Study of Therapeutic Efficacy of Anti-CD19 CAR-T Cell Therapy in Patients With MDR-SRNS

Inclusion Criteria:

1. Age ≥2 years old, gender unlimited;

• 2.Diagnosed with SRNS according to the 2021 Kidney Disease: Improving GlobalOutcomes （KDIGO） Guidelines and have not achieved a complete response after 12months of treatment with two standard doses of hormone replacement drugs withdifferent mechanisms of action or relapse of disease activity after remission (atleast one of the two drugs is a calcineurin inhibitor such as cyclosporine ortacrolimus; Other hormone replacement drugs include Mycophenolate Mofetil,cyclophosphamide, Taitacept or rituximab); Or if no remission has been achievedafter 3 to 6 months of adequate treatment with one calcineurin inhibitor, if theresearcher judges that the benefits outweigh the risks and the patient or guardianhas fully informed consent, the patient can be considered for inclusion.Patientswith other diseases, such as systemic lupus erythematosus, requiring long-termsystemic treatment with glucocorticoids or immunosuppressants, may be considered forinclusion after the investigator determines that the benefits outweigh the risks andthe patient or guardian has fully informed consent;

3. Renal biopsy was performed and the pathological type was determined to beminimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);

4. The functions of important organs are basically normal: Cardiac function: Leftventricular ejection fraction (LVEF) ≥55% with no obvious abnormality inelectrocardiogram; Renal function: eGFR≥30ML/min/1.73m2# Liver function:Asparagus cochinchinensis transaseminase (AST) and Alanine Aminotransferase (ALT)≤3.0 upper limit of normal, Total Bilirubin (TBIL) in serum ≤2.0×upperlimit of normal; Lung function: No serious lung lesions, SpO2≥92%;

5. Met the standards of leukapheresis or intravenous blood collection, Nocontraindication for cell collection;

6. Negative pregnancy test for female Subjects of childbearing age, agree to takeeffective contraceptive measures the first year after CAR-T infusion;

7. Participants or their guardians agrees to participate in the clinical trial andsign the informed consent form which indicating that he/she understands thepurpose and procedure of the clinical trial and is willing to participate inthe study.

Exclusion Criteria:

1. Received CAR T cell therapy or other gene-modified cell therapy previously;

2. Patients had a cerebrovascular accident or seizure, or other active centralnervous system disease within 6 months;

3. Genetic tests have confirmed hereditary kidney disease;

4. Renal biopsy has been confirmed as immunoglobulin A nephropathy, idiopathicmembranous nephropathy or membranoproliferative glomerulonephritis;

5. Renal replacement therapy has been or is being performed within 3 months priorto transfusion. (if acute kidney injury factors were considered, patients withchronic kidney disease were excluded, and the benefits outweighed the risks asdetermined by the investigator and with the full and informed consent of thepatient or guardian could be considered for inclusion);

6. Renal replacement therapy has been or is being performed within 3 months priorto transfusion;

7. Have a history of congenital heart disease or acute myocardial infarctionwithin 6 months prior to screening; Or severe arrhythmias (includingmultisource frequent supraventricular tachycardia, ventricular tachycardia,etc.); Or combined with moderate to massive pericardial effusion, seriousmyocarditis, etc; Or patients with unstable vital signs who need hypertensivedrugs;

8. Received solid organ transplantation or hematopoietic stem cell transplantationwithin 3 months prior to screening; Acute graft-versus-host disease (GVHD) ofgrade 2 or above was present within 2 weeks prior to screening;

9. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb)positive and peripheral blood hepatitis B virus (HBV) DNA titer greater thanthe normal reference value range; Or hepatitis C virus (HCV) antibody positiveand peripheral blood hepatitis C virus (HCV) RNA titer greater than the normalreference value range; Or positive for human immunodeficiency virus (HIV)antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA testpositive;

10. Macrophage activation syndrome occurred within 1 month prior to screening;

11. Received live vaccine within 4 weeks before screening;

12. Patients with malignant diseases such as tumors before screening, or with otherserious life-threatening diseases;

13. Tested positive in Blood pregnancy test;

14. Patients who participated in other clinical study within 1 months prior toenrollment;

15. Any other conditions that the investigators deem it unsuitable for the study.