Research Studies

Biovision (PI: Dr.Azim Gangji; Co-investigators: Dr. Peter Margetts, Dr. Christine Ribic)

Patients admitted to the intensive care unit are critically ill and at high risk of developing kidney failure. These patients are also administered a significant amount of fluid during the resuscitation phase. Although administering fluid in the early resuscitation phase is important, subsequent retention of fluid can lead to increased time spent on the ventilator, development of kidney failure and death. However, assessing how much fluid a patient has is difficult to measure by clinical examination or by current invasive techniques. Bioelectric Impedance Analysis (BIA) is a safe, non-invasive technique that has been shown to predict the amount of fluid present in one’s body my measuring electrical properties. The aim of this study is to determine whether BIA can predict the amount of fluid a critically ill patient has and whether BIA measurements are related to important patient clinical outcomes such as time spent on the ventilator. If BIA can predict volume, then a subsequent trial will be designed to evaluate a BIA-guided fluid management strategy in hopes to reduce lung and kidney injury and death.

CARES (Cognitive Assessment in REnal dialysiS) (Dr. Michael Walsh)

Cognitive impairment is common amongst the 23,000 Canadians that require dialysis for kidney failure. Cognitive impairment is important because it is strongly associated with hospitalizations and death. Cognitive impairment may develop due to many disease processes but the dialysis procedure may worsen cognitive impairment by causing mild brain swelling, inflammation, and low blood pressure all of which may reduce oxygen delivery to the brain. CARES will explore: 1) the frequency of cognitive impairment in dialysis patients; 2) the causes of cognitive impairment in dialysis patients; and 3) the effect of cognitive impairment on patients ability to function independently. By understanding the magnitude of the problem of cognitive impairment as well as the mechanisms by which it occurs, CARES will provide insights into how we may prevent cognitive decline for dialysis patients in the future.


Despite important improvements in 1 year graft survival, the long term outlook for renal transplant has not significantly improved over the past 10 years. Interstitial fibrosis and tubular atrophy (IF/TA) is often described on renal allograft biopsy and the extent of this condition correlates with transplant prognosis. There is increasing evidence that early intervention with an immunosuppressive regimen that minimizes or eliminates calcineurin inhibitors (CNIs) may prevent progression of IF/TA. This strategy must be applied early enough in the transplant course before significant damage to the kidney has occurred. Existing clinical or laboratory predictors for the development of IF/TA are not sensitive enough to be an effective guide for immunosuppressive therapy post transplant when high risk grafts are still amenable to therapeutic intervention. A sensitive test for IF/TA would allow early diagnosis and facilitate treatment strategy. Circulating fibrocytes have been shown to be associated with other disease processes where fibrosis is a central feature. The Fibrocyte In renal Transplant (FIT) study is a prospective, observational study which is examining the role of circulating and tissue fibrocytes in fibrosis and allograft function.

FLUID (Dr. Scott Brimble)

Peritoneal dialysis (PD) is a therapy for the treatment of end-stage renal disease that involves the instillation and subsequent removal of specialty fluids into the peritoneal space to remove toxins and excess salt and water. Evaluation of the fluid status of these patients is challenging. Long-term fluid overload can lead to enlargement of the heart known as left ventricular hypertrophy (LVH), and early cardiac death. Vitamin D deficiency has been implicated in cardiac disease and is common in PD patients. The FLUID study is a multi-centered randomized controlled study, which asks two questions:

  1. Does the use of a technology known as bio-impedance analysis (BIA) improve the fluid management of PD patients and reduce left ventricular hypertrophy?
  2. Does vitamin D supplementation reduce left ventricular hypertrophy in PD patients?

Cardiac magnetic resonance imaging (MRI) is being used to detect LVH as the primary outcome. A number of secondary outcomes are being evaluated and biological samples collected to improve our understanding at a cellular level of what is taking place in the peritoneal membrane – the results of which will inform future clinical studies in PD patients.

HEMO-TIN (Dr Christine Ribic)

Hemodialysis is a life-sustaining therapy for over 18, 000 patients in Canada with end stage renal disease (ESRD) that requires circulation of whole blood through a dialysis circuit and membrane. Unfractionated heparin (UFH) has been used as the anticoagulant of choice to prevent the coagulation cascade that occurs during intermittent hemodialysis secondary to shear, turbulence, stasis and increased thrombin-antithrombin complexes. Without anticoagulation, increased deposition of fibrin-fibrin complexes on the dialysis membrane can lead to clotting of the extracorporeal circuit, reduction of dialysis efficiency and loss of blood from the patient. The benefit of preventing clotting and maintaining efficiency with anticoagulation must however be balanced with the known increased risk of bleeding for patients maintained on dialysis. The HEMO-TIN Trial is designed as a Canadian multicentre, double blind, crossover pilot randomised clinical trial (RCT) comparing unfractionated heparin to a low molecular weight heparin (Tinzaparin) for extracorporeal anticoagulation. Concerns with respect to bioaccumulation and bleeding remain important concerns for physicians and their patients. This pilot study will be the first multicentre blinded RCT which will provide feasibility data for a larger, adequately powered multicentre study examining patient important clinical outcomes of safety in terms of minor and major bleeding, dialysis clotting and efficacy.

HOST (Hemodialysis Outcomes Symptoms assessmenT) Program (Dr. Michael Walsh)

HOST is a program is a series of studies designed to help us understand how physiological changes induced by the dialysis procedure affects dialysis patient’s quality and quantity of life. Health related quality of life for patients that require dialysis for kidney failure is often very poor. Symptoms related to kidney failure and the dialysis treatment are common and are a significant concern to patients. We are systematically reviewing and meta-analyzing the evidence of treatments for common but disturbing symptoms in order to determine optimal treatment strategies to improve patient’s health related quality of life.

MORE Time (Measurement Of REcovery Time) (Dr. Michael Walsh)

Approximately 23,000 Canadians (over 8,000 from Ontario) have kidney failure that requires an artificial kidney machine to clean their blood, a process called dialysis. Most of these patients require dialysis for four hours three times per week for the rest of their lives. Although dialysis reduces the symptoms of kidney failure, patients frequently feel unwell for many hours after the procedure. It is not clear what aspects of dialysis cause patients to feel unwell afterward. To begin to understand this problem, researchers first need to understand what symptoms patients have after dialysis and how these symptoms change as the dialysis sessions change. By understanding the symptoms and how to best measure them we can design studies to reduce symptoms and improve the lives of Ontarians living with kidney failure. The MORE Time study will explore what symptoms patients have after dialysis and how best to measure them. The results of the HOST study will be used to figure out what interventions will be the most likely to help patients with this difficult disease suffer less.

PEXIVAS (Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis: an international randomised controlled trial) (Dr. Michael Walsh)

Severe, anti-neutrophil cytoplasm antibody associated vasculitis (AAV) is an uncommon but serious disease of the immune system that is diagnosed in approximately 1 in 100,000 Canadians each year. AAV is important because up to 50% of patients will die or develop kidney failure within 5 years of diagnosis. There are two major problems in the treatment of AAV: 1) current treatment strategies fail to bring the disease under control quickly, before it causes major organ damage, and 2) current treatments have a serious toxicity profile. We propose a study to examine these problems in patients with severe AAV that affects their kidneys or lungs. Patients will be randomly assigned to receive plasma exchange, a method of rapidly removing harmful antibodies to rapidly gain control of AAV, in addition to standard therapy or standard therapy alone. Patients will also be randomly assigned to receive either a standard dose of steroids or a reduced-dose scheme which is predicted to reduce treatment related toxicity. By addressing both these critical problems we hope to significantly improve patient survival and reduce the frequency of kidney failure in patients with severe AAV.

PHASE-1 (Pilot trial of Hemodialysis patients undergoing Aldosterone antagoniSm with Eplerenone) (Dr. Michael Walsh)

Forty percent of patients that require dialysis for kidney failure die within three years mostly due to heart disease. High blood pressure and heart failure are common problems in patients that require dialysis and are key causes of death due to heart disease. Eplerenone is a drug that is very effective in reducing blood pressure and improving heart failure in patients that do not require dialysis. There is currently no evidence to tell physicians whether eplerenone would have similar benefits in patients that require dialysis. This evidence can only be reliably generated by performing a large scale study. Before such a study is undertaken, we must determine whether eplerenone will be well tolerated and safe in patients that require dialysis. We will perform a pilot trial called the Pilot trial of Hemodialysis patients undergoing Aldosterone antagoniSm with Eplerenone (PHASE) to determine if eplerenone is a well tolerated, safe medication to study in a very large, global study that will show whether or not eplerenone reduces important outcomes for patients like death from heart causes.

PHASE-2 (Protection of the Heart with Aldosterone antagoniSm in End-stage renal disease) (Dr. Michael Walsh)

Forty percent of patients that require dialysis for kidney failure die within three years mostly due to heart disease. Spironlactone is a drug that is very effective at reducing heart related deaths and hospitalizations in patients with heart failure that do not also have kidney failure. It does this by reducing scarring of the heart. Kidney failure appears to trigger progressive changes in the heart that also lead to heart scarring and heart failure which, in turn, is a major cause of heart related deaths. It therefore makes sense that spironolactone would work in patients with kidney failure. However, there are no studies to tell us if spironolactone will benefit patients with kidney failure and as a result, only 1% of kidney failure patients receive spironolactone or spironolactone-like drugs. It is important to determine if spironolactone has benefits for patients with kidney failure because, if it does, there is an opportunity to reduce heart related deaths and hospitalizations. We will perform a large study in several countries that will give physicians and patients the information they need to determine if spironolactone reduces heart related deaths and hospitalizations. We call this study the Protection of the Heart with Aldosterone antagoniSm in End-stage renal disease (PHASE-2) Trial.

REPORT (Dr Christine Ribic)

The majority of patients admitted to hospital for renal transplantation have several risk factors that place them at increased risk for VTE events. This population shares many of the known traditional risk factors for VTE, but is also unique in having additional risk factors for VTE that are likely specific to this group. Despite the proposed increased risk of VTE in the transplant population, the frequency of thromboembolism in the perioperative period has not been extensively studied. Furthermore, there are no available unified guidelines on the administration of VTE prophylaxis in the post transplantation period. Unlike other surgical populations, many patients with renal transplants do not receive routine VTE prophylaxis in post operatively. The “Risk of ThromboEmbolism in Patients POst Renal Transplantation (REPORT) Study” is a prospective, observational cohort study that is designed to study the rate of objectively defined asymptomatic and symptomatic VTE within the first 12 months following renal transplantation. The principal outcomes include objectively identified deep venous thrombosis or pulmonary embolism and bleeding during the initial hospitalization for renal transplantation and within 12 months of the date of surgery. Secondary outcomes include identifying risk factors or predictors of VTE that may be unique to the transplant population. The results of this novel study will eventually aid in the creation of clinical practice guidelines in the renal transplant population.

SIM-CKD (Dr. Scott Brimble)

Kidney function is commonly evaluated by measuring the serum creatinine, incorporating the patient’s age, sex, and race, to estimate the kidney function (eGFR). Further information can be obtained by measuring the amount of albumin in the urine (ACR). These two pieces of information provide independent prognostic information on the risk of developing end-stage renal disease (ESRD) over time. Based on current definitions, a substantial proportion of the population has chronic kidney disease (CKD), however, the vast majority of these patients will not progress to ESRD. Additionally, on repeat testing, many of these patients will no longer be considered to have CKD. These facts make it difficult to determine when it is appropriate to refer a patient to a nephrologist for further evaluation. SIM-CKD is a study that incorporates information about the known variability in the eGFR and ACR based on unreferred patients, and simulates different strategies to determine the optimal approach for measuring eGFR and ACR to predict progression of CKD and the timing or need for referral to a nephrologist. Such information may lead to a reduction in unnecessary referrals and a reduction in waiting time for patients with progressive CKD to be seen by a nephrologist.

TARGET (Two phosphAte taRGets in End-stage renal disease Trial) (Dr. Michael Walsh)

Ninety percent of all patients on hemodialysis are prescribed medications to reduce their serum phosphate based on the observation that patients naturally occurring lower serum phosphate live longer than those with higher serum phosphate. In Canada, the most commonly used medication to lower serum phosphate is calcium carbonate. However, neither calcium carbonate nor any other medication to lower serum phosphate has ever been shown to improve patients longevity. In contrast, because of the number of pills used and the possible side-effects of calcium carbonate (constipation), such a strategy may reduce quality of life for dialysis patients. Despite the lack of evidence supporting the use of medications to lower phosphate, guidelines suggest they be used in inceasing amounts. TARGET will determine if changing the dose of calcium carbonate can effectively change serum phosphate concentrations. If it does, we will plan a large study to determine if using high doses of calcium carbonate to achieve a low serum phosphate reducecs mortality, and vascular events or improves quality of life.

THESIS (Dr. Scott Brimble)

Patients on hemodialysis (HD) are typically physically deconditioned and frail. Studies have been conducted evaluating the impact of exercise in improving physical conditioning and have shown exercise to be beneficial. What is less clear, however, is what type of exercise regimen is most effective. THESIS is a randomized controlled study evaluating three exercise regimens: on-dialysis bicycling, leg strength training before or after dialysis, or the combination of these two, in improving the physical function of HD patients. A number of secondary objectives are also being evaluated, including measures of frailty and ability to perform basic activities of daily living. Additionally, biological samples are being collected from patients to determine whether the various exercise strategies have differential effects on measures of inflammation, which are commonly increased in HD patients and associated with premature death.

TIME (Troponin I Measurement Evaluation) (Dr. Michael Walsh)

Patients who require dialysis for kidney failure live an average of only 3 years mostly due to heart disease. Heart attacks are difficult to diagnose in dialysis patients because the blood tests for heart attacks (troponins) are often positive even when the patients are doing well. Furthermore, dialysis may cause mini-heart attacks. We will study how a new troponin test changes in dialysis patients by doing the test 36 times in each patient over six months.This study will help determine how we use troponins to detect heart attacks in dialysis patients and how often mini-heart attacks occur during dialysis.

WISHED (Dr. Scott Brimble)

Patients with chronic kidney disease (CKD) will often have ongoing loss of kidney function over time, ultimately leading to the need for dialysis or a kidney transplant. Those patients who do not have a suitable donor or are not medically fit for a transplant still have a number of treatment options. These include the home therapies: peritoneal dialysis (PD) and home hemodialysis (HD); or facility-based HD. Although home therapies are frequently associated with improved quality of life for these patients compared to facility-based HD, such a decision can be difficult and overwhelming for patients. WISHED is a multi-centered randomized controlled trial that evaluates the usefulness of a website dedicated to enhancing education and support for home dialysis therapies, as compared to usual care. Current PD and home HD patients write blogs about their overall experiences for CKD patients considering these treatment options. Expert advice is online and supplemental information in a variety of media formats is available for patients to better understand the nature of PD and home HD and how feasible it can be. The primary outcome is the proportion of patients who start a home therapy; a number of secondary outcomes will be evaluated including measures of social support and decision conflict.