Primary Nephrotic Syndrome
Conditions
Brief summary
Primary nephrotic syndrome (PNS) in children is a clinical syndrome characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The main subtypes include steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS), among which frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS) are relatively common in clinical practice. In recent years, anti-CD20 monoclonal antibodies, such as rituximab (RTX), have achieved remarkable efficacy in the treatment of pediatric NS, particularly in SDNS/FRNS and SRNS. However, a subset of children exhibit suboptimal responses to RTX or cannot continue its use due to allergic reactions. Obinutuzumab (OBI) is a novel fully humanized anti-CD20 monoclonal antibody. Compared with RTX, OBI exhibits higher affinity for B cells and can bind to distinct CD20 epitopes, demonstrating stronger anti-B cell activity in vitro. Therefore, OBI has emerged as a potential alternative for patients who are unresponsive or intolerant to RTX \[1\]. Currently, OBI is a next-generation glycoengineered humanized anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) and apoptosis-inducing capabilities compared with RTX. Preliminary studies have shown its favorable efficacy and safety in adult systemic lupus erythematosus, refractory membranous nephropathy, transplant rejection, and pediatric SDNS/FRNS \[2-3\] and SRNS \[4-5\]. Clinical centers both domestically and internationally have already applied OBI in pediatric PNS patients who respond poorly to or are intolerant of RTX; however, no systematic studies have been conducted to date. As a leading pediatric nephrology center in western China, affiliated with the National Clinical Medical Center, our institution plans to use OBI in children with refractory PNS. The goal is to provide a safer and more effective B cell-targeted therapy, with an expected complete or partial remission in over 80% of patients. This approach aims to significantly reduce dependency on steroids, cyclosporine, tacrolimus, and other drugs, offering children with kidney disease a more precise and safer treatment pathway. This study will be the first in China to systematically evaluate the efficacy and safety of obinutuzumab in pediatric refractory PNS-including steroid resistance, frequently relapsing or steroid-dependent cases resistant to standard second-line therapy-and compare it with RTX to determine its ability to maintain disease remission and facilitate steroid withdrawal.
Interventions
None listed
Sponsors
Children's Hospital of Chongqing Medical University
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Inclusion criteria
Diagnostic Criteria for Pediatric Primary Nephrotic Syndrome (PNS): Children aged 1 to 18 years who meet the following criteria: Edema: Prominent edema, typically gravitational, affecting the eyelids and lower limbs. Massive proteinuria: Defined as urine protein-to-creatinine ratio (UPCR) ≥ 200 mg/mmol or 24-hour urine protein ≥ 40 mg/m²·h. Hypoalbuminemia: Serum albumin commonly below 25 g/L. Hyperlipidemia: Such as elevated total cholesterol. Subtypes of Pediatric PNS: Steroid-sensitive nephrotic syndrome (SSNS) Steroid-resistant nephrotic syndrome (SRNS) SSNS can be further divided into steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), with the following definitions: SSNS: An important clinical subtype of PNS. Diagnostic criteria: patients receiving standard-dose prednisone or prednisolone (usually 1.5-2.0 mg/kg/day or 60 mg/m²/day, maximum 60 mg/day) achieve urine protein remission within 4 weeks. SDNS: Initial response to glucocorticoid therapy is good, with proteinuria remission within 4 weeks. At least two relapses occur during steroid tapering or within 14 days after discontinuation, including relapses during dose reduction. FRNS: Occurrence of three or more relapses within 12 months, or two or more relapses within 6 months. A relapse is defined as consecutive 3-day morning urine protein ≥ +++ by dipstick or UPCR ≥ 200 mg/mmol. SRNS: Failure to achieve remission after 4 weeks of full-dose glucocorticoid therapy (prednisone or prednisolone 60 mg/m²/day or 1.5-2 mg/kg/day, maximum 60 mg/day) following PNS diagnosis, with persistent proteinuria (consecutive 3-day urine protein ≥ +++ by dipstick or UPCR ≥ 200 mg/mmol). \-
Exclusion criteria
* Secondary PNS: Chronic kidney disease caused by underlying conditions such as Henoch-Schönlein purpura, systemic lupus erythematosus, hepatitis B, diabetes, hereditary nephritis, severe infections, tumors, or medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of obinutuzumab (OBI) in pediatric refractory nephrotic syndrome | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the safety of obinutuzumab (OBI) in pediatric refractory nephrotic syndrome, including SDNS/FRNS and SRNS. | 12 months |
Countries
China
Outcome results
None listed