Clinical trial NCT02997774: Cooler Dialysis and Liver Perfusion and Function
Official title: Evaluation of the Effects of Cooler Dialysate on Liver Perfusion, Endotoxemia and Uremic Toxin Handling in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Haemodialysis Complication
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2016-12-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: Change in global liver perfusion in mls/min/100g pre, during and post-dialysis with cooler dialysate
timeFrame: 2 years
measure: ICG clearance rate pre, during and post-dialysis with cooler vs standard dialysate
timeFrame: 2 years
measure: Contribution of portal venous flow to hepatic perfusion (PV fraction) pre, during and post-dialysis with cooler vs standard dialysate
timeFrame: 2 years
measure: Endotoxin levels with cooler vs standard dialysate
timeFrame: 2 years
measure: Troponin T levels with cooler vs standard dialysate
timeFrame: 2 years
measure: Number of stunned myocardial segments with cooler vs standard dialysate
timeFrame: 2 years
measure: Uremic toxin levels with cooler vs standard dialysate
timeFrame: 2 years
measure: Uremic symptom scores with cooler vs standard dialysate
timeFrame: 2 years
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Western University, Canada
name: Chris W McIntyre, PhD
role: PRINCIPAL_INVESTIGATOR
References: