Human Umbilical Cord Mesenchymal Stem Cell Injection for Diabetic Nephropathy

Summary

Diabetic nephropathy (DN) is one of the most significant microvascular complications of diabetes mellitus. Its incidence can reach 30%-40% after 20 years of diabetes duration, among which 5%-10% of patients will progress to end-stage renal disease, where renal function is essentially lost, and only hemodialysis or kidney transplantation can sustain or save lives. Given the current lack of effective clinical measures for treating diabetic nephropathy, exploring new strategies for its prevention and treatment is of great significance. Diabetic nephropathy is caused by persistent hyperglycemia, and its key pathological features include chronic inflammatory cell infiltration in kidney tissue, podocyte apoptosis in the glomeruli, pyroptosis of renal tubular epithelial cells, and renal fibrosis. Therefore, the key to treating diabetic nephropathy lies in inhibiting chronic renal inflammation and alleviating the resulting tissue and cell damage; reducing glomerular podocyte apoptosis and renal tubular epithelial cell pyroptosis, lowering proteinuria levels, and delaying the pathological progression of diabetic nephropathy; suppressing renal fibrosis; and regenerating new renal tissue cells to partially restore renal tissue structure and function. Current clinical treatments for diabetic nephropathy primarily involve strict glycemic control and the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists. Numerous clinical studies have shown that these therapeutic measures can only partially delay the onset and slow the progression of diabetic nephropathy, but cannot reverse renal damage. Accumulating evidence indicates that mesenchymal stem cells (MSCs) can migrate and home to injured kidney tissues, directionally differentiate into renal parenchymal cells to repair and regenerate damaged tissue cells; secrete nutritional factors to improve local blood supply and the microenvironment of renal tissue; and release anti-inflammatory and immunomodulatory factors, exerting potent anti-inflammatory and immunomodulatory effects, thereby reducing inflammatory injury and apoptosis of renal tissue cells and alleviating renal fibrosis. Therefore, mesenchymal stem cells have emerged as a new hope for the treatment of diabetic nephropathy.

Eligibility

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.

Conditions2

Interventions1

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