TGen method isolates biospecimens for treatment of kidney disease

Exosomes could lead to less costly, less intrusive, more accurate diagnosis

2012-07-12

(Press-News.org) PHOENIX, Ariz. — July 11, 2012 — Researchers at the Translational Genomics Research Institute (TGen) have developed a method of isolating biospecimens that could lead to a less costly, less invasive and more accurate way of diagnosing chronic kidney disease, or CKD.

CKD is a major complication of diabetes, high blood pressure and a form of kidney disease known as glomerulonephritis, which is characterized by a progressive deterioration of the kidney's ability to filter waste from the blood.

TGen's customized procedure produced high amounts of protein-rich urinary exosomes, which are microscopic vesicles that could help scientists discover biomarkers leading to better diagnosis and treatment of CKD.

TGen's findings were published today in the journal Kidney International, part of the Nature Publishing Group.

"Our method of extracting exosomes from urine is simple, fast and easily adapted to clinical research, so we can ultimately help physicians provide better therapies for their patients," said Dr. Johanna DiStefano, Director of TGen's Diabetes, Cardiovascular and Metabolic Diseases Division, and the study's senior author.

The goal of the study was to identify the best exosome isolation methods for both proteomic analysis and RNA profiling of urinary exosomes as a first step for biomarker discovery.

"Unlike a kidney biopsy — an invasive and expensive procedure that provides only a small sample from one of two kidneys — urinary exosomes provide a full representation of the entire urinary system," said Dr. Lucrecia Alvarez, a post-doctoral fellow at TGen and the study's lead author.

TGen researchers evaluated six different methods of isolating exosomes, which can carry genetic material that, when profiled, can lead to biomarkers that could help identify patients with kidney disease.

One of the six methods in the study tested was based on a commercially available exosome precipitation reagent called ExoQuick-TC, which by itself did not yield high quantities or pure preparations of protein and RNA. However, the TGen modification of the protocol led to the highest yields of miRNA and mRNA, which can subsequently be used in downstream genetic profiling experiments.

CKD typically is diagnosed by detecting increased levels of urinary albumin, a protein that is filtered out of urine in healthy kidneys, or of serum creatinine, a breakdown product of creatine, which is an important part of muscle. Neither measurement, however, can accurately indicate the type of kidney injury or disease. Significant kidney disease can be present with minimal or even no change in levels of albumin or creatinine.

Biomarkers can serve as indicators of normal biological processes, disease development or response to therapeutic drugs.

"In contrast to renal biopsy, urine is an ideal source of biomarkers, particularly for diseases of the kidney and urinary tract because it can be conveniently collected in large amounts without risk to the patient," said Dr. DiStefano.

TGen's method of isolating exosomes in urine is an improvement over the use of today's mostly commonly used centrifuge processes. The current method is time-consuming, requires expensive equipment, can only process low volumes, and only a few samples of urine at a time, which makes it unsuitable for clinical use.

Another current method is ultrafiltration, which tends to retain unwanted proteins that interfere with the isolation of exosomal proteins.

"Faster and more efficient methods of isolating exosomes are needed," Dr. Alvarez said. "The method we developed provides strong potential for identifying and characterizing exosomal biomarkers from urine, which presents favorable implications for the diagnosis and treatment of chronic kidney disorders."

### The Roney Family Foundation funded this study: "Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers."

About TGen The Translational Genomics Research Institute (TGen) is a Phoenix-based non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.

Press Contact: Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

ELSE PRESS RELEASES FROM THIS DATE:

Trigger for past rapid sea level rise discovered

2012-07-12

The cause of rapid sea level rise in the past has been found by scientists at the University of Bristol using climate and ice sheet models. The process, named 'saddle-collapse', was found to be the cause of two rapid sea level rise events: the Meltwater pulse 1a (MWP1a) around 14,600 years ago and the '8,200 year' event. The research is published today in Nature. Using a climate model, Dr Lauren Gregoire of Bristol's School of Geographical Sciences and colleagues unearthed the series of events that led to saddle-collapse in which domes of ice over North America ...

Mayo Clinic finds switch that lets early lung cancer grow unchecked

2012-07-12

JACKSONVILLE, Fla. — Cellular change thought to happen only in late-stage cancers to help tumors spread also occurs in early-stage lung cancer as a way to bypass growth controls, say researchers at Mayo Clinic in Florida. The finding, reported in the July 11 issue of Science Translational Medicine, represents a new understanding of the extent of transformation that lung cancer — and likely many other tumor types — undergo early in disease development, the scientists say. They add that the discovery also points to a potential strategy to halt this process, known as epithelial-mesenchymal ...

Global Budget Payment Model lowers medical spending, improves quality

2012-07-12

A new study suggests that global budgets for health care, an alternative to the traditional fee-for-service model of reimbursement, can slow the growth of medical spending and improve the quality of care for patients. Researchers from Harvard Medical School's Department of Health Care Policy have analyzed claims data from Blue Cross Blue Shield of Massachusetts's Alternative Quality Contract (AQC), a global budget program in which 11 health care provider organizations were given a budget to care for patients who use BCBSMA insurance. Such a model contrasts with widely ...

OxyContin formula change has many abusers switching to heroin

2012-07-12

AUDIO: A change in the formula of a frequently abused prescription painkiller seems to have convinced many drug abusers to switch to a substance that’s potentially more dangerous. Washington university researchers... Click here for more information. A change in the formula of the frequently abused prescription painkiller OxyContin has many abusers switching to a drug that is potentially more dangerous, according to researchers at Washington University School of Medicine in ...

First detailed timeline established for brain's descent into Alzheimer's

2012-07-12

Scientists have assembled the most detailed chronology to date of the human brain's long, slow slide into full-blown Alzheimer's disease. The timeline, developed through research led by scientists at Washington University School of Medicine in St. Louis, appears July 11 in The New England Journal of Medicine. As part of an international research partnership known as the Dominantly Inherited Alzheimer's Network (DIAN), scientists at Washington University and elsewhere evaluated a variety of pre-symptomatic markers of Alzheimer's disease in 128 subjects from families ...

Menopausal hormone therapy associated with increased blood pressure

2012-07-12

Menopausal hormone therapy use is associated with higher odds of high blood pressure, according to research published July 11 in the open access journal PLoS ONE. Longer hormone use was associated with further increased odds of high blood pressure, although this association decreased with subjects' ages. The authors of the study, led by Joanne Lind of the University of Western Sydney, included 43,405 postmenopausal women in their study to identify the association. As Dr. Lind explains, the study shows that "longer use of menopausal hormone therapy is associated with ...

It's not just lunch

2012-07-12

Sharing a meal with a former romantic partner is more likely than other, non-food-related activities to make your current partner jealous, according to a study published July 11 in the open access journal PLoS ONE. The authors, led by Kevin Kniffin of Cornell University, asked undergraduate students to rate their jealousy in response to hypothetical scenarios involving their romantic partner engaging with a former partner, either by email, phone, coffee, or a meal. They found that a meal elicited the highest jealousy ratings, potentially pointing to the importance of ...

Personalized genomic medicine faces many hurdles

2012-07-12

When the human genome project was completed in 2003, some expected it to herald a new age of personalized genomic medicine, but the resulting single "reference" sequence has significant shortcomings for these applications and does not account for the actual variability in the human population, as reported in a study published July 11 in the open access journal PLoS ONE. Using genomic data from a large number of individuals, the authors of the study, led by Todd Smith of PerkinElmer in Seattle, Washington, show that current genomic research resources and bioinformatics ...

Ancient domesticated remains are oldest in southern Africa

2012-07-12

Researchers have found evidence of the earliest known instance of domesticated caprines (sheep and goats) in southern Africa, dated to the end of the first millennium BC, providing new data to the ongoing debate about the origins of domestication and herding practices in this region. The full results are published July 11 in the open access journal PLoS ONE. The researchers, led by David Pleurdeau of the National Museum of Natural History in Paris and Eugène Marais of the National Museum of Namibia, investigated remains from Leopard Cave in Namibia. They could not determine ...

Eye movement direction not correlated with lying

2012-07-12

New research refutes a commonly held belief that certain eye movements are associated with lying. The idea that looking to the right indicates lying, while looking left suggests truth telling, is shown to be false in a report published July 11 in the open access journal PLoS ONE. The researchers, led by Caroline Watt of the University of Edinburgh, completed three different studies to show that there was no correlation between the direction of eye movement and whether the subject was telling the truth or lying. "A large percentage of the public believes that certain eye ...

LAST 30 PRESS RELEASES:

Scientists trace microplastics in fertilizer from fields to the beach

The Lancet Obstetrics, Gynecology, & Women’s Health: Taking paracetamol during pregnancy does not increase risk of autism, ADHD or intellectual disabilities, confirms new gold-standard evidence review