According to the actress Mae West ‘too much of a good thing can be wonderful.’ Unfortunately, this does not hold true for sugar: although it’s an important source of energy for our cells, too much of it can be bad for our health.
High blood sugar—a hallmark of diabetes—can damage the kidneys, promoting the development of diabetic nephropathy, a form of kidney disease that progressively impairs the organ’s function and can lead to kidney failure. Up to 50% of people with diabetes will develop diabetic nephropathy over their lifetime.
Although researchers do not fully understand the causes of diabetic nephropathy or how to prevent it, they have found that diabetic patients with unusually high levels of uric acid in their blood experience higher rates of the disease than those with average levels.
In light of these findings, TGHRI Scientist Dr. David Cherney led a clinical study to determine whether lowering uric acid levels in diabetic patients could help to protect their kidneys against damage. The study included 49 diabetes patients with no history of kidney problems who received the uric acid-lowering drug febuxostat for eight weeks and were subjected to a battery of physiological tests before and after the treatment period.
The researchers found that the drug decreased kidney pressure in several patients, which is beneficial given that high pressure damages the kidneys. However, when patients’ blood sugar was high, the drug triggered the constriction of the kidney’s blood vessels, which promotes kidney damage.
Albeit preliminary, these findings suggest that modulating uric acid levels could potentially protect some patients against diabetes-related kidney damage. They also suggest that an optimal range of uric acid levels exists and levels outside this range—whether too high or too low—can promote kidney damage. Rigorous clinical trials will provide more definitive proof of this and define the optimal range of uric acid levels.
This work was supported by the Canadian Diabetes Association, the Kidney Foundation of Canada, the Canadian Society of Nephrology, the Canadian Institutes of Health Research, the Banting and Best Diabetes Centre, the Heart and Stroke Foundation, the University of Toronto and the Toronto General & Western Hospital Foundation.
Lytvyn Y, Har R, Locke A, Lai V, Fong D, Advani A, Perkins BA, Cherney DZ. Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients with Uncomplicated Type 1 Diabetes. Diabetes. 2017 Apr 13. doi: 10.2337/db17-0168.
Welcome to the first issue of Research Spotlight (formerly known as NRx).
This monthly newsletter highlights top research advancements from the five research institutes and over 800 appointed researchers at UHN. As Canada’s largest research hospital, UHN is a national and international source for discovery, education and patient care.
Stories in this month’s issue:
Read these stories and more online here. To read previous issues, see the newsletter archive.
A new, minimally invasive system which uses radiofrequency energy instead of open surgery to create access for patients needing hemodialysis is reliable and has minimal complications, according to data published in the American Journal of Kidney Disease.
For hemodialysis patients, creating direct access to their blood is critical because they need to have their blood cleaned regularly by a dialysis machine.
A single-arm, prospective study of 80 predialysis and dialysis patients from nine centres in Canada, Australia and New Zealand for one year showed that an arteriovenous fistula (AV-fistula) – the recommended type of vascular access for patients to connect to a hemodialysis machine – was created successfully in 98% of all cases, with 87% being physiologically suitable for dialysis within three months of creation by this new magnet-based endovascular technology.
Regarding complications, 1.8% of AV-fistulas had thrombosis or clots within three months and 10.5% within 12 months – lower than that reported in current AV-fistulas created by open surgery. Studies have reported that from 14-26% of traditional fistulas had clots within 12 months.
Traditional surgical fistulas often need two to three additional procedures before the AV-fistula is ready for use, while the AV-fistulas created by this new technology needed fewer.
Dr. Charmaine Lok, Medical Director of both the Chronic Kidney Diseases and Hemodialysis Programs at the Toronto General Hospital, University Health Network is an internationally renowned specialist on hemodialysis access and the principal investigator of the trial.
“Chronic kidney patients currently do not have a minimally invasive option for creating AV-fistulas and yet it could reduce a significant barrier for patients to have an AV-fistula, which is the preferred access for hemodialysis. Patients often refuse AV-fistula creation because they do not want to undergo open surgery, and this technology can provide another option for patients,” says Dr. Lok, who is also a Senior Scientist at TGHRI.
She notes that the use of AV-fistulas remains low in many regions world-wide. She adds that traditional surgical AV-fistulas can require long wait times, general anesthesia, and pre-operative assessments.
Currently, an AV-fistula is made through a surgical incision in the arm to expose and access the artery and vein, which are then cut and stitched together. The vein grows bigger and stronger (now called an AV-fistula) over six to 12 weeks. The strengthened AV-fistula, which can sometimes last for decades, can then be used for regular hemodialysis treatments.
In contrast to the usual surgical option, the NEAT clinical study examined a new technique to create an AV-fistula without open surgery. Using the everlinQ endoAVF System by TVA Medical, flexible magnetic catheters were inserted into an artery and a vein in the arm of each participating patient. The vessels were drawn together by the magnets. A small burst of radiofrequency energy, given through the catheters, was then used to create a connection between the artery and vein, creating the AV-fistula. The catheters were then removed leaving no surgical scar. These study procedures were performed on outpatients who did not need general anesthesia.
Dr. Dheeraj Rajan, the co-primary investigator in the study and Vascular/Interventional Radiologist at University Health Network’s Joint Department of Medical Imaging, supervised the interventional procedure for all Toronto General Hospital and other study centre patients.
“This novel technology is a substantial benefit to our hemodialysis patients,” he says, “we can now access veins and arteries that otherwise would not be easily accessible via surgery, and we can do this in a safe, quick way that is easy for our patents to tolerate.”
The everlinQ endoAVF System is approved for use in Canada and Europe.
The Novel Endovascular Access Trial (NEAT) was supported by a personnel award from the Heart and Stroke Foundation and TVA Medical. Dr. Rajan is an equity stock owner of TVA Medical.
Endovascular Proximal Forearm Arteriovenous Fistula for Hemodialysis Access: Results of the prospective, multicenter Novel Endovascular Access Trial (NEAT). The American Journal of Kidney Disease, June 8, 2017.
Longtime UHN researcher Dr. Christopher Paige has been named Inventor of the Year for his work in immune-oncology, a promising therapeutic approach based on the premise that a patient's own immune system has powerful cancer-fighting capabilities if correctly activated and targeted.
Dr. Paige, who for close to two decades as UHN's Vice-President of Research, and later as Executive Vice- President (EVP) of Science and Research, championed commercialization as a strategy to transform discoveries into practical medical products to benefit patients, received the award at yesterday's UHN Annual General Meeting in the MaRS Auditorium.
Each year, UHN's Technology Development & Commercialization Office (TDC) selects and celebrates a UHN Inventor who demonstrates outstanding inventiveness in research coupled with important contributions to the advancement of healthcare via successes in commercialization.
The TDC cited Dr. Paige for recognizing back in 2006, "long before immune-oncology was the hot topic in cancer therapy it is today," that cytokines, which are a group of proteins made by the immune system that act as chemical messengers and are expressed in the tumour local environment, could powerfully stimulate a patient's immune system with little risk of side effects.
Working with Dr. Jeffrey Medin, Dr. Paige developed an approach whereby some of a patient's leukemia cells could be removed, engineered to produce IL-12 and re-introduced to the patient, which then stimulates T- cells to fight the cancer. Working with his clinical collaborator, Dr. Mark Minden, Dr. Paige has advanced the work to a clinical trial, which is now underway.
In 2015, leading figures in the cell-therapy industry created a company in Toronto and Boston called AvroBio Inc. and licensed this patented technology from UHN as Avro's first asset.
They successfully raised funds from top-tier American venture capital firms and are currently advancing this technology to market.
The TDC also recognized Dr. Paige for his "leadership in the development of research commercialization at UHN and more broadly in Ontario," during his time as EVP Science and Research, which ended in 2016.
"The fact that UHN technology has been licensed in three of the largest medical research deals in Canadian biotech history is a testament to the initiative that Chris launched and has continuously supported during his tenure as EVP of Science and Research," the TDC said in announcing the award.
The Government of Canada has announced new Canada Research Chair (CRC) awards. In this latest round, Ontario received a total of 52 new or renewed Chairs, valued at $50.3M.
The CRC program was established to attract and retain the world’s most accomplished scientists. Chair holders are expected to improve our depth of knowledge and quality of life through their research, strengthen Canada's international competitiveness and help train the next generation of highly skilled professionals.
UHN Researchers who received CRC funding are:
These outstanding individuals are among the 28 elite scientists who received University of Toronto CRCs in the latest round.
Congratulations to all!
Scientists and clinician scientists at Princess Margaret Cancer Centre will lead four of five large-scale research initiatives launched recently by The Ontario Institute for Cancer Research (OICR).
Ontario Minister of Research, Innovation and Science, Reza Moridi announced a $24-million investment over two years for the OICR's Translational Research Initiatives (TRIs). The TRIs will bring together world-leading scientists to tackle some of the most difficult to treat cancers and test innovative solutions to some of the most serious challenges in cancer.
"This kind of support for collaboration and translational research helps ensure that we can continue to bring cutting-edge science to the clinic to improve care for patients," said Dr. Peter Pisters, UHN President & CEO.
Six clinician scientists at the Princess Margaret will lead the following TRIs:
"Leading four of the five research initiatives is a testament to the extraordinary talent of our researchers and clinicians who are continuing to expand our understanding of cancer, and through collaboration, developing and evaluating new approaches to therapy," says Dr. Brad Wouters, UHN's Executive Vice-President, Science & Research.
To learn more about the initiatives, read the full news release.
