Cooler Dialysis and Liver Perfusion and Function

Evaluation of the Effects of Cooler Dialysate on Liver Perfusion, Endotoxemia and Uremic Toxin Handling in Hemodialysis Patients

Having hemodialysis affects the blood supply to various organs in the body including the heart and the brain. With time, these effects build up and can affect the way these organs function. The investigators have previously shown that the liver (a key organ which works to help clean the blood, make proteins and turn all your food into energy) is also affected. One of the ways to help protect organs from injury due to dialysis has been cooling during dialysis. The investigators want to examine whether cooling during dialysis protects the blood supply to the liver. CT imaging will be used to measure this blood supply during hemodialysis with standard and cooler settings.

Study Overview

• Status: Completed
• Conditions: Haemodialysis Complication
• Intervention / Treatment: Other: Standard Dialysis; Other: Cooler dialysis

Detailed Description

Hemodialysis exerts significant hemodynamic effects with widespread consequences on vulnerable vascular beds. Cardiac injury, including myocardial stunning and subclinical myocardial ischemia, appears to be common and associated with significantly increased mortality. The liver has been shown to have preserved blood flow due to its dual blood supply. Even so, the liver excretory function is decreased and endotoxin levels in the blood increase during hemodialysis. Extracorporeal cooling during dialysis has been associated with protective effects on the brain and heart of dialysis patients. The effects of cooler dialysis on liver perfusion, function and endotoxemia during hemodialysis is unknown.

The investigators therefore propose to use CT perfusion imaging to examine the effect of cooling during hemodialysis on liver perfusion, relating this effect to endotoxin translocation and myocardial dysfunction. Additionally, they intend to investigate the potential effects on hepatic function in this context, examining the relationship between liver perfusion and endotoxemia, the metabolism of uremic toxins and clinical symptoms of uremia.

This is a prospective randomized cross-over study involving a single center recruiting patients from the prevalent dialysis population of London Health Sciences Centre (LHSC) Renal Program. Once recruited, patients will undergo two study hemodialysis sessions - one will use standard dialysate temperature of 36.5 degrees Celsius (HD36.5) and one will use cooler dialysate temperature at 35 degrees Celsius (HD35). The order of these two sessions will be randomly allocated. Before, during and after each session, participants will undergo cardiac and hepatic assessment. This will include CT scans, 2D echocardiography and indocyanine green (ICG) clearance measurements. In addition, participants will answer a number of questionnaires about uremic symptoms and blood tests will also be done.

The investigators' aim is to characterize and compare liver function and perfusion before during and after hemodialysis, with standard and cooler dialysate temperature.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be able to provide informed consent
• Age greater than 18 years
• Hemodialysis for at least 3 months
• No significant residual renal function (<250mls urine/day)

Exclusion Criteria:

• Chronic liver disease of any stage
• Chronic intestinal disease excluding Irritable Bowel Syndrome (IBS)
• Previous liver transplant or liver resection
• Previous Transjugular Portosystemic Shunt (TIPSS) insertion
• Active infection or malignancy
• Pregnant, breastfeeding or intending pregnancy
• Unable to give consent or understand written information
• Diabetic and experiencing hypoglycemia during dialysis within the last 2 months
• Known allergy/intolerance to contrast agent or iodides

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard Dialysis; Patient will undergo dialysis at 36.5 degrees Celsius to assess if this affects the liver function and perfusion	Other: Standard Dialysis; Having dialysis at a standard temperature (36.5 degrees Celsius)
EXPERIMENTAL: Cooler Dialysis; Patient will undergo dialysis at 35 degrees Celsius to assess if this affects the liver function and perfusion	Other: Cooler dialysis; Having dialysis at a slightly cooler temperature (35 vs 36.5 degrees Celsius)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in regional liver perfusion in mls/min/100g from baseline to peak stress during dialysis (3 hours into the dialysis session) with standard versus cooler dialysate temperature.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in global liver perfusion in mls/min/100g pre, during and post-dialysis with cooler dialysate	2 years
ICG clearance rate pre, during and post-dialysis with cooler vs standard dialysate	2 years
Contribution of portal venous flow to hepatic perfusion (PV fraction) pre, during and post-dialysis with cooler vs standard dialysate	2 years
Endotoxin levels with cooler vs standard dialysate	2 years
Troponin T levels with cooler vs standard dialysate	2 years
Number of stunned myocardial segments with cooler vs standard dialysate	2 years
Uremic toxin levels with cooler vs standard dialysate	2 years
Uremic symptom scores with cooler vs standard dialysate	2 years

Collaborators and Investigators

• Sponsor: Chris McIntyre
• Investigators: Principal Investigator: Chris W McIntyre, PhD, Western University, Canada

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 8, 2017
• Primary Completion (ACTUAL): May 4, 2018
• Study Completion (ACTUAL): May 4, 2018

Study Registration Dates

• First Submitted: December 16, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (ESTIMATE): December 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 17, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 108616

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