Rheological Functions of Erythrocyte in ESRD

The Effect of Osmotic Stress in Erythrocyte Rheology in ESRD Patients

End-stage renal disease (ESRD) disrupts erythrocyte deformability due to osmotic imbalances, oxidative stress, and uremic toxins, leading to impaired microcirculation and oxygen transport. Dysregulation of ion channels, particularly the Gardos channel, exacerbates dehydration and eryptosis, further compromising vascular integrity. Given the critical role of erythrocyte flexibility in oxygen delivery, this study investigates its relationship with aerobic capacity in ESRD patients, highlighting potential mechanisms of microvascular dysfunction

Study Overview

• Status: Recruiting
• Conditions: End-stage Renal Disease (ESRD)
• Intervention / Treatment: Other: Blood collection; Other: Cardiopulmonary exercise testing (CPET)

Detailed Description

End-stage renal disease (ESRD) profoundly alters osmotic homeostasis, disrupting erythrocyte deformability and impairing microcirculatory dynamics, ultimately compromising oxygen delivery to tissues. Persistent oxidative stress, hyperosmotic fluctuations, and accumulation of uremic toxins collectively modulate ion channel activity, particularly by stimulating cation influx and perturbing calcium regulation. These disruptions accelerate erythrocyte aging and promote eryptosis, a programmed form of red blood cell death. Furthermore, dysregulation of the Gardos channel exacerbates potassium efflux, leading to excessive cell dehydration, increased blood viscosity, and further deterioration of vascular integrity. Given the pivotal role of erythrocyte flexibility in oxygen transport efficiency, impairments in osmotic deformability may contribute to the reduced aerobic capacity frequently observed in ESRD patients. This study aims to elucidate the interplay between erythrocyte biomechanical properties and cardiopulmonary fitness in this population, shedding light on potential therapeutic targets to mitigate microvascular dysfunction.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Jong-Shyan Wang, PhD; Phone Number: +886-3-2118800 Ext. 5748; Email: s5492@mail.cgu.edu.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung University
    • Contact: Jong-Shyan Wang, PhD; Phone Number: +886-3-2118800 Ext. 5748; Email: s5492@mail.cgu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study included 18 patients with end-stage renal disease (ESRD) and 18 age-matched healthy controls. ESRD patients were recruited and with inclusion criteria requiring a confirmed diagnosis of ESRD and stable dialysis treatment for at least three months. Healthy controls were free of chronic illnesses and were matched by age and sex. Exclusion criteria included a history of hyperkalemia within the past three months, heart failure, pregnancy, or any condition contraindicating cardiopulmonary exercise testing. All participants underwent assessments within one week of enrollment, and written informed consent was obtained before participation."

Description

Inclusion Criteria:

• Receiving hemodialysis and medication at least for 6 weeks
• Kt/V score > 1.2

Exclusion Criteria:

• Under 20 years-old
• Hyperkalemia occurs within 3 month
• Having orthopedic or muscular diseases
• Other concerned medical, psychological or physiological diseases
• Pregnancy
• Other exercise contraindications

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ESRD; ESRD patients under hemodialysis	Other: Blood collection; Erythrocyte osmotic deformability was evaluated via osmotic gradient ektacytometry.; Other: Cardiopulmonary exercise testing (CPET); Cardiopulmonary Exercise Testing (CPET) is a non-invasive assessment that evaluates the integrated function of the cardiovascular, pulmonary, and muscular systems during exercise.
Health control; Healthy sedentary volunteers	Other: Blood collection; Erythrocyte osmotic deformability was evaluated via osmotic gradient ektacytometry.; Other: Cardiopulmonary exercise testing (CPET); Cardiopulmonary Exercise Testing (CPET) is a non-invasive assessment that evaluates the integrated function of the cardiovascular, pulmonary, and muscular systems during exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deformability of erythrocytes	Deformability refers to the cells' ability to adapt their shape to the dynamically changing flow conditions so as to minimize their resistance to flow.	Data collection was completed within one week of participant enrollment
Aggregation of erythrocytes	Erythrocyte aggregation is the reversible clumping of red blood cells (RBCs) under low shear forces or at stasis.	Data collection was completed within one week of participant enrollment
Cardiopulmonary fitness	ESRD patients performed cardiopulmonary exercise testing (CPET) to assess their aerobic capacity. CPET composed of continuous workload increment of 10 W/min until exhaustion (usually within 8-12 minutes). Oxygen consumption, carbon dioxide production, ventilation, respiratory rate would be recorded.	Data collection was completed within one week of participant enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life in ESRD patients	The investigators would use a qusionnaire, The Kidney Disease Quality of Life 36-item short form survey (KDQOL-36), to record and scale the qulaity of life in ESRD patients. The KDQOL-36 (Kidney Disease Quality of Life 36-Item Short Form Survey) measures the quality of life in kidney disease patients. It uses a score range from 0 to 100, where higher scores indicate better quality of life and lower scores indicate worse outcomes. Ensure to note this when reporting results to clarify that higher scores reflect fewer symptoms and better overall well-being.	Data collection was completed within one week of participant enrollment
Gardos function	Gardos channel activation leads to K⁺ efflux, followed by water loss, resulting in erythrocyte dehydration and increased fragility. Dysfunctional regulation of this channel contributes to impaired microcirculation and reduced oxygen delivery, exacerbating vascular complications in ESRD.	Data collection was completed within one week of participant enrollment

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Estimated): March 20, 2025
• Study Completion (Estimated): March 26, 2025

Study Registration Dates

• First Submitted: March 5, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Aerobic capacity; Hemodialysis; Erythrocyte; Deformability
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: 202102279A3102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No