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Archives for October 2017
NephCure Funded Research: Dr. Michelle Denburg
Dr. Denburg is focused on improving outcomes for pediatric Nephrotic Syndrome patients.
In 2012, NephCure and the ASN Foundation awarded Dr. Michelle Denburg, a pediatric nephrologist at the Children’s Hospital of Philadelphia, a research grant to study vitamin D deficiency in the Nephrotic patient. Dr. Denburg is also a Co-Principal Investigator of the NephCure Kidney Network, a patient-reported outcomes registry for individuals with primary Nephrotic Syndrome diseases.
We were thrilled to speak with her recently to learn more about her work and the impact that the NephCure-ASN grant has had on her research.
NKI: In 2012 you received the NephCure-ASN award for your research on vitamin D deficiency in the nephrotic patient. Can you tell us a little bit about your work that NephCure has helped fund?
Dr. Michelle Denburg: There are two studies that were related. One was an ancillary study to NEPTUNE, where we analyzed NEPTUNE baseline samples, measuring vitamin D metabolites and their hormonal regulators. We were looking at the relationships between what we already know in terms of Chronic Kidney Disease (CKD) and vitamin D, but specifically in terms of proteinuric glomerular diseases: the impact of proteinuria and relating some of the abnormalities of vitamin D metabolism to biopsy data and gene expression from the biopsies.
The other study is a trial of vitamin D supplementation in patients with Focal Segmental Glomerulosclerosis (FSGS) and other glomerular diseases with persistent proteinuria—basically, treatment resistant patients.
[editor’s note: The Nephrotic Syndrome Study Network, or NEPTUNE, is a long-term observational study that was formed to help understand the biology behind Nephrotic Syndrome. NEPTUNE has gathered health data and biological samples from close to 2,000 glomerular disease patients nationwide. Researchers can apply for grants, called “ancillary studies,” to conduct research on this de-identified patient data. Besides having helped fund the creation of NEPTUNE, NephCure also now helps provide the funding that make a number of the ancillary studies possible.]
NKI: I know this work has not yet been published, but is there anything from those studies that you can share with us at this time?
Dr. Denburg: There are some important things that we are going to be able to demonstrate and report. It’s fairly novel that we have measured vitamin D levels in the blood as well as the expression of vitamin D related genes in the kidney of people with glomerular disease. A lot of what we know about vitamin D metabolism comes from animal models. The fact that we have the NEPTUNE patients’ biopsy data and can relate the gene expression of these enzymes that are involved in vitamin D metabolism to their serum levels—this is highly novel from the research side.
From the patient and clinician side, this is the largest study of vitamin D related mineral metabolism in a glomerular cohort. The prior literature is small case studies—this study included several hundred people.
NKI: Do you think this work will change how patients are treated in their doctors’ offices?
Dr. Denburg: I can’t comment too much on the results of these studies which have not been published yet, but the findings could have important clinical implications. I think the nephrology community may need to consider updating our guidelines on vitamin D replacement in nephrotic patients. Our current guidelines are based on CKD in general. In other words, there is no guideline for patients with glomerular diseases who may have normal kidney function but a lot of proteinuria, or patients who have glomerular disease and CKD. And we know that patients with glomerular disease in particular have several obstacles to bone health.
One of my motivations behind this project is my interest in what we can modify to improve bone health in children and adolescents. Many of our patients are being exposed to a lot of steroids over time, and this is over the same period of time that they’re accruing the vast majority of their skeletal mass: about 90% of the skeleton is laid down before age 18. I’m interested in learning what we can do to modify and improve bone health in the face of therapies and illnesses we can’t avoid—that is, until we find a cure.
NKI: How do we separate the way steroid use affects bone health for glomerular disease patients to how having CKD in general affects bone health?
Dr. Denburg: I don’t know that glomerular patients need to be considered separately so much as have their unique risk within the CKD population considered. By definition, even someone with normal renal function who has glomerular disease is at CKD stage 1.
At a certain point, everybody starts losing bone. What kids come away with in terms of their skeleton by the time they enter the adult world is a huge determinant of their later fracture risk and other skeletal burden over time. You can never get that opportunity to address bone health back. You do accrue some cortical mass until age 30, but the majority of what you have is what you can accrue in your skeleton by age 18. Children and teenagers with glomerular disease have unique risk factors: high dose and long term steroid therapy, abnormalities in vitamin D metabolism, ongoing, persistent, heavy protein losses, and inflammation. There are a variety of risk factors that we can hopefully address.
NKI: The computable phenotype is another project I know you’re working on, and it sounds like it could be a game-changer. What is your role in that project and what about it excites you for the future of glomerular disease?
Dr. Denburg: That’s a very exciting avenue of research. Much of my effort on that is supported by the NephCure Kidney Network.
The computable phenotype is a way of identifying patients with glomerular disease through electronic health records (EHRs). It’s being developed in collaboration with PEDSnet [a large clinical data research network, composed of eight health institutions], so it represents over 5 million children and adolescents. The idea is that by running a computer programming code with essentially the push of a button, you can very rapidly say, here are the approximately 3,000 kids who have glomerular diseases across PEDSnet. And this is not static data, this is real life clinical care data. You could run the programmatic code again three months later and identify new cases. This is opposed to the traditional method where someone is sitting and going through the charts at each institution, which is not very time or cost effective.
The idea is that this is a means of rapid cohort identification. You can do observational studies on this population’s de-identified data. Or, with regulatory approval, you can contact patients and invite them to be in observational studies and clinical trials. You can also do trials in a more pragmatic way: you can invite patients to participate in a study where they don’t necessarily have to be followed by a typical regimented protocol with extra clinical visits, which is very laborious and cost-intensive. Instead, using this method, if we wanted to do a larger vitamin D study, we could consent individuals for a study and say, we’re going to randomize you to a group that either gets a lot of vitamin D or a group that gets a little vitamin D, abut then after that all your care is going to be your routine care with your clinician. Instead of having you come to separate appointments to track the effects of the vitamin D levels, we’re going to capture your data in regards to this study through your EHR. And we’ll leave it up to your own nephrologist to follow your levels and change your dosage. That’s what I mean by a pragmatic trial. I should say, the study has to lend itself to that—a high risk, new drug study is never going to be implemented in this manner.
NKI: And that more closely mimics real life; how a treatment would be used in real life vs. in a highly-regimented protocol.
Dr. Denburg: Right—so you lose a little of the very protocolized follow up, but you gain the real-life applicability and generalizability.
NKI: What impact did receiving the NephCure-ASN award have on your research?
Dr. Denburg: It was really mission-critical. I was a junior person, two years out of fellowship at that point, and it enabled me to build a research program. It helped me in getting my Career Development (K) Award from the National Institutes of Health, and the combination of those two awards allowed me to develop my research program and to have the ability to pursue multiple directions.
I like that I get to do patient-oriented research where I’m directly enrolling patients in studies of vitamin D treatment or assessing bone quality through imaging, but then I can also do studies where I’m accessing robust samples from NEPTUNE and entering this large data world. There are things you can do in each that really complement the other. And it’s the way to push things forward, moving between the analysis of large sources of data and then taking it back to the patient and vice versa. So I’m very grateful for the funding. I feel lucky. As pediatric nephrologists, Nephrotic Syndrome makes up a significant portion of patients we see and treat. Being a clinician who sees these patients really helps in keeping you attuned with what needs to be addressed from the research side—the patient care really drives the research questions.
We were delighted to learn more about Dr. Denburg’s research. Check back at www.NephCure.org to stay updated on her soon-to-be published work and other advances in the field. Thank you for your passion and commitment to improving the health of patients with Nephrotic Syndrome, Dr. Denburg!
Dr. Michelle Denburg, MD, MSCE, is an Assistant Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania and the Children’s Hospital of Philadelphia. Dr. Denburg’s research focuses on bone and mineral metabolism in childhood kidney diseases, including chronic kidney disease (CKD), glomerular disease, and urinary stone disease. In particular, she has pursued translational work in vitamin D-mediated innate immunity in nephrotic patients and ancillary studies of vitamin D metabolism and vitamin D-binding protein in pediatric patients with CKD. Her collaborative studies have focused on vitamin D metabolism and bone structure in children with CKD, nephrotic syndrome, and inflammatory bowel disease.
Dr. Denburg’s study of incident fracture risk in the Chronic Kidney Disease in Children (CKiD) cohort was the first to evaluate the burden of fractures in a large pediatric CKD cohort. She is a co-principal investigator in a project of the CKD Biomarkers Consortium that seeks to identify novel biomarkers for CKD progression in children. She has conducted several population-based studies of fracture risk in chronic diseases and CKD epidemiology using The Health Improvement Network (THIN) Database. She also has led the development of and serves as co-principal investigator of a Pediatric Glomerular Disease Learning Health System (LHS) within the PEDSnet clinical data research network. Dr. Denburg attended medical school at the Weill Medical College of Cornell University and received her Master of Science in Clinical Epidemiology from the University of Pennsylvania.
Why I Do What I Do: Spotlight on Michael Levine, NephCure Vice President
NKI: How did you first find out about NephCure? How did you get involved?
Michael Levine: I think my wife Dana found NephCure on the internet. That was 12 and half years ago, when my son Matthew was first diagnosed with FSGS. I think it was a few months after the diagnosis that we got connected.
The first event we got involved with was probably the Countdown to a Cure gala, with Ron Cohen and everybody from New York.
NKI: You’ve been involved both directly as a chair for so many of our events, like Countdown to a Cure New York and All In For a Cure on Long Island. What’s been your favorite NephCure event?
Michael: Well, each one is different. Quite frankly I love them all, because they all serve a purpose: to create awareness all over the country and the world, and to bring exposure to NephCure, FSGS and Nephrotic Syndrome. And obviously, the events raise dollars to try and create this miracle of a cure.
I guess my favorite event is Countdown to a Cure, because NephCure gets to put its best foot forward to so many people. Over 500 people attend, we raise over $600,000, and it’s just a very classy, professional event that is seen by so many families and patients around the country. It gives these patients and families hope. Seeing what NephCure does with that dinner, and meeting families from all over the world, it gives everybody so much hope that if we could do more events like that, a miracle of a cure is attainable.
NKI: You have raised an incredible amount of money in the 12 years that you have been volunteering with NephCure, on the NephCure board, and chairing for so many events. Does asking for money get any easier with experience?
Michael: It never does. The only thing that gets any easier is the knowledge of what we’re doing. Talking about what NephCure does and what our goals and dreams are, that gets easier because I talk about it so much. And telling my story gets easier only because it’s so engrained and enveloped in me.
But for me, asking for money is not something that gets any easier. It’s very hard for me to do because I’ve never been a person who is big on asking for help. Many of the fundraising experts say that it should get easier, because you’re asking for money for a very good reason: you’re asking for money to fund a cure and save lives. But for myself personally, it never gets easier.
NKI: Is there anything that you think to yourself just before you initiate that first conversation that helps you get past that feeling that it’s going to be tough to ask for money?
Michael: Well every time I ask, I say to myself, “Think about all the warriors around the country and around the world battling FSGS and Nephrotic Syndrome.” All the people who reach out to me on Facebook with their families’ and children’s stories. All of the Humans of NephCure stories on Facebook, which I read every single week.
You know, sometimes it’s not easy. Sometimes it’s overwhelming. And there are some days that I say, I can’t do this anymore. But then I think about all the families and children that are battling this horrible disease, and I don’t want them to go through the same living hell that my family has gone through over the past 12 years. So that’s my motivation.
There are two phrases that I always carry around when I do this. First of all, when I find out that somebody has made a donation to NephCure for an event that I’m a part of, I always write back to them, “You’re an angel on our shoulders. You allow us to dream that a miracle of a cure is possible. You give us hope against the greatest odds, and you give us the strength to fight every day.” I write that to everybody.
I also often write to people, “We are delivering dreams, miracles, wishes, and cures to the warriors around the world battling two devastating kidney diseases, FSGS and Nephrotic Syndrome. These diseases have no cure, and destroy kidneys, families, and lives in their path.”
Whenever I think of those things—that’s what motivates me to tell my story to ten people a day, and to ask people for help and to donate money, and to ask people to attend all these events around the country.
NKI: What kind of advice would you give someone who wanted to do a big event, like a gala, for NephCure?
Michael: The first year is the toughest. You just have to get through that. After the first year, when people see how heartfelt you are and see that you’re trying to deliver dreams, miracles, wishes, and cures, it will get easier.
NephCure, FSGS and Nephrotic Syndrome need a ton of awareness and exposure and a ton of dollars. So grab some friends, family and business associates, and say, “I want to save some lives today. I want to create a miracle of a cure for the children and adults battling FSGS and Nephrotic Syndrome.”
Whether it’s a bowling tournament, a sporting event, a golf outing, a lemonade stand, a gala, a dinner, just grab some people, form a committee, start having some meetings, and have that committee invite their friends, family, and business associates to the event. It’s like a mushroom, or a plant—it will grow. After you get through the first year, everyone who attends in year one will invite more people for year two, and it just expands. If you want to create a miracle of a cure for FSGS and Nephrotic Syndrome, just create an event. You can do it anywhere in the world.
You might not raise that much money, awareness, or exposure in year one. But it’s the stepping stone to years 2, 3, 4, and 5. And maybe by year 4, 5, or 6 you could be like the Tampa Pig Jig, where they’re raising $800,000 and have 6,000 people attending their event. You can’t get discouraged; you just have to fight through it. Just get started. I think that’s the best advice I can give.
NKI: You make something that might seem complex to someone who has never done it before seem very attainable and possible.
Michael: It’s very possible. You could start an event anywhere, and every dollar you raise brings us one dollar closer to a cure. You’ll get so much out of it, knowing that, and all of your friends and your family can be involved in it with you. And when the event is over each year, the fulfillment of saving lives by doing an event is incredible.
I would just like to add that NephCure has been a godsend to my family. With all the events that NephCure puts on—the Nephrotic Syndrome Symposia, the conference in Chicago, and all the walks and events and the visits to Capitol Hill—all these events bring awareness and exposure to the disease, and they allow us to dream that a miracle of a cure is possible. All these events allow us to participate in so much and know that we’re making a difference. The doctors that are involved, the scientific advisory board, everybody at NephCure—my family considers them angels on our shoulders because they give us hope that one day a miracle of a cure can be found. You really are making a difference.
And I would just stress to people to get involved. People think NephCure just needs money. And we certainly do. But there are so many other ways to help—with your businesses or your workplace; it doesn’t always have to be money. Money is great, but people can also donate their time, goods, services, and supplies. They would be giving hope to so many people. Just get involved in some way.
We are so grateful and lucky to have someone as committed as Michael on our board. Michael continues to devote an incredible amount of time and energy to NephCure each year. We salute you and your work, Michael! Thank you for your dedication to finding better treatments and a cure for all who suffer from FSGS and Nephrotic Syndrome.
The Countdown to a Cure gala will be on Pier Sixty in Manhattan on Nov. 9th at 6pm. We invite you to attend, meet Michael, and help us change lives. You can visit the event page here. If you have any questions, please contact Lorraine Mackin at LMackin@NephCure.org.