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ASN Foundation for Kidney Research: Recipient Profiles

William Henry Fissell, MD

William Henry Fissell, MD
Inspired by Kidney Patients, a Polymath Takes Kidney Care Into the Future

ASN threw me a lifeline.

While working as an EMT during a leave of absence from college, William Henry Fissell, MD often helped care for dialysis patients. “I fell in love with them because they were striving to live despite all the pain and fear of their everyday lives.” The grace with which these patients faced their challenges inspired Dr. Fissell to return to MIT, earn bachelor’s degrees in physics and electrical engineering, and then a medical degree from Case Western Reserve University.

During his residency, Dr. Fissell felt many physicians preferred to let others deal with the calculations and complications involved in caring for kidney patients. “As an engineer and physicist, I didn’t see the calculations as a steep hill to climb,” Dr. Fissell said.

While studying for his medical boards, he had an insight that set him on his eventual research path. “I was looking at electron micrographs of the glomerular capillary wall, when I noticed that the podocytes that comprise the filtration barrier have a remarkable structural resemblance to the submicron structures I’d been making for an X-ray astrophysics experiment at MIT. The light bulb went on: maybe we could use this silicon nanotechnology to make a better membrane and alter the way that we provide dialysis. And that was the genesis of my career in nephrology.”

Unfortunately an early grant ran out and Dr. Fissell encountered a “severe funding drought.” This is a uniquely vulnerable point in the careers of many physician-scientists especially those who are exploring new research territory that may seem higher-risk to funding agencies.

“I developed this peculiar idea that the basement membrane and the glomerular podocyte might interact to create a protein-free ultrafiltrate of plasma. ASN threw me a lifeline that allowed me to continue this line of research when there wasn’t federal funding available. Receiving an ASN Career Development Grant was a make or break thing for my career. If it weren’t for ASN and this grant, I probably wouldn’t have an academic job now. The support put me on a path to become the co-PI of a large NIH-U01 research project working to provide alternatives to dialysis to patients with renal failure,” Dr. Fissell said.

Currently an Associate Professor at Vanderbilt University, Dr. Fissell continues that work as the medical lead of the Kidney Project, a multicenter, interdisciplinary effort to develop an implantable artificial kidney, involving doctors, scientists, and engineers from a dozen universities and companies around the U.S. The ASN Foundation for Kidney Research is honored to have helped Dr. Fissell realize his vision of improving the lives of the patients who inspired him.

Lesley Inker, MD

Lesley Inker, MD
Building Bridges that Advance Kidney Care

The Grant provided opportunities for experience...I would otherwise not have had a chance to pursue.

A psychology professor asking “big questions” put Lesley A. Inker, MD on her path to nephrology. Dr. Inker was attracted to nephrology because it offered her the opportunity to develop long-term relationships with patients and to seek answers to big questions in public health. Her ASN Career Development Grant was a key to making the kind of contributions that mattered.

After medical school and a nephrology fellowship, Dr. Inker moved from Canada to the Boston area for a summer program at the Harvard School of Public Health followed by a two-year research fellowship at Tufts Medical Center.

Under the mentorship of Andrew S. Levey, MD, she joined the Chronic Kidney Disease Epidemiology (CKD-EPI) collaboration which focused on re-examining glomerular filtration rate (GFR) estimation. This was an ambitious goal at a time laboratories were just beginning to report results using the Modification of Diet in Renal Disease (MDRD) Study equation, which had the weakness of being based on data from limited populations. The CKD-EPI equation reflected much more diverse populations, thus providing physicians better decision-making tools.

However, even the improved data omitted community-based elderly—a critical patient group with a high prevalence of risk factors for kidney diseases. Dr. Inker, with the support provided by the ASN Career Development Grant, studied “Accuracy and Reliability of GFR Measurements in the Elderly” building an important bridge to improved clinical care, and opening up professional opportunities for herself as well.

Developing data from which to build future research studies is critical to young investigators with creative, new ideas. It can also be difficult to fund these critical investigations.

Dr. Inker’s Career Development Grant provided financial support to continue at Tufts after her fellowship and because the grant process required that she develop additional mentoring relationships, she expanded her professional network while gaining insights into the nitty-gritty of clinical research.

“The Career Development Grant provided opportunities for experience in research methodologies I would otherwise not have had a chance to pursue,” she says. “I had to plan the study and carry out the details, including recruiting patients, coordinating with the clinical research center, and organizing our research pharmacy. In short, do all the things needed for patient-level research. Understanding how to collect data on the individual patient level is really important for a researcher.”

Dr. Inker is now a recognized expert on GFR as a measure of kidney function. Dr. Inker and Dr. Levey—now working as colleagues—have completed two large studies of GFR measurement in the elderly population.

The KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease recommends that laboratory reports should use the CKD-EPI estimating equation, recognizing it improves the ability of physicians to provide optimum care to people with kidney diseases. The ASN Foundation for Kidney Research is honored to have played a part in advancing Dr. Inker’s success in improving kidney health.

Dr. Inker is currently an Associate Professor at Tufts University School of Medicine in Boston, MA.

S. Ananth Karumanchi, MD

S. Ananth Karumanchi, MD
Beating the Odds: A Researcher’s Creative Vision Realized

ASN took a chance on me.

From his earliest exposure to medicine, S. Ananth Karumanchi, MD was “fascinated by the way the kidney precisely filters out all the toxic material and maintains the electrolytes and acid-base status.”

After graduating from medical school in India, he came to the U.S. for a residency in internal medicine at Henry Ford Hospital in Detroit, drawn by the presence of Robert G. Narins, MD. During his nephrology fellowship at Beth Israel Deaconess Medical Center in Boston he began working in the lab of Vikas Sukhatame, MD. There Dr. Karumanchi focused on tumor angiogenesis, using microarray chips to identify individual proteins. This was a new technology, and exploring it, Dr. Karumanchi was drawn to the pregnancy complication of preeclampsia, where “the primary abnormality is in the vasculature. The kidneys and placenta have damaged blood vessels. And the mother has hypertension, which is a vascular disease.”

His chip studies uncovered a suspicious angiogenesis inhibitor—the protein soluble FLT present at high levels in the blood and placentas of women with preeclampsia. He accumulated evidence of its effects, including from an animal model: Rats given soluble FLT developed hypertension and proteinuria. “Pathologists who looked at sections of these rat kidneys would say they looked exactly like what you would see in a kidney biopsy from patients with preeclampsia,” Dr. Karumanchi noted.

Convinced he’d made a significant discovery that merited further investigation, Dr. Karumanchi faced obstacles common to young, unknown researchers, especially those breaking new ground: he could not get the attention of the scientific world: “It was very discouraging. I submitted numerous grant applications, but all were rejected. I was having a hard time getting the first paper published.”

His fortunes changed when he received an ASN Career Development Grant in 2002: “ASN took a chance on me. Grant funding at an early stage allowed me to explore this discovery. If I hadn’t received it, I may have quit and pursued something else.”

Dr. Karumanchi broke through barriers with several papers which helped convince NIH to begin funding his research. Some 15 years later, with the significance of his early work validated by a host of other researchers, diagnostic tests based on soluble FLT are available. He is working with Dr. Ravi Thadhani, chief of nephrology at the Massachusetts General Hospital, to test strategies to lower soluble FLT levels in preeclamptic women.

“I was at the right place at the right time asking the right questions. Many people had tried to solve this problem, but I had access to new technology. ASN’s Career Development Grant really built my career, and I think that is the point—we have to fund young people. When you are young you tend to take chances. You ask new questions, and sometimes you luck out and find something big,” Dr. Karumanchi said.

Dr. Karumanchi is currently a Professor of Medicine at Beth Israel Deaconess Medical Center of Harvard Medical School in Boston, MA.