Blinatumomab for CNI-Resistant/Intolerant SRNS in Children

• Inclusion Criteria:

Subjects must meet all of the following criteria to be included in the study:

1.Age between 2 and 17 years, regardless of gender. 2.Meet the 2021 KDIGO definition of steroid-resistant nephrotic syndrome (SRNS), and fulfill either of the following:

1. Have received an adequate dose of calcineurin inhibitors (CNIs) for more than 6months without achieving at least partial remission.

2. Or have contraindications to CNI use, including:

1. Significant renal impairment, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², or presence of acute kidney injury at the time of diagnosis; 2)Renal biopsy showing prominent acute or chronic tubular injury, such as tubularatrophy or interstitial fibrosis involving more than 50% of the sampled tissue; 3)Elevated urinary markers (β2-microglobulin, α1-microglobulin, or retinol-bindingprotein) exceeding three times the upper limit of normal; 4) Abnormal glucosetolerance; 5) Severe uncontrolled hypertension, defined as systolic and/or diastolicblood pressure ≥ the 95th percentile + 12 mmHg for age, sex, and height, or ≥ 140/90mmHg; 6) Concomitant use of medications known to have significant interactions withCNIs, leading to increased toxicity or reduced efficacy; 7) Known allergy orhypersensitivity to CNIs or any of their components. (3) Or have demonstratedinadequate response or disease relapse after treatment with at least twoimmunosuppressive agents, including CNIs and at least one of the following:

1. Conventional immunosuppressive agents: cyclophosphamide, mycophenolate mofetil,azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide

2. Biologic agents: abatacept, ofatumumab, obinutuzumab, rituximab Inadequate responseis defined as failure to achieve complete remission after 12 months of therapy orrelapse following initial response.

3. Renal biopsy performed prior to screening confirms a diagnosis of minimal changedisease (MCD) or focal segmental glomerulosclerosis (FSGS).

4. The subject and/or their legal guardian must provide written informed consent,indicating understanding of the study's purpose and procedures, with the right towithdraw consent at any time without affecting the subject's future medical care.

-Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. eGFR &lt; 60 mL/min/1.73 m² (using the modified Bedside Schwartz formula);

2. Stroke or seizure within 6 months prior to screening, or other active centralnervous system disorders;

3. Genetic nephropathy confirmed by genetic testing;

4. Renal biopsy confirming IgA nephropathy, membranous nephropathy, ormembranoproliferative glomerulonephritis;

5. Severe congenital heart disease or history of acute myocardial infarction within 6months, or severe arrhythmias (e.g., frequent multifocal ventricular orsupraventricular tachycardia, ventricular tachycardia), or moderate to largepericardial effusion, severe myocarditis, or unstable vital signs requiringvasopressors to maintain blood pressure;

6. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with hepatitis B virus (HBV) DNA levels above the normal range; positive forhepatitis C virus (HCV) antibodies with HCV RNA levels above the normal range; orpositive for human immunodeficiency virus (HIV) antibodies, syphilis, orcytomegalovirus (CMV) DNA;

7. Abnormal laboratory values prior to screening: moderate to severe neutropenia (≤1.0×10⁹/L); moderate to severe anemia (hemoglobin ≤90 g/L); thrombocytopenia (≤75×10⁹/L); or liver dysfunction (ALT, AST, or bilirubin greater than 2.5 times theupper limit of normal and persisting for 2 weeks);

8. Subjects with tumors or other life-threatening diseases prior to screening;

9. Positive blood pregnancy test;

10. Participation in other clinical trials within 1 month prior to enrollment;

11. Received rituximab or cyclophosphamide therapy within the past 3 months;

12. Any other condition deemed by the investigator to be unsuitable for participation;

13. Vaccination with live vaccines within 4 weeks prior to screening.