October 1, 2009 (Newswise) - For men with type 2 diabetes, a cell type linked to allergic inflammation is closely linked to a key indicator of diabetic kidney disease (nephropathy), suggests a study in the November Clinical Journal of the American Society of Nephrology (CJASN). "Allergy is a common disease that is increasing worldwide, so our findings may have important implications for diabetic nephropathy," comments Michiaki Fukui, MD (Kyoto Prefectural University of Medicine, Japan).The researchers compared the eosinophil count with albumin excretion rate in nearly 800 patients with type 2 diabetes. Eosinophils are a type of white blood cell that contributes to inflammation in allergic diseases. The albumin excretion rate is a key indicator of kidney disease, one of the major complications of diabetes.

In men, a higher number of eosinophils in the blood correlates with higher urinealbumin-a critical early sign of diabetic kidney disease. Surprisingly, the link between eosinophil count and albumin excretion rate was even stronger than for known risk factors like high blood pressure and poor diabetes control. The eosinophil count was unrelated to albumin excretion in diabetic women.

Previous studies have suggested that patients with asthma and other allergic diseases are at increased risk of heart disease. Heart disease is the main cause of death in diabetics, and nephropathy is a major risk factor for heart disease. If the results are confirmed by future studies, then the eosinophil count might help in estimating the risk of diabetes-related kidney and heart disease in men.

Some of the anti-inflammatory treatments used by patients with allergies can lower the eosinophil count, and it's possible that these treatments could also benefit male patients with diabetes, Fukui believes. He adds, "The intriguing concept of a role for eosinophils in diabetic nephropathy holds great promise for the development of new preventive measures involving anti-allergic agents."

The study can't prove any cause-and-effect relationship between eosinophil count and albumin excretion rate. More research will be needed to determine why the relationship was found only in men, and whether a similar link is also present in patients without diabetes.

The authors reported no financial disclosures. Other authors were Muhei Tanaka, Masahide Hamaguchi, Takafumi Senmaru, Kazumi Sakabe, Emi Shiraishi, Ichiko Harusato, Masahiro Yamazaki, Goji Hasegawa, all of Kyoto Prefectural University of Medicine.

October 1, 2009 (EurekAlert) - A new study reports that transplanted pigment-containing visual cells derived from human embryonic stem cells (hESCs) successfully preserved structure and function of the specialized light-sensitive lining of the eye (known as the retina) in an animal model of retinal degeneration. The findings, published by Cell Press in the October 2nd issue of the journal Cell Stem Cell, represent an exciting step towards the future use of cell replacement therapies to treat devastating degenerative eye diseases that cause millions of people worldwide to lose their sight.The retinal pigment epithelium (RPE) is a layer of pigmented cells sandwiched between the visual retinal cells, called photoreceptors, and the nourishing blood vessels at the back of the eye. The RPE provides essential support to the retinal photoreceptors and is critical for normal vision. Deterioration of the RPE plays a central role in the progression of diseases such as age-related macular degeneration and sub-types of retinitis pigmentosa. These conditions are associated with a progressive loss of vision that often leads to blindness.

"Although there are a variety of therapeutic approaches under development to delay the degenerative process, the grim reality is that many patients eventually lose their sight," explains Dr. Benjamin Reubinoff, a senior author of the study. "Cell therapy to replenish the degenerating RPE cells may potentially halt disease progression." Dr. Reubinoff and Dr. Eyal Banin who led the study, with their colleagues from Hadassah-Hebrew University Medical Center in Jerusalem, developed conditions to guide hESCs to differentiate into functional RPE-like cells in the laboratory.

The researchers found that nicotinamide (vitamin B3, NIC) and Activin A, an important growth factor, promoted differentiation of hESCs towards an RPE fate. The hESC-derived RPE-like cells, which could be identified by their characteristic black pigment, exhibited multiple biological properties and genetic markers that define authentic RPE cells. Further, the cells successfully delayed deterioration of retinal structure and function when they were transplanted into an animal model of retinal degeneration caused by RPE dysfunction.

Taken together, the results demonstrate that NIC and Activin A promoted the differentiation of hESCs towards an RPE fate. The hESC-derived cells exhibited the defining characteristics associated with RPE and successfully rescued the retina when transplanted into an animal model of retinal degeneration. "Our findings are an important step towards the potential future use of hESCs to replenish RPE in blinding diseases," concludes Dr. Banin.

October 1, 2009 (EurekAlert) - Both household food insecurity (HFInsec) and childhood overweight are significant problems in the United States. Paradoxically, being food-insecure may be an underlying contributor to being overweight. A study of almost 8,500 low-income children ages 1 month to 5 years, published in the October 2009 issue of the Journal of the American Dietetic Association, suggests an association between household food insecurity and overweight prevalence in this low-income population. However, sex and age appear to modify both the magnitude and direction of the association.Food insecurity is defined as the lack of access to enough food for an active, healthy life, which results from limited or uncertain access to nutritionally adequate and safe foods in socially acceptable ways. In 2004, 11% of households in the United States reported household food insecurity, and households with children younger than 6 years old and black and Hispanic households experienced higher rates of household food insecurity and hunger. Prevalence of household food insecurity and overweight has increased over time and are more prevalent in low-income families.

This cross-sectional study is based on demographic, anthropometric, food security and other health-related data collected from November 1998 through December 1999, on a sample of children and mothers from low income families participating in the Massachusetts Department of Public Health's WIC (Special Supplemental Nutrition Program for the Women, Infants, and Children) Program. Data on the children's age, sex, parental/caretaker report of child race/ethnicity and maternal education were also collected.

Of the 8,493 children with complete data, 31% of the children were from food-insecure households (8.3% with hunger), and 18.4% of the sample was overweight. Prevalence of HFInsec did not differ significantly by age, sex or maternal education.

Because significant interactions were found between HFInsec and age-group and sex, the researchers separated the subjects into four groups, boys < 2 years old, girls < 2 years old, boys 2-5 years old and girls 2-5 years old. In girls < 2 years old, HFInsec was associated with a lower likelihood of being overweight. No correlation was found for boys < 2 years. In contrast, 2- to 5-year- old girls from households reporting HFInsec with hunger had a 47% higher odds of overweight than those from food secure households. No association was found for HFInsec without hunger among 2-5 year old girls, and again, no association was found among 2-5 year old boys.

Writing in the article, Elizabeth Metallinos-Katsaras, Associate Professor, Department of Nutrition, School for Health Sciences, Simmons College, Boston, states, "The findings of this study suggest that HFInsec is associated with overweight prevalence in low income ethnically and racially diverse girls. Age and sex, however, appear to modify both the magnitude and the directionality of the association. Future research should examine these associations using a longitudinal research design. Moreover, qualitative research is needed to establish the underlying behaviors that may affect the development of childhood overweight among families with uncertain and limited food availability and how these behaviors may vary by sex."

October 1, 2009 (EurekAlert) - Kidneys recovered from deceased donors with acute renal failure (ARF) - once deemed unusable for transplant - appear to work just as well as kidneys transplanted from deceased donors who do not develop kidney problems prior to organ donation, according to a new study by researchers at Wake Forest University Baptist Medical Center.The findings, reported in the October issue of Surgery, suggest the possibility of safely expanding the donor kidney pool by at least 10 to 15 percent, potentially making an additional 1,000 kidneys or more per year available to those waiting for a donor organ.

"There is a critical shortage of donor organs and we are continually making efforts to expand the donor pool," said Robert J. Stratta, M.D., professor of surgery and director of transplantation at Wake Forest Baptist and senior investigator on the study. "While kidneys from deceased donors with ARF have been considered unusable in the past, our study shows they can work quite well. The function of the new kidney may be slow or delayed - and patients may have to continue dialysis for a week or two until the kidney is up and running - but that's really the only downside. Choosing to utilize these kidneys will greatly shorten the waiting time for people who are willing to accept a kidney from this kind of donor."

Stratta and colleagues transplanted 25 kidneys from 17 deceased donors with ARF, which is impaired kidney function that can result from many things, including traumatic injury, exposure to medications toxic to the kidneys, infection, dehydration, shock, and the breakdown of muscle fibers. Unlike chronic kidney failure, ARF can often be reversed if the underlying cause is treated or removed, Stratta said.

All of the kidneys were refused by multiple centers before being offered for transplantation at Wake Forest Baptist. The patients receiving the kidneys had an average waiting time of 24 months until a donor kidney was made available to them and each chose to accept the organ. All of the recipients were monitored for at least 11 months post-transplant. At an average follow-up of 20 months, patient and graft survival rates were 100 percent and 92 percent, respectively - comparable, Stratta said, to the outcomes typically seen when healthy deceased donor kidneys are transplanted.

"As long as the donor kidneys are still producing urine and do not have evidence of scarring from pre-existing conditions such as diabetes or a history of high blood pressure, they appear to restore to a healthy condition when transplanted," he said.

"Each transplant center has its own level of comfort regarding the criteria they use to determine what organs they will and will not accept for transplant," Stratta added. "In the past, kidneys from donors with ARF were considered an absolute 'no.' Then they became a relative 'no.' After this study, I think it's safe to say that they are a relative 'yes' - there is a subset of these donor kidneys that can be safely and successfully transplanted with very good short-term results."

Over the last decade, the number of patients waiting for a kidney transplant has outpaced growth in the number of transplants performed each year. Between 1997 and 2006, the number of patients waiting for a kidney transplant increased by 81 percent from 49,208 to 88,877. During the same time, the number of annual kidney transplants performed in the United States increased by only 41 percent from 11,703 to 16,483. This escalating disparity in the number of end stage renal disease patients on the waiting list relative to those actually receiving kidney transplants has been accompanied by a startling increase in the number of deaths while waiting for transplants, from 2,184 in 1997 to 4,456 in 2006. In addition, median waiting times for kidney transplants have doubled in the last decade.

"Now that we know we can successfully transplant these kidneys and they will work just as well as other deceased donor kidneys, it becomes a decision of personal preference - the transplant center's level of comfort with using these kidneys, the patient's preference with accepting the kidney, and the general public's decision on whether or not to donate life," Stratta said.

September 29, 2009 (EurekAlert) - A study by Monash University researchers has shed new light on the microscopic antennas in the kidney that are involved in the organ's repair process.
The work may be a crucial step towards a cure for polycystic kidney disease, a potentially fatal disease that affects more than one in 1000 people.

The study, led by Dr James Deane a researcher at the Centre for Inflammatory Disease at the Monash Medical Centre, showed how kidney repair processes are controlled and helps explain the cause of polycystic kidney disease.

The findings have appeared in the latest edition of world's leading kidney research publication, the Journal of the American Society of Nephrology.

"We have shown for the first time that the hair-like structures on kidney cells, called cilia, change their length in response to injury in human patients, growing up to four times their original length in the later stages of kidney repair," Dr Deane said.

"These hair-like structures are antennas and the increases in their length amplify the signals they send to kidney cells at vital stages of repair. We think this is how they turn off the repair process when it is complete and allow the kidney to start working normally again"

Dr Deane said that if the switching on and off the repair process is not properly controlled, rapidly reproducing cells will distort the tubes of the kidney and prevent them from functioning properly, which is what appears to happen in people that have polycystic kidney disease, a condition which is currently untreatable.

"Our research helps put a logical framework behind what is happening in polycystic kidney disease, as the mutations that cause the disease can damage the hair-like structures of kidneys cells," Dr Deane said.

"We hope that this work will lead to new ways of treating both kidney injury and polycystic kidney disease."

The kidney is made up of about a million tiny living tubes that produce urine to rid the body of waste products. The cells that make up these tubes have hair-like structures, which are two thousandths of a millimetre long and respond to urine flow by sending reassuring signals back to the cells.

In an injured kidney there is a reduction in urine flow and reassuring signals from the hair-like structures are diminished. This causes kidney cells go into repair mode. Surviving kidney cells take on a new form that allows them to reproduce rapidly to replace cells that have died. When enough cells have been produced it is important that kidney cells stop reproducing and return to their normal form. This is where some extra input from the hair-like structures appears to be required.

September 25, 2009 (FDA) - FDA is revising the prescribing information for Januvia (sitagliptin) and Janumet (sitagliptin/metformin) to include information on reported cases of acute pancreatitis in patients using these products.Sitagliptin, the first in a new class of diabetic drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors, is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Eighty-eight post-marketing cases of acute pancreatitis, including two cases of hemorrhagic or necrotizing pancreatitis in patients using sitagliptin, were reported to the Agency between October 16, 2006 and February 9, 2009. Based on these reports, FDA is working with the manufacturer of sitagliptin and sitagliptin/metformin to revise the prescribing information to include:

• Information regarding post-marketing reports of acute pancreatitis, including the severe forms, hemorrhagic or necrotizing pancreatitis.
• Recommending that healthcare professionals monitor patients carefully for the development of pancreatitis after initiation or dose increases of sitagliptin or sitagliptin/metformin, and to discontinue sitagliptin or sitagliptin/metformin if pancreatitis is suspected while using these products.
• Information noting that sitagliptin has not been studied in patients with a history of pancreatitis. Therefore, it is not known whether these patients are at an increased risk for developing pancreatitis while using sitagliptin or sitagliptin/metformin. Sitagliptin or sitagliptin/metformin should be used with caution and with appropriate monitoring in patients with a history of pancreatitis.

This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

September 25, 2009 (EurekAlert) - Teenagers' attitudes to diet and weight are shaped by their social class, according to new research funded by the Economic and Social Research Council.Policymakers have long insisted on the importance of understanding young people's health and eating habits but this is the first study to show how everyday practices and perceptions of different social classes contribute to variation in the diet, weight and health of teenagers.

'It is evident that children are moulded according to their parents' expectations about behaviour,' says Dr Wendy Wills of the University of Hertfordshire, who led the research. The study reveals the ideals and beliefs of both family life and parenting by looking at the diet, weight and health of middle class teenagers, their parents and comparing them with an earlier study of working class families.

Middle class families look towards their children's future, expecting young teenagers' tastes to develop and have a good body shape to actively participate in adult life. Parents expressed concern that if children were overweight they would have poor health in later life. They also felt that being overweight would affect the children's self-esteem and ability to take part in life's opportunities.

In working class families, concern for the future is dominated by more pressing concerns about everyday life. 'In the context of risk and insecurity for working class families, the ideal body shape has little value,' says Dr Wills.

Although working class families express the desire to improve the diet and lifestyle of their children, they sometimes lack the social and cultural abilities as well as money to make such changes happen.

At the same time, the independence of teenagers to make their own food choices and take responsibility for their health is seen as an important sign of being working class. This contrasts with middle class families where parents supervise and control young teenagers' food choices on a daily basis.

Middle class teenagers saw obesity as the result of being lazy, unhealthy or unable to control a desire for 'bad foods'. Middle class parents feel a moral urgency to ensure their children to stay an 'acceptable' size. Being seen to be 'respectable' in this regard is a significant sign of middle class distinctions.

The findings of the study have proved important for understanding why inequalities in diet, health and weight continue to persist. NHS Health Scotland have used to them to help Health Boards implement child healthy weight initiatives and the Department of Health's new Healthy Living social marketing initiative also uses the project's research.

However, policymakers should not expect quick results, the study warns. 'Given the complex, embedded nature of familiar practices and beliefs,' says Dr Wills, 'policy and practice targets need to be realistic in terms of the timescale needed for achieving change.'

September 24, 2009 (Newswise) - Women who have had a kidney transplant and have good kidney function can get pregnant and give birth without jeopardizing their health or the health of their transplant. Having children does not affect patients' kidney function or their life-span compared with transplanted women who do not have children, according to a matching cohort study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN).There is little information on the health effects of pregnancy and childbirth in women with a functioning kidney transplant. To determine whether getting pregnant and having a baby are safe for these women, Vicki Levidiotis, MD (Royal Prince Alfred Hospital, Australia), and her colleagues analyzed 40 years' worth of pregnancy-related data for transplant recipients in Australia and New Zealand.

The investigators compared 120 women who gave birth after receiving their kidney transplant with 120 transplanted women who did not have children. There were no differences in kidney function or patient survival 20 years after the transplant in these two groups. "In transplanted women who achieve a live birth, and have good kidney function at the time, the birth does not adversely impact on their transplanted kidney or life-span," said Dr. Levidiotis. The authors noted that their findings are good news for kidney transplant women who fear getting pregnant because they fear that their pregnancy may worsen their kidney function or shorten their lifespan and keep them from raising their children.

The birth rate in women who have received a kidney transplant is much lower than in the general population. Dr. Levidiotis and her team found that 444 live births were reported from 577 pregnancies among female kidney transplant recipients in Australia and New Zealand over the past 40 years. The proportion of births doubled during the last decade but the birth rate was approximately 80% lower than that seen in women in the general population, confirming the "relative infertility" of women with kidney transplants. Among women with a functioning kidney transplant who became pregnant, 83% of them went on to give birth.

The authors report no financial disclosures. Study co-authors include Sean Chang, MBBS, (Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, Australia), and Stephen McDonald, MBBS, PhD (ANZDATA Registry and Queen Elizabeth Hospital, Australia).

The article, entitled "Pregnancy and Maternal Outcomes Among Kidney Transplant Recipients," will appear online at http://jasn.asnjournals.org/ on September 24, 2009, doi 10.1681/ASN.2008121241.

September 22, 2009 (Newswise) - University of Utah medical ethics expert Jeffrey R. Botkin will chair a federal panel that will review scientists' requests to conduct government-funded research using embryonic stem cells left over from couples who used "test-tube fertilization" to have babies."Stem cells have the capability of developing into any tissue type in the human body," says Botkin, a pediatrician and associate vice president for research integrity at the University of Utah. "If scientists can better understand the development of stem cells into different body tissues, then it may be possible to use stem cells to treat a wide variety of diseases that are caused by tissue aging, damage or degeneration."

"For example, if stem cells can be coaxed into developing into pancreas cells, it may be possible to use them to treat diabetes," he adds. "This is a very exciting area of biomedical research that offers great promise down the road."

Expanded use of cells from embryos left over from in vitro fertilization is made possible by an executive order signed March 9 by President Barack Obama. The order loosened the more restrictive policy under former President George W. Bush.

National Institutes of Health Director Francis S. Collins announced Monday his agency now is accepting requests for lines of human embryonic stem cells to be approved for use in NIH-funded research. Collins also named a new nine-member Working Group for Human Embryonic Stem Cell Eligibility Review, with Botkin as its chair.

Botkin - who also is chief of the University of Utah School of Medicine's Division of Medical Ethics and Humanities - says he was picked as chair due to his background in research ethics, and his past service on federal advisory committees, including one dealing with the protection of human subjects in research.

"Also, the fact that the University of Utah does not have an active program using human embryonic stem cells was probably a factor because this eliminated any conflicts of interest in that respect," Botkin says.

NIH guidelines published on July 7 and the new panel "will address which embryonic stem cell lines will be eligible for use in research supported by federal funds," he says. "These stem cell lines are created by taking cells from the inner cell mass of early-stage embryos. The process of extracting the cells from the inner cell mass destroys the embryo, which is, of course, the reason for the ethical debates over these cells since they were first successfully created in 1998."

Botkin emphasizes that under both the Bush and Obama guidelines, "it is not possible to use federal funds for the actual destruction of the embryos to create the stem cell lines. Rather, the guidelines address whether federal funds can be used for research using stem cells that were originally created using non-federal sources of funding."

Existing law and regulation allows private companies to conduct research that creates and uses human embryonic stem cells. But, says Botkin, "given the large amount of research funding provided by the federal government, the new guidelines will permit a significant increase in the number of projects using embryonic stem cells."

Botkin says "it is unclear" how many requests for approval the NIH will receive, although many researchers are eager to move forward with stem cell work.

"Under the previous policy formulated by the Bush administration, research with a limited number of stem cell lines was supported by the NIH," he says. "Only lines that were created before Aug. 9, 2001 (the date of the Bush policy announcement) were eligible for funding because the embryos had been destroyed already and the policy sought not to foster additional destruction of human embryos. However, the small number of available lines did not support many investigators who want to pursue this research, and questions were raised about the biological quality of some existing lines."

"Current estimates suggest there are hundreds of thousands of embryos that remain in fertility clinics from couples who created them for reproductive purposes," Botkin says. "Many of these couples have fulfilled their reproductive goals, meaning the leftover embryos will ultimately be discarded."

He says that under the Obama administration, the new NIH guidelines state "that these 'spare' embryos can be used for stem cell research if the couple who produced the embryos has given their full informed consent."

"For stem cells created after July 7, 2009, the guidelines are clear about the nature of the informed consent from couples who have 'spare' embryos," Botkin says. "The committee will not review proposed cell lines created after that date, although they will be reviewed administratively at the NIH. However, for lines created before July 7, 2009, review of the consent forms and the process by which the stem cells were created will be the responsibility of the committee."

He says the panel will ask, "Can we be assured that the couple fully understood their options, including use of their embryos in research, and agreed to the donation without any element of coercion or manipulation?"

Embryonic stem cell lines created in other nations often don't meet U.S. standards for informed consent, but the panel will ask whether the consent and process used to obtain the cells adequately fulfill the ethical principles in NIH guidelines. "If so, lines created internationally may be eligible for research using federal funds," Botkin says.

NIH Guidelines for Human Stem Cell Research may be found at:
http://stemcells.nih.gov/policy/2009guidelines.htm

September 17, 2009 (Newswise) - Losing weight may preserve kidney function in obese people with kidney disease, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN). The findings indicate that taking off the pounds could be an important step kidney disease patients can take to protect their health.More than a third of US adults are either obese or overweight. Weight loss can improve a number of health problems; for example, it can improve control of diabetes, lower blood pressure and cholesterol levels, and reduce the effects of heart disease.

To see if losing weight might also have beneficial effects on the kidneys, Sankar Navaneethan, MD, (Cleveland Clinic), and his colleagues analyzed the studies that examined the effects of weight loss interventions in obese kidney disease patients. The investigators searched the medical literature and identified data from thirteen relevant studies that assessed the impact of diet, exercise, and surgical procedures on kidney function.

The analysis revealed that weight loss attained through diet and exercise reduces proteinuria (excess excretion of protein in the urine-a hallmark of kidney damage) and may prevent additional decline in kidney function in obese patients with kidney disease. Studies also showed that surgical interventions normalize the filtration rate of the kidneys in obese patients with high filtration rates (a risk factor for the development of kidney disease).

While the findings imply that weight reduction may prevent the progression of kidney disease in obese kidney disease patients, the authors noted that there were only a small number of studies available for analysis and additional high-quality long-term studies on this topic are needed.

The authors report no financial disclosures. Study co-authors include Hans Yehnert, MD (Acoma-Canoncito-Laguna Hospital); Fady Moustarah, MD, Philip Schauer, Martin Schreiber, MD (Cleveland Clinic); and Srinivasan Beddhu, MD (Salt Lake Veterans Affairs Healthcare System).

The article, entitled "Weight Loss Interventions in Chronic Kidney Disease: A Systematic Review and Meta-analysis," will appear online at http://cjasn.asnjournals.org/ on Thursday, September 17, 2009, doi 10.2215/CJN.02250409.