#KidneyWk 2015: A Tour of the Plenary Sessions

Every day at Kidney Week begins with the plenary session which are a combination awards show and scientific exposition. Here is a brief tour of this year’s plenary sessions.

Thursday

ASN Kidney Week always begins with  The Presidential Address given by the outgoing president, this year it is Jonathon Himmelfarb. He welcomed the new councilor Sue Quaggin and recognized and thanked the program chairmen, Lloyd Cantley and Patrick Nachman. He reported that the ASN is growing and is up to nearly 16,000 members. Kidney Week has reached the top 40 largest medical meetings in the World. The tenor of the speech then changed as Himmelfarb started to talk about the challenges the specialty faces. He recognized that nephrology is struggling. Himmelfarb channeled Darwin saying we need to adapt in order to survive. He advocated for the new match policy saying that part of adaptation is adopting the all-in policy for fellowship. He argued that it a policy that is best for fellows is in nephrology’s long term interest. He explained that ASN is expanding the Kidney STARS and the Kidney TREKS programs.

Himmelfarb then spoke about about the great success that APOL1 has had in explaining the high risk of ESRD seen in African Americans.

Then Himmelfarb launched into his bold idea of leaving the CKD staging system behind. He said that a system that puts GFR over diagnosis does a disservice to our patients and to our specialty. We know how important diagnosis is, CKD staging removes a lot of that nuance from our hands.

People were shocked by this suggestion.

Himmelfarb then explained that we need to do better for our patients on dialysis so more of them can take river trips down the Grand Canyon, like Bill Peckam. He advocated for individualized dialysis prescriptions that focused on the patient not the disease.

It was an impressive and hard hitting speech that was also well delivered.

After Himmelfarb’s speech, he awarded the ASN Presidential Award. This years recipient was comedian and kidney transplant recipient, George Lopez. Mr Lopez gave a short speech about his kidney disease and how he got involved in transplant advocacy.

After that Lloyd Cantley introduced the State of the Art speaker, Christopher Murray, professor of global health. He authored this review of global burden of disease in the NEJM. He described the way they measure disease and morbidity. It is fairly sophisticated that takes into account not only years of life lost but also quality of life and disability. He showed data that communicable disease mortality has been really improving improving. The burden of non-communicable disease, however, is growing. But when non-communicable disease mortality is adjusted for population size then it is flat. If you adjust it for both age and population it is actually decreasing. He cautioned about being too optimistic about the fact that when adjusted it is falling, because resources must be spent to cover the full extent of the burden and the aging and increasing size of the population are real problems.

In fully developed countries the number of years lost to disease is minimal but they have a large amount of disability. Then Dr. Murray fired up his organization’s website and began to manipulate and drill through the data in realtime over the web. It was a very cool presentation technique. He showed that only a few diseases are both mortal and growing. Kidney disease is one of them. He used the data to do a heat map of disease burden around the world by diagnosis. Central America immediately lights up with kidney disease burden over 50 times higher than other areas.

He concluded with some predictions including this dreary one: over the next 25 years, CKD deaths will rise 4-fold. Dr. Murray gave a great plenary talk that showed what can be done with a combination of inspiration, perspiration, and technology.

Friday

The plenary started with Dr. Himmelfarb welcoming the PKD Foundation into the Founding Circle. They created a named fellowship, called the Jared J Grantham, named after the co-founder of the PKD Foundation and founding editor of JASN.

Then they showed a video reviewing the life and accomplishments of Homer Smith.

The 2015 winner of the Homer Smith award was Dontscho Kerjaschki. Dr. Kerjaschki begins his talk by discussing the classic animal model of membranous nephropathy, Haymann’s nephropathy. He was key to discovering the antigen for this mouse model, Megalon. Unfortunately, this was not the antigen in humans. He explained with beautiful pictures that “complement turns the podocyte into an oxygen radical synthesizing machine.”

Then he turned his focus to newer work looking at micro-RNAs and their role in podocyte pathophysiology. One micro-RNA in particular, miRNA-193a causes FSGS in mice. It also appears to play a role at least some role in human FSGS. miRNA-193a is also found in crescent GN. He teased the audience by saying this may be a therapeutic target and they are starting work on this using locked nucleic acids (LNA) to block the micro-RNAs.

The State of the Art lecture was by Helen Hobbs. She spoke on the genetics of CV disease. She started the talk by telling the story about how her husband is a nephrologist and has been coming the Kidney Week for years. Every year she stayed home with the kids during ASN. Well the table has turned. I wonder if he ever gave plenary talk? Then she told how legendary nephrologist, Dr. Don Seldin, was instrumental to giving her early encouragement to pursue a scientific career. Mentorship.

She lead off her science lecture by showing a figure of two bell curves showing the frequency of different cholesterol levels. One curve for people with coronary heart disease and the other without CHD. The shocking thing is how much the two curves overlap. Cholesterol alone says very little about heart risk.

But as a geneticist she was not interested in the averages but the very extremes. At the highest ranges of cholesterol over 90% of the population had CHD, while at the lowest levels only 1 in a thousand had CHD. In order to study these extremes she needed to look at people both with and without the disease. Since people without disease are rarely patients she needed to set up a study to look at health and illness. This became the Dallas Heart Study. In this study they discovered a protein, PCSK-9. Increased expression increased the LDL and decreased expression lowered the LDL. Bench research showed that PCSK-9 regulated LDL receptors in the liver responsible for clearing LDL from the blood. Truncating mutations of PCSK-9 reduce CHD by 80%. One of their interesting findings was that reductions in LDL from various alleles of PCSK-9 had much greater influence on CHD than drug induced reductions in LDL. Dr. Hobbs suspected this was from a lifetime of low LDL burden. Possibly an argument for earlier and more aggressive use of cholesterol medications.

She then spent some time discussing there two new PCSK-9 inhibitors approved by the FDA. As of today she said we didn’t have compelling data showing a reduction hard outpoints but early, open label studies showed a dramatic reduction in CHD in only a year of use. Multiple, large, and rigorous outcomes trials are underway.

It was an interesting talk that did a great job showcasing how epidemiology, genetic and bench research can work together to go from observation to drug therapy.

Saturday

The Plenary session began with the passing of the presidency from Jonathon Himmelfarb to the next president, Ray Harris.

Then Eleanor Lederer, chair of the awards committee bestowed three awards:

The Narins award for teaching goes to Mark Zeidel. He created the Mount Desert Island Research experience for fellows.

The next award was the John P Peters award. It went to Roger Wiggin of the University of Michigan.

The last award is the Belding Scribner award and that was given to Glenn Chertow.

One of the best parts of these awards is the video that is shown prior to the award that explains who the award was named after. Scribner is still held in highest regard by the nephrology community.

After this, was the State of the Art lecture given by Gerald Shulman. He talked about the cellular mechanisms of insulin resistance, obesity and metabolic syndrome. He started by stating that there will be 582 million people with diabetes by 2035. By 2050 the CDC estimates that a third of people in the US could have type two diabetes. Shulman used NMR spectroscopy on living tissue in real time to make his measurements. This allowed him to use human data to look at rates of glucose consumption and glycogen synthesis. He used this technique to tease out that the rate limiting step in glucose absorption. Though absorption of glucose from the blood stream to the muscles is a multistep process, the GLUT4 transporter is the rate limiting step. The GLUT4 transporter is slowed by intramyocyte fat.

The intramyocyte fat resulted in increased diacylglycerol which appeared to block translocation of GLUT4 into the myocyte membrane. You can see a review article by Shulman in the NEJM about this. He then talked about an interesting case of lipodystrophy syndrome that they successfully managed with administration of leptin.

He talked a bit about how modest weight loss, not enough to get to a normal weight, is able to reduce hepatic triglyceride content and this normalizes fasting glucose.

He then described the metabolic syndrome and explained that in the natural history of the syndrome the first abnormality that is seen is myocyte insulin resistance. When the muscle stops accepting glucose, carbohydrates are directed toward the liver and converted to fat. A single 45-minute bout of exercise can restore muscle insulin sensitivity.

Dr. Shulman began a theme that was also demonstrated on Sunday showing the value of real-time observation of living, intact, tissue and cells. This appears to be a valuable research technique.

Sunday

The final session began with a film disclosing some facts about Kidney Week

Then President Himmelfarb announced a moment of silence for members of the ASN who died in the last year. Two notables on the list, former ASN Executive Director, Karen L. Campbell and Dr. Brickner, the first president of the ASN.

Then the ASN announced the winners of the educational contest. There were two. The first was an animated video and interactive lesson on water homeostasis. This was a product of Jon Danzinger and Mark Zeidel. The second winner made a board game to teach renal physiology called Nephropoly. The board games being ported to iOS and will be available in the App Store for free in a few months.

Young Investigator Award

The winner of the Young Investigator Award 2015 was Janos Petit-Peterdi.

He explains that his whole life was dedicated to nephrology because he wanted to heal his mother who developed ESRD from post-strep GN.

He advanced his research primarily through an imaging technology called in vivo multiphoton microscopy. This allowed him to look inside living tissues and see changes in real time. Through out his lecture he showed videos of living glomeruli. It was incredible.

He used flourescent tags to track cells and their progeny so he can see what cell types multiply in response to disease and injury.

He is used this technology plus a three dimensional microscope technique called CLARITY to show that macula density cells control the homing of progenitor cells for tissue repair. His goal is to provide evidence that dysfunctional macula densa cells are the root cause of glomerular disease.

It was an inspiring speech by a creative and dedicated researcher. Congratulations to Janos Peti-Peterdi for winning the Young Investigator Award.

State of the Art Lecture by Don Ingber

He is the leader of the Wyss Institute. The mission of the Wyss Institute is to fix a broken drug development system that spends too much money developing and testing drugs that don’t pan out. He laid much of the dysfunction at the feet of bad animal models and simplistic tissue cultures. The Wyss Institute sounds like a publishing powerhouse. Ingber claims that they have published a study in Nature and Science every month for the last 14 months. They also have over 1,000 patents and 1,400 papers.

His solution for the problem of drug development is biomimetric microsystems than simulate organ systems. Essentially they build mechanical simulations at the nano scale by combining microchip lithography technology with tissue engineering.

His first example is a lung on a chip. Detailed in Science back in 2010. Lungs are good place to start, because they are relatively simple: a single layer of endothelium separating blood from gas. The key to making this work was adding cyclic expansion and contraction to provide stretch and shear forces on the cells to bring out accurate behavior. This lung simulator behaved just like intact alveoli and even allowed for a compelling pneumonia simulation with translocation of PMNs. The lung machine, patent number 8,647,861, is now in the New York Museum of Modern Art.

The alveoli work then lead to a machine to simulate small airways. These are more complex than alveoli as they have cilia, and mucus producing cells. This allows them to simulate COPD, asthma and smoking related pathology. He claims there are no good animal models of COPD so this is a unique opportunity for drug development for a major disease.

He then went on to describe the work they have done on the GI tract and liver. One of the common themes is that to make the machines be accurate organ simulators requires motion:

  • In the lungs it was breathing
  • In the GI tract it was peristalsis
  • In the liver it was flow
  • In the kidney it was flow

The kidney model was initially limited to tubules, but after two years of work they just achieved a breakthrough in glomeruli and are able to grow convincing podocytes. There is something really cool about Ingber talking about his podocytes allowing inulin to pass but be an effective barrier to albumin.

The next step is linking these organs together to be a body simulator, so that you can measure absorption in the gut machine, track metabolism in the liver machine and excretion in the kidney machine.

His website wyss.harvard.edu won a Webby in 2012. Their 5 word acceptance speech, “When Nature calls, we listen.”

 

That was the plenary sessions of Kidney Week 2015. An excellent collection of State of the Art lectures, and award winners.

 

Post by Dr. Joel Topf, AJKD Blog Advisory Board member.

Check out all of AJKD Blog’s coverage of Kidney Week 2015!

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