An Exploratory Clinical Study on the Safety and Efficacy of Anti-CD19/BCMA U CAR-T Cells in the Treatment of Relapsed/Refractory Immune-mediated Kidney Disease

Inclusion Criteria: 1. Age: ≥ 18 years old and ≤ 70 years old, male or female; 2. 2 B cell CD19 positive expression in peripheral blood detected by flow cytometry; 3. The functions of critical organs meet the following requirements: 1. Neutrophil count ≥ 1 x 10\^9/L, Hemoglobin ≥60g/L, platelets ≥ 50×109/L, 2. Liver function: ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN, 3. Coagulation function: International standardized ratio (INR) ≤ 1.5x ULN, prothrombin time (PT) ≤1.5 x ULN, 4. Cardiac function: good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥55%. 4. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential are required to use medically approved contraception or abstain from sex for at least 6 months during and at least 6 months after the end of the study treatment period; female subjects of childbearing potential have had a negative serum HCG test within 7 days prior to study enrollment and are not lactating; 5. Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up. Specific inclusion criteria: High-risk or relapsed/refractory primary membranous nephropathy 6. Primary membranous nephropathy diagnosed pathologically by renal biopsy; 7. Meets the clinical criteria for high-risk or recurrent/refractory membranous nephropathy, defined as: Subjects at risk who meet any of the following criteria: a) estimated glomerular filtration rate (eGFR, CKD-EPI equation) \<60 mL/min/1.73m², and/or urine protein \>8g/day persisting for more than 6 months;b) normal GFR, urinary protein \>3.5 g/d, treated with ACEI/ARB for 6 months, urinary protein reduction \<50%, and serum albumin \<25 g/l or aPLA2R \>50 RU/mL; Refractory membranous nephropathy subjects are defined as those who have shown poor response or resistance to previous immunosuppressive treatments (including corticosteroids and/or cytotoxic drugs, immunosuppressants and/or biologics), defined as persistent proteinuria ≥3.5g/day with a reduction of \<50% compared to baseline; Recurrent membranous nephropathy is defined as a relapse (24-hour urinary protein ≥3.5 g) in subjects who have achieved complete or partial remission following treatment; 8. Subjects with relapsed/refractory MN and eGFR ≥ 45 mL/min/1.73 m2 during the screening period; 9. Primary IgA nephropathy pathologically confirmed by renal biopsy; 10. Subjects have medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per local SOC and applicable guidelines, for at least 3 months preceding screening; 11. Subjects have been treated with hormones and/or cytotoxic drugs, immunosuppressants and/or biological agents (including but not limited to anti-CD20 monoclonal antibodies) for more than 6 months, and the 24-hour urine protein is ≥1.0 g; subjects with a rapidly progressive decline in kidney function (eGFR decreases by ≥50% within 3 months); or The subject relapsed after achieving complete remission/partial remission (CR/PR) following treatment (24-hour urine protein ≥1.0 g); 12. Estimated glomerular filtration rate (eGFR, CKD-EPI formula) ≥30 mL/min/1.73m2 at screening; 13. Meets the 2022 ACR/EULAR diagnostic criteria for ANCA-associated vasculitis, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis; 14. ANCA-related antibodies positive (MPO-ANCA or PR3-ANCA positive); 15. Kidney biopsy pathology is consistent with ANCA-associated vasculitis renal damage; 16. Birmingham Vasculitis Activity Score (BVAS) ≥15 points (total score 63 points), indicating active vasculitis; 17. At least two abnormalities related to the kidneys in the BVAS score; 18. Subjects meeting the definition of relapsed/refractory: standard treatment is ineffective or disease activity recurs after remission. Definition of conventional treatment: using glucocorticoids (more than 1mg/kg/day) and cyclophosphamide, along with any one of the following immunomodulatory drugs for ≥3 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, and thalidomide; 19. Estimated glomerular filtration rate (eGFR, CKD-EPI formula) ≥30 mL/min/1.73m2 at screening Exclusion Criteria: Subjects who meet any of the following common exclusion criteria or disease-specific exclusion criteria will not be eligible for this study Common exclusion Criteria: 1. Subjects known to have allergic reactions, hypersensitivity, intolerance, or contraindications to CD19/BCMA universal CAR-T or any drug components that may be used in the study (including fludarabine, cyclophosphamide, and tocilizumab), or who have previously experienced severe allergic reactions; 2. The subject has or is suspected of having uncontrolled or treatable fungal, bacterial, viral, or other infections; 3. Subjects with central nervous system disorders caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychiatric disorders, organic brain syndrome, cerebrovascular accidents, encephalitis, central nervous system vasculitis); 4. Subjects with more serious heart conditions, such as angina, myocardial infarction, heart failure, and arrhythmias; 5. Subjects with congenital immunoglobulin deficiency; 6. The subject has other malignant tumours (excluding non-melanoma skin cancer and carcinoma in situ of the cervix, bladder cancer, and breast cancer with disease-free survival of over 5 years); 7. Subjects with end-stage renal failure; 8. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and have peripheral blood HBV DNA titres above the detection limit; subjects who are positive for hepatitis C virus (HCV) antibodies and peripheral blood HCV RNA; subjects who are positive for human immunodeficiency virus (HIV) antibodies; subjects who test positive for syphilis; 9. Subjects have mental illness and severe cognitive impairment; 10. Subjects who have participated in other clinical trials within 6 months prior to enrolment; 11. Female participants who are pregnant or planning to conceive; 12. Subjects with hypertension and diabetes uncontrolled by medication; 13. Researchers believe that there are other reasons why some subjects cannot be included in this study; Specific exclusion Criteria: Relapsed/Refractory Primary Membranous Nephropathy 14. Secondary membranous nephropathy (e.g., hepatitis B, systemic lupus erythematosus, drug-associated, malignancy-associated, etc.), or in combination with other renal diseases confirmed by renal biopsy; Relapsed/Refractory IgA Nephropathy 15. Exclude secondary IgA nephropathy, including but not limited to: anaphylactic purpura, ankylosing spondylitis, systemic lupus erythematosus, desiccation syndrome, viral hepatitis, cirrhosis of the liver, rheumatoid arthritis, and mixed connective tissue disease; or in combination with other renal diseases confirmed by renal biopsy; 16. Crescentic nephritis (pathologic diagnosis of \>50% crescentic bodies), micrognathic nephropathy with IgA deposition, and other specific types of pathologic or clinical renal disease; Relapsed/refractory ANCA-associated vasculitis kidney damage 17. Estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m2; 18. If subjects have alveolar haemorrhage and requires invasive lung ventilation, the expected duration exceeds the screening time.