Past Studies

Does peritoneal dialysis preserve brain blood flow, maintain structure and prevent injury? A neuroimaging study.

Principal Investigator: Dr. Arsh Jain

Background:
Abnormalities of cognitive impairment (predominately in decision making) are almost universal in dialysis patients and appear early after starting dialysis. Around 75% of hemodialysis patients exhibit mild cognitive impairment (MCI) and a high proportion (~ 15%) have dementia. The injury is multifactorial, and amendable to HD-based intervention. Although the effects of hemodialysis on cerebral blood flow have been well studied, the effects of peritoneal dialysis on cerebral blood flow remain unclear. There is evidence that hemodialysis and peritoneal dialysis may affect the brain differently. In observational studies, peritoneal dialysis compared to hemodialysis is associated with a 16% lower risk of hemorrhagic stroke and a 25% lower risk of a new diagnosis of dementia. It may be that peritoneal dialysis offers a gentler alternative for cerebral blood flow with less acute hemodynamic changes.

Study Objective:
The purpose of this study was to measure how peritoneal dialysis affects the brain using magnetic resonance imaging (MRI). Patients underwent two study visits (as able), one year apart. During the first (baseline) visit, patients had two MRI scans – the first occurred before a PD treatment, the second scan occurred during a PD treatment. During the second study visit, one year later, patients had one MRI done without PD. The scans captured images of the brain structure, blood flow, and injury. The results will be compared to hemodialysis patients.

To read about the results from this study previously done in our hemodialysis patients, please click here:

Hemodialysis Patients Have Impaired Cerebrovascular Reactivity to CO2 Compared to Chronic Kidney Disease Patients and Healthy Controls: A Pilot Study - ScienceDirect

Results and associated papers for this study will be linked once all data is analyzed.

A phase 1 interventional study to test short-term safety, tolerability, and preliminary efficacy of sodium-free intraperitoneal 30% Icodextran/10% Dextrose solution in peritoneal dialysis patients

Principal Investigator: Dr. Christopher McIntyre

Background:
Currently used peritoneal dialysis solutions consist of high levels of salt, which in turn limits the removal of sodium. This can lead to the accumulation of sodium in the skin and other soft tissues. Over time, this accumulation of sodium leads to long-term adverse outcomes for dialysis patients. Additionally, conventional peritoneal solutions may also be insufficient at removing extracellular fluid, adding to the complications and adverse outcomes patients experience. Therefore, PD solutions optimized to improve extracellular volume and sodium management are needed.
 
Study Objective:
The aim of this study was to see if a single 8-hour dwell of 500 mL of intraperitoneal sodium-free 30% Icodextran/10% Dextrose solution is safe, tolerable, and effective in achieving sodium and fluid removal in peritoneal dialysis patients. This is a significant area of study as sodium and volume balance in kidney failure patients is critical. Extracellular volume overload has been consistently associated with cardiovascular morbidity and mortality.
 
Study protocol:
Patients underwent a single 8-hour dwell (using their current PD catheter) and were monitored the entire treatment plus 1-hour post drain at the end of the 8 hours. During the dwell, patients had the following data collected: pain scores (infusion, dwell, and drain pain assessments), hemodynamic stability (continuous blood pressure monitoring etc. using a Finapes), blood work at different intervals including glucose and serum sodium levels as well as other biomarkers, dialysate and urine samples at different intervals, and ultrafiltration (with weights pre and post intervention).

Results and associated papers will be linked once all data is analyzed.

Initial feasibility pilot study of interdialytic peritoneal ultrafiltration to manage volume status in hemodialysis patients

Principal Investigator: Dr. Christopher McIntyre

Study Objective:
Tissue sodium deposition is harmful to patients on chronic hemodialysis. For this study, 5 chronic hemodialysis patients underwent a 5-week, pilot, interventional study to test the efficacy of tissue sodium removal in between hemodialysis sessions, twice per week, for three weeks. Tissue sodium removal was achieved using a 10% dextrose solution by peritoneal dialysis - all patients already had surgically inserted peritoneal dialysis catheters. Patients had symptomatic and hemodynamic monitoring throughout the study for safety assessment. Total tissue sodium removal was assessed at the beginning and at the end of the study with sodium magnetic resonance imaging.

Results and associated papers will be linked once all data is analyzed.

Interventional study to assess the effect of extended dialysis using the Theranova dialyzer on patient reported symptoms using the London Evaluation of Illness (LEVIL)

Principal Investigator: Dr. Christopher McIntyre

Background:
We know that many patients who are on dialysis suffer from the burden of unwanted symptoms, which can affect quality of life. In this study, we looked at symptom burden using the London Evaluation of illness “LEVIL,” an application-based platform where patients can self-report their symptoms with each hemodialysis treatment using an iPad or mobile phone. We looked at 9 different symptom domains including general well-being, pain, energy, sleep quality, shortness of breath, appetite, bodily itch, restless legs, and time to recovery. The Theranova dialyzer is capable of removing large middle molecules (15,000 - 60,000 Da) because of its highly permeable membrane that have been linked to the development of complications such as cardiovascular disease.

Study Objective:
We hypothesized that the clearance of large middle molecules would have a direct and translatable effect on patient reported symptoms.

Study Results:
Patients with lower LEVIL scores (<70/100) at baseline showed improvement in overall HRQoL after 8 weeks of therapy with similar carryover effect. General well-being, energy, and sleep quality were improved significantly as a consequence of HDx therapy. There were no detrimental effects of HDx detected in patients with higher baseline HRQoL.
Dynamic PROM assessment effectively identified patients with lower HRQoL and higher symptom burden, demonstrating durable time/dose-dependent improvements across a range of symptom domains. The use of this instrument may allow targeted selection of patients most likely to benefit from HDx therapy and assist in monitoring response and defining effect size and treatment duration to allow optimal design of further definitive randomized controlled trials of this newly introduced technology.

This study is complete – to view corresponding publications, please click the following links:

•    Impact of Expanded Hemodialysis Using Medium Cut-off Dialyzer on Quality of Life: Application of Dynamic Patient-Reported Outcome Measurement Tool
•    POS-604 MIDDLE MOLECULE CLEARANCE & EXPANDED DIALYSIS: WHAT IS THE IMPACT ON PATIENT-REPORTED SYMPTOM BURDE, THROUGH THE LENS OF THE LONDON EVALUATION OF ILLNESS (LEVIL)
•    Pruritus: Is there a grain of salty truth?
•    P1062 EXPANDED DIALYSIS (HDX): IS THERE AN IMPACT ON PATIENT REPORTED SYMPTOM?

Novel extracorporeal treatment to modulate hyperinflammation in COVID-19 patients

Principal Investigator: Dr. Christopher McIntyre

Background:
In recent years, we faced a global COVID-19 outbreak that forced the majority of the population to stay home. Unfortunately, in severe cases, COVID-19 caused a potentially fatal condition known as acute respiratory distress syndrome (difficulty to breathe). Patients who suffered from severe respiratory illness were admitted to the ICU due to worsening health because of the virus. It is thought that worsening health is caused by a “cytokine storm”. Cytokines are small proteins secreted by cells of the immune system that control inflammation. A cytokine storm refers to an overproduction of these small proteins, which occurs when too many white blood cells (which help the body fight infection and other diseases) are activated. In turn, these small proteins activate more white blood cells leading to a vicious cycle. This increased stimulation of inflammation can become damaging to a patient’s organs, leading to multi-organ injury (i.e. lung, heart).
 
Study Objective:
We configured a dialysis machine to potentially decrease this cytokine storm by inactivating white blood cells through a dialysis circuit. We were able to treat 10 patients during the study in the intensive care units in London Ontario. This therapy potentially allows for a reduced intubation time, length of hospital admission, and a decrease in mortality rates.

Study Results:
This was the first report of leukocyte modulation delivered using an intermittent treatment regime and extracorporeal system constructed from modified non-proprietary components, to treat COVID-19 in patients requiring mechanical ventilation and vasopressor support. This preliminary study demonstrated that the treatment is feasible (all treatments delivered as planned) and safe (no significant treatment related adverse events, no treatments terminated early due to lack of tolerability). There appears to be a strong initial signal of biological effect using the leukocyte modulation device (LMOD) with respect to the pre-defined primary outcome of pressor dose.

Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach. Furthermore, this therapy potentially expands the available armamentarium with a treatment that can be delivered within an existing model of care (similar to renal replacement therapy) and by current staff using low-cost non-proprietary components potentially- even within an austere resource setting.

This study is complete – to view corresponding publications, please click the following links:
 
•    Initial evaluation of extracorporeal immunomodulatory therapy for the treatment of critically ill COVID-19 infected patients
•    Calcium Repletion and Regional Citrate Anticoagulation in Hemodialysis and Hemodiafiltration: Using Dialysate Calcium to Modify Hypocalcemia
•    Check out the latest story here or below 'Canadian research team becomes first in the world to treat COVID-19 patients with dialysis'

Evaluation of sodium deposition in soft tissues of patients with kidney disease and its association

Principal Investigator: Dr. Christopher McIntyre

Background:
Our body maintains sodium (salt) balance by getting rid of excess sodium through urine. When the kidneys stop working, sodium accumulates in the skin and muscles. We already know that sodium accumulation is higher in men, older patients, and patients with high blood pressure, and that sodium accumulation may have a number of other side effects such as inflammation.

Study Method:
We measured sodium content in the tissues with magnetic resonance imaging (MRI) in patients at various stages of chronic kidney disease (CKD), on various dialysis therapies, and in patients with heart failure. Based on earlier findings, we know that high sodium concentration is linked to age, high blood pressure, diabetes, and CKD. The threshold of sodium accumulation in pediatric patients is likely lower, but it has never been explored. Therefore, we began to scan healthy children and those with CKD to determine tissue sodium level. More recently, we have observed more salt in the skin in patients on dialysis and more salt in the skin and muscle in CKD patients’ stage 1-4. We also observed that skin sodium is higher in patients who have a higher sodium dialysate concentration. Our next question will be, “Is salt in the skin higher in patients who have heart failure with renal dysfunction compared to patients with only heart failure.”

To view articles from this study and about this topic please click the following links:

•    Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys
•    Effects of pediatric chronic kidney disease and its etiology on tissue sodium concentration: a pilot study
•    MO645: Does Sodium Magnetic Resonance Imaging Help for Initiation of Incremental Dialysis?
•    Outcomes and predictors of skin sodium concentration in dialysis patients
•    Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target?
•    FC 054 Functional Sodium Magnetic Resonance Imaging of the Human Kidney
•    Pruritus: Is there a grain of salty truth?
•    SO027 Assotiations of Muscle Sodium Deposition with Sodium-23 MRI in Hemodialysis Patients
•    P0215 Excessive Tissue Sodium Storage in Patients with Non-Dialysis Dependent Cardio-Renal Syndrome is Comparable to Hemodialysis Patients
•    Tissue sodium concentrations in chronic kidney disease and dialysis patients by lower leg sodium-23 magnetic resonance imaging

Renal Community Photo Initiative

Principal Investigator: Dr. Christopher McIntyre

Background:
This collaborative research effort between the Kidney Clinical Research Unit and the Visual Arts Department at Western University aimed to understand how persons with chronic kidney disease, persons receiving chronic dialysis treatments or those who have received a kidney transplant respond to treatment through imagery. Participants were invited to photograph, share and discuss their photos, and experience the images of other participants.

Study Objectives:
- To explore how photographic image-making and the use of different camera types can influence the patient photographer, the types of photographs that are produced and those with whom the photos are shared
- To share these photographs and artistic representations in order to educate, inform and raise awareness among caregivers, healthcare providers, those overseeing policy, funding, and key stakeholders

Thirty-nine participants selected one of 4 different cameras or cyanotype papers and participated in the main study with 12 of these participants also in the sub-study. The sub-study was designed to obtain participant feedback regarding use of these images to obtain the study objective. Such visuals include large banners, a “post-card” display, “Bringing Healing into Focus” - a site created by Schulich School of Medicine and Dentistry for their website, media attention from CTV London and a blog written for Home Dialysis Central.

This study is complete – to view corresponding publications, please click the following links:

•    The Renal Community Photo Initiative
•    The Renal Community Photo Initiative: A Program Report in Ontario, Canada

Investigation of electrophysiological substrate of arrhythmia in hemodialysis patients

Principal Investigator: Dr. Christopher McIntyre

Study Objective:
Computed tomography (CT) imaging is a useful tool in studying blood flow defects in organs such as the lungs and heart during a dialysis treatment. In this study, our aim was to observe the changes in blood flow in the heart muscle during hemodialysis and determine whether or not this response is related to irregular heart rhythms in patients on hemodialysis treatment.

To detect irregular heart rhythms, patients enrolled in this study had a small implantable loop recorder (heart monitoring device) placed directly under the skin near the heart. By doing this, we were able to study a patient’s heart rhythm continuously for up to one year.

This study is complete – corresponding articles are under review and will be linked once accepted and available.

Multimodal assessment of dyspnea, cardio-pulmonary structure and function in hemodialysis patients

Background:
Dyspnea in the hemodialysis (HD) population has not been addressed systematically by scientific literature and its pathophysiology is not well understood. The nature of underlying respiratory disorders in end stage renal disease patients on HD may be due to complications related to chronic kidney disease, the HD treatment itself or other unrelated etiologies. This study intended to explore the pathophysiology of cardio-pulmonary involvement and dyspnea in the chronic HD population, by employing state-of-the-art imaging techniques, pulmonary function tests and dyspnea questionnaires.

Study design: Exploratory, observational study

Study Objectives:
-    Pulmonary abnormalities are highly prevalent among chronic HD patients
-    Pulmonary, cardiac, functional, metabolic abnormalities and soft tissue sodium accumulation are related to severity of dyspnea
-    The burden of pulmonary, functional, metabolic abnormalities and soft tissue sodium accumulation increases with dialysis vintage
-    Dyspnea severity correlates with 1-year outcomes (mortality, cardiovascular events, hospital admissions)

Study Interventions (during a one-day study visit):
-    Lung MRI
-    Sodium MRI
-    Chest CT
-    Spirometry
-    Plethysmography
-    Fractional exhaled nitric oxide
-    Six-minute walk test
-    2D transthoracic echocardiography
-    Blood sampling
-    Dyspnea questionnaires

Study Significance:
This was the first study investigating the pathophysiology of dyspnea in HD patients, employing multimodality imaging techniques and functional tests.

This study is complete; however, results were not published. To view material published by our group regarding this topic, please click on the following links:

Why Are Chronic Hemodialysis Patients Short of Breath? A Novel Symptom-Centered Study | C37. SYMPTOMS, PLEURAL DISEASE, BEHAVIORAL SCIENCE, AND OTHER TOPICS (atsjournals.org)

Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease - Salerno - 2017 - Seminars in Dialysis - Wiley Online Library


Reducing hemodialysis-induced recurrent brain injury to improve patients’ lives

Principal Investigator: Dr. Christopher McIntyre

Background:
Chronic kidney disease patients undergoing hemodialysis often begin to experience difficulties with executive function and the ability to plan and make decisions. These cognitive changes are associated with abnormalities in their brain scans. We believe this arises from issues with blood flow to the brain during and following hemodialysis sessions. As well, hemodialysis treatments are often associated with negative complications related to microcirculatory stress (blood vessel injury). It is already shown that cells within the blood vessels respond to injury by releasing biological factors. Of these biological factors in the blood are microparticles, which are fragments of injured cells.

Our group tested a new therapy in hopes of protecting the brain during hemodialysis. This was done by priming the body with restrictions in blood flow in the lower leg for a few minutes, administered monthly before a dialysis treatment. This is safe and it has been shown to prevent injury in other organs, including the liver, kidneys, and heart. This study involved cognitive tests and brain scans before and during dialysis, twice over the course of one year. Follow up scans were done to help us determine if the new therapy helped to maintain brain health.

Study Objective:
This research study focused on measuring microparticles within the blood of patients who underwent hemodialysis. We wanted to understand if microparticles could be used as an indicator of microcirculatory stress brought upon by dialysis, and determine whether they can be used to identify if patients were responding to different dialysis modalities.

Study Results:
We found intradialytic changes, including the development of multiple regions of white matter exhibiting increased fractional anisotropy with associated decreases in mean diffusivity and radial diffusivity—characteristic features of cytotoxic edema (with increase in global brain volumes). We also observed decreases in proton magnetic resonance spectroscopy–measured N-acetyl aspartate and choline concentrations during HD, indicative of regional ischemia.

This study demonstrates for the first time that significant intradialytic changes in brain tissue volume, diffusion metrics, and brain metabolite concentrations consistent with ischemic injury occur in a single dialysis session. These findings raise the possibility that HD might have long-term neurological consequences. Further study is needed to establish an association between intradialytic magnetic resonance imaging findings of brain injury and cognitive impairment and to understand the chronic effects of HD-induced brain injury.

This study is complete – to view corresponding publications, please click the following links:

Hemodialysis-Related Acute Brain Injury Demonstrated by Application of Intradialytic Magnetic Resonance Imaging and Spectroscopy | Request PDF (researchgate.net)

Update on HD-Induced Multiorgan Ischemia: Brains and Beyond (researchgate.net)
 
Study to compare the cerebral blood flow response to C02 between chronic kidney disease patients, hemodialysis patients, and healthy individuals

Principal Investigator: Dr. Christopher McIntyre

Background:
Patients with chronic kidney disease (CKD) and those who are on dialysis experience higher rates of brain vascular disease (ex. stroke) and cognitive decline compared to the general population. These changes may be related to worsening of brain blood flow, and specifically to its ability to respond to sudden changes in blood pressure or carbon dioxide that can occur during a normal day or during a dialysis treatment. Brain blood flow response to carbon dioxide can be used to assess brain vascular function non-invasively, allow early detection, evaluation, and monitoring of vascular disease progression, and provide means for evaluating effectiveness of preventative, therapeutic and rehabilitative interventions in these patients.
Study Objective:
The goal of this study was to determine if measuring brain blood flow response to carbon dioxide is possible in CKD and dialysis patients, and to compare it to that from healthy volunteers.
Study Protocol:
Participants attended a one-time study visit at the Kidney Clinical Research Unit where a transcranial doppler (ultrasound) was applied to their head to measure blood flow in the main arteries of the brain. Devices were applied to the patients to continuously monitor heart rate, oxygen, and other physiologic parameters. A mask was applied to the participant’s face that delivered a higher concentration of carbon dioxide. Participants underwent a sequence of breathing in normal oxygen and carbon dioxide levels for 5 minutes, then increased carbon dioxide levels for 5 minutes, and then normal oxygen and carbon dioxide levels again for the last 5 minutes. The goal was to see brain blood flow changes with the increased carbon dioxide levels.
Study Results:
Hemodialysis patients had lower cerebrovascular reactivity than chronic kidney disease or healthy participants during both intervention (increase in carbon dioxide) and recovery. There were no differences in cerebrovascular reactivity between healthy and chronic kidney disease participants during either intervention or recovery. The impaired cerebrovascular reactivity in hemodialysis patients was independent of carbon dioxide- induced changes in blood pressure, heart rate, cardiac output, or dialysis vintage, suggesting that impaired cerebrovascular reactivity may occur early after initiation of hemodialysis. Cerebrovascular reactivity was not impaired in chronic kidney disease patients and was not associated with the degree of renal impairment which suggests that cerebrovascular reactivity impairment in renal disease is not simply a result of worsening renal function or uremia but potentially also the result of insults specific to hemodialysis treatments.
Our study showed that hemodialysis patients have impaired cerebrovascular reactivity relative to chronic kidney disease and healthy participants. This renders hemodialysis patients vulnerable to ischemic injury during the circulatory stress of dialysis and may contribute to the pathogenesis of cognitive impairment.

This study is complete – to view the corresponding publication, please click the following link:

Hemodialysis Patients Have Impaired Cerebrovascular Reactivity to CO2 Compared to Chronic Kidney Disease Patients and Healthy Controls: A Pilot Study - ScienceDirect

Percutaneous perfusion monitoring for the detection of hemodialysis induced cardiovascular injury

Principal Investigator: Dr. Christopher McIntyre

Background:
The safe delivery of hemodialysis (HD) faces dual challenges; the accurate detection of systemic circulatory stress-producing cardiovascular (CV) injury, and the ability to enable effective preemptive intervention for such injury. We performed a pilot study to examine the capability of a new noninvasive, real-time monitoring system to detect the deleterious effects of HD on CV stability.
Study Methods:
Eight patients were evaluated with echocardiography prior to the initiation of HD and again at peak HD stress. Continuous CV physiologic monitoring was performed throughout using oximeter-based pulse waveform analysis (CVInsight® Monitoring System, Intelomed, Inc., Warrendale, PA, USA). Longitudinal strain (LS) values for 12 left ventricular segments were generated using speckle-tracking software (EchoPac, GE), to assess the presence of HD-induced regional wall motion abnormalities (RWMA), indicative of myocardial stunning.
Study Results:
A reduction in pulse strength (PS) of ≥40% detected by CVI was associated with the development of RWMA (P = 0.005). This reduction occurred in 6/8 patients, all of whom exhibited myocardial stunning. Two patients had no significant reduction in PS nor evidence of myocardial stunning.
Discussion:
Percutaneous perfusion monitoring, using pulse wave analysis, appears to be useful in identifying circulatory stress during HD and predicting the development of HD-induced myocardial stunning with a lead time long enough to consider timely intervention.
This study is complete – to view the corresponding publication, please click the following link:

Percutaneous perfusion monitoring for the detection of hemodialysis induced cardiovascular injury - Penny - 2018 - Hemodialysis International - Wiley Online Library

Evaluation of the effects of cooler dialysate on liver perfusion, endotoxemia and uremic toxin handling in hemodialysis patients

Principal Investigator: Dr. Christopher McIntyre

Background:
Residual renal function (RRF) characteristically declines after patients with ESRD initiate dialysis. Although RRF preservation correlates with improved outcomes, poor understanding of the pathophysiology underlying RRF decline limits protection strategies. Previous research found that dialysate cooling reduces hemodialysis-induced circulatory stress and protects the brain and heart from ischemic injury. To examine renal perfusion, decline during hemodialysis and the effects of cooling, we used computed tomography perfusion imaging to scan patients undergoing dialysis with or without dialysate cooling.
Study Methods:
We used renal computed tomography perfusion imaging to scan 29 patients undergoing continuous dialysis under standard (36.5°C dialysate temperature) conditions; we also scanned another 15 patients under both standard and cooled (35.0°C) conditions. Imaging was performed immediately before, 3 hours into, and 15 minutes after hemodialysis sessions. We used perfusion maps to quantify renal perfusion. To provide a reference to another organ vulnerable to hemodialysis-induced ischemic injury, we also used echocardiography to assess intradialytic myocardial stunning.
Study Results:
During standard hemodialysis, renal perfusion decreased 18.4% (P<0.005) and correlated with myocardial injury (r=−0.33; P<0.05). During sessions with dialysate cooling, patients experienced a 10.6% decrease in perfusion (not significantly different from the decline with standard hemodialysis), and ten of the 15 patients showed improved or no effect on myocardial stunning.
Conclusions
This study showed an acute decrease in renal perfusion during hemodialysis, a first step towards pathophysiologic characterization of hemodialysis-mediated RRF decline. Dialysate cooling ameliorated this decline but this effect did not reach statistical significance. Further study is needed to explore the potential of dialysate cooling as a therapeutic approach to slow RRF decline.
Hemodialysis redistributes liver perfusion, attenuates hepatic function, and results in endotoxemia. Higher endotoxin levels in end-stage renal disease (ESRD) patients may result from the combination of decreased hepatic clearance function and increasing fraction of liver perfusion coming from the toxin-laden portal vein during hemodialysis. The protective potential of dialysate cooling should be explored further in future research studies.
This study is complete – to view the corresponding publications, please click the following links:
Renal Perfusion during Hemodialysis: Intradialytic Blood Flo... : Journal of the American Society of Nephrology (lww.com)
Exploring the Link Between Hepatic Perfusion and Endotoxemia in Hemodialysis - ScienceDirect

Randomized controlled trial of remote ischemic preconditioning to protect against dialysis-induced cardiac injury in hemodialysis: low vs. high intensity

Principal Investigator: Dr. Christopher McIntyre

Background:
During hemodialysis, the patient is exposed to hemodynamic stress resulting in an ischemic insult, the cumulative effect of which, over time, leads to remodeling of the heart and a greater risk of heart failure and sudden death. The administration of remote ischemic preconditioning (RIPC) stimulus in the form of a blood pressure cuff inflated on the lower limb appears to provide protection from this ischemic insult.

Study design:
Unblinded, parallel, four-arm, randomized controlled trial. Patients were randomly allocated to receive one of the following: “sham” or “control” dose (4 cycles of BP cuff inflation at 40 mmHg), a single administration of the RIPC stimulus at a low dose (2 cycles of blood pressure cuff inflation to 200 mmHg), a single standard dose (4 cycles of cuff inflation), or a high intensity regime of one standard dose weekly, all prior to starting their hemodialysis treatment.

Study Objective:
To determine if the use of higher “doses” of RIPC stimulus provides increased cardio-protection in hemodialysis patients over the course of 28 days.

Study Hypothesis:
The administration of RIPC prior to dialysis provides protection against dialysis-induced cardiac injury and more frequent administration provides a greater degree of cardio-protection for a longer duration.

Study Outcomes:
The primary outcome was a reduction in the number of left ventricular segments undergoing a greater than 30% reduction in longitudinal strain as detected by echocardiography.

Study Significance:
This was the first randomized controlled trial assessing the dose-response relationship to RIPC in the hemodialysis population. RIPC could be developed as a therapeutic option to reduce rates of heart failure in the dialysis population.

Study Results:
This study suggests that a single application of 4 ischemia-reperfusion-cycles (RIPC) may reduce HD- induced RWMA for up to 48 hours. Further work is needed to define the optimal RIPC dose and the duration of its effects, guiding the design of suitably robust clinical trials.
This study is complete – to view the corresponding publication, please click the following link:
Remote Ischemic Preconditioning Protects Against Hemodialysis-Induced Cardiac Injury - ScienceDirect


Study to examine the hemodynamic responses in hemodialysis patients to blood flow restriction using non-pneumatic anti-shock garments

Principal Investigator: Dr. Christopher McIntyre

Background:
Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. Chronic exposure to intermittent hemodialysis may be a source of added stress to the cardiovascular system; intradialytic hypotension is a common complication of hemodialysis, and repeated events may lead to hemodynamic stress and ischemic injuries. Administration of non-pneumatic compression stockings to the lower limbs has demonstrated hemodynamic stabilizing effects in other settings and may provide similar benefits in the kidney disease population. Therefore, we conducted this pilot study assessing the feasibility and tolerability of the application of non-pneumatic compression stockings to patients with kidney disease. We also assessed the changes in hemodynamic measurements following the application of the compression stockings to explore the biological feasibility of this being an effective intervention for intradialytic hypotension.

Study Methods:
Fifteen individuals were enrolled in the study (5 healthy, 5 chronic kidney disease patients, and 5 dialysis patients). Outcomes including hemodynamic parameters such as cardiac output, peripheral vascular resistance, and blood pressure were measured using continuous pulse wave analysis. Changes in global longitudinal strain were measured via echocardiography. These outcome measurements were made before and after the application of compression stockings.
Study Results:
All study participants tolerated the compression garments well and without complication. Hemodynamic response to lower body compression caused varying effects on cardiac output, mean arterial pressure and global longitudinal strain. Some individuals saw large improvements in hemodynamic parameters while in others the opposite effect was observed. No consistent response was elicited.
Conclusions:
Application of compression stockings to patients with renal dysfunction is well-tolerated. However, significant variations in hemodynamic outcomes exist, and may be a barrier for larger scale trials without prior identification of specific patient characteristics indicating likely benefit from the application of external compression.
This study is complete – to view the corresponding publication, please click the following link:

Hemodynamic response to non-pneumatic anti-shock compression garments in patients with renal dysfunction | BMC Nephrology | Full Text (biomedcentral.com)


Pilot Study to Determine Whether Cooled Peritoneal Dialysis Fluids Confers Cardio-Protective Effects

Principal Investigator: Dr. Christopher McIntyre

Background:
The aim of this study was to gather more information about the heart of peritoneal dialysis patients. We know that patients who are on peritoneal dialysis have a much higher level of heart disease than the general population. However, we are not sure of the exact causes of these very high rates of heart problems. In the general population, the cause of heart disease is disease of the blood vessels (coronary arteries) that supply the heart.
We used a very advanced form of Computerized Tomography (CT) scanning to examine how well the heart performed under stress. We also looked at whether or not changing the temperature of peritoneal dialysate had any effect on how well a peritoneal dialysis patient is able to ‘resist’ stress to the heart.
Study Design:
The study involved two separate visits a week apart. During the first visit, a CT scan was done twice which took very detailed images of the vessels around the heart, scarring present, and how good the blood flow was to the heart muscle. During the second visit, we instilled cooled peritoneal dialysate (32.5 degrees centigrade) into the patient for a total of 4 hours, and repeated the CT scans to compare how the heart responded to stress while being cooled by the peritoneal dialysate.
Results:
The observed effect may be sufficient to meaningfully alter cardiovascular outcomes in PD patients. The protective effect of hypothermia may be mediated by a reduction in myocardial perfusion heterogeneity, however, further study on a larger sample size to determine the mechanism of effect is warranted.

This study is complete; however, results were not published. To view material produced by our research group relating to this topic, please click on the following link:
Frontiers | Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia (frontiersin.org)