Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Lee, Ting-Yim

2nd Supervisor

McIntyre, Christopher W.

Joint Supervisor

Abstract

Hemodialysis (HD) is the most common form of renal replacement therapy for end-stage renal disease. However, patients develop complications that are driven by HD-induced circulatory stress from rapidly removing large fluid volumes during HD, making various vascular beds vulnerable to ischemia. By assessing how HD-induced circulatory stress affects different organs, it may be possible to characterize the mechanisms behind these complications and evaluate therapeutic interventions. This thesis aims to explore how HD affects renal and hepatic blood flow and function using CT perfusion imaging. For this work, patients received either standard or cooled HD first in a two-visit, crossover study design, where imaging was performed before, during and after each HD session.

Residual renal function is linked to improved clinical outcomes, yet characteristically declines upon HD initiation. In the first thesis project, we determined that renal perfusion deceases during HD, which could be an early manifestation of HD-mediated residual renal function loss.

Although the liver normally clears endotoxin, increased circulating endotoxin levels have been found in HD patients. In the second thesis project, we showed that concurrent hepatic perfusion redistribution and decreased liver function during HD are likely responsible for increased circulating toxin levels.

Dialysate cooling is a low-cost, feasible intervention that ameliorates HD-induced circulatory stress. In the first and second thesis projects, we found that cooling trended towards mitigating the drop in renal perfusion during HD and ameliorating the changes in liver perfusion and function during HD.

If it were possible to accurately assess glomerular filtration rate (GFR) in HD patients, HD prescriptions could be adjusted in accordance with residual renal function to preserve remaining function. In the third thesis project, we extended the CT perfusion technique to measure GFR in HD patients, yielding physiologically realistic GFR values, thus demonstrating the feasibility of this approach in terms of reliability and accuracy.

These findings help explain residual renal function loss and endotoxemia in HD patients, and showcases the protective potential of dialysate cooling. In addition, this work demonstrates the benefit of using CT perfusion as a functional imaging technique to further characterize and evaluate therapies for end-stage renal disease pathologies.

Summary for Lay Audience

Patients with end-stage kidney failure require kidney replacement therapy, with the most common type being hemodialysis (HD). This treatment removes several litres of fluid in a 3- to 4-hour session, which stresses the ability of a patient’s heart to pump blood throughout the body (“circulatory stress”). The goals of this thesis are to explore how circulatory stress:

  • affects blood flow to, and function of, different organs
  • leads to other health problems besides kidney failure
  • can be prevented to minimize adverse effects on HD patients

These goals were achieved using computed tomography perfusion (CTP), a scanning technique that measures organ blood flow. We performed CTP on patients before, during and after HD treatment.

The small remaining kidney function is linked to improved quality of life of HD patients but declines with HD. In the first thesis project, we found that kidney blood flow deceases during HD, which could damage the kidney and cause further loss of what little remaining function there is.

The liver normally clears toxins that it receives from the gut, but HD patients have abnormally high blood toxin levels. In the second thesis project, we showed that liver blood flow redistributes to receive more toxin-filled blood from the gut and that the liver’s detoxification ability was also compromised during HD, leading to increased toxin levels in HD patients.

Previous research has shown that by slightly lowering the temperature of the HD fluid, circulatory stress can be lessened. In the first and second thesis projects, we found that cooling helped to maintain kidney and liver blood flow during HD.

There is currently no rapid, reliable and accurate method to measure remaining kidney function in HD patients. In the third thesis project, we extended the CTP technique to also measure kidney function in our HD patients. This approach yielded realistic values, thus demonstrating the practicality and utility of our unique method.

These results help explain important health concerns of HD and showcase the protective potential of cooling. This work demonstrates the benefit of using CTP as a powerful imaging technique to explore and evaluate therapies for end-stage kidney failure.

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