Study Finds Racial and Social Disparities in Kidney Allocation Among Young Transplant Recipients

 

• Among kidney transplant recipients younger than 40 years of age, African Americans and individuals with less education were more likely to receive lower-quality organs than Caucasians and those with college degrees.
• African Americans with higher education levels were not more likely to receive a lower-quality kidney than Caucasians with college degrees.

Newswise — Washington, — Among younger kidney transplant recipients, a disproportionate number of African Americans and individuals with less education receive organs that are of lower quality or are considered marginal, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN). The findings suggest that there are racial and social disparities in the allocation of transplanted organs that need to be addressed.

Older kidney disease patients who have a high risk of dying while on dialysis may benefit from accepting a so-called extended criteria donor (ECD) kidney—which is more likely to fail than a standard criteria donor kidney—rather than remaining on a transplant wait list. But younger patients and those with short wait times are usually better off holding out for a standard criteria donor kidney. Despite this, some young patients still end up receiving ECD kidneys.

Rajesh Mohandas MD, MPH, Mark Segal MD, PhD (University of Florida), and their colleagues looked to see if demographic factors play a role in whether younger patients accept ECD kidneys. They analyzed all first single-kidney transplants documented in the United States from 2000 to 2009 in patients 18 to 40 years of age and waitlisted less than three years.

Among the major findings:
• Of 13,615 ECD transplants, 591 (4.3%) kidneys went to recipients between 18 and 40 years of age who were waitlisted less than three years.
• African Americans were 1.7 times more likely to receive an ECD kidney than Caucasians.
• Individuals with less education were 2.3 times more likely to receive an ECD kidney than those with a college degree; however, African Americans with higher education levels were not more likely to receive such a lower-quality kidney than Caucasians with college degrees.

“To our knowledge, this is the first report showing that there are racial and social disparities in the quality of allocated transplanted organs. Understanding that such disparities exist is the essential first step to addressing inequalities in health care and to attempt to improve patient outcomes,” said Dr. Mohandas. He added that it is important to ensure that kidney transplant candidates are not just informed, but also educated about their choices.

Study co-authors include Michael Casey, MD, Robert Cook, MD, MPH, Kenneth Lamb, PhD, and Xuerong Wen, MS.

Disclosures: The authors reported no financial disclosures.

The article, entitled “Racial and Socioeconomic Disparities in the Allocation of Extended Criteria Donor Kidneys,” will appear online at http://cjasn.asnjournals.org/ on October 10, 2013, doi: 10.2215/CJN01430213.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

Founded in 1966, and with more than 14,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.

Recently published research by the founder of ClinMet and UC San Diego team demonstrates value of metabolomics based on urine to translational medicine

 

SAN DIEGO, Oct.11, 2013 - ClinMet announced today that researchers of the University of California, San Diego School of Medicine have published new research of metabolomics that uncovers a novel, feature and very consistent biochemical signature in urine associated with diabetic kidney disease. The results, which form a basis of the proprietary clinical metabolomics of ClinMet platform, have implications for the identification of biomarkers clinically useful for kidney function and to sharpen the development of drugs and clinical trials related to chronic kidney disease, as well as diabetes, obesity and cardiovascular disease.

The new research, authored by U.C. San Diego Professor and founder scientific ClinMet, Kumar Sharma, M.D., F.A.H.A (Director of the Center for translational medicine Renal Division of Nefrologia-hipertension and the Institute of Medicine of the metabolomics) and his colleagues, appears online in the journal of the American Society of Nephrology. ClinMet has an exclusive license to use this set of metabolites in the development of drugs and other applications, based on patents requested by UC San Diego.

The researchers quantified 94 metabolites in the urine in patients with diabetes (type 1 or type 2) and chronic kidney disease (CKD), subjects with diabetes but no kidney disease and healthy controls. They found that 13 of the metabolites were significantly different in people with disease compared with healthy controls (p-values between 10-3 to 10-18), and 12 of 13 was still highly significant in comparison with patients with type 1 or type 2 and not CKD. In addition, 12 of the 13 metabolites were linked to Mitochondrial Metabolism and suggested global suppression of mitochondrial activity in subjects with chronic kidney diseases in relation to healthy individuals. This conclusion is in sharp contrast to prevailing beliefs about excess activity mitochondrial having a causal relationship with diabetic complications. The conclusions based on urine metabolomics studies were independently validated based on protein and DNA analysis, indicating reduced mitochondrial contents in the kidneys of patients with diabetic nephropathy.

"It is evident from this study that urine and plasma-based metabolomics can be a rich source of biomarkers to understand and treat kidney disease diabetes and possibly related to cardiovascular complications," said Dr. Sharma. "This approach also offers direct insights into the biochemical pathways associated with kidney dysfunction".

Power of clinical metabolomics

"Genomics can help to predict the overall risk of disease or potential response of a patient to a drug, but you can not capture the effects that changes in diet, environmental factors or other diseases in the progression of the disease or improvement," said Yesh Subramanian, President, CEO and co-founder of ClinMet. "Clinical metabolomics, by contrast, allows us to quickly see biochemically what happens in the specific pathways of the disease over time and in the context of other factors that affect the health of the patient, including drug therapy. This makes clinical metabolomics a highly useful platform for research and translational drug development".

"We see clinical metabolomics allowing pharmaceutical and biotech clients to effectively apply the medicine precision today", said Mr. Subramanian. "The ability to predict which patients are likely to respond better to specific treatments holds immense promise for sharpening of phase 2 and 3 clinical trials now and improve the clinical medicine in the future".

About ClinMet (clinical metabolomics Inc.)

ClinMet, founded in 2011, is a privately held company headquartered in San Diego, CA that provides pharmaceutical companies with clinically relevant insights and useful data on the effectiveness of the medication, safety and mechanism of action using its proprietary platform urine biomarker metabolomics for diabetes, kidney disease, obesity, and cardiovascular disease. ClinMet applies its unique combination of clinical expertise, in-depth proprietary metabolomics experience and computer skills to improve the rate of speed and the success of drug development. The company helps drug developers efficiently transform compounds promising safe and effective medicines and to effectively develop and implement its strategy of companion Diagnostics.

ClinMet technology and clinical experience is based on the legacy of research of William Nyhan, M.D., Ph.d., founder of head of the biochemical genetics and laboratory of metabolomics and founding Chair of the Department of Pediatrics at UC San Diego. Dr. Nyhan, one of the founders of the field of metabolic diseases human and his team have developed many methods of diagnosis standard of gold of the mass spectrometry and analysis metabolomic which are used by the centres of excellence in human genetics and metabolism around the world. On the other hand, cientifico-fundador ClinMet, Kumar Sharma, is an expert recognized worldwide in diabetic nephropathy and translational research. He has conducted several studies milestone in diabetic nephropathy in a level of translational research and has dedicated his career to develop new therapies for patients with chronic kidney disease.

 

Boomboxes Amplify Predatory Bird Sounds and Are Used as Cues

 Using boomboxes to amplify predator bird sounds in the wild, University of Florida researchers have found that smaller birds listen to vocal cues to avoid areas populated by predators.

In her study, doctoral student Fangyuan Hua set up above-ground boomboxes mounted in camouflaged boxes on half-acre plots at the Ordway-Swisher Biological Station near Melrose.

Powered by car batteries, these boomboxes were programmed for four months to broadcast predator sounds according to a schedule that simulated when and how predators would normally call.

“Such broadcasting was to create the perception for forest birds that there was increased abundance of predators in the forest,” Hua said. “We were very interested in knowing whether forest birds that are prey to these predators would use such cues and respond by altering their decision about where to breed.”

The study looked at three types of predators and compared how their cues affected forest birds. It turned out that forest birds recognized vocal cues of the Eastern screech-owl, blue jay or Cooper’s hawk as indications of different threats: While different predator cues altered bird community make-up, their effects were distinctive.

Researchers determined that while some bird species clearly avoided plots with feared predators, other species seemed to alter their behavior to make themselves less conspicuous.

The study was published in the June issue of the Proceedings of the Royal Society B. It was co-authored by Kathryn Sieving, a professor in UF’s Department of Wildlife Ecology and Conservation and a co-chair of Hua’s dissertation committee. Robert Fletcher, an associate professor in the department of wildlife ecology and conservation, also co-chaired the dissertation panel. Robert Dorazio, a statistician with the U.S. Geological Survey’s Southeast Ecological Science Center in Gainesville, also helped write the paper.

“Results from this study are exciting because they support growing understanding that animals are using acoustic cues to make important survival decisions,” Sieving said. “Species actually listen to each other and predators’ calls to detect whether a predator is lurking nearby.”

While the findings apply to fear-based behaviors of birds, the study also reflects important trends in the science of human-environment interactions, she said.

This reflects an emerging field called “soundscape ecology,” which is focused on understanding how animals rely on natural sounds, Sieving said.

“So, we are learning that we can’t just protect natural habitat for wildlife, we have to protect natural soundscapes, too, which is difficult for us noisy humans with all of our planes and trucks and oil rigs and fracking machines,” she said.

 

Newly Discovered Gene Regulator Could Precisely Target Sickle Cell Disease

 A research team from Dana-Farber/Boston Children's Cancer and Blood Disorders Center and other institutions has discovered a new genetic target for potential therapy of sickle cell disease (SCD). The target, called an enhancer, controls a molecular switch in red blood cells called BCL11A that, in turn, regulates hemoglobin production.

The researchers—led by Daniel Bauer, MD, PhD, and Stuart Orkin, MD, of Dana-Farber/Boston Children's—reported their findings today in Science.

Prior work by Orkin and others has shown that when flipped off, BCL11A causes red blood cells to produce fetal hemoglobin that, in SCD patients, is unaffected by the sickle cell mutation and counteracts the deleterious effects of sickle hemoglobin. BCL11A is thus an attractive target for treating SCD.

The disease affects roughly 90,000 to 100,000 people in the United States and millions worldwide.

However, BCL11A plays important roles in other cell types, including the immune system's antibody-producing B cells, which raises concerns that targeting it directly in sickle cell patients could have unwanted consequences.

The discovery of this enhancer—which regulates BCL11A only in red blood cells—opens the door to targeting BCL11A in a more precise manner. Approaches that disable the enhancer would have the same end result of turning on fetal hemoglobin in red blood cells due to loss of BCL11A, but without off-target effects in other cell types.

The findings were spurred by the observation that some patients with SCD spontaneously produce higher levels of fetal hemoglobin and enjoy an improved prognosis. The researchers found that these individuals possess naturally occurring beneficial mutations that function to weaken the enhancer, turning BCL11A's activity down and allowing red blood cells to manufacture some fetal hemoglobin.

"This finding gives us a very specific target for sickle cell disease therapies," said Orkin, a leader of Dana-Farber/Boston Children's who serves as chairman of pediatric oncology at Dana-Farber Cancer Institute and associate chief of hematology/oncology at Boston Children's Hospital. "Coupled with recent advances in technologies for gene engineering in intact cells, it could lead to powerful ways of manipulating hemoglobin production and new treatment options for hemoglobin diseases."

"This is a very exciting study," said Feng Zhang, PhD, a molecular biologist and specialist in genome engineering at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, who was not involved in the study. "The findings suggest a potential new approach to treating sickle cell disease and related diseases, one that relies on nucleases to remove this regulatory region, rather than adding an exogenous gene as in classic gene therapy."

The study was supported by the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Doris Duke Charitable Foundation and the Howard Hughes Medical Institute.

The Dana-Farber/Boston Children’s Cancer and Blood Disorders Center brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since 1947. The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children’s Hospital and outpatient care at the Dana-Farber Cancer Institute’s Jimmy Fund Clinic. Dana-Farber/Boston Children’s brings the results of its pioneering research and clinical trials to patients’ bedsides through five clinical centers: the Blood Disorders Center, the Brain Tumor Center, the Hematologic Malignancies Center, the Solid Tumors Center, and the Stem Cell Transplant Center.

$1 5 M gift of Chobani supports dairy innovation

Newswise, ITHACA, New York - through the production of 692 million pounds of yogurt, New York surpassed California as the leading producer in the United States in 2012. A gift of $1.5 million from industry leader Chobani, a company based in new Berlin, N.y., will support research and training in dairy quality work force to help maintain the competitive advantage of New York.

"Today is an exciting day for Chobani - formalize and strengthen our commitment to food innovation and quality," said Chobani President and Chief Operating Officer David Denholm. "Cornell's Food Science Department is one of the leading programs of its kind in the world - a match for the role of Chobani Greek yogurt in."

The gift will benefit the dairy industry through staffing and training programs that support the quality dairy, leadership and innovation. The funding will be used to create opportunities on the site for teachers, students, and staff, which includes workshops of quality and food safety, as well as graduate student support initiatives of relevant research.

"This partnership will strengthen the science behind industry dairy and help us better achieve our land-grant mission to bring new information, technologies and a staff that is well prepared for this expansive industry, New York", said Kathryn J. Boor, Ronald P. Lynch Dean of the College of agriculture and life sciences. "Our goal is not only high quality dairy products, but also the economic growth in the communities that need it most."

Yogurt, including high-protein Greek yogurt, has become an economic power in the North of the State of New York, with New York firms now account for 70 percent of all sales of Greek yogurt. Founded in 2005, Chobani now has nearly 3,000 employees worldwide and sales of more than $1 trillion a year.

Horacio Valeiras and Bernard Saint-Donat Elected to Scripps Research Institute Board of Trustees

The Scripps Research Institute (TSRI) Board of Trustees has elected two new members: Horacio Valeiras of La Jolla, CA, who is managing partner of investment firm HAV Capital, and Bernard Saint-Donat of New York, who is president of financial consulting firm Saint-Donat & Co.

“We would like to offer Horacio and Bernard a warm welcome,” said Dick Gephardt, President/CEO of Gephardt Government Affairs and chairman of the Scripps Research Board of Trustees. "We are confident their contributions to the board will help foster the Institute's continued preeminence in biomedical research and graduate education."

“We are honored to have Horacio and Bernard join our board,” said Scripps Research President and CEO Michael A. Marletta. “Their deep financial and business experience will be invaluable to Scripps as we chart our future course. All of us enthusiastically look forward to working with them.”

 

At the La Jolla, California-based HAV Capital, Valeiras manages the start-up investment firm’s asset allocation, alternative investment and real estate services.

Previous positions include chief investment officer and managing director at Allianz Global Investors Capital and president of Nicholas Applegate Institutional Funds, both in the San Diego region, as well as senior positions with Morgan Stanley Investment Management, Miller, Anderson & Sherrerd and Credit Suisse First Boston. At the beginning of his career, Valeiras was also an instructor at the Massachusetts Institute of Technology and a research engineer for Chevron Research Company.

Valeiras holds two degrees in chemical engineering—a BS from Virginia Polytechnic Institute and State University and a master’s from the Massachusetts Institute of Technology—as well as an MBA in finance from the University of California, Berkeley. He is also a Chartered Financial Analyst (CFA).

A resident of La Jolla, Valeiras serves on the San Diego Foundation’s Board of Governors and on the boards of The Bishop’s School in La Jolla and InHand Electronics in Rockville, Maryland. He has also chaired the Virginia Tech Foundation board and is a past board member of the San Diego Rowing Club.

Bernard Saint-Donat

At his New York-based firm, Saint-Donat offers independent advice to families in areas including asset allocation, manager selection, estate planning, charitable giving and corporate advisory.

Previously, he held senior positions at Lehman Brothers, Lazard Frères & Company, Crédit Commercial de France (now part of HSBC) and La Compagnie Financière Edmond de Rothschild.

Saint-Donat, who holds a doctorate in mathematics from Harvard University and the University of Paris, has been a faculty member at Columbia and Yale Universities, a member of Harvard University’s Overseer’s Committee for Mathematics and founder and president of the Friends of the Institut des Hautes Études Scientifiques. He is currently chairman of the Friends of the Mathematics Department at Harvard.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation.

Urine Biomarkers Reveal Mitochondrial Dysfunction in Diabetic Kidney Disease

Newswise — Researchers at the University of California, San Diego School of Medicine have identified 13 metabolites – small molecules produced by cellular metabolism – that are significantly different in patients with diabetes and chronic kidney disease compared to healthy controls.

Twelve of the 13 metabolites are linked to mitochondrial function, suggesting that suppression of mitochondria – the powerhouses of cells – is a fundamental characteristic of diabetic kidney disease. The findings are published in the November edition of the Journal of the American Society of Nephology.

“This work provides strong evidence that reduced mitochondrial function is a dominant feature of human diabetic kidney disease,” said first author Kumar Sharma, MD, professor of medicine and director of the Center for Renal Translational Medicine at UC San Diego. “We found that a specific cellular pathway, AMPK-PGC1a, likely plays a key role to reduce mitochondrial function and content, which means that new therapeutic approaches that restore and increase mitochondrial function and content could ameliorate or perhaps even arrest chronic kidney disease.”

Diabetic kidney disease is the leading cause of end-stage kidney disease, which is the eighth leading cause of death in the United States and a major risk factor for cardiovascular disease, the nation’s leading killer. An estimated 26 million American adults have chronic kidney disease (CKD), with millions more at increased risk. These patients often require dialysis or an organ transplant.

The primary causes of CKD are high blood pressure and diabetes. Rates of both CKD and diabetes have risen dramatically in the last decade, particularly among people aged 65 and older. According to the National Kidney and Urologic Diseases Information Clearinghouse, the annual mortality rate for end-stage renal disease rose from 10,478 in 1980 to 90,118 in 2009, though it has declined somewhat in recent years.

After analyzing a total of 193 urine samples from patients with diabetes and CKD, diabetes but no CKD and healthy controls with neither condition, Sharma and colleagues quantified 94 metabolites in the samples. Thirteen metabolites were significantly different between patients with diabetes and CKD versus controls. Twelve remained significant when compared to patients with diabetes but not CKD. Twelve metabolites play a role in mitochondrial metabolism and were present in lower levels in patients with diabetes and CKD, suggesting that this major diabetic complication is at least partly the consequence of suppressed mitochondrial activity.

Sharma said measuring urine metabolites to detect and assess diabetic kidney disease is a major diagnostic step forward. “The urine metabolites can indicate the underlying function of the kidney at a biochemical and intracellular level,” he said, “and are well-conserved compared to many cell-based and protein measurements. Urine metabolomics also offers an opportunity to gauge effects of new treatments which will be an advantage to guide precision medicine.”

Co-authors include Bethany Karl and Maggie Diamond-Stanic, UCSD Institute of Metabolic Medicine, UCSD Center for Renal Translational Medicine and Division of Nephology-Hypertension, VA San Diego Healthcare System; Anna V. Mathew, UCSD Center for Renal Translational Medicine and Division of Nephology-Hypertension, VA San Diego Healthcare System, now at the University of Michigan; Jon A. Gangoiti, Bruce Barshop, William Nyhan, Biochemical Genetics Program and Institute of Metabolomic Medicine, UCSD; Christina L. Wassel and Minya Pu, Department of Family and Preventive Medicine, UCSD; Rintaro Saito, UCSD Institute of Metabolic Medicine, UCSD Center for Renal Translational Medicine and Division of Medical Genetics, UCSD; Shoba Sharma and Young You, UCSD Center for Renal Translational Medicine; Lin Wang, Mitochondrial and Metabolic Disease Center, UCSD; Maja T. Lindenmeyer and Clemens D. Cohen Division of Nephology, University Hospital Zurich, Switzerland; Carol Forsblom, Folkhalsan Institute of Genetics, Helsinki Finland; Wei Wu and Sanjay K. Nigam, Departments of Pediatrics and Cell and Molecular Medicine, UCSD; Joachim H. Ix, Division of Nephology-Hypertension, VA San Diego Healthcare System, UCSD Center for Renal Translational Medicine; Trey Ideker, Division of Medical Genetics, UCSD; Jeffrey B. Koop, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health; Per-Henrik Groop, Folkhalsan Institute of Genetics, Helsinki, Finland and IDI Baker Heart and Diabetes Institute, Melbourne, Australia; Loki Natarajan, UCSD Institute of Metabolomic Medicine and Department of Family and Preventive Medicine, UCSD; and Robert K. Naviaux, Mitochondrial and Metabolic Disease Center, UCSD, UCSD Institute of Metabolomic Medicine, Division of Medical Genetics, UCSD, Biochemical Genetics Program, UCSD.

Support for this research includes funding from the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, the Folkhalsan Research Foundation, the Wilhelm and Else Stockmann Foundation, the Liv och Halsa Foundation, the UCSD Christini Fund, the Wright Family Foundation, the Lennox Foundation, the Else Kroner-Fresnius Foundation, the Swiss National Center of Competence in Research and National Institutes of Health grants P41 GM103505 and P50 GM085764.