2019 ◽

Vol 9 (2) ◽

Keyword(s):

Vitamin D ◽

Nephrotic Syndrome ◽

Interleukin 6 ◽

Idiopathic Nephrotic Syndrome ◽

Steroid Resistant ◽

Steroid Sensitive

Download Full-text

Therapies for Glomerular Diseases in Children

Annals of the National Academy of Medical Sciences (India) ◽

10.1055/s-0040-1712821 ◽

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.

Download Full-text