Tuesday, July 30, 2013

FDA postpones hypotension treatment candidate review over technical problems

The AP (7/30) reports Chelsea Therapeutics International Ltd. announced Monday that there has been “another delay in the review” of its experimental neurogenic orthostatic hypotension treatment, Northera (droxidopa). Chelsea said the Food and Drug Administration told the company that problems were found with the “formatting of electronic datasets and statistical programs describing the methods that were used to generate tables and listings.” The Charlotte, North Carolina-based pharmaceutical firm “said it expects to send a response to the FDA in August.” The AP notes that initially, the agency was slated to make a decision on whether to approve the treatment by Jan. 3, but the delay makes it more likely that a ruling will be made in February.

        In its coverage of the FDA response, the Wall Street Journal (7/30, Stynes, Subscription Publication, 2.29M) notes that Northera, which Dainippon Sumitomo Pharma Company developed, has been approved in Japan since 1989. Bloomberg News (7/30, Izlar) also covers the story.

Monday, July 29, 2013

'Caution' Warranted if Consuming Artificial Sweeteners

Troy Brown

Jul 10, 2013

Consumption of noncaloric, artificially sweetened beverages (ASBs) is associated with an increased risk for disease variety of chronic diseases, according to an opinion article by Susan E. Swithers, PhD, a professor of behavioral neuroscience at Purdue University in West Lafayette, Indiana, published online July 10 in Trends in Endocrinology & Metabolism.

"[F]requent consumers of these sugar substitutes at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease," Dr. Swithers writes.

"This somewhat counterintuitive result may reflect negative consequences of interfering with learned relationships between sweet tastes and typical post-ingestive outcomes, which may result in impaired ability to compensate for energy provided when caloric sweeteners are consumed," Dr. Swithers writes.

The prospective studies Dr. Swithers reviewed found an elevated risk for weight gain and obesity, metabolic syndrome, type 2 diabetes, coronary heart disease, and hypertension in those who consumed ASBs. No decreased risk for weight gain or increased body fat percentage was associated with ASB intake.

It was often difficult to compare the magnitude of increased risk with that of participants who consumed sugar-sweetened beverages (SSBs), in part because of differences in intake.

Participants who regularly consumed ASBs tended to have higher baseline body mass indexes compared with participants who did not, but some models that adjusted for that difference still found an increased risk. Studies that separately assessed risk among those who were not overweight or obese at baseline found that the risks of becoming overweight or obese, developing type 2 diabetes, and experiencing vascular events were increased even when considering baseline body mass indexes.

Hormones, Brain Response Altered

Dr. Swithers reviewed 2 interventional studies. The first found that children of normal weight who consume ASBs may have decreased weight gain compared with those who consume SSBs. The study did not compare children who consume ASBs with those who consume unsweetened beverages. In the second study, overweight and obese adults who substituted water or ASBs for SSBs had no greater weight loss at 6 months than an attentional control group. ASB intake was not associated with improved fasting glucose, but water intake was.

Brain responses are altered in those who consume artificial sweeteners compared with those who consume caloric sweeteners. In imaging studies of the human brain, sucrose activates dopaminergic midbrain areas involved with reward, but sucralose does not. Sucralose also reduces activation in other pathways related to taste when compared with sucrose.

In addition, studies in humans have found that the release of hormones and markers of postprandial glucose homeostasis typically seen does not occur after ingestion of artificial sweeteners.

Studies that combined artificial sweeteners in various ways with nutrients found that "artificial sweeteners may not augment nutrient-dependent release of insulin or the incretins in the same way that caloric sugars do," Dr. Swithers writes.

"[C]urrent findings suggest that caution about the overall sweetening of the diet is warranted, regardless of whether the sweetener provides energy directly or not," Dr. Swithers concludes.

Frank Hu, MD, PhD, a professor of nutrition and epidemiology and codirector of the program in obesity epidemiology and prevention at Harvard School of Public Health in Boston, Massachusetts, commented on the article in an email interview with Medscape Medical News.

"Overall, I think the jury is still out regarding whether drinking diet sodas instead of SSBs is truly related to obesity and [cardiovascular disease] outcomes, in part because of the complex methodological problems in studying the effects of diet sodas in epidemiological studies. Small, short-term, [randomized controlled trials] do show that drinking diet sodas instead of SSBs reduces weight gain or induces more weight loss in controlled settings," Dr. Hu said.

"Because [the] intense sweetness of ASBs may condition people towards greater preference for sweets and may enhance appetite, and because of the possibility that some consumers of diet soda may use this as a rationale for consuming other higher-calorie foods, caution is needed for recommending regular consumption of ASBs," Dr. Hu explained.

"In [the] short-term, ASBs is preferable to the use of SSBs. For those who want to kick the habit of drinking sugary soda, diet soda may be the beverage equivalent of a nicotine patch: it can be used in small amounts, for a short time. For most people, plain water and unsweetened coffee or tea are more healthy alternatives to either SSBs or ASBs," Dr. Hu concluded.

Walter Willett, MD, DrPH, Fredrick John Stare professor of epidemiology and nutrition and chair of the Department of Nutrition at Harvard School of Public Health in Boston, Massachusetts, commented on the article in an email interview with Medscape Medical News. He said that although he agrees with the author "that regular consumption of artificial sweeteners is not optimal, as these leave us conditioned to a high level of sweetness, which can distort our food choices," he considers a substantially better option than regular sugar-based choices.

He notes, however, that the review by Dr. Swithers excludes a large analysis of beverages and weight gain, and some studies are misrepresented. "The risk of obesity, diabetes, and cardiovascular disease associated with artificial sweeteners is less than the risk associated with consumption of sugar," he emphasizes.

This research was supported by the National Institutes of Health. Dr. Hu and Dr. Willett have disclosed no relevant financial relationships.

Trends Endocrinol Metabol. Published online July 10, 2013. Full text


Energy Drinks May Prolong QT Interval, Raise BP

Medscape Link

New Orleans, Louisiana — Tossing back one to three energy drinks may result in more than just a buzz. A small-meta analysis found that immediately afterward, subjects had increased systolic blood pressure and, more troubling, they also had, on average, a 10-msec prolongation in their QT interval [1].

The study, by Dr Sachin Shah (University of the Pacific, Stockton, CA) and colleagues, was presented at EPI-NPAM 2013, the Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions.

"The blood-pressure finding falls in line with what we would suspect because of the caffeine content," Shah told heartwire . "The QT prolongation that we are seeing--I was very surprised with that. It's a bit of a wake-up call for us investigators to start studying it a bit more thoroughly, and it needs to happen sooner rather than later."

The group aimed to see how energy drinks affect heart health, given that these drinks, along with dietary supplements, are not regulated as stringently as new drugs that must meet Food and Drug Administration (FDA) safety requirements, Shah said.

In a literature search, they identified seven observational and interventional trials that evaluated the impact of energy drinks on QT interval, blood pressure, and heart rate.

Three studies with a pooled sample of 93 subjects had QT/QTc data. Six studies with a pooled sample of 132 subjects had blood-pressure data, and seven studies investigated heart rate.

The patients, who were all young (aged 18 to 45) and healthy, underwent ECG and blood-pressure testing before and just after drinking one to three cans of energy drink--most commonly Red Bull, but also others such as Full Throttle and Meltdown RTD. An 8.4-oz can of Red Bull contains 80 mg of caffeine, compared with 35 mg of caffeine in a 12-oz Coke or about 100 mg of caffeine in an average cup of coffee, Shah said.

Shortly after drinking the energy drinks, the pooled subjects had a systolic blood pressure increase of an average 3.5 mm Hg. "If people are drinking energy drinks every day, that change in blood pressure could be very significant," Shah noted, adding that, as reported by heartwire , research on torcetrapib was terminated because of a similar 3-mm-Hg increase in blood pressure.

People who don't normally drink coffee might have a heightened blood-pressure response to an energy drink, he added.

In a clinical setting, physicians are usually concerned if a patient has a QT-interval increase of about 30 msec from baseline, Shah noted. He acknowledges that this was a small study, but it did uncover a disturbing signal that needs to be further investigated.

Diastolic BP and heart rate increased nonsignificantly.

Although the 10-msec prolongation in the QT interval is a "small number, if it were consistently produced by a drug being considered by the FDA, the FDA would require more testing to make sure that there was not a liability for producing further, more serious, and life-threatening prolongation of the QT interval and associated arrhythmias," AHA spokesperson and past president Dr Gordon F Tomaselli (Johns Hopkins University, Baltimore, MD) commented.

Both Shah and Tomaselli pointed out that people who are older or who have underlying CVD might have even more heart-related side effects from energy drinks than the young, healthy people in this meta-analysis.

Sunday, July 28, 2013

Intermittent Renal Replacement Therapy Linked with Dialysis Dependence in AKI Patients.

In a systematic review and meta-analysis of 23 studies of dialysis dependence among survivors of severe acute kidney injury treated with either intermittent renal replacement therapy (IRRT) or continuous RRT (CRRT), pooled analyses of randomized clinical trials showed no difference in the rate of dialysis dependence among survivors. However, pooled analyses of observational studies found that patients receiving IRRT having a twofold increased risk of dialysis dependence. The analysis examined 23 studies that included seven randomized controlled trials with 472 patients and 16 observational studies with 3499 patients. The findings (7/26) are published in Intensive Care Medicine.

Many Current Medical Tests and Procedures Offer No Net Benefits.

A new analysis documents 146 contemporary medical practices, such as tests and procedures, that have subsequently been reversed over the past 10 years. Investigators evaluated 1344 original articles from the New England Journal of Medicine that examined a new medical practice or tested an established one. Only 27% of articles testing a practice tested an established one. Of the articles that tested current medical practice, 40.2% found these practices to be ineffective. Another 38% reaffirmed the value of current practice, and 21.8% were inconclusive. The findings are published in Mayo Clinic Proceedings.

Obese Kidney Failure Patients Receive Survival Benefit from Transplantation

Obese kidney transplant recipients with a BMI less than 40 kg/m² derived a similar survival advantage from transplantation as nonobese patients, equating to more than a 66% reduced risk of dying within 1 year. Between 1995 and 2007, obese patients with a BMI of 40 or higher derived a lower survival advantage from transplantation (48% reduced risk of dying within 1 year), and a survival advantage was uncertain in black patients with a BMI of 40 or higher. Differences in obese and nonobese patients were not as profound with live donor transplantations, according to the American Journal of Transplantation study.

Frequent and Longer Patient-Doctor Contact May Prolong Dialysis Patients’ Lives

Compared with patients in dialysis facilities having frequent patient-doctor contact (more than once per week), those with intermediate contact (once per week) and infrequent contact (less than once per week) had a 6% and 11% higher risk of dying, respectively, during the 12-year study period. Each 5 minutes shorter duration of contact was linked with a 5% higher risk of dying. More frequent and longer contact was also linked with fewer hospitalizations. The JASN study, which included 24,498 patients, involved information from 1996 to 2008 from 778 dialysis facilities in numerous countries.

Bendeavia Protects Kidney From AKI

Bendeavia Protects Kidney From AKI
A novel agent SS-31 (Bendavia) can accelerate ATP recovery after ischemia and reduce AKI, but its MOA remained unclear. Latest research shows Bendavia helps protect a unique cardiolipins on the inner mitochondrial membrane that is critical in the pathway to generate ATP. May be a first therapeutic option to reduce the incidence of AKI.

Yearly Increase in Renal Replacement Therapy Population Slowing

The percentage of early dialysis starts—defined as the initiation of renal replacement therapy (RRT) at an eGFR ≥10 mL/min/1.73 m²—grew from 19% to 54% of all new starts between 1996 and 2009 but stabilized between 2009 and 2011. Similarly, the incident RRT population increased between 1996 and 2005, with early dialysis starts accounting for most of the increase. Between 2005 and 2010, the increase slowed dramatically. The JASN results suggest that later dialysis starts and greater use of conservative and palliative care will continue to attenuate the increase in the RRT population observed in previous years.

Poor Adherence to Antihypertensive Therapy Increases Stroke Risk

Poor adherence to antihypertensive therapy increases short- and long-term risk of stroke among hypertensive patients, according to aEuropean Heart Journal study using records from Finnish national registers. At 2 and 10 years after starting continuous antihypertensive medication, nonadherent patients had 3.81 and 3.01 times higher odds of dying from a stroke compared with adherent patients. The odds for stroke hospitalization was 2.74 at year 2 and 1.71 at year 10 for nonadherent patients. Associations between nonadherence and stroke followed a dose–response pattern: the poorer the adherence, the greater the risk of death and hospitalization due to stroke.

Non–Calcium-Based Phosphate Binders Linked with Decreased Risk of Mortality

According to a systematic review of clinical trials between August 2008 and October 2012, patients with CKD who were assigned to non–calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders. The analysis included 11 randomized trials (4622 patients). The findings are published in The Lancet. Phosphate binders are recommended to lower serum phosphate and prevent hyperphosphatemia in patients with CKD, but the drugs’ effects on mortality and cardiovascular outcomes have been unknown.

Discovery May Lead to New Small Molecule Treatment for Hypertension

Researchers have discovered a compound that mimics the action catestatin, a hormone that controls the secretion of catecholamines, which in turn regulate blood pressure. After studying how catestatin binds nicotinic acetylcholine receptors, the team developed a 3D model of its active centers and screened a library of compounds for molecules matching this fingerprint. Seven compounds met the requirements and were tested in live cells to gauge their effects on catecholamines. Investigators tried one compound (TKO-10-18) on hypertensive mice and showed that it produced the same antihypertensive effect as catestatin. The findings are published inBioorganic & Medicinal Chemistry.

Skipping breakfast may be linked to higher heart attack risk in older men.

The AP (7/23, Stobbe) reports that “a study of older men found those who regularly skipped breakfast had a...higher risk of a heart attack than those who” did not skip breakfast. For the study, published in Circulation, investigators surveyed approximately “27,000 men about their eating habits in 1992.” Roughly 13 percent indicated that they usually did not eat breakfast. Respondents “all were educated health professionals...and were at least 45.”
        The Los Angeles Times (7/23, Macvean, 692K) “Science Now” blog reports that the investigators “found that men who skipped breakfast had a 27% higher risk of coronary heart disease than men who ate their morning meal.”
        On its website, CBS News (7/23) reports, “younger men were more likely to skip breakfast than older ones, as were smokers, the unmarried, alcohol drinkers, people who were less physically active and those who had full-time jobs.”
        NBC News (7/23) reports on its website that “another key finding was that men who reported ‘eating late at night’ had a 55 percent higher coronary heart disease risk compared to those who didn’t, but the subgroup of participants was very small, just 313 men, or about 2 percent.” Also covering the story are Forbes (7/23, 928K), the Huffington Post (7/23), HealthDay (7/23, Thompson), and MedPage Today (7/23, Neale).

Resistant Hypertension Common Among Chronic Kidney Disease Patients

More than 50% of individuals with moderate chronic kidney disease have hypertension that is resistant to medications, according to aJASN study. Blacks and those with a larger waist circumference, diabetes, and a history of heart attacks or strokes are especially at risk. The findings come from an analysis of 10,700 kidney disease patients who were treated for hypertension in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Identifying individuals at high risk of developing resistant hypertension who may benefit from intensive blood pressure monitoring and early treatment should be a high priority, the authors said.

Weight Loss in Pre-Diabetics May Prevent Diabetes

People with pre-diabetes who lost 10% or more of their weight through a lifestyle intervention program had an 85% reduced risk of developing diabetes within 3 years. Those who lost 5% to 7% of their weight reduced their risk by 54%. More than 3000 overweight, hyperglycemic participants were randomized to receive an intense lifestyle intervention, the diabetes drug metformin, or a placebo. Those given metformin did not lose significant amounts of weight on average, but those whose blood sugar levels were significantly lowered reduced their diabetes risk. The Journal of General Internal Medicine findings come from the Diabetes Prevention Program.

Androgen Deprivation Therapy Linked to Acute Kidney Injury

In a study of more than 10,000 patients with newly diagnosed nonmetastatic prostate cancer, those who used androgen deprivation therapy had nearly 2.5 times the odds of developing acute kidney injury compared with those who never used the therapy, which corresponds to a rate difference of 4.43/1000 persons per year. This association was mainly driven by a combined treatment of gonadotropin-releasing hormone agonists with oral antiandrogens, estrogens, other combination therapies, and gonadotropin-releasing hormone agonists. Bilateral orchiectomy and monotherapy with an antiandrogen did not significantly affect the risk of acute kidney injury. The findings are published in JAMA.

Colistin associated with higher rate of AKI than polymyxin B in critically ill

Critically ill patients who were given intravenous colistin had a greater incidence of acute kidney injury (AKI) than those given polymyxin B, a study found.
In a retrospective cohort study, researchers examined data on 67 adult patients who received intravenous polymyxin B (PB) between January 2008 and June 2009 and 106 patients who received colistin from January 2009 through June 2010, both for at least 72 hours. Patients with normal renal function had PB dosed at 15,000 to 25,000 units/kg per day as a continuous infusion over 24 hours. Colistin was dosed at 5 mg/kg of ideal body weight per day or actual body weight or as a fixed dose of 150 mg every 12 hours. RIFLE (risk, injury, failure, loss and end-stage kidney disease) criteria were used to define nephrotoxicity and to evaluate the severity of acute renal failure. Both agents were mostly used to treat multidrug-resistant Pseudomonas aeruginosa andAcinetobacter baumannii infections, and most patients were in the ICU.
The mean treatment duration was 11.7 days for colistin and 12.5 days for PB (P=0.66). Nephrotoxicity developed in 60.4% of colistin patients and 41.8% of PB patients (P=0.02). Among those who developed it, the difference in time to peak serum creatinine wasn't significantly different between groups. Most patients who developed acute renal failure fell into the reversible kidney injury category. Only one patient progressed to end-stage renal disease (from the colistin group). Results were published online July 9 in Clinical Infectious Diseases.
The study is limited by its retrospective nature and small sample size and by the fact that the drugs were studied in two different time periods, so potential variations in practice could have affected results. Also, dose adjustments or drug discontinuations due to acute renal failure weren't captured. Overall, the study adds more strength to previous results showing a temporal relationship between using these agents and development of nephrotoxicity, the authors wrote, and patients who take them should be closely monitored.

Elevated blood pressure becoming more common in children.

NBC Nightly News reported that new research has “found an alarming increase in children with high blood pressure.”
        The Los Angeles Times (7/16, Morin, 692K) “Science Now” blog reports that researchers found that “the risk of elevated blood pressure among children and teens has risen 27% over a 13-year period, and is probably caused by over-consumption of salt and rising obesity.” For the study, published in Hypertension, investigators “examined health and nutrition data for more than 11,600 children ages 8 to 17” who were participating in National Health and Nutrition Examination Surveys. The researchers “concluded that changes in eating habits over the last two decades, dependence on processed foods and excessive salt intake were putting more U.S. children at future risk of stroke, heart disease and kidney failure.”
        On its website, NBC News (7/16) reports, “The damage from far too much dietary sodium has been especially pronounced in African-American girls, accounting for much of the higher rate of increase in girls compared to boys, said Daniels, chair of the Department of Pediatrics at the University of Colorado School of Medicine, and the chair of the National Heart, Lung and Blood Institute’s panel that created guidelines for cardiovascular health and risk reduction in children.”

Kidney disease kills more in US than breast, prostate cancers combined.

A 1,000-word entry in the New York Times (7/15, Brody, 1.68M) “Well” blog discusses the human toll and the cost of kidney disease in the US. In the US, kidney disease causes more deaths than breast and prostate cancer combined. According to the blog, “the cost of treating end-stage kidney disease through dialysis or a kidney transplant is astronomical, more than fivefold what Medicare pays annually for the average patient over age 65.” These “charges do not include the inestimable costs to quality of life among patients with advanced kidney disease.” The blog profiles an individual diagnosed with minimal-change disease.

Treatment candidate helps increase, maintain CKD patients’ hemoglobin levels.

The Wall Street Journal (7/12, Chaudhuri, Subscription Publication, 2.29M) reports Rockwell Medical Inc. on Thursday announcedpositive results from the first of two Phase III clinical trials testing it investigational treatment for anemia in patients with chronic kidney disease who are undergoing hemodialysis.
        According to the AP (7/12, Seaman), the Wixom, Michigan-based biopharmaceutical company said the participants in the late-stage study who were administered its treatment candidate, soluble ferric pyrophosphate (SFP), had increased hemoglobin levels and were “also better able to maintain their hemoglobin levels.” Rockwell suggested that “small, frequent doses” of SFP, “designed to travel directly to the bone marrow” to avoid liver damage, “could be safer and more effective than the standard treatment, which involves large doses of intravenous iron.”
        Reuters (7/12, Dey, Manocha) adds that Rockwell said it expects results from the second Phase III trial testing SFP, which is nearing completion, to confirm the results released yesterday, after which the company plans to submit the combined data with a new drug application to the US Food and Drug Administration. MedPage Today (7/12, Fiore) also covers the story.

People Who Eat at Least Five Servings of Fruits and Vegetables Per Day Live Longer

In an American Journal of Clinical Nutrition study of more than 71,000 Swedes, those who said they never ate fruit and vegetables died an average of 3 years sooner than those who ate five or more servings a day. Participants who ate at least one serving of fruit daily lived an average of 19 months longer than those who never ate fruit. Those who ate at least three servings of vegetables per day lived an average of 32 months longer than people who reported never consuming vegetables. Participants were aged 45 to 83 years and were followed for 13 years.

Proteinuria Correlates with Rate of Renal Decline.

In a JASN study of 638,150 adults, heavy proteinuria and a baseline eGFR of 45 mL/min/1.73 m² to 59.9 mL/min/1.73 m² correlated with a change in eGFR of −2.16 per year in men, while mild proteinuria and a baseline eGFR of 30 to 44.9 correlated with a change in eGFR of −0.51 per year. Similar trends were observed for female, elderly, and diabetic patients. Normal protein levels and a lower baseline eGFR correlated with stable or improved kidney function. The results suggest that proteinuria of increasing severity is associated with a faster rate of renal decline, regardless of baseline eGFR.

Telmisartan and Valsartan Linked with Lower Risk of Heart Disease in Diabetics

Two angiotensin-receptor blockers, telmisartan and valsartan, were each linked with about a 15% lower risk of hospitalization for heart attack, stroke, or heart failure than other drugs in their class (candesartan, irbesartan, and losartan). The CMAJ study examined data from 54,186 Ontario residents with diabetes who were older than age 65 and who took angiotensin-receptor blockers between 2001 and 2010. The findings suggest that important differences exist in the effectiveness of angiotensin-receptor blockers when used for the prevention of diabetes-related macrovascular disease.

New Cancer Imaging Technique Could Provide Alternative to Nephrotoxic Contrast Dyes

A new MRI technique that detects glucose uptake could provide a safe and simple option for detecting cancer and assessing response to therapy. Because tumors consume more glucose than normal tissues, sensitizing an MRI scanner to glucose uptake caused colorectal tumors to appear as bright images on MRI scans of mice, researchers report in Nature Medicine. The new technique—glucose chemical exchange saturation transfer (glucoCEST)—allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water, and could potentially provide an alternative to nephrotoxic contrast mediums.

Saturday, July 27, 2013

Researchers use stem cells to create human liver “buds.”

Research suggesting stem cells may be used to create human liver “buds” received moderate coverage in print and online, but no mention on the national news broadcasts. While some sources and experts hailed the findings as a breakthrough, others pointed out that the research is at a very early stage, and it remains to be seen whether the technique can actually be used to benefit humans.
        The Wall Street Journal (7/5, Naik, Subscription Publication, 2.29M) reports that scientists have used stem cells to create human liver “buds,” according to a paper (7/5) published in Nature.
        USA Today (7/3, Vergano, 1.71M) reported that the “buds,” which were “implanted in...mice, represent a first experimental step in growing replacement organs from stem cells for transplants, such as liver, pancreas and kidneys, says the research team headed by Japan’s Takanori Takebe of the Yokohama City University Graduate School of Medicine.”
        The Los Angeles Times (7/3, Kaplan, 692K) “Science Now” blog reports that the team used induced pluripotent stem cells and grew them “into liver buds in about 48 hours” then they implanted them in mice. “It took another two days for the buds to grow blood vessels and connect to the circulatory system.” Eventually “the buds grew into organs that resembled mature livers and expressed the same genes.”
        The New York Times (7/4, A3, Kolata, Subscription Publication, 1.68M) reports that Dr. Hillel Tobias, chairman of the American Liver Foundation’s national medical advisory committee, called the findings “a major breakthrough of monumental significance.”
        On its website, NBC News (7/4, Fox) reported, however, that “other experts were cautious about the findings.” Dr. John Gearhart, a stem cell expert at the University of Pennsylvania, said, “This is a good start, again employing basic science to form a bud, but long way off for producing truly functional hepatic...tissue for the clinic.”
        The U-T San Diego (7/3, 242K) reports, “Other organs...can be produced by the bud process, Takebe said,” although “it will take about 10 years before the method is ready for human clinical trials.”
        On its website, CBS News (7/5, Castillo) reports that Takebe “hopes in the future researchers can create liver buds small enough to be transfused intravenously, and forsees that this method could also be used to create new pancreas or kidney cells.”
        Also covering the story were Reuters (7/4, Kelland), Bloomberg News (7/5, Lopatto), MedPage Today (7/4, Gever), and HealthDay(7/5, Goodman).

Olmesartan Medoxomil: Drug Safety Communication - Label Changes To Include Intestinal Problems (Sprue-Like Enteropathy)

AUDIENCE: Health Professional, Cardiology, Patient
ISSUE: FDA is warning that the blood pressure drug Olmesartan Medoxomil (marketed as Benicar, Benicar HCT, Azor, Tribenzor, and generics) can cause intestinal problems known as sprue-like enteropathy. Symptoms of sprue-like enteropathy include severe, chronic diarrhea with substantial weight loss. FDA has approved changes to the labels of these drugs to include this concern. Sprue-like enteropathy has not been detected with ARB drugs other than olmesartan. 
FDA will continue to evaluate the safety of olmesartan-containing products and will communicate again if additional information becomes available.
BACKGROUND: Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) approved for the treatment of high blood pressure, alone or with other antihypertensive agents, and is one of eight marketed ARB drugs. 
RECOMMENDATION: Health care professionals should tell patients to contact them if they develop severe, chronic diarrhea with substantial weight loss while taking an olmesartan-containing product, even if it takes months to years for symptoms to develop. Patients should contact their health care professional right away if they take an olmesartan-containing product and experience severe diarrhea, diarrhea that does not go away, or significant weight loss.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
  • Complete and submit the report Online:
  • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:

Medicare Releases Proposed Cuts to ESRD Bundle

The Centers for Medicare & Medicaid Services has proposed a rule to update payment policies and rates under the ESRD Prospective Payment System for dialysis services for 2014. It would reduce the composite rate in the ESRD bundle by 12%. The cut would actually amount to 9.4%, because the kidney community would receive a 2.6% increase based on the market basket analysis for 2014. The rule also proposes changes to the ESRD Quality Incentive Program: adopting five new clinical and reporting measures, continuing to use six existing measures, revising two measures, and expanding one measure.

6 Easy Ways To Prevent Kidney Stones

National Kidney Foundation link

Did you know that one in ten people will have a kidney stone over the course of a lifetime? Recent studies have shown that kidney stone rates are on the rise across the country. Those in the know believe that some major misconceptions may be the culprit.
The National Kidney Foundation has teamed up with Dr. Allan Jhagroo, a kidney stone specialist at the University of Wisconsin School of Medicine and Public Health, to help you stay stone-free this summer by debunking some of the major kidney stone myths and misconceptions.
"It's not just patients who have fallen prey to kidney stone misconceptions. It's surprising how many practicing doctors and nephrologists have the information all wrong when it comes to stones," said Dr. Jhagroo.
Have you succumbed to any of these myths? Find out by learning the latest kidney stone facts! The National Kidney Foundation sets the record straight with the top 6 kidney stone prevention tips:
  1. Watch the Sweat. Saunas, hot yoga and heavy exercise may be good for your health, but they also may lead to kidney stones. Why? Loss of water through sweating - whether due to these activities or just the heat of summer—leads to less urine production. The more you sweat, the less you urinate, which allows for stone-causing minerals to settle and bond in the kidneys and urinary tract.
    Instead: Hydrate with H2O. One of the best measures you can take to avoid kidney stones is to drink plenty of water, leading you to urinate a lot. So, be sure to keep well hydrated, especially when engaging in exercise or activities that cause a lot of sweating.
  2. Don't Reduce the Oxalate. Oxa-what? Oxalate is naturally found in many foods, including fruits and vegetables, nuts and seeds, grains, legumes, and even chocolate and tea. Some examples of foods that contain high levels of oxalate include: peanuts, rhubarb, spinach, beets, chocolate and sweet potatoes. Calcium oxalate kidney stones are the leading type of kidney stones. A common misconception is that cutting the oxalate-rich foods in your diet will reduce the likelihood of forming calcium oxalate kidney stones. While in theory this might be true, this approach isn't smart from an overall health perspective. Most kidney stones are formed when oxalate binds to calcium while urine is produced by the kidneys.
    Instead: Eat and drink calcium and oxalate-rich foods together during a meal. In doing so, oxalate and calcium are more likely to bind to one another in the stomach and intestines before the kidneys begin processing, making it less likely that kidney stones will form.
  3. Calcium is Not the Enemy. But it tends to get a bad rap! Most likely due to its name and composition, many are under the impression that calcium is the main culprit in calcium-oxalate stones. "I still see patients who wonder why they are getting recurring stones despite cutting down on their calcium intake," said Dr. Jhagroo. "I've even had patients say that their doctors told them to reduce their calcium intake." A diet low in calcium actually increases one's risk of developing kidney stones.
    Instead: Don't reduce the calcium. Work to cut back on the sodium in your diet and to pair calcium-rich foods with oxalate-rich foods.
  4. It's Not One and Done. Passing a kidney stone is often described as one of the most painful experiences a person can have, but unfortunately, it's not always a one-time event. Studies have shown that having even one stone greatly increases your chances of having another. "Most people will want to do anything they can to ensure it doesn't happen again," said Dr. Jhagroo. "Unfortunately, it doesn't seem to be the case that people make the changes they need to after their first stone event." Research conducted by Dr. Jhagroo shows that those with kidney stones do not always heed the advice of their nephrologists and urinary specialists. About 15% of kidney stone patients didn't take prescribed medications and 41% did not follow the nutritional advice that would keep stones from recurring.
    Instead: Take action! Without the right medications and diet adjustments, stones can come back, and recurring kidney stones also could be an indicator of other problems, including kidney disease.
  5. When Life Hands You Kidney Stones… don't fret. And as the saying goes, "make lemonade." It's important to consider dietary remedies alongside prescription medications. While it may seem easier to just take a pill to fix a medical problem, consider what lifestyle changes will also make a big impact on your health.
    Instead: Next time you drive past a lemonade (or limeade) stand, consider your kidneys. Chronic kidney stones are often treated with potassium citrate, but studies have shown that limeade, lemonade and other fruits and juices high in natural citrate offers the same stone-preventing benefits. Beware of the sugar, though, because it can increase kidney stone risk. Instead, buy sugar-free lemonade, or make your own by mixing lime or lemon juice with water and using a sugar substitute if needed. "We believe that citrate in the urine may prevent the calcium from binding with other constituents that lead to stones," said Dr. Jhagroo. "Also, some evidence suggests that citrate may prevent crystals that are already present from binding with each other, thus preventing them from getting bigger."
  6. Not All Stones are Created Equal. Behind calcium oxalate stones, the second most common type of kidney stones is uric acid stones. Meat and most high-protein foods have high concentrations of a natural chemical compound known as purines. "High purine intake leads to a higher production of uric acid and produces a larger acid load for the kidneys to excrete," said Dr. Jhagroo. Higher uric acid excretion leads to lower overall urine pH, which means the urine is more acidic. The high acid concentration of the urine makes it easier for uric acid stones to form.
    Instead: To prevent uric acid stones, mind your meats. Cut down on high-purine foods. These include organ meats such as liver, tongue, and sweetbreads, anchovies, sardines, bacon, beef, cauliflower, codfish, ham, veal and venison.
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©2013 National Kidney Foundation. All rights reserved. This material does not constitute medical advice. It is intended for informational purposes only. Please consult a physician for specific treatment recommendations.

Top 5 Things Kidney Patients Need to Know About Healthcare Reform

Dendritic Cell Therapy May Improve Graft Survival after Kidney Transplantation

Injecting donor dendritic cells prior to kidney transplantation was linked to significantly longer graft survival durations in an animal model. A new American Journal of Transplantation study found administering specialized immune cells derived from donor blood monocytes 7 days before surgery extended median survival to 113.5 days compared to 39.5 days for controls. Both the groups received the same experimental immunosuppressive regimen designed to induce rejection. No adverse effects or evidence of host sensitization were observed in the dendritic cell group. This could potentially lead to regimens that reduce the need for immunosuppressive therapies.

Arteriovenous Fistulas and Grafts Provide Similar Survival Advantages for Elderly Dialysis Patients

Although using an arteriovenous fistula improved survival compared with an arteriovenous graft in dialysis patients in their late 60s and 70s, patients in their 80s and 90s experienced similar survival rates with the two procedures. The findings come from a 4-year study of 115,000 patients over 66 years of age. Catheter use was linked with more than a 74% increased risk of death in patients of any age. The JASN results suggest that vascular access procedures should be tailored to individual elderly patients—a graft may be a reasonable alternative to a fistula for some.

Intensive Blood Pressure Lowering May Protect Against Kidney Failure in CKD

Compared with standard regimens, a more intensive blood pressure-lowering strategy reduced the risk of kidney failure events (defined as either a composite of doubling of serum creatinine level and 50% decline in GFR, or ESRD) by approximately 20% in a recent systematic review of all relevant reports published between 1950 and 2011. Intensive blood pressure lowering reduced the risk of kidney failure by 27%, but not in patients without proteinuria at baseline. The CMAJ review found no clear effect on the risk of cardiovascular events or death.

CKD Linked with High Risk for Recurrent Coronary Heart Disease

The risk for recurrent coronary heart disease (CHD) events associated with CKD is similar or greater than established high-risk factors including diabetes, metabolic syndrome, and cigarette smoking. In an American Heart Journal study of 3938 individuals aged 45 years and older with CHD, the incidence of recurrent CHD events over a median of 4.1 years was 12.1 among those without CKD or high-risk factors, 18.9 among those with very high-risk factors alone, 35.0 among those with CKD alone, and 34.2 among those with both CKD and very high-risk factors. CKD and/or other high-risk factors also increased mortality risk.

Short walk after meals could improve health.

The New York Times (6/24, O’Connor, 1.68M) reports in its “Well” blog on the findings of various studies where “researchers have found that a post-meal walk, as short as 15 minutes, can in fact help with digestion and improve blood sugar levels.” A recent study published in Diabetes Care “found that in older adults who were overweight and sedentary, walking for 15 minutes shortly after each meal improved daily blood sugar levels to a greater extent than a single 45-minute walk in the morning.”

Study shows weight loss, exercise don’t reduce heart risks in T2D.

The Wall Street Journal (6/25, D1, Dooren, Subscription Publication, 2.29M) reports long-term weight-loss study involving 2,600 overweight adults with Type 2 diabetes did not reduce the rate of heart attacks and strokes, but it did show a reduction in developing chronic kidney disease, as well as other benefits, such as a decrease in medicine use, depression and hospital visits. The results of the study were published in the New England Journal of Medicine and presented Monday at the American Diabetes Association’s annual meeting. The 13-year-study, titled Look AHEAD (Action for Health in Diabetes), was ended early by the National Institute of Health after it became evident that the study would not show a reduction in cardiovascular events. When the study was terminated, participants in an intensive group that exercised and reduced calories had only loss 6% of their body weight, compared to the control group that lost 3.5%. Researchers are not sure the 2.5% difference between the groups is enough to conclude a reduction in cardiovascular events.
        USA Today (6/24, Hellmich, 1.71M) reports Rena Wing, a professor of psychiatry and human behavior at Brown University and chairman of the Look AHEAD study, said “Weight loss is still important, but the reasons why it is important are different than we thought.” Wing also said that “there was no difference between the two groups in the incidence of heart attacks and strokes, but the incidence was low in both groups.” Tim Church, director of preventive medicine research at the Pennington Biomedical Research Center in Baton Rouge, added, “Other short-term studies have shown the benefits of weight loss (for people with diabetes), but this is the first large, long-term trial examining a diverse set of health benefits.”
        Contributor Larry Husten writes in Forbes (6/24, 928K) that a ray of hope in the study “was that people in the intervention group were less likely to be treated with insulin during the first year of the trial and were more likely to have a partial remission of diabetes during the initial 4 years of the trial. In addition, as the trial investigators had previously reported, during the early years of the trial people in the intervention group had reductions in urinary incontinence, sleep apnea, and depression and improvements in quality of life, physical functioning, and mobility.” Additionally, the study’s authors “speculated that a larger weight loss in the intervention group might have produced better results,” but they noted the “weight loss achieved in the intervention group is representative of the best that has been achieved with current lifestyle approaches.”
        HealthDay (6/25, Goodman) and MedPage Today (6/25, Fiore) also cover this story.

Thyroid Hormone Replacement Slows Kidney Function Decline in CKD Patients with Subclinical Hypothyroidism

Before patients with CKD and subclinical hypothyroidism received thyroid hormone replacement therapy (THRT) with L-thyroxine, eGFR declined by 4.31 mL/min/1.73 m² each year on average, but after they received THRT, kidney function declined by 1.08 mL/min/1.73 m² each year. Based on the slope of eGFR decline prior to THRT, 53 of the 113 patients in the study (46.9%) would reach stage 5 CKD within 10 years. However, with THRT, researchers estimated that only 10 patients (8.8%) would reach this outcome in 10 years. Thus, THRT delayed kidney failure in 43 of 53 (81%) of patients. The findings are published in Thyroid.

Iron Dosing Affects Dialysis Patients’ Infection Risk

Providing a large amount of intravenous iron over a short period of time (bolus dosing) was associated with increased risks of serious infection and infection-related death in a JASN study of 117,050 dialysis patients who were followed for 3 months. Twelve percent received bolus dosing of iron, 49% received maintenance dosing, and 38% received no iron. With bolus dosing, there were 25 additional infections per 1000 patient-years compared with maintenance dosing. Risks were particularly high among patients who used a catheter for dialysis and for those with a history of recent infection. Maintenance dosing did not increase patients’ infection risk.

Intense workouts, races may be dangerous for middle-aged men.

In a 1,500-word article, Bloomberg News (6/21, Khan, Pettypiece) reports that “as the average age of competitors in endurance sports rises, a spate of deaths during races or intense workouts highlights the risks of excessive strain on the heart through vigorous exercise in middle age.” Although the “benefits of exercise are well-known, researchers now suspect that there may be a point at which exertion becomes dangerous, especially for middle aged men.”

American Medical Association Says Obesity is a Disease

The American Medical Association has officially recognized obesity as a disease, a move that may help in the fight against diabetes and heart disease by improving reimbursement for medications, surgery, and counseling. The vote of the AMA House of Delegates went against the conclusions of the association’s Council on Science and Public Health, which stated that BMI measurements, which are usually used to define obesity, are simplistic and flawed. Also, opponents said declaring obesity a disease would define one-third of Americans as being ill and could lead to more reliance on drugs and surgery rather than lifestyle changes.