Archive for ‘Kidney Stone’

Researchers create 3D map of rod sensory cilium architecture affected by mutation

Researchers create 3D map of rod sensory cilium architecture affected by mutation

Using a new technique called cryo-electron tomography, two research teams at Baylor College of Medicine (www.bcm.edu) have created a three-dimensional map that gives a better understanding of how the architecture of the rod sensory cilium (part of one type of photoreceptor in the eye) is changed by genetic mutation and how that affects its ability to transport proteins as part of the light-sensing process.

Almost all mammalian cells have cilia. Some are motile and some are not. They play a central role in cellular operations, and when they are defective because of genetic mutations, people can go blind, have cognitive defects, develop kidney disease, grow too many fingers or toes or become obese. Such mutations cause cilia defects known in the aggregate as ciliopathies.

“The major significance of this report lies in our being able to, for the first time, look in three dimensions at the structural alterations in ciliopathies,” said Dr. Theodore G. Wensel (http://www.bcm.edu/biochem/index.cfm?pmid=3795), chair of biochemistry and molecular biology at BCM and corresponding author of the report that appears in the journal Cell (www.cell.com). The report is spotlighted on the issue’s cover.

In collaboration with the National Center for Macromolecular Imaging (http://ncmi.bcm.edu/ncmi/), led by Dr. Wah Chiu (http://www.bcm.edu/biochem/index.cfm?pmid=3715), professor of biochemistry and molecular biology at BCM, Wensel and his colleagues established such three dimensional images for cilia in three examples of mice known to have cilopathies.

These mice have genetic mutations that lead to defects in the structure of the rod outer segment. The rod outer segment is part of the photoreceptor in the retina called a rod. The rod outer segment contains photosensitive disk membranes that carry rhodopsin, the biological pigment in photoreceptor cells of the retina responsible for the first events that result in the perception of light.

Using cryo-electron tomography, the scientists compared the structures of the rod outer segment in the mutant mice to those in normal mice.

“This is one of the few places in the world where you could do this,” said Wensel. The Center, run by Chiu, has powerful cryo-electron microscopes that make tomography possible. To achieve the three-dimensional reconstruction, Dr. Juan T. Chang (http://www.bcm.edu/pda/index.cfm?PMID=8208) in Chiu’s Center froze the photoreceptors purified by then-graduate student Jared Gilliam in a special way that made it possible to perform electron microscopy. During the microscopy session, the frozen samples were carefully tilted allowing the researchers to take many two-dimensional images that were used in the computer reconstruction of the three-dimensional map.

The light-sensing outer segments of photoreceptors in the retina are connected to the machinery responsible for protein production in the inner segment by a thin cylindrical bundle of microtubules known as the connecting cilium.

“There is a huge flux of material from the inner segment to the outer segment of the photoreceptor,” said Wensel. “When there is a defect, then the animal or patient goes blind.”

The three-dimensional structure showed that there are vesicles (small sacs) tethered to membrane filaments.

“It looks as though these vesicles that are tethered contain material that will fuse to the plasma membrane and go up the membrane to the outer segment,” said Wensel.

In studies of a mouse model of a disease called Bardet Biedl syndrome, developed by the laboratory of Dr. James Lupski (http://www.bcm.edu/genetics/index.cfm?pmid=10944) professor of molecular and human genetics at BCM, Wensel and first author Gilliam saw something that was almost shocking – a huge accumulation of these vesicles. The Bardet Biedl genes contain the code for a BBsome that forms a membrane coat that makes transport possible through the connecting cilium to the outer coat.

“We would now surmise that the BBsome coat is required for fusion of the plasma membrane or transport up to the outer segment,” said Wensel. “It gives us a whole new model for how this works. We need to do more now to nail it down.”

“It suggests that aberrant trafficking of proteins is responsible for photoreceptor degeneration,” said Gilliam, who is now a postdoctoral associate at The University of Texas Health Science Center at Houston.

Source : http://www.news-medical.net/news/20121123/Researchers-create-3D-map-of-rod-sensory-cilium-architecture-affected-by-mutation.aspx

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Researchers create 3D map of rod sensory cilium architecture affected by mutation

Researchers create 3D map of rod sensory cilium architecture affected by mutation

Using a new technique called cryo-electron tomography, two research teams at Baylor College of Medicine (www.bcm.edu) have created a three-dimensional map that gives a better understanding of how the architecture of the rod sensory cilium (part of one type of photoreceptor in the eye) is changed by genetic mutation and how that affects its ability to transport proteins as part of the light-sensing process.

Almost all mammalian cells have cilia. Some are motile and some are not. They play a central role in cellular operations, and when they are defective because of genetic mutations, people can go blind, have cognitive defects, develop kidney disease, grow too many fingers or toes or become obese. Such mutations cause cilia defects known in the aggregate as ciliopathies.

“The major significance of this report lies in our being able to, for the first time, look in three dimensions at the structural alterations in ciliopathies,” said Dr. Theodore G. Wensel (http://www.bcm.edu/biochem/index.cfm?pmid=3795), chair of biochemistry and molecular biology at BCM and corresponding author of the report that appears in the journal Cell (www.cell.com). The report is spotlighted on the issue’s cover.

In collaboration with the National Center for Macromolecular Imaging (http://ncmi.bcm.edu/ncmi/), led by Dr. Wah Chiu (http://www.bcm.edu/biochem/index.cfm?pmid=3715), professor of biochemistry and molecular biology at BCM, Wensel and his colleagues established such three dimensional images for cilia in three examples of mice known to have cilopathies.

These mice have genetic mutations that lead to defects in the structure of the rod outer segment. The rod outer segment is part of the photoreceptor in the retina called a rod. The rod outer segment contains photosensitive disk membranes that carry rhodopsin, the biological pigment in photoreceptor cells of the retina responsible for the first events that result in the perception of light.

Using cryo-electron tomography, the scientists compared the structures of the rod outer segment in the mutant mice to those in normal mice.

“This is one of the few places in the world where you could do this,” said Wensel. The Center, run by Chiu, has powerful cryo-electron microscopes that make tomography possible. To achieve the three-dimensional reconstruction, Dr. Juan T. Chang (http://www.bcm.edu/pda/index.cfm?PMID=8208) in Chiu’s Center froze the photoreceptors purified by then-graduate student Jared Gilliam in a special way that made it possible to perform electron microscopy. During the microscopy session, the frozen samples were carefully tilted allowing the researchers to take many two-dimensional images that were used in the computer reconstruction of the three-dimensional map.

The light-sensing outer segments of photoreceptors in the retina are connected to the machinery responsible for protein production in the inner segment by a thin cylindrical bundle of microtubules known as the connecting cilium.

“There is a huge flux of material from the inner segment to the outer segment of the photoreceptor,” said Wensel. “When there is a defect, then the animal or patient goes blind.”

The three-dimensional structure showed that there are vesicles (small sacs) tethered to membrane filaments.

“It looks as though these vesicles that are tethered contain material that will fuse to the plasma membrane and go up the membrane to the outer segment,” said Wensel.

In studies of a mouse model of a disease called Bardet Biedl syndrome, developed by the laboratory of Dr. James Lupski (http://www.bcm.edu/genetics/index.cfm?pmid=10944) professor of molecular and human genetics at BCM, Wensel and first author Gilliam saw something that was almost shocking – a huge accumulation of these vesicles. The Bardet Biedl genes contain the code for a BBsome that forms a membrane coat that makes transport possible through the connecting cilium to the outer coat.

“We would now surmise that the BBsome coat is required for fusion of the plasma membrane or transport up to the outer segment,” said Wensel. “It gives us a whole new model for how this works. We need to do more now to nail it down.”

“It suggests that aberrant trafficking of proteins is responsible for photoreceptor degeneration,” said Gilliam, who is now a postdoctoral associate at The University of Texas Health Science Center at Houston.

Source : http://www.news-medical.net/news/20121123/Researchers-create-3D-map-of-rod-sensory-cilium-architecture-affected-by-mutation.aspx

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Kidney Cell Layer Grown in Laboratory Environment

Kidney Cell Layer Grown in Laboratory Environment

Kidney Cell Layer Grown in Laboratory Environment

The key to this success is a new kind of bioactive synthetic membrane. This membrane, which is developed at TU/e, has a structure resembling that of human basement membrane in the kidney. The ultimate aim of the scientists is to be able to grow whole biological artificial kidneys using autologous cells.

Kidney function is vitally important; for example the kidneys filter toxic metabolic waste products from the blood. Many people suffer from kidney failure, and more than 6000 people in the Netherlands (and over 350.000 in the United States) require artificial blood cleansing by kidney dialysis. Unfortunately this technique is not yet perfect: its purifying capacity is only 15 to 20% of that of healthy kidneys. Scientists are therefore looking for ways to restore kidney function using cultured kidney cells.

Nanofibers

Dr. Patricia Dankers, who has a central role in this research, explains that there are two essential characteristics of the synthetic membranes on which she cultures the kidney cells: their structure and their bioactivity. Structurally the membranes consist of nanofibers that are part of larger, micrometer-size fibers. This structure resembles that of a human kidney membrane. The kidney cells grow on this fibrous membrane, but cease to function after several days. Dankers was only able to maintain the cell function by adding bioactive signals to the synthetic membrane.

Signals

These signals enable the kidney cells to adhere and survive, and ensure that they continue to function. Dankers was able to achieve this by supramolecular attachment of bioactive peptides (small pieces of protein) to the synthetic membranes. To do this Dankers used a kind of ‘Velcro’ binding, also relatively recently developed at TU/e. This allows the bioactive groups to be coupled to the membrane without the complex processes that were formerly needed.

Better dialysis

The researchers now intend to work on a biological artificial kidney to supplement the existing dialysis systems. This will increase the quality of dialysis treatment, because the kidney cells are able to filter exactly the right substances out of the blood. Dankers also hopes that the kidney cells will, in the longer term, produce hormones made by normal kidneys. These are important in making red blood cells, for example. However she is unable to say how long it may take to reach this stage. “It’s difficult to predict, and we don’t want to create unrealistic expectations.”

After that the next step will be to develop a mobile dialysis system, so that kidney patients do not repeatedly have to visit hospitals. “Our ultimate dream is to make an implantable, living artificial kidney”, says Dankers.

The results are published in two articles in scientific journals. The research about the fibrous structure appears in the November edition of Macromolecular Bioscience, while the addition of bioactive signals is published in Biomaterials (DOI: 10.1016/j.biomaterials.2010.09.020).

This animation video from the animation studio of ICMS (Institute for Complex Molecular Systems) shows the most important processes in this research.

Dankers (TU/e department of Biomedical Engineering) carried out her research together with the University Medical Center Groningen (UMCG), the Nierstichting (Kidney Foundation), SupraPolix BV and the TU/e Institute for Complex Molecular Systems (ICMS). The follow-up research project is being carried out, among others, through the Biomedical Materials (BMM) program of the BioKid consortium, in which a number of Dutch universities and academic medical centers, two companies and the Nierstichting are working together.

A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypothesized that this can be improved by electro-spun, supramolecular polymer membranes which show clear benefits in ease of processability. We found that after 7 d, in comparison to conventional microporous membranes, renal tubular cells cultured on top of our fibrous supramolecular membranes formed polarized monolayers, which is prerequisite for a well-functioning bioartificial kidney. In future, these supramolecular membranes allow for incorporation of peptides that may increase cell function even further.

Dutch scientists at Eindhoven University of Technology (TU/e) and the University Medical Center Groningen managed to culture a layer of kidney cells using a locally developed bioactive synthetic membrane resembling human basement membrane in the kidney. It is hoped that this research will lead to lab-grown artificial kidneys using autologous cells.

Dr. Patricia Dankers, who has a central role in this research, explains that there are two essential characteristics of the synthetic membranes on which she cultures the kidney cells: their structure and their bioactivity. Structurally the membranes consist of nanofibers that are part of larger, micrometer-size fibers. This structure resembles that of a human kidney membrane. The kidney cells grow on this fibrous membrane, but cease to function after several days. Dankers was only able to maintain the cell function by adding bioactive signals to the synthetic membrane.

These signals enable the kidney cells to adhere and survive, and ensure that they continue to function. Dankers was able to achieve this by supramolecular attachment of bioactive peptides (small pieces of protein) to the synthetic membranes. To do this Dankers used a kind of ‘Velcro’ binding, also relatively recently developed at TU/e. This allows the bioactive groups to be coupled to the membrane without the complex processes that were formerly needed.

The researchers now intend to work on a biological artificial kidney to supplement the existing dialysis systems. This will increase the quality of dialysis treatment, because the kidney cells are able to filter exactly the right substances out of the blood. Dankers also hopes that the kidney cells will, in the longer term, produce hormones made by normal kidneys.

Source : http://w3.tue.nl/en/news/news_article/?tx_ttnews[tt_news]=10191&tx_ttnews[backPid]=361&cHash=08e3981bc6

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Ardian’s Hypertension Treatment Outperforms Traditional Medical Treatment in Clinical Trial

Ardian’s Hypertension Treatment Outperforms Traditional Medical Treatment in Clinical Trial

Ardian’s Hypertension Treatment Outperforms Traditional Medical Treatment in Clinical Trial

CHICAGO–(BUSINESS WIRE)–Late-breaking data presented today at the American Heart Association Scientific Sessions 2010 and simultaneously published in The Lancet demonstrated that the landmark Symplicity HTN-2 trial evaluating Ardian’s Symplicity® Catheter System™ met its primary endpoint.

“Combined with findings from the earlier Symplicity HTN-1 study, which demonstrated the safety and durability of the therapy out to two years, these results fuel our enthusiasm for the potential of this treatment to significantly impact the standard of care for the large number of patients suffering from this disease.”

The study showed that, after six months, patients treated with Ardian’s device experienced an average drop in blood pressure of 32/12 mmHg compared to an increase in blood pressure of 1/0 mmHg in the control group of patients treated with medical therapy alone (p<0.0001).

Research has shown that each incremental 20/10 mmHg increase of blood pressure above normal levels is associated with a doubling of cardiovascular mortality over a 10 year period1 and that reducing systolic blood pressure by as little as 5 mmHg can reduce the risk of stroke by almost 30 percent.2

“The impressive results of this study show that Ardian’s Symplicity System has the potential to become a truly revolutionary treatment,” said Murray Esler, M.D., Ph.D., principal investigator of the trial and associate director of the Baker IDI Heart and Diabetes Institute of Melbourne, Australia. “Combined with findings from the earlier Symplicity HTN-1 study, which demonstrated the safety and durability of the therapy out to two years, these results fuel our enthusiasm for the potential of this treatment to significantly impact the standard of care for the large number of patients suffering from this disease.”

The Symplicity HTN-2 trial was an international, multi-center, prospective, randomized, controlled study of the safety and effectiveness of renal denervation in patients with uncontrolled hypertension. One hundred-six patients were enrolled from 24 investigational sites. At baseline the randomized treatment and control patients had similar high blood pressures: 178/97 mmHg and 178/98 mmHg, respectively, despite both receiving an average daily regimen of five antihypertensive medications. After six months, the average blood pressure of the renal denervation group was reduced to 146/85 mmHg, compared to an average blood pressure of 179/98 mmHg for the control group.

The study also found that the therapy was safe, with no serious device or procedure-related events, no cardiovascular complications and no kidney-related complications.

“Hypertension is often described as a ‘silent killer’ as it frequently has no symptoms yet significantly increases a patient’s risk of heart attack, stroke or death,” said Andrew Cleeland, president and CEO of Ardian, Inc. “Positive data from the Symplicity HTN-2 trial reinforces our belief that this treatment has the potential to significantly improve the quality of life for the millions of people around the world with uncontrolled hypertension. We look forward to beginning a U.S. pivotal study of the device to gather data needed to bring this promising therapy to patients and physicians in the United States.”

About the Symplicity® Catheter System™

The Symplicity Catheter System is used to perform a procedure termed renal denervation (RDN). In a straight-forward endovascular procedure, similar to an angioplasty, the physician inserts the small, flexible Symplicity Catheter into the femoral artery in the upper thigh and threads it into the renal artery. Once in place within the renal artery, the device delivers low-power RF energy to deactivate the surrounding renal sympathetic nerves. This, in turn, reduces hyper-activation of the sympathetic nervous system, which is often the cause of chronic hypertension. The one-time procedure aims to permanently reduce blood pressure. RDN may also allow patients to reduce or eliminate the need for lifelong antihypertensive medications.

In addition to hypertension, the therapy may hold promise for treating heart failure, diabetes and chronic kidney disease, conditions also characterized by elevated sympathetic nerve activity. The Symplicity Catheter System has received CE Mark approval in the European Union and is investigational in the United States. Visit http://www.ardian.com/patients/symplicity.shtml to view an animation of the device and the procedure.

About Hypertension

Though it has no symptoms, hypertension (high blood pressure) is the number one risk factor for premature death worldwide, affecting about one in three adults.3 Nearly half of Europeans suffer from hypertension4 and in the United States, approximately 75 million people are affected, only two-thirds of whom are treated.5 Of those receiving treatment, approximately half are not achieving target blood pressure levels. The medications often prescribed for hypertension must be taken daily for the duration of a patient’s life, can be costly, and often result in side effects that can negatively impact quality of life. Globally, the estimated annual healthcare expenditure directly related to hypertension is approximately $500 billion.6

About Ardian

Privately held Ardian Inc., based in Mountain View, Calif., develops catheter-based therapies to treat hypertension and related conditions. Ardian is the eighth company created by The Foundry, a leading medical device incubator based in Menlo Park, Calif. Ardian’s investors include Morgenthaler Ventures, Advanced Technology Ventures, Split Rock Partners, Medtronic and Emergent Medical Partners. For more information, please visit www.ardian.com.

Mountain View, CA based Ardian Inc. has announced the results of a six month study which evaluated the company’s Symplicity Catheter System for treatment of chronic drug resistant hypertension. The study compared the outcomes of patients taking three or more antihypertensive drugs to those treated with the Symplicity. The results of the study, reported in the Lancet, demonstrated that a six month treatment with Ardian’s technology proved more effective than traditional medical treatment in patients with sustained grade 2 hypertension (baseline SBP of 160 mm Hg or more). The Symplicity System is a catheter-based low-power radiofrequency (RF) renal denervation device, thought to permanently treat hypertension by reducing or eliminating the sympathetic innervation of the renal arteries, hence “reducing both the pathologic central sympathetic drive to the kidney and the renal contribution to central sympathetic hyperactivity.”

More from the press release:

q4gwr Ardians Hypertension Treatment Outperforms Traditional Medical Treatment in Clinical Trial

The Symplicity HTN-2 trial was an international, multi-center, prospective, randomized, controlled study of the safety and effectiveness of renal denervation in patients with uncontrolled hypertension. One hundred-six patients were enrolled from 24 investigational sites. At baseline the randomized treatment and control patients had similar high blood pressures: 178/97 mmHg and 178/98 mmHg, respectively, despite both receiving an average daily regimen of five antihypertensive medications. After six months, the average blood pressure of the renal denervation group was reduced to 146/85 mmHg, compared to an average blood pressure of 179/98 mmHg for the control group.

The study also found that the therapy was safe, with no serious device or procedure-related events, no cardiovascular complications and no kidney-related complications.

Source : http://www.businesswire.com/news/home/20101117005602/en

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Artificial Organ Waiting List… Coming Soon to a Hospital

Artificial Organ Waiting List… Coming Soon to a Hospital

Artificial Organ Waiting List… Coming Soon to a Hospital

A $750,000 gift from the John and Marcia Goldman Foundation is spurring a UCSF-led effort to create the first implantable artificial kidney for patients with kidney failure.

The new funds, which augment a $2.25 million grant for the project from the National Institutes of Health (NIH) this summer, will enable the team of bioengineers, physicians and scientists to conduct the critical research needed to bring the proposed device to clinical trials by 2017.

“Kidney failure takes a terrible toll on the world, both economically and in human suffering,” said Shuvo Roy, PhD, an associate professor in the UCSF School of Pharmacy who is leading the Kidney Project through the UCSF Department of Bioengineering & Therapeutic Sciences. “These funds are a critical step in helping us move this project forward more quickly and ultimately bring real solutions to patients throughout the world.”

Related Stories:

UCSF Unveils Model for Implantable Artificial Kidney to Replace Dialysis

UCSF Artificial Kidney Project Tapped for Accelerated FDA Program

Working with the project’s medical director, William Fissell, MD, at Vanderbilt University, UCSF’s Roy is coordinating researchers in nine institutions nationwide to create an implantable device that aims to mimic the filtration functions of a kidney, as well as its ability to maintain water and salt balances, produce Vitamin D, and regulate blood pressure and pH.

Roy estimates that the project will require an additional $13 million to bring that technology through the range of tests needed to enter clinical trials in humans.

The Kidney Project has been identified as a campus priority by UCSF and the UCSF School of Pharmacy for its potential to develop a breakthrough therapy to help solve a pressing health need. The school focuses on therapeutics, including medical devices and diagnostic tests, in addition to medications.

The Goldmans said they contributed to this unique research because of the project’s specific goal of addressing the dire shortage of donated kidneys and eliminating the need for dialysis.

“We know how debilitating dialysis is, and how few options are available for people with kidney failure,” said Marcia Goldman, who directed the gift with her husband through the John and Marcia Goldman Foundation. “The opportunity to be part of a potential solution of this scale was very appealing to us.”

Roughly 2 million people worldwide live with end-stage renal disease (ESRD), commonly known as chronic kidney failure, including 600,000 Americans — a figure that is rising 5 percent per year in lockstep with the growing rate of diabetes. The disease is best treated via a kidney transplant, yet fewer than 18,000 of the 93,000 people on the transplant waiting list will actually receive an organ this year, and those who do are likely to need a replacement within 10 years.

Shuvo Roy, PhD

Shuvo Roy, PhD

As a result, roughly 400,000 Americans with ESRD survive on dialysis, which comes at a high price: the U.S. Medicare system spends upwards of $29 billion per year, or 6 percent of its total budget, to treat kidney failure, including $24 billion each year to pay for dialysis. Only 34 percent of dialysis patients survive beyond five years.

Silicon Technology Used for Nano-Filter

The UCSF team has used silicon technology from the computer industry to design a nano-filter for the first compartment of the device, which would offer the same level of filtration as dialysis in a box smaller than a coffee cup. A second compartment would hold live kidney cells that perform the other biological actions of a real kidney.

The entire device would be implanted in the abdomen and powered by the body’s blood pressure, without a need for external pumps or tubes. The device also is designed to be used without the immunosuppressant drugs needed in transplants.

Earlier this year, the project was selected by the U.S. Food and Drug Administration (FDA) as one of the first three pilots for a collaborative FDA review process, which aims to address potential regulatory obstacles for the device up front, before it enters the approval process. The Kidney Project was chosen for its transformative potential in treating chronic kidney failure, a major health concern.

The Goldman support is the largest philanthropic grant to date for the project, which has drawn support from a number of individuals throughout the world, as well as grants from the NIH, NASA and the U.S. Department of Defense.

The UCSF School of Pharmacy is the nation’s premier, graduate-level pharmacy school, the oldest of its kind in the western United States, and a wellspring for discovery and innovation in the therapeutic sciences, education, and the pharmaceutical care of patients. Go here for more information.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. Visit www.ucsf.edu.

End stage renal disease is a devastating condition in which dialysis may help prolong life, but the only real cure is a kidney transplant. The pioneering of the kidney transplant has saved countless numbers of lives, however end-stage renal disease continues to grow in prevalence and the supply of kidneys remains limited. Patients wait for years to obtain kidneys, and even once a kidney is finally transplanted patients face a lifetime of immunosuppressive drugs and fears about the donor kidney being rejected.

bbb2fg8l UCSFs Artificial Kidney Protoype UnveiledUCSF has been working on an ambitious project to create an artificial kidney using a combination of tissue engineering and MEMS (microelectromechanical systems) technology. The scientists hope that one day this device can actually be used in lieu of a kidney transplant and not just as a stop-gap measure. The device has been shown to be effective in a larger external version, and as an implantable animal model.

Here is more from the press release:

The device, which would include thousands of microscopic filters as well as a bioreactor to mimic the metabolic and water-balancing roles of a real kidney, is being developed in a collaborative effort by engineers, biologists and physicians nationwide, led by Shuvo Roy in the UCSF Department of Bioengineering and Therapeutic Sciences.

The treatment has been proven to work for the sickest patients using a room-sized external model developed by a team member in Michigan. Roy’s goal is to apply silicon fabrication technology, along with specially engineered compartments for live kidney cells, to shrink that large-scale technology into a device the size of a coffee cup. The device would then be implanted in the body without the need for immune suppressant medications, allowing the patient to live a more normal life.

The team has established the feasibility of an implantable model in animal models and plans to be ready for clinical trials in five to seven years.

The two-stage system uses a hemofilter to remove toxins from the blood, while applying recent advances in tissue engineering to grow renal tubule cells to provide other biological functions of a healthy kidney. The process relies on the body’s blood pressure to perform filtration without needing pumps or an electrical power supply.

The Kidney Project at UCSF, supported by funds courtesy John and Marcia Goldman Foundation and the NIH, is identified as a “transformative potential in treating chronic kidney failure.” Approximately 2 million people worldwide including 600,000 Americans suffer from chronic kidney failure and the numbers are growing rapidly partly due to the growing rate of diabetes. Dialysis, a very costly “solution,” is the primary form of treatment because fewer than 19% of people on the transplant list receive an organ and will need one or more replacements within a lifetime.

The Kidney Project is focused on a compartmented device which utilizes a silicone nano-filter in the first compartment to separate fluid and wastes, while keeping normal proteins and cells in the bloodstream. The second compartment would perform the other biological actions of a real kidney. The device is designed as an implant for the abdomen which attaches to the circulatory system and is powered by blood pressure – advantageous because electrical power, external pumps and / or tubes are unneeded. Even more important is the lack of dependency on immunosuppressant drugs which are necessary for transplants.

The research team is targeting clinical trials of the device in humans by 2017.

Source : http://www.ucsf.edu/news/2012/10/12810/artificial-kidney-project-ucsf-receives-3-million-new-funding

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Simple assay to improve treatment for idiopathic membranous nephropathy

Simple assay to improve treatment for idiopathic membranous nephropathy

Simple blood tests could help physicians decide which patients with a particular autoimmune kidney disease can forgo potentially toxic medications and which need to be treated, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

Idiopathic membranous nephropathy is an autoimmune kidney disease that leads to kidney failure in at least half of patients if left untreated. Immunosuppressive therapy is effective, but toxic. “It is unclear who should be treated, when treatment should be started, and how long treatment should be continued. We need better tools to aid decision-making,” said Julia Hofstra, MD, PhD (Radboud University Nijmegen Medical Center, in The Netherlands).

Researchers have recently identified antibodies—called antiPLA2R autoantibodies—that form and damage the kidneys when the disease develops. Clinicians do not have a standard technique for measuring these autoantibodies nor do they know whether autoantibody levels provide any information about the severity of patients’ disease.

Hofstra, in collaboration with Hanna Debiec, PhD (Institut National de la Santé et de la Recherche Médicale, in France), Paul Brenchley, PhD (University of Manchester, in the United Kingdom), and others compared two different blood tests (called IIFT and ELISA) to measure antiPLA2R autoantibodies in 117 patients with idiopathic membranous nephropathy.

Among the major findings:

•74% of patients tested positive for antiPLA2R antibodies by IIFT and 72% tested positive by ELISA.

•Concordance between both tests was excellent, with 94% agreement.

•Antibody levels significantly correlated with the severity of patients’ disease.

•Spontaneous remissions occurred much less frequently among patients with high antibody levels (38% versus 4% in the lowest and highest groups, respectively).

The findings reveal high agreement between IIFT and ELISA measurements of antiPLA2R antibody levels and highlight the important role of these antibodies in idiopathic membranous nephropathy, given the relationships between antiPLA2R levels, disease severity, and remission rates.

“The data provide hope that in the near future, antiPLA2R antibodies can be detected with a simple assay and measuring the antibody levels may improve optimal treatment in patients with idiopathic membranous nephropathy,” said Dr. Hofstra.

Source : http://www.news-medical.net/news/20120907/Simple-assay-to-improve-treatment-for-idiopathic-membranous-nephropathy.aspx

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Test to identify potentially deadly calcium deposits in tissues and blood vessels

Test to identify potentially deadly calcium deposits in tissues and blood vessels

A new test could help identify and treat individuals at risk of developing potentially deadly calcium deposits in their tissues and blood vessels, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). Heart disease is the number one killer of patients with chronic kidney disease (CKD), and vascular calcification is thought to play a major role.

Patients with CKD often have abnormally high blood calcium levels due to their compromised kidney function and the effects of commonly used medications. An accumulation of excess calcium can cause potentially deadly calcifications in tissues and blood vessels; however, physicians currently have no tools to determine an individual’s calcification risk.

Now Andreas Pasch, MD (University Hospital and University of Bern, Inselspital, in Switzerland) and his colleagues have developed the first test capable of measuring the propensity for calcification to occur in blood. Using their new assay, the investigators found that both the blood of mice deficient in a protein that inhibits calcification and the blood of CKD patients on dialysis had a reduced ability to inhibit calcification. Blood from healthy volunteers did not.

“Our test may identify patients at risk for the development of calcification, may become an important tool for identifying and testing calcification inhibitors, and may provide the basis for treatment monitoring in patients who receive such inhibitors,” said Dr. Pasch.

Source : http://www.news-medical.net/news/20120907/Test-to-identify-potentially-deadly-calcium-deposits-in-tissues-and-blood-vessels.aspx

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Finding, Pushing Kidney Stones Using Ultrasound

Finding, Pushing Kidney Stones Using Ultrasound

Finding, Pushing Kidney Stones Using Ultrasound

Just the mention of kidney stones can cause a person to cringe. They are often painful and sometimes difficult to remove, and 10 percent of the population will suffer from them. In space, the risk of developing kidney stones is exacerbated due to environmental conditions. The health risk is compounded by the fact that resource limitations and distance from Earth could restrict treatment options.

Scientists with the National Space Biomedical Research Institute (NSBRI) are developing an ultrasound technology that could overcome some medical care challenges associated with kidney stone treatment. The new technology detects stones with advanced ultrasound imaging based on a process called “Twinkling Artifact” and provides treatment by “pushing” the stone with focused ultrasound. This technology could not only be beneficial for health care in space, but could also alter the treatment of kidney stones on Earth.

The project is led by NSBRI Smart Medical Systems and Technology Team Principal Investigator Dr. Lawrence Crum and Co-Investigator Dr. Michael Bailey; both are researchers at the Applied Physics Laboratory at the University of Washington (APL-UW). Bailey said their technology is based on equipment currently available.

“We have a diagnostic ultrasound machine that has enhanced capability to image kidney stones in the body,” said Bailey, a principal engineer at APL-UW. “We also have a capability that uses ultrasound waves coming right through the skin to push small stones or pieces of stones toward the exit of the kidney, so they will naturally pass, avoiding surgery.”

Currently on Earth, the preferred removal method is for patients to drink water to encourage the stones to pass naturally, but this does not always work, and surgery is often the only option. In space, the threat from kidney stones is greater due to the difficulty of keeping astronauts fully hydrated. Another factor is that bones demineralize in the reduced-gravity environment of space, dumping salts into the blood and eventually into the urine. The elevated concentration of salts in the urine is a risk factor for stones.

Crum, who is a principal physicist at APL-UW, said kidney stones could be a serious problem on a long-duration mission. “It is possible that if a human were in a space exploration environment and could not easily return to Earth, such as a mission to an asteroid or Mars, kidney stones could be a dangerous situation,” Crum said. “We want to prepare for this risk by having a readily available treatment, such as pushing the stone via ultrasound.”

Before a stone can be pushed, it needs to be located. Standard ultrasound machines have a black and white imaging mode called B-mode that creates a picture of the anatomy. They also have a Doppler mode that specifically displays blood flow and the motion of the blood within tissue in color. In Doppler mode a kidney stone can appear brightly colored and twinkling. The reason for this is unknown, but Crum and Bailey are working to understand what causes the Twinkling Artifact image.

“At the same time, we have gone beyond Twinkling Artifact and utilized what we know with some other knowledge about kidney stones to create specific modes for kidney stones,” Bailey said. “We present the stone in a way that looks like it is twinkling in an image in which the anatomy is black and white, with one brightly colored stone or multiple colored stones.”

Once the stones are located, the ultrasound machine operator can select a stone to target, and then, with a simple push of a button, send a focused ultrasound wave, about half a millimeter in width, to move the stone toward the kidney’s exit. The stone moves about one centimeter per second. In addition to being an option to surgery, the technology can be used to “clean up” after surgery.

“There are always residual fragments left behind after surgery,” Bailey said. “Fifty percent of those patients will be back within five years for treatment. We can help those fragments pass.”

The ultrasound technology being developed for NSBRI by Crum and Bailey is not limited to kidney stone detection and removal. The technology can also be used to stop internal bleeding and ablate (or destroy) tumors. Crum said the research group has innovative plans for the technology. “We envision a platform technology that has open architecture, is software-based and can use ultrasound for a variety of applications,” he said. “Not just for diagnosis, but also for therapy.”

NSBRI’s research portfolio includes other projects seeking to develop smart medical systems and technologies, such as new uses for ultrasound, that provide health care to astronauts in space. Crum, who served eight years as an NSBRI Team Leader, said the innovative approaches to overcome the restrictive environment of space can make an impact on Earth.

“Space has demanded medical care technology that is versatile, low-cost and has restricted size. All of these required specifications for use in a space environment are now almost demanded by the general public,” Crum said. “One of the reasons that translation from one site to another is possible is because of NSBRI’s investment.”

The ultrasound work by Crum and Bailey has also received support from the Defense Advance Research Projects Agency, the National Institutes of Health, and the University of Washington and foundations associated with it to promote commercialization.

Ultrasound has been a welcome tool for many years to break up kidney stones, but finding the stones still requires radiograph or CT imaging. Researchers from the University of Washington and the National Space Biomedical Research Institute (NSBRI) believe they developed a method of detecting renal calculi using a modified diagnostic ultrasound equipment found in every modern hospital. Moreover, once detected, they are able to apply ultrasound in a controlled way so as to be able to push the stones in a desired direction. This may create a new treatment option, allowing physicians to guide stones toward the kidney exit that are refusing to pass naturally.

kidney stone pushed with ultrasound Finding, Pushing Kidney Stones Using Ultrasound

Detection of the stones is done thanks to the unexplained “twinkling artifact” phenomena that makes stones sparkle under Doppler ultrasound. Because X-rays are not used in detection, patients and clinicians would be less exposed to radiation, and diagnosis could be done faster and right at the point of care.

From a NSBRI press release:

“At the same time, we have gone beyond Twinkling Artifact and utilized what we know with some other knowledge about kidney stones to create specific modes for kidney stones,” [Dr. Michael] Bailey said. “We present the stone in a way that looks like it is twinkling in an image in which the anatomy is black and white, with one brightly colored stone or multiple colored stones.”

Once the stones are located, the ultrasound machine operator can select a stone to target, and then, with a simple push of a button, send a focused ultrasound wave, about half a millimeter in width, to move the stone toward the kidney’s exit. The stone moves about one centimeter per second. In addition to being an option to surgery, the technology can be used to “clean up” after surgery.

“There are always residual fragments left behind after surgery,” Bailey said. “Fifty percent of those patients will be back within five years for treatment. We can help those fragments pass.”

The ultrasound technology being developed for NSBRI by [Dr. Lawrence] Crum and Bailey is not limited to kidney stone detection and removal. The technology can also be used to stop internal bleeding and ablate (or destroy) tumors. Crum said the research group has innovative plans for the technology. “We envision a platform technology that has open architecture, is software-based and can use ultrasound for a variety of applications,” he said. “Not just for diagnosis, but also for therapy.”

Source : http://www.nsbri.org/newsflash/indivArticle.asp?id=454&articleID=155

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