Simple ultrasound could prevent post-op kidney damage

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Main Category: Urology / Nephrology
Also Included In: Preventive Medicine
Article Date: 05 Aug 2013 - 0:00 PDT Current ratings for:
Simple ultrasound could prevent post-op kidney damage

Acute kidney injury, in which the kidneys suddenly stop working properly, is a potentially severe condition that often follows major surgery and causes serious complications for patients. Now for the first time, researchers show that treatment with ultrasound beforehand can help prevent the problem in mice.

The protection from acute kidney injury (AKI) comes from the anti-inflammatory effects of this simple, drug-free, non-invasive treatment, the scientists believe.

Mark Okusa and Joseph Gigliotti of the University of Virginia and colleagues report their findings in the Journal of the American Society of Nephrology.

Dr. Mark Okusa told the press:

"Our studies using non-invasive ultrasound now provide us with an active treatment that appears to be simple, effective, and nontoxic for the prevention of acute kidney injury.

"To our knowledge this has never been described for the prevention of tissue or organ injury."

Acute kidney injury is becoming an increasingly common complication in patients who have major surgery. It occurs because sometimes during major surgery the normal blood flow to the kidneys is disrupted. Once AKI sets in, it is very difficult to treat.

Acute kidney injury not only affects quality of life for patients, but also increases healthcare costs, and raises the risk of death following major surgery, note the authors.

A study published in 2008, showed that risk of death persists in heart patients with AKI even after discharge from hospital.

For their study, the researchers exposed anesthetized mice to ultrasound 24 hours before disrupting the blood supply to their kidneys.

They used the same kind of device that clinicians use to take regular ultrasound images.

Once blood flow was restored, they found that the health of the animals' kidneys had been preserved.

Another group of mice that received a sham treatment did not show preserved kidney health: their kidneys showed significant injury.

On further analysis, the researchers found that the ultrasound seemed to have stimulated the spleen to produce an anti-inflammatory response that protected the kidneys.

The researchers believe that the mechanisms that cause the acute kidney injury may also be responsible for similar damage to lung, heart and liver and that this type of treatment could prevent injury in other organs too.

Experts suggest the study offers numerous and promising possibilities because there are many procedures that carry a high risk of AKI.

In an editorial in the same issue of the journal, Alain Le Moine of Erasme Hospital in Belgium, and colleagues, note that:

"In searching for novel approaches to prevent and even cure AKI, we believe that splenic ultrasound stimulation has a bright future ahead."

Progress is also being made in predicting which post-operative patients are at higher risk for acute kidney injury. Current methods - such as measuring serum creatinine and urine output - may not show changes for several days, allowing time for serious kidney damage to have happened already.

But in an international study published earlier this year, researchers found two biomarkers that spot AKI risk sooner.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our urology / nephrology section for the latest news on this subject. "Ultrasound prevents renal ischemia-reperfusion injury by stimulating the splenic cholinergic anti-inflammatory pathway," Gigliotti JC, Huang L, Ye H et al, JASN, published online ahead of print, 1 August 2013; DOI: 10.1681/ASN.2013010084; Abstract/summary. Please use one of the following formats to cite this article in your essay, paper or report:

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Teens' kidney transplants more likely to fail

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Main Category: Transplants / Organ Donations
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
Teens' kidney transplants more likely to fail

Adolescents who have their first kidney transplant between 14 and 16 years of age could have a higher risk of transplant failure, according to a study published in the journal JAMA Internal Medicine.

Researchers from the University of Florida, Gainesville, analyzed 168,809 patients between 1987 and 2010. All participants had their first kidney transplant and their ages ranged up to 55.

Data was analyzed from the Organ Procurement Transplantation Network Standard Transplant Analysis and Research Database.

The study population characteristics analyzed in the study included the recipients' sex, race and insurance type, and the donors' living vs deceased status, sex, health and their combined Human Leukocyte Antigens (HLA) match information.

Results of the study showed that patients aged between 14 and 16 years had the highest risk of graft loss of all age groups.

The researchers found that graft loss started at 1 year after the transplant was carried out, and increased at 3-, 5- and 10-year points.

The study also revealed that black adolescents have an even higher risk of graft failure, compared with non-black adolescents.

The study authors say that using age at transplant as the risk factor, there was a decreasing relative hazard of graft failure in different insurance groups.

The researchers found the following range, in order of highest to lowest, for graft failure risk:

Deceased donor - government insurance groupDeceased donor - private insurance groupLiving donor - government insurance groupLiving donor - private insurance group

They add that in the death-censored analysis, this order of risk was consistent from infancy to 55 years of age.

Additionally, the results showed that among 14-year-old patients, there was an increased death risk of 175% in the deceased donor-government insurance group, compared with the living donor-private insurance group.

The researchers conclude that comprehensive programs are needed for adolescent transplant recipients, as current medical literature "does not adequately describe the risks of graft failure among kidney transplant recipients by age."

They say: "The realization that this age group is at an increased risk of graft loss as they are becoming young adults should prompt providers to give specialized care and attention to these adolescents in the transition from pediatric to adult-focused care."

The researchers conclude:

"Implementing a structured health care transition preparation program from pediatric to adult-centered care in transplant centers may improve outcomes."

Written by Honor Whiteman

Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our transplants / organ donations section for the latest news on this subject.

"Age-related kidney transplant outcomes health disparities amplified in adolescence," JAMA Internal Medicine, July 29, 2013.

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Adolescent kidney transplant recipients appear to be at higher risk of transplant failure

Main Category: Transplants / Organ Donations
Article Date: 29 Jul 2013 - 13:00 PDT Current ratings for:
Adolescent kidney transplant recipients appear to be at higher risk of transplant failure

Patients who received their first kidney transplant at ages 14 to 16 years appear to be at increased risk for transplant failure, with black adolescents having a disproportionately higher risk of graft failure, according to a report published by JAMA Internal Medicine, a JAMA Network publication.

Existing medical literature does not adequately describe the risks of graft failure among kidney transplant recipients by age. Organ losses by adolescents are partly due to physiologic or immunologic changes with age but psychological and sociological factors play a role, especially when they affect medication adherence, according to the study background.

Kenneth A. Andreoni, M.D., of the University of Florida, Gainesville, and colleagues analyzed 168,809 first kidney-only transplants from October 1987 through October 2010. Age at transplant was the primary factor studied.

"Adolescent recipients aged 14 to 16 years had the highest risk of any age group of graft loss ... starting at one year after transplant, and amplifying at three, five and 10 years after transplant," according to the study results. "Black adolescents are at a disproportionate risk of graft failure at these time points compared with nonblack adolescents."

In the study, researchers also note that donor type (deceased vs. living) and insurance type (government vs. private) also had an impact along with a kidney transplant recipient's age.

"Among 14-year-old recipients, the risk of death was 175 percent greater in the deceased donor-government insurance group vs. the living donor-private insurance group (hazard ratio, 0.92 vs. 0.34), whereas patient survival rates in the living donor-government insurance and deceased donor-private insurance groups were nearly identical (hazard ratio, 0.61 vs. 0.54)," the study results indicate.

Researchers suggest that comprehensive programs are needed for adolescent transplant recipients.

"The realization that this age group is at an increased risk of graft loss as they are becoming young adults should prompt providers to give specialized care and attention to these adolescents in the transition from pediatric to adult-focused care. Implementing a structured health care transition preparation program from pediatric to adult-centered care in transplant centers may improve outcomes," the study concludes.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our transplants / organ donations section for the latest news on this subject.

JAMA Intern Med. Published online July 29, 2013. doi:10.1001/jamainternmed.2013.8495.

The Organ Procurement and Transplantation Network (OPTN) is supported by a Health Resources and Services Administration contract. The Ohio State University Comprehensive Transplant Center supported expenses for statistical evaluation of data. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Discovery of gene function may help prevent kidney stones

Main Category: Genetics
Also Included In: Urology / Nephrology
Article Date: 26 Jul 2013 - 2:00 PDT Current ratings for:
Discovery of gene function may help prevent kidney stones

The discovery of a gene's function in E. coli and other bacteria might lead to a probiotic to prevent the most common type of kidney stone, according to a Purdue University study.

Human cells can't metabolize oxalate, an acidic chemical found in nearly all plants we eat, so any oxalate we absorb from food must be excreted from the body. Calcium-oxalate urinary stones can form when oxalate reaches a high concentration in the kidneys. About 80 percent of kidney stones are composed of insoluble calcium oxalate.

T. Joseph Kappock, assistant professor of biochemistry, and his research team made the discovery during a study of genes in Acetobacter aceti, a harmless bacterium that is typically used to convert wine to vinegar. Acetobacter aceti, which normally lives on plant tissue, thrives in acidic conditions that easily kill most other bacteria, Kappock said.

The researchers were searching for other acids in addition to acetic acid, the acid present in vinegar, that the bacterium can metabolize.

"We were very excited when we realized E. coli has the same genetic setup as Acetobacter aceti," said Kappock, whose findings were published in the journal PLOS ONE.

Kappock and doctoral students Elwood A. Mullins and Kelly L. Sullivan found that Acetobacter aceti and E. coli each contain an enzyme with a previously unknown function, called YfdE in E. coli.

DNA sequencing had identified related genes in each bacterium, but provided little insight about its function.

"When we look at a bacterial genome by DNA sequencing, we can't tell what many of the proteins in the organism do," Kappock said. "I compare it to knowing that a vehicle has an internal combustion engine. You don't know if it's in an Indy car or a diesel truck. DNA sequencing tells us we have an internal combustion engine in this organism, but we don't know what it's for or what it can do."

Many other bacteria have the same genes but don't seem to be capable of using them.

"A few bacteria in the gastrointestinal tract eat oxalate, and we think we know how those work," Kappock said. "But we don't know why so many others are killed by oxalate, even though they have genes that would seem to be able to protect them. Oxalate is a very hard nut to crack. It's a very stable molecule that is difficult to decompose. The enzymes that process it are pretty specialized and don't seem to connect to normal bacterial metabolic pathways in an obvious way."

The researchers determined which chemicals are processed by the YfdE enzyme, following a hunch that it would use oxalate. Their results connected oxalate degradation to the core of bacterial metabolism.

Assigning a function to YfdE may help identify beneficial bacteria that could serve as probiotic agents in the human gastrointestinal tract to reduce the risk of kidney stone formation. Kidney stones, which affect more than 5 percent of the U.S. population, can cause painful blockages of the urinary tract.

"If we understand what bacteria need to degrade oxalate, then we might have a better idea how to identify strains that can do that, and thereby suppress the uptake of dietary oxalate" he said. "There are probably bacteria out there that have engineered themselves to do this for us."

Genome-sequencing information will increase the speed of the search, Kappock said.

"Because we've figured out what the gene product does, we will be able to find it in any organism and can zero in on those that might be beneficial," he said.

The researchers used X-ray crystallography to pinpoint the most important regions of the YfdE enzyme.

Kappock said the information has other applications, as well. Scientists and engineers who are interested in mapping and reprogramming microbial metabolism now know what one more gene product does.

"Our one piece of the puzzle will help others understand other metabolic networks," he said.

Agricultural Research at Purdue, the National Science Foundation and the U.S. Department of Energy funded the research.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Abstract:

Acetyl-CoA:Oxalate CoA-transferase 1 Function and X-ray Crystal Structure of Escherichia coli YfdE

Elwood A. Mullins 1, 2; Kelly L. Sullivan 1; T. Joseph Kappock 1;

1 Dept. of Biochemistry, Purdue University, West Lafayette, Indiana, USA

2 Dept. of Chemistry, Washington University, St. Louis, Missouri, USA

Many food plants accumulate oxalate, which humans absorb but do not metabolize, leading to the formation of urinary stones. The commensal bacterium Oxalobacter formigenes consumes oxalate by converting it to oxalyl-CoA, which is decarboxylated by oxalyl-CoA decarboxylase (OXC). OXC and the class III CoA-transferase formyl-CoA:oxalate CoA-transferase (FCOCT) are widespread among bacteria, including many that have no apparent ability to degrade or to resist external oxalate. The EvgA acid response regulator activates transcription of the Escherichia coli yfdXWUVE operon encoding YfdW (FCOCT), YfdU (OXC), and YfdE, a class III CoA-transferase that is ~30% identical to YfdW. YfdW and YfdU are necessary and sufficient for oxalate-induced protection against a subsequent acid challenge; neither of the other genes has a known function. We report the purification, in vitro characterization, 2.1- A crystal structure, and functional assignment of YfdE. YfdE and UctC, an orthologue from the obligate aerobe Acetobacter aceti, perform the reversible conversion of acetyl-CoA and oxalate to oxalyl-CoA and acetate. The annotation of YfdE as acetyl-CoA:oxalate CoA-transferase (ACOCT) expands the scope of metabolic pathways linked to oxalate catabolism and the oxalate-induced acid tolerance response. FCOCT and ACOCT active sites contain distinctive, conserved active site loops (the glycine-rich loop and the GNxH loop, respectively) that appear to encode substrate specificity.

Purdue University

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Study Clarifies Surgical Options for Kidney Cancer

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 28 Jul 2013 - 0:00 PDT Current ratings for:
Study Clarifies Surgical Options for Kidney Cancer

Surgery is often the first step in treating kidney cancer, and new data from the University of Rochester Medical Center, which contradicts earlier research, questions whether removal of only the tumor (partial nephrectomy) is better than removing the entire kidney (radical nephrectomy).

The decided trend for the past decade has been toward a partial resection in the case of smaller cancers. It was based on several earlier studies suggesting that it's better to save as much kidney tissue as possible, and thus preserve kidney function and reduce the likelihood of kidney failure in the long run. Many physicians inferred that a radical nephrectomy would be worse for kidney cancer patients, due to a concern that even mild or moderate dysfunction in the remaining kidney could lead to an earlier death.

However, the URMC found the opposite to be true: that losing a whole kidney to surgery does not translate into poorer outcomes for patients. In fact, those people who received a partial nephrectomy did not have improved survival, according to the study published this month in European Urology.

"Our data appears to seriously question the assumption that by saving kidney tissue, we are helping patients avoid future kidney failure," said Edward Messing, M.D., chair of Urology at URMC. "It may be that losing kidney tissue from surgery is not the same as losing kidney function from medical diseases like diabetes or hypertension."

The latter point is an important one for patients who're weighing surgical options, Messing added. Often, all types of kidney impairments are lumped into one category. It may be, however, that common medical conditions such as high blood pressure or diabetes take the biggest toll on kidney health. Therefore, if a patient is otherwise healthy and the second kidney is functioning well, he or she can safely consider a radical nephrectomy, if that seems to be the best option for cancer removal, he said.

Emelian N. Scosyrev, Ph.D., an epidemiologist and assistant professor of Urology, led the analysis of more than 500 patients registered by the European Organization for Research and Treatment of Cancer randomized trial from 1992 to 2003.

In collaboration with EORTC investigators, Scosyrev looked at various stages of renal dysfunction based on the EORTC trial data.

Specifically researchers compared the incidence of moderate kidney dysfunction, advanced kidney disease, and kidney failure among two groups: 255 people who were treated with a partial nephrectomy and 259 patients who had a radical nephrectomy. (The latter surgery removes the entire organ, adrenal gland, and surrounding tissue.) All patients had been diagnosed with a small kidney cancer and had a normal-functioning second kidney.

The URMC analyzed each patient's kidney function for a median of seven years after surgery, and continued to follow the cohort for approximately nine years, to determine the impact of both surgeries on patient survival.

At the median follow-up of 6.7 years, the frequency of moderate kidney dysfunction was 20% lower among those patients who received a partial nephrectomy, compared with those randomized to a radical nephrectomy. However, the better overall kidney function in the partial nephrectomy group did not result in improved survival. Indeed, at the last follow-up point of about nine years, fewer deaths had occurred in the radical nephrectomy group, the study showed.

Kidney failure was the same in both groups, at about 1.5 percent. This outcome was a bit surprising, Messing said, as it demonstrated that patients in the radical nephrectomy group who had initially suffered a mild or moderate degree of kidney dysfunction did not see their condition progress to kidney failure. When choosing a surgery, therefore, it's important to consider the best option for removing the cancer in the broader context of other medical conditions that impact kidneys.

The most common type of kidney cancer is renal cell carcinoma, which forms in the lining of the tubes that filter blood and remove waste. An estimated 65,000 new cases of kidney cancer will be diagnosed in the United States this year, and approximately 13,700 deaths are expected to occur, according to the National Cancer Institute.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Obese kidney failure patients receive survival benefit from transplantation

Main Category: Transplants / Organ Donations
Also Included In: Urology / Nephrology;  Obesity / Weight Loss / Fitness
Article Date: 25 Jul 2013 - 0:00 PDT Current ratings for:
Obese kidney failure patients receive survival benefit from transplantation

Most obese individuals with kidney failure can prolong their lives by receiving a kidney transplant, although this survival benefit is lower in severely obese individuals. That's the conclusion of a new study published in the American Journal of Transplantation. The findings will hopefully decrease differences in access to transplantation for obese patients.

Obesity is increasing in patients with kidney failure. In some studies, obese kidney failure patients who are on dialysis have a lower risk of dying prematurely than non-obese patients. In contrast, obese kidney transplant recipients have a higher risk of dying prematurely than non-obese recipients. Therefore determining the survival benefit of transplantation in obese transplant recipients is an important issue.

Using data from the United States between 1995 and 2007, John Gill, MD, MS, of the University of British Columbia, in Vancouver, and his colleagues determined the risk of premature death in transplant recipients grouped by body mass index (BMI) compared with transplant candidates with the same BMI who were on the transplant waiting list. The analysis included 208,498 patients, and obesity was defined as a BMI of 30 kg/m2 or higher.

Among the major findings:

Obese patients with a BMI of 30 to 39 kg/m2 derived a similar survival advantage from transplantation as non-obese patients, which equated to more than a 66 percent reduced risk of dying within one year of transplantation.Obese patients with a BMI of 40 or higher derived a lower survival advantage from transplantation (a 48 percent reduced risk of dying within one year), and a survival advantage was uncertain in Black patients with a BMI of 40 or higher.Differences in obese compared with non-obese patients were not as profound with transplantations using kidneys from live donors.

The risk of dying early after transplantation was greater in obese compared with non-obese patients.

"Our study shows that obese patients derive a survival advantage from transplantation, and obesity should not exclude patients from consideration of transplantation," said Dr. Gill. "Also, improved early post-transplant care may help reduce the early risk of death in obese patients, and living donor transplantation may be a useful strategy to mitigate the risks of transplantation in obese transplant candidates."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our transplants / organ donations section for the latest news on this subject.

Gill et al. The Survival Benefit of Kidney Transplantation in Obese Patients, American Journal of Transplantation; Published Online: July 25, 2013 (DOI: 10.1111/ajt.12331).

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