Join us on Nov. 9th, 2017 as we raise funds and awareness for FSGS and Nephrotic Syndrome
by Lauren Eva
by Lauren Eva
Join us on Nov. 9th, 2017 as we raise funds and awareness for FSGS and Nephrotic Syndrome
by Lauren Eva
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.
by Lauren Eva
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.
by Chelsey Fix
Senators Lindsey Graham (R-SC), Bill Cassidy (R-LA), Dean Heller (R-NV), and Ron Johnson (R-WI) recently introduced legislation known as Graham-Cassidy to repeal and replace the Affordable Care Act (ACA). The hope of these lawmakers was to hold yet another vote on repeal before October 1st, so a simple majority (51 votes) is all that is needed to pass the measure.
Unfortunately, the Graham-Cassidy proposal is more extreme than other recent Senate proposals and would be particularly harmful to individuals and families impacted by chronic health conditions. Specifically, the new proposal would:
While this effort was initially dismissed by many as a “Hail Mary,” it has quickly gained support and could be voted on next week. In order to protect patients with chronic conditions, please contact your Senators and ask them to oppose the Graham-Cassidy repeal and replace proposal.
Template For Emailing / Calling / Faxing Your Senators
My name is _________ and I am a constituent from [home town]. On behalf of patients with chronic health conditions, I urge the Senator to oppose the Graham-Cassidy healthcare proposal. This proposal would be absolutely devastating to individuals and families affected by chronic illness that rely on access to quality, affordable health care.
[Explain a little about your particular situation]
Thank you for your consideration of my request. Please tell me how you have responded to my request.
by Lauren Eva
In 2014, the Nobel Prize for Chemistry went to a group of scientists who’ve created a new technique to change the scale at which we are able to see cell structures. In the same year, NephCure awarded a Young Investigator Award to Hani Suleiman, MD, PhD, an instructor at the Washington University School of Medicine, to use this new microscopy approach to look at kidney podocyte cells.
Recently, we spoke with Dr. Suleiman to hear about his work using this new microscopy approach, and how it might be used in the future to diagnose and potentially change how we approach creating new treatments for FSGS, Minimal Change Disease, and other diseases that cause Nephrotic Syndrome.
NKI: You received the Young Investigator Award from NephCure in 2014. Could you give us an overview on what you’ve been studying since receiving this grant?
Dr. Hani Suleiman: Glomerular diseases like Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are diseases of the podocyte, an important component of the kidney’s glomerular filtration barrier. Studying podocytes in living tissue has been limited due to the types of microscopy techniques that we use. The problem with seeing and understanding the podocyte and its changes is in its scale: important structures in the podocyte range from 200-300 nanometers. This resolution is below the limit of conventional microscopy techniques. Thus, we have been hindered from studying in detail the molecular changes that accompany podocyte injury and proteinuria.
Until the invention of super-resolution microscopy, the only way to view changes in podocytes after injury was to use electron microscopy techniques [electron microscopy was invented in the 1930s]. However, electron microscopy only allows us to see the structural changes in the podocyte. There is another technique that is capable, to some extent, to view the molecular patterns in podocyte structures after injury, but this technique has its own limitations. This is where super-resolution microscopy, a revolutionary new technique, comes in. We were the first people to adapt this technique to the kidney field.
In kidney diseases such as FSGS and MCD, podocytes go though a massive change in their shape as they lose their foot processes and form what is called foot process effacement. This is when the finger-like protrusions that you see in a normal podocyte change and basically disappear. This usually accompanies a leaky glomerular filtration barrier, as the patient starts spilling protein in the urine (proteinuria). Proteinuria, by itself, is an important indicator that the kidney is not functioning correctly as a filter.
Foot process effacement is a phenomenon that we see in almost all podocyte injuries, no matter how the injury starts: whether it’s immune-related, MCD or FSGS. All these diseases have foot process effacement and are accompanied with a loss of the glomerular filter.
In the paper that we just got accepted in the Journal of Clinical Investigation-Insight, we studied the molecular changes that accompany foot process effacement using super-resolution microscopy to try to understand the enigmatic phenomenon of foot process effacement and how foot process effacement is related to the cause of the injury. I think that, by mapping the earlier molecular changes in the injured podocytes, we can potentially intervene and stop this massive change and maintain the foot processes and the barrier.
This effort may be a good first step towards actually interfering with the pathways that we think interplay with this phenomenon [i.e., a first step towards treating proteinuria at a molecular level]. And for that, super-resolution will be an instrumental technique, since we are able to see the molecular changes of the cell on a nanoscale.
NKI: So podocyte foot process effacement is basically the fingerlike protrusions of the podocytes pulling up and away and leaving the podocyte with just the cell membrane. And without the fingerlike protrusions there, there’s nothing preventing the protein from leaking through the kidney?
Dr. Suleiman: As a response to injury, we think that foot process effacement is a survival mechanism for the podocytes. Podocyte number, like neurons, is a fixed number, and they must survive throughout life as they don’t reproduce. We can speculate that podocytes sense the dangers around them and respond by changing their shape in order to hold on to the basement membrane tightly as a precaution, in order to not fall into the urine. As I mentioned earlier, foot process effacement is usually accompanied with proteinuria, indicating that the retracted podocytes are unable to cover the whole basement membrane and prevent the protein leakage.
My work is to try to understand the earlier changes that cause the podocytes to go through this tremendous morphological change (i.e., foot process effacement), and how foot process effacement is related to the cause of the injury. I think that, by mapping the earlier molecular changes in the injured podocytes, we can potentially interfere and stop this massive change and maintain the foot processes and the barrier.
NKI: Are you mostly looking at mouse models right now?
Dr. Suleiman: In our recently accepted paper, we studied podocyte injury in three different mouse models. We included a small group of human tissue samples of FSGS, MCD and diabetic nephropathy in the study. We found that, similar to our mouse injury models, injured human podocytes show molecular changes that involve the motor molecules, myosin IIA.
As these results are in their early stages, I recently received a NEPTUNE (Nephrotic Syndrome Study Network) grant to study the biological significance of myosin IIA changes in human tissue samples. This study might allow us to find better diagnostic or prognostic tests for diseases such as MCD, FSGS and diabetic nephropathy.
NKI: So what you’re saying is that you think one day we might be able to use the super-resolution microscopy technique to diagnose patients?
Dr. Suleiman: Yes, I can see that the super-resolution microscopy will be instrumental in the future to diagnose and predict the outcome of diseases like glomerular diseases. The whole problem with imaging the podocyte in the past was the scale. Super-resolution, and the recently developed near super-resolution microscopy techniques, has the right scale to view the molecular changes in the podocytes.
NKI: Did the NKI Young Investigator Award have a big impact on what you have been able to do? Where were you at in your research when you received it?
Dr. Suleiman: Oh sure! That was my first grant ever. So for the last two years I have been relying on this grant to do my research. Of course, my previous mentor, Dr. Andrey Shaw, was highly supportive; I was still in his lab when I received the NKI award. This award has helped me publicize my work, refine my hypothesis and maintain my focus on the podocyte biology. It helped a lot. Thank you so much.
We were thrilled to learn more about Dr. Suleiman’s research. Check back at www.NephCure.org to stay updated on his work and other advances in the field. You can also view his most recent article on the super-resolution technique here. Thank you for your passion and commitment to learning about glomerular diseases, Dr. Suleiman!
Hani Suleiman, MD, PhD, is an Instructor in the Nephrology Division at the Washington University School of Medicine in St. Louis. Upon establishing the use of super-resolution microscopy, STORM in the kidney field, Dr. Suleiman has been focused on utilizing this technique to study various kidney diseases such as diabetic nephropathy, focal segmental glomerulosclerosis, and minimal change disease. In 2017, he received the Nephrotic Syndrome Study Network (NEPTUNE) Career Development Fellowship.
Dr. Suleiman has developed new ways to image the podocyte’s actin cytoskeleton in both animal models and human. These methods will allow us to ask new questions regarding how podocytes regulate their unique shape and maintain their function throughout life.
by Chelsey Fix
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the branch of the National Institutes of Health (NIH) that focuses on funding research related to FSGS, Nephrotic Syndrome, and other kidney diseases. In 2016, they funded $574 million worth of research projects, and they continue to be a leader in clinical trials.
Currently, there are two clinical trials being held at the NIDDK that are relevant to the Nephrotic Syndrome community:
You can learn more about these clinical trials and other opportunities by using our clinical trial finder, called Antidote.
by Lauren Eva
Laci Weatherford is now in her 7th year as a volunteer leader for the St. Louis NephCure Walk. Her incredible efforts have helped grow the walk to a massive event, with more than 100 people in attendance and raising around $15,000 each year! We spoke to her recently to learn about her journey with FSGS and how she manages such a successful fundraiser.
NKI: How did you become involved with NephCure? How long have you been involved?
Laci: I believe the first time I found NephCure was in 2009 when I was diagnosed with FSGS. I researched on the internet and found the NephCure website. I must have provided my information and said I would like to get involved, because in 2011 I received an email saying they were going to have a walk in St Louis. The email asked if I would like to be on the committee. I said yes. The day I was on my first planning committee call, I discovered I was the committee, the only volunteer for the event that was about a month away. So that year I learned the very basics of putting together a walk and have been working on improving and growing our annual event ever since.
NKI: Why do you devote your time and energy to this cause? If you feel comfortable explaining, what’s your personal connection to kidney disease?
Laci: After I was diagnosed in 2009, I began my personal journey with FSGS and learned firsthand the terrible side effects of the drugs available and the lack thereof. I learned how precious the little things were and struggled to just get by day-to-day, enjoy my 2 year old baby, and take care of myself. I began to read more on the internet about this disease: sometimes it would be good and encouraging, sometimes not. It quickly became too overwhelming to read the stories from parents who had children struggling with these drugs and side effects. It broke my heart, and I felt it was so unfair. I had lived a good life up until my diagnosis; I enjoyed my childhood, but they were being robbed of simple joys.
I received a referral for a specialist in NY and became so encouraged by his accomplishments and his knowledge of the disease. I have tremendous hope and belief the cure and proper treatments are out there. We just need the right people to have the right tools to make it happen. It takes a lot of work to put all the proper channels in motion, and I’m so grateful NephCure is there doing the work to keep progress in motion. I want to do what I can to help fund this process.
NKI: What’s the hardest part about being a walk leader?
Laci: The hardest part is getting the word to participants. Since this is a rare disease, not many people have ever heard of FSGS or NephCure. Unless you or a loved one is personally impacted, then you are probably not looking for another charitable event to go to. I’ve got to find a way to find the patients and their families. Doctors aren’t willing to help most of the time because of HIPAA policies and various other reasons.
NKI: What’s the best part?
Laci: There is so much that warms my heart about the event. The first is my family. They drive 3 hours just to be in St. Louis with me on this special day. They also coordinate 75% of the activities and volunteer in any area I need. If it wasn’t for them, I literally couldn’t do this. Second is seeing the other patients. To see them smile and enjoy a day dedicated to them encourages me to keep going. I also love to see the growth in the event, which is the proof we are getting the word out there. My first walk had about 20 people and we raised around $2,400. The walk is now averaging between 100-120 people each year and we raise on average $15,000. That is just amazing to me.
NKI: What has surprised you the most throughout your years of leading this walk?
Laci: I’m surprised by how generous and easy is it to get donations. Most of the time all you have to do is ask. There are so many business that will gladly give you a gift card, services, or products to help you raise funds. There is no secret to fundraising or formula for getting donations—all you have to do is ask! Mostly likely you are going to get a yes.
Congratulations and a big thank you to Laci and her supportive team for their incredible efforts each year! With their help, we are one step closer to finding better treatments and a cure for FSGS and Nephrotic Syndrome. We couldn’t do it without them!
Interested in volunteering at a walk or creating a walk team? Great! Just email us at firstname.lastname@example.org to get started.
by Chelsey Fix
Summer is a great time to catch up on reading! If you’re sick of beach novels or historical biographies, consider catching up on science reading with our pick of recently published articles.
We combed through the literature and found some interesting and relevant publications that may be relevant to Nephrotic Syndrome patients and families. The articles are listed in no particular order, and we do not endorse or prefer any of the research studies.
Hayek SS, Koh KH, Grams ME, Wei C, Ko YA, Li J, Samelko B, Lee H, Dande RR, Lee HW, Hahm E, Peev V, Tracy M, Tardi NJ, Gupta V, Altintas MM, Garborcauskas G, Stojanovic N, Winkler CA, Lipkowitz MS, Tin A, Inker LA, Levey AS, Zeier M, Freedman BI, Kopp JB, Skorecki K, Coresh J, Quyyumi AA, Sever S, Reiser J.
Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels. Mechanistically, surface plasmon resonance studies identified high-affinity interactions between suPAR, APOL1 and αvβ3 integrin, whereby APOL1 protein variants G1 and G2 exhibited higher affinity for suPAR-activated avb3 integrin than APOL1 G0. APOL1 G1 or G2 augments αvβ3 integrin activation and causes proteinuria in mice in a suPAR-dependent manner. The synergy of circulating factor suPAR and APOL1 G1 or G2 on αvβ3 integrin activation is a mechanism for CKD.
Published in Nature Medicine and accessible here.
Nathan T. Beins and Katherine M. Dell
Steroid-resistant nephrotic syndrome (SRNS) is an important cause of chronic kidney disease (CKD) in children that often progresses to end-stage renal disease (ESRD). Calcineurin inhibitors (CNIs) have been shown to be effective in inducing short-term remission in some patients with SRNS. However, there are little data examining their long-term impact on ESRD progression rates. We performed a retrospective chart review of all patients treated for SRNS with CNIs at our institution from 1995 to 2013. Data collected including demographics, initial response to medical therapy, number of relapses, progression to ESRD, and treatment complications. A total of 16 patients met inclusion criteria with a mean follow-up of 6.6 years (range 0.6–17.6 years). Histopathological diagnoses were focal segmental glomerulosclerosis (8), mesangial proliferative glomerulonephritis (4), IgM nephropathy (3), and minimal change disease (1). Three patients (18.8%) were unresponsive to CNIs while the remaining 13 (81.2%) achieved remission with CNI therapy. Six patients (37.5%) progressed to ESRD during the study period, three of whom did so after initially responding to CNI therapy. Renal survival rates were 87, 71, and 57% at 2, 5, and 10 years, respectively. Non-Caucasian ethnicity was associated with progression to ESRD. Finally, a higher number of acute kidney injury (AKI) episodes were associated with a lower final estimated glomerular filtration rate. Despite the majority of SRNS patients initially responding to CNI therapy, a significant percentage still progressed to ESRD despite achieving short-term remission. Recurrent episodes of AKI may be associated with progression of CKD in patients with SRNS.
Published in Frontiers in Pediatrics and available here
Séverine Beaudreuil, Hans Kristian Lorenzo, Michele Elias, Erika Nnang Obada, Bernard
Charpentier, and Antoine Durrbach
Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular kidney disease that is revealed by proteinuria or even nephrotic syndrome. A diagnosis can be established from a kidney biopsy that shows focal and segmental glomerulosclerosis. This histopathological lesion may be caused by a primary podocyte injury (idiopathic FSGS) but is also associated with other pathologies (secondary FSGS). The first-line treatment for idiopathic FSGS with nephrotic syndrome is a prolonged course of corticosteroids. However, steroid resistance or steroid dependence is frequent, and despite intensified immunosuppressive treatment, FSGS can lead to end-stage renal failure. In addition, in some cases, FSGS can recur on a graft after kidney transplantation: an unidentified circulating factor may be implicated. Understanding of its physiopathology is unclear, and it remains an important challenge for the scientific community to identify a specific diagnostic biomarker and to develop specific therapeutics. This study reviews the treatment of primary FSGS and the recurrence of FSGS after kidney transplantation in adults.
Published in International Journal of Nephrology and Renovascular Diseases and available here
Eva Königshausen and Lorenz Sellin
The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS)) since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs) in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications.
Published in BioMed Research International and available here
Santoro D, Vadalà C, Siligato R, Buemi M, Benvenga S.
Autoimmune thyroiditis (AIT) is generally associated with hypothyroidism. It affects ~2% of the female population and 0.2% of the male population. The evidence of thyroid function- and thyroid autoantibody-unrelated microproteinuria in almost half of patients with AIT and sometimes heavy proteinuria as in the nephrotic syndrome point to a link of AIT with renal disease. The most common renal diseases observed in AIT are membranous nephropathy, membranoproliferative glomerulonephritis, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic autoantibody (ANCA) vasculitis, and amyloidosis. Different hypotheses have been put forward regarding the relationship between AIT and glomerulopathies, and several potential mechanisms for this association have been considered. Glomerular deposition of immunocomplexes of thyroglobulin and autoantibodies as well as the impaired immune tolerance for megalin (a thyrotropin-regulated glycoprotein expressed on thyroid cells) are the most probable mechanisms. Cross-reactivity between antigens in the setting of genetic predisposition has been considered as a potential mechanism that links the described association between ANCA vasculitis and AIT.
Published in Frontiers in Endocrinology and available here
Yeo SC, Cheung CK, Barratt J
IgA nephropathy is the most common form of glomerulonephritis in many parts of the world and remains an important cause of end-stage renal disease. Current evidence suggests that IgA nephropathy is not due to a single pathogenic insult, but rather the result of multiple sequential pathogenic “hits”. An abnormally increased level of circulating poorly O-galactosylated IgA1 and the production of O-glycan-specific antibodies leads to the formation of IgA1-containing immune complexes, and their subsequent mesangial deposition results in inflammation and glomerular injury. While this general framework has formed the foundation of our current understanding of the pathogenesis of IgA nephropathy, much work is ongoing to try to precisely define the genetic, epigenetic, immunological, and molecular basis of IgA nephropathy. In particular, the precise origin of poorly O-galactosylated IgA1 and the inciting factors for the production of O-glycan-specific antibodies continue to be intensely evaluated. The mechanisms responsible for mesangial IgA1 deposition and subsequent renal injury also remain incompletely understood. In this review, we summarize the current understanding of the key steps involved in the pathogenesis of IgA nephropathy. It is hoped that further advances in our understanding of this common glomerulonephritis will lead to novel diagnostic and prognostic biomarkers, and targeted therapies to ameliorate disease progression.
Published in Pediatric Nephrology and available here.
by Lauren Eva
by Chelsey Fix
The Senate recently released a revised version of its healthcare reform bill entitled The Better Care Reconciliation Act (BCRA). This bill, like the House version, proposes state waivers, continuous coverage penalties, and deep cuts to Medicaid that would harm patients with costly and chronic health conditions. David O. Barbe, M.D., President of the American Medical Association, stated that “the revised bill does not address the key concerns of physicians and patients regarding proposed Medicaid cuts and inadequate subsidies that will result in millions of Americans losing health insurance coverage.”
This version of the BCRA adds an amendment from Senator Ted Cruz that would allow insurers to offer plans that do not meet Essential Health Benefits requirements, as long as these insurers offer at least one plan that does. Chris Hansen, President of the American Cancer Society Cancer Action Network, stated that the amendment and the bill as it stands would “leave patients and those with pre-existing conditions paying more for less coverage and would substantially erode the progress our nation has been trying to make in providing affordable, adequate, and meaningful coverage to all Americans.”
This bill harms patients with chronic and complex illnesses in the following ways:
The Congressional Budget Office (CBO) is anticipated to release its analysis of the bill by Monday, and a vote on the bill could take place anytime before the Congressional recess in August.
My name is _________ and I am a constituent from _________. I am also an advocate for (your health condition). I write to urge you to vote NO on the Senate’s healthcare bill.
The Senate healthcare bill would:
I write to urge you to maintain stability for chronic disease patients as you and your colleagues consider healthcare reform. It is my hope that you and your colleagues in the Senate will preserve key patient protections and respect the circumstances of those combatting chronic and costly illnesses.
Specifically, please ensure any Senate proposal:
[Add a paragraph of brief information about your condition. Tell your story.]
Patients need a transparent, bipartisan effort to stabilize the insurance market, bring down premiums, and retain the patient protections that are so critical to patients, consumers and their families. We urge the Senate to go back to the drawing board, and work together to find ways to protect patients with serious illness.
Thank you for your time and your consideration of this letter. Please tell me how you have responded to my request.
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