This is a single-center, open-label, exploratory clinical study designed to evaluate the safety and efficacy of a single-session injection of SC101, a small interfering RNA (siRNA) agent, into the perirenal fat. This study plans to enroll 3 participants, aged 18 to 65 years, who have a clinical diagnosis of resistant hypertension and moderate to severe chronic kidney disease (CKD).

This is a single-center, open-label, investigator-initiated, exploratory clinical trial. It serves as a proof-of-concept study for a novel anti-hypertensive intervention: the local injection of SC101, a siRNA agent, into the perirenal adipose tissue. This study plans to enroll 3 participants, aged 18 to 65 years, who have a clinical diagnosis of resistant hypertension and moderate to severe CKD. "Resistant hypertension" is defined as blood pressure (BP) that remains uncontrolled despite the use of at least 3 antihypertensive drug classes (including one diuretic) administered at stable, tolerated, and appropriate doses for at least 4 weeks, alongside lifestyle modifications. "Moderate to severe CKD" is defined as as an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m^2 and <40 mL/min/1.73m^2 using the Cockcroft-Gault equation.

• Study Objectives:

• Primary Objective: To evaluate the safety of a single-session injection of SC101 into the bilateral perirenal fat in patients with resistant hypertension and concomitant moderate to severe CKD.

• Secondary Objectives:

  1. To assess the initial effectiveness and durability of BP reduction following a single-session injection of SC101 into the bilateral perirenal fat.
  2. To validate the "perirenal fat-dorsal root ganglion" axis as a mechanism for hypertension.
  3. To evaluate the safety profile specifically associated with the perirenal fat injection procedure, providing a basis for establishing localized siRNA interference technique.

• Exploratory Objective: To explore the impact of a single-session injection of SC101 on renal function.

Inclusion Criteria:

• Age ≥ 18 and ≤ 65 years.
• Participants with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m^2 and <40 mL/min/1.73m^2 during the screening period (eGFR is calculated using the Cockcroft-Gault equation).
• Diagnosed with resistant hypertension: blood pressure (BP) remains uncontrolled after at least 4 weeks of treatment with at least 3 types of antihypertensive drugs (including one diuretic) at tolerated and sufficient doses, in addition to lifestyle modification. At the end of the screening and run-in period (baseline), resting office systolic BP (OSBP) ≥ 140 mmHg, resting office diastolic BP (ODBP) ≥ 90 mmHg, and 24-hour mean ambulatory systolic BP (MASBP) ≥ 130 mmHg.
• Received stable doses of antihypertensive drugs for at least 4 weeks prior to screening, and can accept stable doses of antihypertensive drugs for 2 weeks during the run-in period.
• The inferior perirenal fat volume is judged by the investigator to be sufficient for SC101 injection.
• Agreement to use effective contraceptive measures throughout the trial (within 1 year after SC101 injection), and women of childbearing potential must have a negative pregnancy test during the screening period.
• Capable of understanding and voluntarily signing the informed consent form, and able to complete the study in accordance with the protocol requirements.

Exclusion Criteria:

• Obvious pseudo-resistant hypertension caused by white-coat effect, incorrect BP measurement, poor medication adherence, use of drugs affecting antihypertensive efficacy, insufficient dosage, unreasonable combination therapy, or secondary hypertension (except obstructive sleep apnea) as judged by the investigator.
• Confirmed history of secondary hypertension (including but not limited to renal artery stenosis, primary aldosteronism, pheochromocytoma, aortic coarctation, etc.).
• Congenital renal abnormalities that may affect the safety and/or efficacy evaluation of the trial, including but not limited to solitary kidney or polycystic kidney disease.
• Cardiovascular-related diseases that may affect safety evaluation, including but not limited to: uncontrolled symptomatic tachyarrhythmia or bradyarrhythmia (e.g., untreated persistent atrial fibrillation, second-degree or higher heart block, sick sinus syndrome); congestive heart failure NYHA Class III or IV; myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within the past 6 months; severe structural heart disease (including moderate or higher valvular lesions, cardiomyopathy, congenital heart disease).
• Abnormal liver function, defined as Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 2 times the Upper Limit of Normal (ULN).
• Hematological diseases that may affect safety evaluation, including but not limited to anemia (Hemoglobin < 90 g/L) or abnormal coagulation function (INR > 1.5 or fibrinogen less than the lower limit of normal).
• Type 1 diabetes mellitus or poorly controlled hyperglycemia at screening (defined as HbA1c ≥ 7.5%).
• Urinary system diseases requiring surgical intervention at screening.
• Conditions unable to tolerate perirenal fat injection under local anesthesia, including but not limited to local skin problems or structural abnormalities adjacent to perirenal fat.
• Contraindications related to anesthetics (such as lidocaine).
• Life expectancy < 1 year.
• History of malignant tumors (except those cured for more than 5 years without recurrence) or confirmed malignant tumors or precancerous lesions.
• Known Acquired Immunodeficiency Syndrome (AIDS) or HIV-positive status, or previous diagnosis of immunodeficiency with absolute neutrophil count < 1000/mm^3.
• Active liver disease participants, such as positive HAV antibody, positive HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, HBV DNA quantification), or positive HCV antibody (HCV Ab) and HCV RNA quantification above the detection limit.
• Positive Syphilis antibody and positive Rapid Plasma Reagin (RPR) test.
• Vaccination with live (attenuated) vaccines within 4 weeks before screening or planned during the trial.
• Currently participating in other clinical trials, or received other interventional clinical trial drugs within 3 months prior to enrollment.
• Currently using corticosteroids or immunosuppressants, where the investigator judges that dose adjustments will be required during the trial.
• Women who are breastfeeding.
• Other conditions that the investigator believes may affect compliance or make the participant unsuitable for the study.