NephCure Funded Research: Dr. Hani Suleiman August 1, 2017 by Lauren Eva Dr. Suleiman is using a Nobel-prize winning microscopy technique to look at the kidney cells injured in FSGS. 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. Dr. Hani Suleiman in his lab. 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. Normal kidney podocyte. 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. Dr. Suleiman, top row, second from the left, at the 2016 St. Louis NephCure Walk. 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.
NephCure Funded Research: Dr. Evren Azeloglu April 3, 2017 by Lauren Eva NephCure Funded Research: Dr. Evren Azeloglu Dr. Evren U. Azeloglu In 2015, Dr. Evren Azeloglu, a biomedical engineer and an Assistant Professor at the Icahn School of Medicine at Mount Sinai, was awarded the NephCure Kidney International-ASN Foundation for Kidney Research Grant. He planned to use this grant to explore how kidney cells retain their structural integrity against mechanical injury. Much of the work done in Dr. Azeloglu’s lab involves the podocyte, the specialized kidney cell that is affected by glomerular diseases like FSGS. Podocytes play an important role in glomerular function. Together with other cells, they help form a filtration barrier in the kidney, and they cooperate with other cells to support the structure and function of the glomerulus. Below, we discuss Dr. Azeloglu’s latest research and what it means for people living with glomerular kidney diseases in our search for better treatments and a cure. NKI: You’ve recently released two articles (here and here), both from research funded in part by NephCure. Can you tell us about your latest research? Dr. Azeloglu: Well, podocytes have a very beautiful structure, and we used cutting-edge imaging technology to capture the three-dimensional geometry of these cells. This paper is essentially about how the podocyte shape is not just pretty and sophisticated, but also very necessary for their function. And their shape has certain consequences for disease: some of the glomerular diseases may be directly borne out of the fact that these cells are shaped this way. If you look at the below gif, you will see how these cells look in the body. This is the first time anyone has ever visualized them with this kind of precision. NKI: Can you elaborate on what you mean when you say that their form suits the function? Dr. Azeloglu: Well let’s say that you want to build a drawbridge, and you want to be able to have tall ships travel below or through it. So you can either spend a lot of money and build a very tall bridge that is stationary, or you can build one that opens and closes. Basically, you are proposing a “functional upgrade” to a regular bridge. Unfortunately, that comes at a cost. The bridge needs to be able to separate in the middle. Following that analogy, podocytes have this special shape that allows them to do something that no other cell can do. What we are showing in our paper is that this special shape also comes with a price: incredible fragility. This works in the same way that a drawbridge has less stability than a regular arched bridge and would not be able to sustain the same level of, for example, an earthquake. You sacrifice that stability because you want to be able to open it up. In the same way, podocytes have incredible surface area; they have this amazing structure that allows them to filter blood plasma into urine, but what we’re showing is that only at this shape, the cells start showing this incredibly fragile behavior, and even a little change of their chemistry leads to disease. This ties in very well with the current knowledge that the podocytes are sort of the first guys to fail, if you will. This is one of the reasons why, for example, diabetic patients, whose cells are under constant stress because of insulin spikes, high levels of glucose, and all sorts of other oxidizing agents, are much more likely to develop nephropathy. So, what we are trying to show here is that these cells are incredibly fragile compared to most other cells in our body. NKI: What does it mean to be a biomedical engineer studying podocytes, and from a larger perspective, kidney disease? Dr. Azeloglu: I approach kidney research from an engineer’s perspective: the same way we study machines, buildings, and structures that have to withstand physical stress, which is exactly what podocytes have to do day in and day out. What we’re looking for, and what most of the projects in my lab focus around is: can we understand what makes these cells more susceptible to physical damage, and perhaps reinforce their structure? When all’s said and done, podocytes form a filter, which has a biological function, but to achieve that function, the podocyte uses a very simple physical mechanism: forming a sieve. So we ask, can we come up with therapeutic strategies that can make the podocytes stronger and more resilient? Or can we identify how specific chemical and biomechanical assaults weaken them? NKI: So is your lab directly looking at ways to fortify the cell? Or is that something you’re laying the groundwork for, for someone else to build from. Dr. Azeloglu: To be able to fortify something, you want to be able to understand it first. There’s been a lot of science over the last two decades showing that a lot of what these cells do is basically prepare for constant physical abuse, for lack of a better word. It’s just not very pleasant to be a podocyte. It’s biologically expensive to try to maintain physical integrity. So “Part One” of my lab’s research program is: to try to understand what makes these cells unique and special, what is the repertoire of these cells for withstanding physical stress. And “Part Two” is: if we can understand it, can we eventually fortify it? Can we prevent this structure from failing under disease conditions? These cells are very fragile, and they need all the help they can get. We’re expecting them to stick around for 80 years — that’s a long time to be under constant physical abuse. Dr. Azeloglu (pictured second from left) and his Systems Bioengineering Laboratory team at the Icahn School of Medicine at Mount Sinai. NKI: The podocyte is such a specific cell—how did you become interested in studying it exclusively? Dr. Azeloglu: Partly because of the video that you’re looking at—they’re really unique. They’re also almost a poster child of physical cellular stamina. They’re a great example of a microscopic structure that has evolved to do a very specialized physical task and do it for an extended period of time. It’s sort of a dream come true for an engineer. NKI: What stage were you at in your research when you received this award? Did it have a big impact on what you were able to do? Dr. Azeloglu: Oh, absolutely! I had just received my appointment as an Assistant Professor, and I had just started setting up my own lab. Without this, I basically wouldn’t have been able to do that. I come from a cardiac background—as a biomedical engineer, I trained in a cardiac biomechanics lab. And the heart, being a mechanical pump, is another example of a living tissue that’s doing a physically demanding job. I studied that for ten years and as I was transitioning into nephrology, the NephCure-ASN Award was critical. It helped me establish myself as an expert in this field as well. It’s sort of a rite of passage—a lot of the fellows who’ve received this award have moved on to successful careers, so it’s almost expected for you to have one to establish yourself in the field. I also think my goals and the goals of the NephCure-ASN Award align very well. I want to understand these cells from an engineer’s perspective, which I think is very relevant to their function, and if we can understand it, I think we’ll be able to cure diseases like FSGS. We’ll be able to not only help patients in terms of their symptoms, but also actually cure the disease. I’m in a pharmacology department, so I know that our standard methods can only help us so far; hopefully, this new, fresh perspective will be able to take us to the next level: instead of just dealing with the symptoms, we’ll be able to cure kidney disease. Hopefully. We were delighted to speak with Dr. Azeloglu on the results of his current research. If you want to stay updated on his work, you can follow him on Twitter (@azeloglu) or visit his lab’s website at http://labs.icahn.mssm.edu/azeloglulab. Thank you for your dedication to this work, Dr. Azeloglu and team! Dr. Evren U. Azeloglu is an Assistant Professor in the Department of Pharmacological Sciences at the Icahn School of Medicine at Mount Sinai. He was originally trained as a mechanical engineer, but later went on to receive his Ph.D. in biomedical engineering from Columbia University. In 2010, Dr. Azeloglu was awarded the Howard Hughes Medical Institute Fellowship from the Life Sciences Research Foundation. His background in biomechanics and systems biology is uniquely positioned to study complex diseases such as hypertension and diabetic nephropathy. He aspires to design transformative therapeutic tools using nanotechnology and tissue engineering.
NephCure Accelerating Cures Institute: Worldwide Launch and US Expansion March 23, 2017 by Lauren Eva The NACI Network is expanding worldwide to speed more effective treatments to individuals with Nephrotic Syndrome Thanks to a significant funding contribution, we’re proud to announce that the NephCure Accelerating Cures Institute (NACI) Care Network is expanding. An investment from Pfizer’s Centers for Therapeutic Innovation (PFE) and Retrophin (RTRX) will help grow the network from 8 sites to 30 sites worldwide. For patients living with Nephrotic Syndrome, more NACI sites means greater access to specialized care and trial opportunities specific to their unique kidney condition. Equally important, a more robust Network gives families across the globe a hub for community building and support at their individual care sites. NephCure Accelerating Cures Institute Global Trials Network The NACI story began in 2014, when leaders from NephCure Kidney International sought advice from leading medical professionals about ways to get better treatment options to patients faster. That following year, NKI launched NACI in partnership with the University of Michigan. Today, NACI is co-led by veteran representatives from NKI in suburban Philadelphia and an expert team from the University of Michigan, Ann Arbor. NephCure Accelerating Cures Institute United States Trials Network To read more about NACI, you can view the full press release here, or visit the NACI website at www.nephcureaci.org. If you have any questions or want to learn more, please send us an email at info@nephcure.org, and we will direct your message to the appropriate party.
NephCure Funded Research: Dr. Martin Pollak’s Lab January 30, 2017 by Chelsey Fix NephCure Funded Research: Dr. Martin Pollak’s Lab Through generous donations from the NephCure Kidney International community, NephCure has been able to support Dr. Martin Pollak’s kidney disease research at Beth Israel Deaconess Medical Center (a Harvard Medical School teaching hospital) since 2007. Dr. Pollak’s lab works on identifying genetic causes of kidney diseases, like FSGS. They have made some very exciting progress over the past few years, leading to Dr. Pollak’s election into the prestigious National Academy of Sciences in 2014. Dr. Pollak’s research has identified that two common variations in the apolipoprotein L1 (APOL1) gene impart up to a ten-fold increased susceptibility to FSGS among African Americans. African Americans and others of recent African ancestry suffer disproportionately from chronic kidney disease: although they make up 13% of the U.S. population, they represent 35% of all individuals on dialysis. Other researchers have calculated that 1 in 8 African Americans are at risk for developing kidney disease due to APOL1—stark numbers that may indicate that some forms are FSGS would not be classified as a “rare disease.” But the research being done at Dr. Pollak’s lab may one day help prevent treat—and prevent—this disease from occurring. Dr. Pollak was recently featured in an article on SFGate.com as saying that “We want to put our own [kidney disease research] division out of business by preventing this disease to begin with.” We are thrilled to offer a “progress report” on this work directly from Dr. Pollak’s lab. We spoke recently with Andrea Knob, a genetic counselor, clinical research coordinator, and key player in Dr. Pollak’s study, who gave us some background on the work the study is doing, what we can expect from this lab in the future, and how you can get involved in this research yourself. Q: What is the goal of the research being done in Dr. Pollak’s lab? Andrea: The purpose of our study is to learn more about the causes of kidney conditions including FSGS, Nephrotic syndrome, unexplained proteinuria, and renal failure by studying genetics. We identify and study genetic factors that may contribute to the development of these conditions. We hope that this will further the knowledge required for scientists to develop better treatments in the future. Q: What is your role at Dr. Pollak’s lab? Andrea: I am the clinical research coordinator for Dr. Pollak’s lab. With my background in genetic counseling, I help patients and families navigate the research process, assist them in documenting their personal and family health histories, and serve as a resource for any questions surrounding genetics and research. I am the liaison between our patients/families and our physicians/scientists. Q: What do you enjoy about CKD research? Andrea: Every person and family has a story to share, and this information is so valuable and so important. It is amazing to witness this generosity, and to be a part of a team that is so dedicated to making progress in this field. Research answers the questions that otherwise would be left unknown, and that in turn provides hope. Q: What is APOL1? Andrea: APOL1 is one of several genes that we study in the Pollak lab. Variations in this gene have been found to confer resistance to trypanosomiasis, a serious disease in some African regions, and as such these variations have risen in frequency in parts of Africa. We are investigating how these gene variants contribute to kidney disease in persons of African ancestry. Q: Why did the lab decide to focus on APOL1? Andrea: APOL1 is one of several genes that we study as we try to learn more about the causes of FSGS, Nephrotic syndrome, and related conditions in patients and families. Our lab’s interest in the genetics of FSGS led us to explore the basis of the high rate of FSGS in persons of African ancestry. Certain specific variations in the APOL1 gene contribute to this disparity. Q: What impact can diagnosing an APOL1 mutation have on treatments for patients? Andrea: We need to learn more about genes, including APOL1, that may contribute to the development of kidney disease. (We also think there are more to be discovered!) Diagnosing a gene mutation helps doctors determine who might be at increased risk of developing kidney disease. While it may not affect the treatment for patients at this time, the goal is to acquire the information we need about these gene variations in order to develop better treatments in the future. Q: What is involved for patients in this study? Andrea: Participation involves a questionnaire, a saliva sample, and a urine sample (if possible) that can be given from home. (If participants prefer to give a blood sample instead of a saliva sample we can help arrange this.) Q: Who can participate in this study? Andrea: • Anyone with FSGS, Nephrotic syndrome, or unexplained proteinuria • Anyone with a family member who has FSGS, Nephrotic syndrome, or unexplained proteinuria • Anyone with African ethnicity with non diabetic kidney failure • Any healthy individual without kidney disease Andrea Knob – Genetic Counselor and Study Coordinator for Dr. Pollak’s study Q: How do I get more information about the study? Contact Andrea Knob with any study related questions by phone at 617-667-0467 or by email at aknob@bidmc.harvard.edu. You can also read more about the research study by clicking here.
Dr. Anna Greka, Kidney Researcher at Harvard, Receives PECASE from President January 30, 2017 by Chelsey Fix Dr. Anna Greka, Kidney Researcher at Harvard, Receives PECASE from President In early January, President Obama honored 102 early career scientists with a Presidential Early Career Award for Science and Engineering. It is considered the highest honor for scientists that are in the dawn of their career—the award is given to federally funded researchers that have done exceptional work in advancing their field. Dr. Anna Greka, long-time friend of NephCure and kidney disease researcher at Harvard University, was a recipient of this award. Pres. Obama praised Greka and the other recipients, saying, “These innovators are working to help keep the United States on the cutting edge, showing that Federal investments in science lead to advancements that expand our knowledge of the world around us and contribute to our economy.” Dr. Greka received a Young Investigator Grant from NephCure in 2008, and has continued to support NS patients and families with her hard work and dedication to research. Her research lab focuses on the development of targeted therapies to treat kidney diseases like FSGS and MCD. Dr. Greka also founded the Glom-NExT conference to bring brilliant minds together and focus exclusively on finding therapies for these kidney diseases. She will also be collaborating with NephCure to host a Regional Symposium in the spring. You can read more about Dr. Greka’s lab and her work here – http://grekalab.bwh.harvard.edu You can read the full statement from the White House about the PECASE awards here.
Q&A with Dr. Kopp of the NIH December 1, 2016 by Chelsey Fix Dr. Jeffrey Kopp is a physician and researcher who focuses on FSGS and related diseases. He currently leads a group in the kidney disease section (officially called the National Institute of Diabetes and Digestive and Kidney Diseases, or NIDDK) of the National Institutes of Health (NIH). Dr. Kopp is also working on a new clinical trial for FSGS, MCD, and MN patients at the NIH headquarters near Washington D.C. We had the awesome pleasure of sitting down and catching up with Dr. Kopp about his fascinating job and new clinical trial. Keep reading to learn more, and read about some of his other research projects here. Interview highlights: Dr. Kopp works at the National Institute of Health’s kidney branch, where he studies glomerular diseases such as FSGS and MCD. He also serves as Captain for the United States Public Health Service, and has been deployed to help with medical care during natural disasters. Dr. Kopp is leading a new clinical trial for FSGS, MCD, and MN patients at the NIH studying a compound called ManNAc as a treatment option. ManNAc is a sugar that occurs naturally in your body. Another researcher at the NIH found that mice without ManNAc developed MCD, and adding ManNAc to their diet was helpful in treating it. Therefore, it may be effective at treating MCD, FSGS, and MN in humans (Dr. Kopp describes the full mechanism below—make sure you read the article!) This study requires people to stay at the NIH for 11 days total, but it can be split up into 2 trips. Luckily, there is a lot to do to pass free time you may have at the NIH, including movie marathons, exercise programs, an art gallery, and an in-house business center. Learn more about taking part in the study by clicking here or contacting Emily Brede, RN at emily.brede@nih.gov Full interview: NKI: What is your job at the NIDDK? Jeffrey B. Kopp, M.D. Dr. Kopp: I am fortunate to lead a translational research group at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which is part of the National Institutes of Health. Our mission is to develop a better understanding of the disease mechanisms responsible for focal segmental glomerulosclerosis (FSGS) and to develop more effective and less toxic therapies. I also serve in the United States Public Health Service, with a rank of Captain. My primary mission at NIH is to carry out basic and clinical research in FSGS. I also deploy for public health emergencies, such as natural disasters. Thus, I participated in the medical response to Hurricanes Katrina and Ike. SIDE NOTE: What is NIH? Dr. Kopp: The NIH is a federal biomedical research facility located in Bethesda, MD. The campus includes a 240-bed Clinical Research Center and extensive outpatient clinics. Every patient who comes to NIH participates in a research protocol. Some protocols involve novel treatments and other protocols involve giving samples for research. NIH physicians may give advice about standard therapies that can be used. There are no charges for any medical care provided by the NIH Clinical Center. NKI: What do you enjoy about CKD research? Dr. Kopp: CKD, and particularly glomerular diseases (such as FSGS), are incompletely understood, and the available therapies are not ideal. I like the challenge of understanding and treating these diseases, and most of all I like the opportunity to improve the lives of patients with these conditions. NKI: The newest clinical trial for FSGS, MCD, and MN patients at the NIH is looking at MaNAc as a treatment option. Why did you decide to study MaNAc? Dr. Kopp: A colleague at NIH developed mice unable to make ManNac. She found that these mice developed glomerular disease soon after birth. This disease resembled a human glomerular disease, minimal change disease. Providing extra ManNAc orally to the mice cured the kidney disease. This prompted the question: can we use ManNAc to induce remissions in our patients? Chemical Structure of ManNAc NKI: What is ManNAc? Dr. Kopp: Perhaps the word sounds to you like manna, the food the Israelites found in the desert and that helped sustain them. There is a tree in Europe that exudes a sweet white resin, similar to the sap of the sugar maple, and people who knew the Bible story called the tree the manna tree. A chemist found a distinctive and novel sugar in the manna resin, and he called the new sugar “mannose”. NKI: Does ManNAc occur naturally in the body? Is it found in food? Dr. Kopp: ManNAc is a natural product and essential for good health. Our food does not contain much ManNAc. Our bodies make ManNAc, which is converted in our cells to mannose. This in turn is converted to sialic acid, which is put on many proteins. All of these are sugars, but they differ from glucose in that they are not related to diabetes and they are present in very small amounts, so that they do not add calories in the diet. NKI: What is the reason for believing that ManNAc might be useful in treating glomerular diseases? Dr. Kopp: Podocytes are cells on the outside of the kidney glomeruli and serve to prevent plasma proteins from leaking into the urinary space. Many patients with glomerular diseases have lost sialic acid from the proteins on the podocyte. We think that providing extra ManNAc might promote the return of sialic acid to podocyte proteins and that this might improve podocyte function. We see some evidence in mouse models of FSGS that supplemental ManNAc in the diet helps treat these mice. NKI: What is involved for patients in this study? Dr. Kopp: Patients will provide their medical records for review by the NIDDK team. We also review the kidney biopsy materials from past kidney biopsy. No kidney biopsy is done as part of this study. If patients appear to qualify for the study, they will come to NIH for an outpatient visit for evaluation and to discuss study participation. NKI: Is travel to NIH paid for? Dr. Kopp: Travel to NIH can be arranged and provided by NIH. If overnight accommodation is needed, NIH can provide this also. NKI: Why are patients required to stay at the NIH during this study? NIH Headquarters Dr. Kopp: The study requires being an inpatient for 11 days, either as a single stay or as two stays of five and six days. The reason for the inpatient stay is allow frequent sampling of blood and urine and for safety, to be sure there are no side effects. NKI: What can patients do with any “free time” during the study? How much free time do you expect patients to have? Dr. Kopp: During the first five days, there are frequent time points for sample collection. During the second six days, samples are needed at 8 am and 8 pm. There is extensive free time that patients can use as they like. There are many activities that can help pass the time at NIH • Patient Computers combination television and computer (with Internet access) at most patients’ bedsides to provide access to games, web browsing, and personal e-mail via the Internet • Patient Library has more than more than 5,000 books, including a selection of current best-sellers, reference, foreign language, large-print, picture, and audio books • Clinical Center’s Fine Art Program has more than 2,000 works of art. Most artwork remains on permanent display throughout the hospital, but there are six galleries on the first floor that change every eight weeks. A walking tour is available to assist patients, caregivers and visitors in their enjoyment of the artwork on display. •Recreation Therapy programs include: o Arts and crafts o Music o Games and sports o Social events o Exercise o A large selection of DVD movies o Instruction in coping skills such as relaxation, enhanced communication, and stress management • Spiritual Care Department offers Catholic, Jewish, Islamic, and Protestant services in the interfaith chapel • Business Center has four PCs and four MACs (all with Internet connection) as well as a combined printer/copier/FAX and telephones are available. NKI: Who can participate in the ManNAc study? Dr. Kopp: We are recruiting adults (age ≥18 years) with a primary glomerular disease, including minimal change disease, FSGS, and membranous nephropathy, and with nephrotic range proteinuria (urine protein/creatinine ratio > 2 g/g). Exclusion criteria include having diabetes mellitus and receiving pulse therapies, such as rituximab. Monetary compensation is provided. NKI: How do I get more information about the study? Dr. Kopp: The study, like all clinical research studies, is described at clinicaltrials.gov. You also contact the study research nurse, Emily Brede, RN at Emily.brede@nih.gov
Watch the Demystifying Research Webinar! July 21, 2015 by Chelsey Fix Watch NKI and special guest speaker Dr. Jonathan Hogan from The University of Pennsylvania, as we demystify Nephrotic Syndrome research! Research is important to all members of the NS community- so why not learn about it! We talk about how research works, what is happening in the NS research world, and what patients and their families can do to help. Come with your research questions, and prepare to have them answered! CLICK HERE TO WATCH THE WEBINAR
The Silver Lining Found In Nephrotic Syndrome – A Story by Lauren Bentley (former NKI Intern) March 10, 2015 by Jessica Martin The summer before 8th grade, I began to experience extreme fatigue. No matter how long I slept at night, I could not keep up with my friends. I often woke up with swelling in my neck, face and eyes. Sometimes I vomited for no apparent reason. My parents had been taking me to doctors for years but nobody could pinpoint the cause of my symptoms. I was tested for a variety of diseases and visited almost every unit in the children’s hospital. Finally, we landed in the Rheumatologist’s office. She told us that nothing abnormal showed up in my blood work but to come back if my symptoms grew worse or I experienced swelling in my feet or legs. One night while I was at camp, our counselors told us to get ready to play capture the flag. I ran to put on my sneakers but no matter how hard I pushed my foot into my sneaker, it would not slip in. I looked down and realized the entire bottom half of my body, from my toes to knees, had swelled up like a balloon. The counselors and doctor on hand attributed the swelling to being out in the heat, walking around campus and eating salty foods. When I mentioned the swelling to my mom, she thought the same thing. However, after I returned home from camp, the swelling did not disappear. In fact, it stayed exactly the same. My mom made an appointment with my Rheumatologist, who ordered blood work immediately. Two weeks later, I found myself sitting on the examination table in a Nephrologist’s office. The blood work showed I had signs of protein spillage and kidney damage. The team of doctors suspected I had Nephrotic Syndrome, a rare form of kidney disease. I could not believe this was happening. I felt as though I did not belong to my body, and instead, was watching this unfold on a movie screen. I can only describe it as an out of body experience. I spent two days in the hospital after undergoing a kidney biopsy. The results confirmed I did in fact have a form of Nephrotic Syndrome known as Membranous Nephropathy. In everyday words, this meant I had a kidney disease and damage as a result of Lupus that went undetected for years. Lupus is an autoimmune disorder in which the body cannot tell the difference between good and bad cells. As a result, it attacks healthy tissues, such as joints and major organs. It is difficult to describe the feelings I had while receiving this diagnosis. Part of me was confused over all the medical terminology. Part of me was sad. Part of me was overwhelmed and angry that my body had failed me. But after hearing how the doctors would treat my disease, almost all of me became scared. Along with diet and activity restrictions, I was prescribed several heavy-duty medications. Prednisone was one of the medications that would give me the most side effects. As the doctor rambled off the side effects I grew increasingly frightened. She said I would have mood swings, low energy, an upset stomach, grow “chipmunk cheeks,” and gain as much as thirty pounds – all in the course of just a few weeks after starting treatment. I remember this like it was yesterday. After my doctor’s appointment, my mom dropped me back off at school. I did not want to show I was upset or worried, so I told her I wanted to go back to class. As I sat in my desk in the back of Mrs. LaFave’s English classroom, I stared straight ahead of me. She rambled on and on about the Masque of the Red Death and all these other Edgar Allan Poe pieces, but all I could hear was my doctor’s voice rattling off the symptoms of Prednisone. What would people think? I was on a heavy dose of Prednisone throughout my 8th grade year. Without fail, the Prednisone showed its nasty side effects. By November, I gained about 15 pounds, was always exhausted and had round, chubby, chipmunk cheeks. As I stood in front of the mirror, I did not recognize the person staring back at me. Going to school everyday was challenging. As I walked down the hall I heard whispers. Rumors circulated about why my appearance drastically changed in such a short amount of time. “Did you have some kind of weird surgery?” random students asked me. “What’s wrong with Lauren’s face?” they would ask my friends. I did not want to share my health problems with anyone. I was worried people would treat me differently if they knew about my disease. I did not want my teachers to feel bad for me and give me special privileges. I also wanted to appear strong for myself and my family. The last thing I wanted was my parents to worry about me. One afternoon, I sat in the cafeteria eating lunch with three of my girl friends. I looked up and noticed the girls sitting in the next booth were staring at me. One of them leaned over and whispered something in her friend’s ear. It was clear they were gossiping about me. This was probably my breaking point. I had experienced other incidents like this before since being on Prednisone. Girls, who never cared to give me the time of day before, asked me what happened to my face. A group of kids in my math class whispered about it constantly, as if I could not hear them. When I left class every second period to go take my medicine at the nurse’s office, kids asked me why I always left class. But it was something about this one particular incident that broke me. I held in my feelings all day. By the time I walked through the door at home, I could not take it anymore. I burst into tears. My mom held me and rubbed my back as I lay in bed. This was one of the first times in my life I felt completely shattered. It boggled my mind to think that my peers could be so critical of someone’s appearance when I had no control over it. This may seem weird to say, but during this time, I also realized I had been so blessed. My condition could have been so much worse than it actually was. I could have needed a transplant. My doctors could have put me on dialysis. I could have been admitted to the hospital for weeks instead of a few days. As I went to the hospital for my monthly checkup and blood work, I saw children who were hooked up to a million machines. Newborn babies were being poked for blood work. Children were battling cancer and fighting for their lives. I was still able to sleep in my own bed at night. I didn’t need to have different IVs pump fluids into my body. Instead, I just had to take some medicine. I could run around outside and go to a real school. My friends and I still hung out on the weekends. During this time, I was also showered by so much love and support. My parents were amazing. They made me special low-salt dinners. When I cried, they listened and wiped away my tears. My doctors went above and beyond their job description. They provided me with emotional support and hugged me after every appointment. My friends at school stood up for me when other students gossiped and spread rumors. My church family visited me in the hospital, sent cards and spoiled me with special treats. Looking back now as an adult, I am extremely grateful for this experience. It taught me so much about myself. I learned how to be disciplined to eat healthy, get enough sleep and take my medicine on time. I learned to listen to my body and identify when it told me to slow down. As of today, I still have Lupus but my kidney disease is in remission. I am thankful everyday for a healthy body that allows me to lead a happy, normal life. It also taught me life lessons. I never judge a person based on the outside or first impressions. Everyone has a story that has shaped who they are today. Until you have walked in their shoes, it is unfair to place judgment. During the teenage years where gossip spread like wild fire, I learned just how hurtful rumors can be. I learned how important it is to be kind to everyone, regardless of how they dress, speak, or who they hang out with. Today, I intern for NephCure Kidney International. I love interacting with patients, hearing their stories, and sharing my own personal experience with them. I realized this struggle was put in my life so I could share my story with other people. For those who are still struggling with Nephrotic Syndrome or FSGS, there IS light at the end of the tunnel. It may not seem like it at the time, but things do get better. Those chipmunk cheeks don’t stay round forever. The kids who may be gossiping or picking on you, won’t mean a thing in a few years. Nothing is ever as bad as it may seem at the time. You will realize this experience made you a stronger person.
NEW!! Clinical Studies Map! October 14, 2014 by Chelsey Fix NephCure Kidney International Introduces Clinical Research Map October 14, 2014 We are excited to introduce a new user-friendly, interactive clinical research map. This map includes current clinical research sites and studies available to patients affected by FSGS and other Nephrotic Syndrome diseases. The map, which can be found here, will help patients sort through studies available to them. Categories include studies specific to adults, pediatrics, Nephrotic Syndrome, and FSGS, to name a few. “Patient participation is key to advancing research and treatment options available to patients,” says Marilyn Hailperin, the National Director of Research at NephCure. “This site map allows patients to view studies underway in their area.” This map is another way NephCure is living out our mission to support research seeking the causes of Nephrotic Syndrome diseases, to improve current treatments and, ultimately, to find a cure. Here at NephCure, we value the supportive role we play for our patients. Spreading the word about clinical research to our patients is a crucial aspect of this role, because, after all, patients power research! Link to the map: here. For more information about the risks and benefits of participating in clinical research, click here.
NephCure Kidney International Announces NKN Steering Committee Co-Chairs October 2, 2014 by Chelsey Fix We are pleased to share that Kathleen Broderick and Randall Snyder were recommended and have accepted their nominations as Steering Committee Co-Chairs for the NephCure Kidney Network (NKN). Kathleen was considered a strong candidate due to her dual experience as a patient caregiver as well as a patient advocacy representative. Similarly, Randy’s dual perspective as a patient caregiver and clinical provider give him unique insight relevant to the NKN. Kathleen is a member of the NephCure Board of Directors and Research Committee and an editor at DeGruyter Publishing, a Science, Technology, and Medicine (STM) publisher of professional books and scholarly journals in Boston, Massachusetts. Additionally, Kathleen cares for her 16-year-old son, who was diagnosed with Nephrotic Syndrome at 20 months. Randy is an interventional radiologist with his master’s in molecular biology living in Medford, New Jersey, who cares for his son who was diagnosed with focal segmental glomerulosclerosis. Kathleen and Randy will be facilitating Steering Committee calls and communication moving forward. Please join us in welcoming Kathleen and Randy as the inaugural NKN Steering Committee Co-Chairs!