The Renal Protective Effects of Remote Ischemic Preconditioning in Patients With Chronic Kidney Disease

Official title

The Renal Protective Effects of Remote Ischemic Preconditioning in Patients With Chronic Kidney Disease: Randomized, Parallel-controlled, proof-of Concept Trial

Overview

The incidence of Chronic kidney disease (CKD) is showing an upward trend, but the therapeutic effect of treatment is limited. Remote ischemic conditioning (RIC) has the potential to safeguard remote organs via the repeated application of brief ischemic stimuli. the aim of our study is to investigate whether RIC can protect the renal function in patients with CKD.

Detailed description

Chronic kidney disease (CKD) is characterized by progressive and irreversible loss of nephrons. Currently, due to the increasing prevalence of diabetes, hypertension, obesity, and the impact of population aging, the incidence of CKD is showing an upward trend. The treatment of CKD is mostly aimed at delaying the progression of renal function, but the therapeutic effect is limited, causing a continuous economic burden for CKD patients. Therefore, there is an urgent need to develop new treatment methods to prevent or reverse the progression of the disease.

Remote ischemic conditioning (RIC) is a process that involves repeatedly applying brief ischemic stimuli to a certain organ or tissue, which stimulates the body's endogenous anti-ischemic injury ability, enabling other organs or tissues besides the stimulated one to adapt to ischemia and improve their tolerance to ischemic injury, thereby reducing the damage caused by ischemia to relevant organs or tissues. Current studies have confirmed that RIC can protect remote organs such as the heart, brain, and kidneys through multiple pathways, including humoral mechanisms, neural conduction regulation mechanisms, and immune inflammatory regulation mechanisms. However, current research in the field of kidney diseases has been mostly limited to acute kidney injury caused by contrast agents, surgery, etc., and there are no reports on the intervention and treatment of CKD patients using RIC. Therefore, exploring whether RIC can delay the progression of renal function in CKD patients is of great significance.

Interventions

• Device Remote ischemic conditioning
  RIC is a non-invasive therapy that performed by an electric auto-control device with cuff placed on arm. RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs.

Primary outcome measures

• change in eGFR [Time frame: 3 months and 12 months]

Secondary outcome measures (2)

• Changes in renal tissue oxygen saturation (SrtO2) compared to baseline. [Time frame: 3 months and 12 months]
• Changes in blood pressure [Time frame: 3 months and 12 months]

Eligibility criteria

Inclusion criteria

• CKD Patients with eGFR ≥ 15ml/min/1.73m2
• Age ≥ 18 years old
• 24-hour urine protein excretion ≤ 3.5g
• Subjects who have signed the informed consent form

Exclusion criteria

• Patients with nephrotic syndrome
• Patients with acute kidney injury
• Patients who have undergone renal replacement treatment in the past
• Patients who may have medication changes during RIC or sham-RIC intervention
• Patients with a history of diabetes or glycated hemoglobin > 8%
• Patients with familial hypercholesterolemia (>5.5 mmol/L) accompanied by high low-density lipoprotein (>2.5 mmol/L)
• Patients with contraindications to RIC, such as vascular injury, soft tissue injury, fracture, infection, or known peripheral vascular disease in both arms
• Patients with a history of hemostatic disorders, systemic bleeding, or thrombocytopenia
• Patients with cardiogenic embolism (atrial fibrillation) or other severe arrhythmias (severe bradycardia, third-degree atrioventricular block, or ventricular tachycardia), previous myocardial infarction, or severe heart failure (New York Heart Association Class III and IV)
• Uncontrolled hypertension (defined as systolic blood pressure ≥ 200 mmHg despite antihypertensive treatment)
• Patients with respiratory failure, malignant tumors, or other autoimmune diseases
• Women who are pregnant or breastfeeding at the time of enrollment or any time during the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

China · 1 center

• chinese PLA general hospital — Beijing

Publications

• Ruiz-Ortega M, Rayego-Mateos S, Lamas S, Ortiz A, Rodrigues-Diez RR. Targeting the progression of chronic kidney disease. Nat Rev Nephrol. 2020 May;16(5):269-288. doi: 10.1038/s41581-019-0248-y. Epub 2020 Feb 14. PMID 32060481
• Zhou D, Ding J, Ya J, Pan L, Wang Y, Ji X, Meng R. Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection. Aging (Albany NY). 2018 Aug 16;10(8):1825-1855. doi: 10.18632/aging.101527. PMID 30115811
• Zhang YN, Dai YJ, Cui Y, Wu Q, Zhang NN, Chen HS. Diabetes, fasting blood glucose and the efficacy of remote ischaemic conditioning: A secondary analysis of the RICAMIS trial. Diabetes Obes Metab. 2023 Sep;25(9):2689-2696. doi: 10.1111/dom.15156. Epub 2023 Jun 8. PMID 37288603

Identifiers

NCT: NCT06501222 · CKDRIC-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗