Human Umbilical Cord Mesenchymal Stem Cell Injection for Diabetic Nephropathy

Inclusion criteria

• Type 2 diabetes with a disease duration of ≥ 5 years (no age limit for subjects diagnosed with diabetic nephropathy by renal biopsy).
• Age 30-70 years, no gender restriction.
• Diagnosis of diabetic nephropathy (see Appendix 1).
• Estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m².
• During the 3-month period prior to enrollment, received antihypertensive therapy centered on renin-angiotensin system inhibitors (RASIs) to control blood pressure, achieving the following targets: systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤ 100 mmHg.
• At the screening/baseline visit, must have received a stable dose of an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) for ≥ 3 months, or a stable dose of nateglinide for ≥ 3 months, or a stable combination of an SGLT2 inhibitor and nateglinide for ≥ 3 months, and continue the same stable dose throughout the trial.
• No positive exclusion criteria.
• Voluntary participation in the clinical trial, good compliance, ability to understand and sign the informed consent form for this study, and capability to complete the entire trial treatment and follow-up schedule according to the study protocol.

(Final eligibility will be determined by the investigator based on comprehensive clinical symptom assessment.)

Exclusion criteria

• Patients with type 1 diabetes mellitus.
• Patients with a prior history of primary glomerulonephritis, lupus nephritis, ANCA-associated vasculitis with renal involvement, Henoch-Schönlein purpura nephritis, or hepatitis B-associated nephritis.
• Poor glycemic control.
• Active liver disease or significantly abnormal liver function test results (ALT or AST ≥ 2× the upper limit of normal).
• Presence of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, etc.
• White blood cell count < 3.0×10⁹/L, hemoglobin < 80 g/L, platelet count < 100×10⁹/L, or other hematologic disorders (severe anemia, idiopathic thrombocytopenic purpura, splenomegaly, coagulation disorders, etc.).
• Severe and unstable cardiovascular or cerebrovascular disease (as assessed by the investigator).
• Uncontrolled infection or a history of tuberculosis.
• Current or previous malignancy; patients with tumor markers exceeding 1× the upper limit of normal.
• Current or previous blood-borne infectious diseases (HIV, syphilis, hepatitis B, and hepatitis C).
• Pregnancy, planned pregnancy, or possibility of breastfeeding.
• Use of systemic corticosteroids (e.g., cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, beclomethasone, triamcinolone acetonide) within 3 months prior to screening; use of systemic immunosuppressive agents other than corticosteroids (e.g., cyclosporine A, cyclophosphamide, rituximab, mycophenolate mofetil, mycophenolate sodium, leflunomide, azathioprine) within 12 months prior to screening; use of hydroxychloroquine within 8 months prior to screening; use of tacrolimus within 3 months prior to screening. Exceptions: topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term continuous use (≤3 days) of corticosteroids for non-autoimmune conditions or to prevent possible allergic reactions to the study drug (e.g., a single injection of 3 mg dexamethasone to prevent allergy).
• Allergy to human albumin.
• Psychiatric disorders that may affect voluntariness, decision-making ability, or communication ability.
• History of known drug abuse.
• Participation in another clinical trial within the last 3 months.
• Prior treatment with stem cell therapy.
• Severe uncontrolled pulmonary disease, including pulmonary fibrosis, interstitial lung disease, acute exacerbation of chronic obstructive pulmonary disease, active pulmonary infection, etc.
• Poor compliance, inability to complete the entire study.
• Patients deemed unsuitable for the study by the investigator.

Appendix 1:

After establishing diabetes mellitus as the cause of renal injury and excluding other causes of chronic kidney disease, the diagnosis of diabetic kidney disease (DKD) can be established upon meeting at least one of the following criteria:

• At least 2 out of 3 measurements within a 3- to 6-month period show a urine albumin-to-creatinine ratio (UACR) ≥30 mg/g or a 24-hour urinary albumin excretion rate (UAER) ≥30 mg/24 h;
• eGFR <60 mL/min/1.73 m² persisting for more than 3 months;
• Renal biopsy findings are consistent with the pathological changes characteristic of diabetic kidney disease.