Northwestern University Feinberg School of Medicine recently announced a $5.8 million, five-year award from the National Institute of Diabetes and Digestive and Kidney Diseases to expand translational research into the prevention and treatment of kidney diseases. The grant will fund the Northwestern University George M. O’Brien Kidney Core Center (NU-GoKIDNEY), bringing together basic and clinical scientists in a collaborative hub dedicated to identifying, testing and translating discoveries into novel therapeutics for patients with kidney diseases.
The successful proposal was spearheaded by Chemistry of Life Processes member Susan Quaggin, MD, Director of the Feinberg Cardiovascular & Renal Research Institute, Chief of Nephrology and Hypertension in the Department of Medicine, and the Charles H. Mayo, MD, Professor. Quaggin will be the center’s new director along with co-directors Alfred George, Jr., MD, chair and Magerstadt Professor of Pharmacology, and Karl Scheidt, PhD, professor of Chemistry at the Weinberg College of Arts and Sciences and executive director of NewCures.
All three directors are CLP members.
In addition, each of the three cores is led by exceptional researchers from Feinberg and CLP: Guillermo Oliver, Professor of Medicine and Director, Center for Vascular and Developmental Biology, and Evangelos Kiskinis, Assistant Professor of Neurology, (preclinical models core), Jason Wertheim, MD, Vice Chair for Research, Department of Surgery Edward G. Elcock Professor of Surgical Research, and Evan Scott, Assistant Professor of Biomedical Engineering, (therapeutics core) and Tamara Isakova, MD, Associate Professor of Medicine and Director, Institute for Public Health and Medicine (clinical core).
Q: First of all, what is kidney disease and how widespread is it?
A: It’s much more widespread than people recognize. More than 850 million individuals worldwide have some form of kidney disease and in the US about 30 – 40 million individuals have kidney disease. In the US, roughly 650,000 have end stage kidney disease, which means they require either a kidney transplant or dialysis to survive. Most patients with kidney disease die before they are able to go on to renal replacement therapy. When a patient has kidney disease, they are at much higher risk of dying from cardiovascular disease. Kidney disease can be viewed as ‘accelerated aging’ for the vascular system, so it’s a huge problem.
Q: What drew you to this field of study?
A: Nephrology was my first clinical rotation as an intern. Nephrology is the medical discipline of looking after patients with kidney disease. As an intern -a long time ago now! – I looked after an 18-year-old patient who came into the emergency department with kidney failure. He had been perfectly healthy two weeks before and had suddenly gained a huge amount of fluid and swelling of his entire body – almost 30 pounds-worth! This type of swelling is known as edema and occurred because his kidneys were spilling a lot of protein from the blood into the urine. He had a rare kidney condition that attacks the kidney filters, which caused him to lose his kidney function. He needed to go on dialysis as there were no effective treatments available.
The following year he received a kidney transplant from his dad. The disease recurred on the operating table, and he started spilling protein into the urine again. We knew he must have something in his bloodstream that was attacking the filters in the new kidney – just as it had attacked his own kidneys the year before – but we had no idea what the ‘blood factor’ was or how it caused the kidneys to fail. It was patients like him and many, many others as well as the fact that we didn’t have a lot of treatment options that led me to choose nephrology. Thirty years later, nephrology is still my lifelong passion. As an intern, I had never done research, but I realized there was a huge need to find new therapies, so after completing my clinical training, I uprooted my family and moved to Yale to embark on training in basic science. In 1997, I returned to Canada to do both clinical nephrology and research. To this day, I see patients and I also have a lab.
Q: What’s the idea behind the grant and the Go-Kidney center?
A: We decided to go big, so the overarching theme of the Center is kidney therapeutics -translating new treatments to prevent, manage and cure kidney disease. We wanted to catalyze discoveries for patients with kidney diseases without focusing on a single disease and we felt the best way to do that was to open up the resources at Northwestern to researchers here on campus that might not know about them, to kidney researchers in the Chicagoland area who might not know about them, and to the rest of the US and the rest of the world. We felt that the unique resources here at Northwestern, the division of Nephrology, the department of medicine – very much in collaboration with the CLP- the nanomedicine institutes and the incredible “We Will” spirit here at NU were a huge opportunity to facilitate important discoveries.
Q: How did CLP support this effort?
Karl Scheidt [a resident member of CLP] is one of the PIs on the center grant, so this is very much a partnership between the downtown campus and CLP in Evanston. The entire idea and writing of the grant was also a partnership. Sheila Judge [Senior Director for Research, Education and Administration, CLP] was incredible in helping us put together a cohesive project and also introduced us to a variety of very talented people in CLP and in Evanston. Going forward, the plan is to have multiple outreach programs for the community for education as well as kidney disease awareness. For example, the SciHigh program will focus on bringing STEM in kidney research to high schools in disadvantaged neighborhoods where the burden of kidney disease is actually much higher.
INVO [the university’s Office for Innovation and New Ventures] was also incredibly helpful. We will have a kidney accelerator with a grant program associated with it to move very exciting projects with great potential into the therapeutics space.
CLP will play a role from the translational piece to the discovery piece. We go the entire spectrum from discovery to development of new therapeutics through testing in patients and clinical trials. We will span the spectrum, so I see back and forth engagement with CLP throughout the whole process. It’s going to involve pulling together investigators in CLP, clinicians who may not even be investigators, and kidney investigators and access of these folks to people outside of the Northwestern community for new ideas to come out of this. I think most people have no idea what’s going on, even downtown here on this campus, certainly in the hospital – they don’t know how amazing it is up in CLP. I’m sure the new center is going to accelerate all sorts of great things.
Q: How will people with kidney disease benefit from the new center?
A: The ultimate goal is to develop new therapies to cure kidney disease. In the short term, one of the big goals is to enhance education and outreach to stakeholders – communities, patients, patient families, patient advocates – so that we can prevent kidney disease.
We have a web portal, nephrohub.org, that outlines all the resources we have, but also will be a home to all the events and the community programs that we plan to launch.
Q: How can someone who doesn’t do kidney research plug in?
A: I could see a basic researcher who doesn’t even think of the kidneys but has developed something incredibly novel – it could be a chemical compound, a delivery system or a device. There are technologies that are clearly not kidney-focused, but could be applied to the kidney. Patients with kidney disease also have, as I mentioned, accelerated cardiovascular disease/early mortality. Once you’re diagnosed with end stage kidney disease, your five-year mortality rate is about 55%, so it’s worse than a lot of cancers. If we could have an impact on cardiovascular disease, bone disease, nerve dysfunction, or anemias that are all part of kidney disease, it could have a significant impact.
Q: How do you prevent kidney disease?
A: I always say the most important thing, and it seems overly simple, “have your blood pressure checked and your blood sugar checked”. The commonest causes of kidney failure in North America are diabetes and high blood pressure. There are lots of other causes, but that’s the two. And we do know there are certain things we can do to prevent, or at least slow the progression of kidney disease and if you can slow it down so you don’t end up on dialysis, that is a huge win!
Also, as we start to understand new genetic causes of kidney disease we may be able to move upstream and prevent it from happening in family members, and in children. There will also be new therapies coming down the pipeline from large pharma companies that we want to be at the forefront of being able to test here at Northwestern. And some of those things will be able to prevent kidney disease. This center will also allow us to reach a large group of patients, and enroll patients more rapidly into clinical trials for some of these really exciting new therapies.
Q: What new breakthroughs do you think are on the horizon 10 years from now for kidney disease?
A: New kidneys! I think that we are going to have bio-artificial kidneys as replacement therapy. I also think we are going to have genome editing treatments for specific kidney diseases and new ways to deliver dialysis, which is archaic right now. We’re going to be using some of the nano-based approaches that they are already using in other diseases. We’re on the brink of some really fantastic new innovations!
by Lisa La Vallee