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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Device: Remote ischemic conditioning

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.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yisha Li, PhD; Phone Number: 18911772124; Email: xiaoyixueda@qq.com
• Study Contact Backup: Name: Dayang Xie, PhD; Phone Number: 01055499332; Email: 460436948@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese Pla General Hospital
      • Contact: Yisha Li, PhD; Phone Number: 18911772124; Email: xiaoyixueda@qq.com
      • Contact: Dayang Xie, PhD; Phone Number: 01055499332; Email: 460436948@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. CKD Patients with eGFR ≥ 15ml/min/1.73m2
2. Age ≥ 18 years old
3. 24-hour urine protein excretion ≤ 3.5g
4. Subjects who have signed the informed consent form

Exclusion Criteria:

1. Patients with nephrotic syndrome
2. Patients with acute kidney injury
3. Patients who have undergone renal replacement treatment in the past
4. Patients who may have medication changes during RIC or sham-RIC intervention
5. Patients with a history of diabetes or glycated hemoglobin > 8%
6. Patients with familial hypercholesterolemia (>5.5 mmol/L) accompanied by high low-density lipoprotein (>2.5 mmol/L)
7. Patients with contraindications to RIC, such as vascular injury, soft tissue injury, fracture, infection, or known peripheral vascular disease in both arms
8. Patients with a history of hemostatic disorders, systemic bleeding, or thrombocytopenia
9. 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)
10. Uncontrolled hypertension (defined as systolic blood pressure ≥ 200 mmHg despite antihypertensive treatment)
11. Patients with respiratory failure, malignant tumors, or other autoimmune diseases
12. Women who are pregnant or breastfeeding at the time of enrollment or any time during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIC group; The RIC protocol involves five cycles of alternating inflation of both upper arms, utilizing an automated device to alternately inflate to 200 mmHg for 5 minutes and deflate for 5 minutes.	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.
Sham Comparator: sham-RIC group; The sham-RIC protocol involves five cycles of alternating inflation of both upper arms, utilizing an automated device to alternately inflate to 60 mmHg for 5 minutes and deflate for 5 minutes.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in eGFR	eGFR is calculated using the CKD-EPI formula, eGFR in mL/min/1.73m²	3 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in renal tissue oxygen saturation (SrtO2) compared to baseline.	SrtO2 is measured by Near Infrared Spectroscopy	3 months and 12 months
Changes in blood pressure	blood pressure in mmHg	3 months and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour urine protein quantitation compared to baseline.	The 24-hour urine protein quantitation is monitored through urine.	3 months and 12 months
change in Pulse Wave Velocity compared to baseline.	brachial-ankle Pulse Wave Velocity in cm/s	3 months
change in Flow-mediated vasodilation compared to baseline.	FMD in %	3 months

Collaborators and Investigators

• Sponsor: Yuanjun Yang
• Investigators: Study Director: Guangyan Cai, Chinese Pla General Hospital

Publications and helpful links

General 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: June 16, 2024
• First Submitted That Met QC Criteria: July 8, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; chronic kidney disease; renal function
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: CKDRIC-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No