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Thu, Jul 13 8:45am · The curious link between tall men, small babies and kidney disease

We are born with a lifetime supply of something you may not think about every day: Nephrons.

Nephrons act as filters within the kidneys. They fine tune blood composition which in turn maintains our blood’s pressure, volume, and cleanliness. During pregnancy nephron development ends as a fetus reaches the last weeks in the womb. But unlike our standard ten fingers and toes, nephron numbers vary widely—from 200,000 to 2.5 million according to researchers. Genetic influence, maternal diet and health, as well as exposures to certain substances (antibiotics, alcohol, non-steroidal anti-inflammatory drugs) contribute to variation in nephron numbers, as does preterm birth. For this reason, birth weight is linked to nephron number.

Who cares about nephrons?

Nephrons do not often trouble my mind, but I came across an interesting statement in a recent New England Journal of Medicine paper. The senior author is Andrew Rule, M.D., a physician scientist within the division of nephrology and Hypertension at Mayo Clinic. The paper presents the case for assessing kidney health using two methods: total function of all the nephrons in the kidney or the average function of individual nephrons. The authors conclude that while they have similarities, the single nephron assessment (not standard of care) provides additional information on risks for kidney disease. But in the discussion there was another statement. It said, “… tall stature in a person who had a low birth weight (and for whom there may be low nephron endowment) has been linked to hypertension, which is risk factor for chronic kidney disease.”

Low birth weight in a baby can equal low nephron numbers and if that baby becomes a tall adult, possibly a higher risk for hypertension and chronic kidney disease? How does that work, I wondered.

Dr. Rule and coauthors cite two population-comparison studies in Sweden and Finland. In the Finland study, the highest hypertension risk was linked to low-birth-weight babies with continued accelerated growth past age seven. The Swedish paper found that males born at less than 7.2 pounds who were above 5’7” at age 50 had particularly high blood pressure compared to the other participants in the study. They add, however, that it was only problematic for those in the upper 1/3rd of body mass index (in this case, with BMI of 26 or higher).

The idea is this: In low birth weight babies the growth potential of the fetus was not reached. But as these infants catch up to their peers and attain full growth, those who grow taller or heavier (or both) than the norm may eventually outstrip their kidney’s innate filtering capacity. The result? Higher risk for chronic kidney disease and cardiovascular disease.

We should all care about nephrons.

So there you have it.

But what if you were a normal weight baby who has grown into an average height adult? Well, considering the kidney’s filtering ability seems to decline naturally after age 40, you’re not off the hook. For you, the National Kidney Foundation has a six step guide to kidney health and of course, you should always talk to your doctor for accurate assessment of your health, kidneys and otherwise.

Not sure about you, but I’m off to drink a nice glass of water in solute (chemistry joke!) to my hard working nephrons.

Sep 13, 2016 · Mayo Clinic Investigator Pushes for more Research on Osteoporosis Treatment


Osteoporotic bone

Crumbling infrastructure puts us at risk, especially if it’s our own internal, bony frame.

But patients dealing with thinning bone in hips and spine have a choice to make.

They can accept the inevitable slumping spine and eventual hip fracture with all its associated disability that is quite likely to occur, or roll the dice with complications from osteoporosis medications.

“Many, many patients who really need treatment are not taking it because of those concerns,” says Sundeep Khosla, M.D., practicing endocrinologist at Mayo Clinic.

Dr. Khosla is one of the top osteoporosis experts in the world and a past president of the American Society for Bone and Mineral Research and he is the society’s Louis V. Avioli lecturer this year at the groups annual conference.

Dr. Khosla has spent the last 28 years translating clinical need into discovery, and discovery into clinical therapy to meet the needs of patients experiencing bone loss. If there’s one thing he knows, it’s the progression of therapeutic options for osteoporosis patients.

Osteoporosis Treatment: Research Success, Patient Concern

Sundeep Khosla, M.D.

Sundeep Khosla, M.D.

“When I joined Mayo in 1988, I could offer calcium, vitamin D, estrogen, and that was pretty much it,” says Dr. Khosla.

But through collaboration and explorations of the fundamental nature of bone biology, Dr. Khosla has witnessed a blossoming of therapeutic options. From examining the spiral of spine and hip fractures leading to immobility, loss of independence, and premature death; came a host of options to turn off the cells that breakdown bone, slow bone loss and help prevent those first debilitating fractures.

Some patients and physicians, however, are concerned about these medications because of the relatively rare risks of jawbone deterioration, leg fracture, or abnormal heart rhythm.  Just when the future of osteoporosis therapy seemed bright, uncertainty has led to under-utilization of these therapies.

“I’ve been pushing to address this head on,” says Dr. Khosla, “because it has the potential to completely undo all of the wonderful research and translation that’s been done in the field.”

[Read Dr. Khosla’s editorial, “Crisis in the Treatment of Osteoporosis” in the Journal of Bone and Mineral Research.]

Researcher and Physician: The Patient’s Best Resource

Although research duties take up much of Dr. Khosla’s time, he is a clinician and actively sees patients. This allows him to identify the unmet patient needs and push his research team, and the field of endocrinology, to find solutions. It also allows him to separate likely findings from unlikely ones published in his field.

“The cross talk between what I’m doing in my research versus what I do in my clinical activities is important,” says Dr. Khosla. “It both helps to guide the research in new directions but also shuts off directions that don’t make sense from my understanding of what’s happening in the clinic.”

It’s this ability to see both his patients’ concerns and the clarity of the research that has led Dr. Khosla to push for more research on the subset of patients who will develop complications from osteoporosis treatment.

“I think the field has to be more proactive,” says Dr. Khosla, “and listen to what patients are saying and directly address the concerns they have.”

New Therapies on the Horizon

Some areas of research Dr. Khosla is investigating include better monitoring or adaptation of current bone density imaging to pick up the earliest signs of complications. Pharmacogenomics approaches may also help identify patients who may be at risk for complications. New bone remodeling pathways and new therapeutics in the drug discovery pipeline may also offer options for patients dealing with bone loss.

So while alleviating concerns over treatment complications poses a huge challenge for physicians, Dr. Khosla has high hopes for the field and its ability to get the answers patients need.

“The osteoporosis field over the past 25 plus years is really a great example of how a better understanding of the fundamental biology can drive new therapeutics,” says Dr. Khosla, “and it continues today.”

Sep 2, 2016 · Looking Back to Move Forward: Medical Surveys are Worth Your Time

Surveys can be a pain when you’re buying coffee or shoes, or surfing the web. Or maybe you find them fun—what color or literary character are you anyway?

But is the current survey deluge training us to ignore the ones that actually matter? Ask Ann Harris, associate director of Mayo Clinic’s Survey Research Center, and she’ll nod.

“Now everyone has a survey,” she says. “I think we’ve just over-surveyed people and our challenge coming up is how do we do this?”

Survey Says…

Mayo Clinic sends thousands of surveys a year to patients.

They flow out over the internet of course, but also by phone and (snail) mail. But the surveys don’t flow back in like they used to.

Ann Harris, associate director of Mayo Clinic's Survey Research Center

Ann Harris

“When I first started here,” says Harris, 25 years ago, “our response rates were 90 to 86 percent and they’re now closer to 50 to 60 percent depending on what the subject matter is.”

But regardless of the subject matter, health and health care-related surveys do matter. They help answer clinical questions that make a real difference in patients’ lives. For example:

  • After following high-risk patients who chose to have prophylactic mastectomies, investigators concluded that the risk of breast cancer is substantially reduced with this procedure.
  • Gelatin was added to the list of vaccine allergens after a case study led to a survey investigating the prevalence of this reaction.
  • Surveys of patients with congenital heart defects helped researchers find that it was important to intervene early, and plan subsequent operations over the patient’s lifetime, to decrease the total number of operations to increase survival. While a number of papers have been published using this survey data, the most recent publication is on heart transplant after Fontan procedure.
  • Lymphedema (swelling) in the lower body was more common than expected following surgery for endometrial (uterine) cancer. This finding contributed to practice changes aimed at reducing the risk of lymphedema in future patients.

…Your Responses are Important

So when if you get a survey request from Mayo Clinic, think about the people you help with your responses.

And thanks in advance for taking the time to respond.

Jul 26, 2016 · Mayo Clinic Research and Practice Offer New Drug Development Model

Success is built on top ofotp past failures.

But the costs associated with bringing a drug from idea to market run into the billions, making drug companies highly risk averse. And in the academic world, timelines or project shifts can slow down discovery, limiting the innovative potential of academic research.

Regardless, patients still need medical advances now, as well as a pipeline of innovation to improve treatment in the future.

Thomas “TC” Chung, Ph.D., associate director of the Mayo Clinic Center for Clinical and Translational Science (CCaTS) Office of Translation to Practice (OTP) at Mayo Clinic, has worked in both the academic and pharmaceutical worlds. Now he and the OTP help bring new products into clinical practice by connecting those worlds and rooting them firmly in clinical practice.

The OTP organizes strategic alliances, collaborations and partnerships between Mayo Clinic experts, who have experience in both academic research and clinical practice, and collaborators in industry and academia.

This week Dr. Chung will present a keynote talk about the innovative nature of the OTP model at the second International Conference on Clinical Sciences and Drug Discovery in Dundee,

Thomas "TC" Chung, Ph.D.

Thomas “TC” Chung, Ph.D.

Scotland. He was invited to speak because pharmaceutical companies have an innovation problem and Mayo Clinic offers one solution.

“Pharma companies over the last ten years have addressed the lack of innovation by accessing academic discoveries,” says Dr. Chung. “But there’s this valley of death converting the academic idea into something that can be further optimized and put on a development pathway. It’s that gap that Mayo Clinic is addressing.”

Unique Value

“Mayo’s sweet spot is preclinical research up to the first trials in man,” says Dr. Chung, slightly earlier than the phase two trial level, which is where pharma would like to step in. “But the key differentiator for someone in pharma or another collaborator is our translation boards.”

The OTP offers four main resources to internal and external collaborators: strategic collaborations, project management, novel technology pathways, and translation boards. The translation boards are comprised of Mayo Clinic researchers and clinical key opinion leaders who identify and vet projects.

“Mayo Translation boards have a real opportunity to address the four deficiencies of clinical trials,” says Dr. Chung, “Wrong population, wrong indication, wrong endpoint, and wrong pharmacology.” He says that collaborators and partners are often unaware of the depth board members offer, or the array of patient populations seen at Mayo Clinic.

Dr. Chung says, “It used to be that Mayo Clinic was brought in as sort of a passive clinical partner. Very quickly we asserted ourselves and asked questions, and we’ve changed the course of what was going to be the initial indication and clinical trial design three times in the last year.” Now says Dr. Chung, partners seek Mayo’s advice before getting too far down the pathway.

Case in Point

One example of how the OTP’s new model works can be seen in the quest to develop a drug that blocks cyclophilin B. This protein is abounds in two types of nervous system tumors, glioblastomas and medulloblastomas.

After Mayo Clinic researchers made the initial discovery, they partnered with an external group to test compounds that would bind to the target protein.  After testing about 385,000 compounds, 314 were advanced to review and ultimately 99 were selected for testing. [Read the full story in Discovery’s Edge, “Mayo Plugs into Drug Discovery”]

Currently the OTP is shepherding a full pipeline of drug discovery targets through various stages of development. And Dr. Chung has a message for those who will see his keynote speech this week:  “I’m saying we’re open for business and looking for active collaborators.”


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