IM19 CAR-T Cell Therapy for IgA Nephropathy Patients and Membranous Nephropathy Patients

Inclusion Criteria： * IgA nephropathy 1. IgA nephropathy diagnosed through renal biopsy 2. When screening, urine protein should be ≥0.5g/gCr and 20mL/min/1.73m\^2≤eGFR\<60mL/min/1.73m\^2 3. Age≥18years old 4. Liver, kidney, heart, lung function, and coagulation function meet the following requirements: 4.1 ALT and AST ≤ 2.5 × ULN,total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert syndrome, ALT and AST ≤ 5 × ULN, total bilirubin ≤ 3 × ULN); 4.2 Left ventricular ejection fraction ≥ 50%; 4.3 International ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 4.4 Finger pulse oxygen saturation\>92% in non oxygen state; 5. Women of childbearing age who have a negative blood pregnancy test before the start of the trial and agree to take effective contraceptive measures during the trial period until the last follow-up; Male participants with reproductive partners agree to take effective contraceptive measures during the trial period until the last follow-up; 6. Doctors evaluate patients with the optimal benefit risk ratio 7. Those who voluntarily participate in this experiment and sign the informed consent form * Primary membranous nephropathy: 1. Diagnosis of primary membranous nephropathy through renal biopsy; 2. Primary membranous nephropathy at medium or high risk that has not improved after 6 months of treatment with CNI and rituximab: 2.1. Moderate risk assessment criteria 2.1.1. EGFR is normal, 24-hour urine protein is\>4g, and conservative treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers has been continuously used for 6 months or more before screening. The 24-hour urine protein has not decreased by less than 50% 2.1.2. PLA2R antibody\<50RU/mL+ 2.1.3. Low molecular weight urinary protein 2.1.4. Selectivity index\<0.15 2.1.5. Urinary immunoglobulin UIgG\<250mg/day 2.2 High risk assessment criteria 2.2.1. eGFR\<60ml/min/1.73m\^2 2.2.2. 24-hour urine protein\>4g and lasting\>6 months 2.2.3. PLA2R antibody\>150RU/mL+ 2.2.4. High molecular weight urinary protein 2.2.5. Urine immunoglobulin UigG\>250mg/day 2.2.6. Selectivity index\>0.20 3. Age ≥ 18 years old; 4. Liver, heart, lung function, and coagulation function meet the following requirements: 4.1. ALT and AST ≤ 2.5 × ULN, total bilirubin ≤ 1.5 × ULN (for) Subjects with Gilbert syndrome, ALT and AST ≤ 5 × ULN, total bilirubin ≤ 3 × ULN); 4.2. Left ventricular ejection fraction ≥ 50%; 4.3. International ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 4.4. Finger pulse oxygen saturation\>92% in non oxygen state 5. Women of childbearing age who have a negative blood pregnancy test before the start of the trial and agree to take effective contraceptive measures during the trial period until the last follow-up; Male participants with reproductive partners agree to take effective contraceptive measures during the trial period until the last follow-up 6. Doctors evaluate patients with the optimal benefit risk ratio 7. Those who voluntarily participate in this experiment and sign the informed consent form Exclusion Criteria: * IgA nephropathy: 1. Kidney diseases other than IgA nephropathy, as well as primary and secondary nephrotic syndrome 2. After examination by the researchers, it was determined that the subjects had diseases that were not suitable for participation in this study, such as life-threatening conditions (such as catastrophic antiphospholipid syndrome, acute severe renal failure, and acute severe central nervous system disease manifestations) 3. Serious complications unrelated to IgA nephropathy 4. Use or increase the dosage of corticosteroids, immunosuppressants, biologics (including but not limited to CD20 monoclonal antibodies, taceptil, etc.), anticoagulants (warfarin), and n-3 fatty acids (fish oil) for the drug treatment of IgA nephropathy within 3 months 5. Uncontrollable hypertension or hyperglycemia 6. Perform palatal tonsillectomy within 6 months 7. Study subjects with a history of alcohol or drug abuse within the past 24 weeks 8. Have undergone major surgery (including joint surgery) within 24 weeks prior to screening, or plan to undergo surgery within 24 weeks after enrollment in the study 9. Used other cell therapies 10. Have participated in or participated in other clinical trials within the past 3 months 11. Within 3 years or planning to undergo a kidney transplan 12. Active hepatitis B or hepatitis C virus, defined as: subjects with positive hepatitis B B virus surface antigen (HBsAg) and/or hepatitis B B core antibody (HBcAb, Hepatitis B core antibody) and HBV DNA titer in peripheral blood higher than the lower limit of detection; Individuals with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA (HCV RNA); Syphilis infected individuals 13. Active EB virus and cytomegalovirus, defined as: subjects with positive or negative IgM antibodies in EB virus serum but EBV-DNA higher than normal values; Subjects with IgM antibody positive or IgM antibody negative but CMV-DNA higher than normal in the serum of cytomegalovirus (CMV) 14. Serious history of cardiovascular and cerebrovascular diseases, including but not limited to: 14.1. Serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, third degree atrioventricular block, etc; 14.2. At rest, QT interval prolongation (QTc\>450 milliseconds in males or\>470 milliseconds in females); 14.3. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events occurred within 6 months prior to the first administration; 14.4. There is heart failure with NYHA functional class ≥ II in the United States; 15. History of symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months prior to the start of screening; 16. History of malignant tumors other than non melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) (unless in a disease-free state for at least 3 years) 17. Infections (fungal, bacterial, viral, or other) that require intravenous injection of antibiotics for control or are uncontrollable, such as simple urinary tract infections and bacterial pharyngitis, may be included if the researcher evaluates that they can be controlled through treatment 18. The researchers believe that it does not meet the criteria for joining this clinical trial 19. During pregnancy or lactation, it may be due to pregnancy or the male and female not agreeing to undergo contraception under the guidance of the researcher during the study period. * Primary membranous nephropathy: 1. Secondary membranous nephropathy; 2. Urinary protein decreased by more than 50% within the first 6 months of screening; 3. After examination by the researchers, it was determined that the subjects had diseases that were not suitable for participation in this study, such as life-threatening conditions (such as catastrophic antiphospholipid syndrome, acute severe renal failure, and acute severe central nervous system disease manifestations); 4. Serious complications unrelated to primary membranous nephropathy; 5. Uncontrollable hypertension or hyperglycemia; 6. The study subjects have a history of alcohol or drug abuse within the past 24 weeks; 7. Have undergone major surgery (including joint surgery) within 24 weeks prior to screening, or plan to undergo surgery within 24 weeks after enrollment in the study; 8. Have used other cell therapies; 9. Have participated in or taken part in other clinical trials within the past 3 months; 10. Within 3 years or planning to undergo kidney transplantation; 11. Active hepatitis B or hepatitis C virus, defined as: subjects with positive hepatitis B B virus surface antigen (HBsAg) and/or hepatitis B B core antibody (HBcAb, Hepatitis B core antibody) and HBV DNA titer in peripheral blood higher than the lower limit of detection; Individuals with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA (HCV RNA); Syphilis infected individuals; 12. Active EB virus and cytomegalovirus, defined as: subjects with positive or negative IgM antibodies in EB virus serum but EBV-DNA higher than normal values; Subjects with IgM antibody positive or IgM antibody negative but CMV-DNA higher than normal in the serum of cytomegalovirus (CMV); 13. History of serious cardiovascular and cerebrovascular diseases, including but not limited to: severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, third degree atrioventricular block, etc; At rest, QT interval prolongation (QTc\>450 milliseconds in males or\>470 milliseconds in females); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events occurred within 6 months prior to the first administration; There is heart failure with NYHA functional class ≥ II in the United States; 14. History of symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months prior to the start of screening; 15. History of malignant tumors other than non melanoma skin cancer or carcinoma in situ (such as cervix, bladder, breast) (unless in a disease-free state for at least 3 years); 16. Infections (fungal, bacterial, viral, or other) that require intravenous injection of antibiotics for control or are uncontrollable, such as simple urinary tract infections and bacterial pharyngitis, may be included if the researcher evaluates that they can be controlled through treatment; 17. The researcher believes that it does not meet the criteria for joining this clinical trial; 18. During pregnancy or lactation, it may be due to pregnancy or the male and female not agreeing to undergo contraception under the guidance of the researcher during the study period.