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 KDIGO 2021 definitionof steroid-resistant nephrotic syndrome (SRNS) and have received an adequate dose ofCNI for more than 6 months without achieving at least partial remission; or havecontraindications or i intolerance to CNI use, including:

2. Significant renal impairment with eGFR < 60 mL/min/1.73 m² or acute kidney injuryat the time of diagnosis;

3. Renal biopsy showing significant acute or chronic tubular injury (e.g., tubularatrophy or interstitial fibrosis greater than 50%);

4. Elevated urinary β2-microglobulin, α1-microglobulin, or retinol-binding proteinlevels greater than three times the upper limit of normal;

5. Impaired glucose tolerance;

6. Severe uncontrolled hypertension (systolic and/or diastolic blood pressure ≥ the 95th percentile +12 mmHg for children of the same sex, age, and height, or ≥140/90mmHg);

7. Concomitant use of medications that have significant interactions with CNIs,resulting in increased toxicity or decreased efficacy;

8. Known allergy to CNIs or any of their components. 3. Renal biopsy prior to screeningconfirming a diagnosis of minimal change disease (MCD) or focal segmentalglomerulosclerosis (FSGS); 4. The subject or legal guardian must agree toparticipate in the study and sign an informed consent form indicating understandingof the purpose and procedures of the study, with the ability to withdraw consent atany time without affecting future medical care.

• Exclusion Criteria:

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

1. eGFR < 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 timesthe upper 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.