Common Herbicide May Devastate Future Generations

Common Herbicide May Devastate Future Generations

The study provides evidence that glyphosate-induced changes to exposed rats could be used as biomarkers for determining propensity in subsequent generations for prostate and kidney diseases as well as obesity and incurring multiple diseases at once. In fact, by the time third- and fourth-generation rats whose predecessors had been exposed to the chemical were middle-aged, 90% had one or more of these health problems, a dramatically higher rate than the control group.

Epigenome-wide association study for glyphosate induced transgenerational xxxxx DNA methylation and histone retention epigenetic biomarkers for disease

https://www.tandfonline.com/doi/full/10.1080/15592294.2020.1853319

#glyphosate #herbicide #epigenome

Glyphosate, herbicide, transgenerational, histone, DNA methylation, prostate, kidney, obesity, epigenetic transgenerational inheritance of pathology, toxicology, pesticide, organic, generation, diagnostic tests, germline epimutation, include imprinted-like gene characteristics

Lung Scarring Reversed

Lung Scarring Reversed

Lung Scarring Reversed
In an unexpected discovery scientists witnessed fibrosis going into remission and the lungs begin to normalize function in only 4 weeks, with the introduction of RAGE into the cells.

Citation:
Homeostatic nuclear RAGE–ATM interaction is essential for efficient DNA repair Nucleic Acids Research, Volume 45, Issue 18, 13 October 2017, Pages 10595–10613, DOI:10.1093/nar/gkx705

New research shows clear association between ACE inhibitors and acute kidney injury

Contact: Genevieve Maul gm349@admin.cam.ac.uk 44-012-237-65542 University of Cambridge

These and similar drugs are the second most prescribed on the NHS

Cambridge scientists have found an association between ACE inhibitors (and similar drugs) and acute kidney injury – a sudden deterioration in kidney function. The research is published today, 06 November, in the journal PLOS ONE.

ACE inhibitors and related drugs known as angiotensin receptor antagonists (ARAs or ‘sartans’) are the second most frequently prescribed medicines in UK clinical practice, and are used to treat common conditions such as high blood pressure, heart disease and kidney problems, especially in people with diabetes. Although concerns about a link between these drugs and kidney function have been raised in the past, the size of the problem had previously been unknown.

The researchers therefore examined the issue using data from the whole of England. They compared the admission rates for acute kidney injury to English hospitals with the prescribing rates of ACE inhibitors and ARAs. From 2007/8 to 2010/11, there was a 52 per cent increase in acute kidney injury admissions. During this same period of time, there was an increase in the number of prescriptions for ACE inhibitors and ARAs issued by GP surgeries by 16 per cent.

The results show a clear association between the increase in prescriptions and the increase in hospital admissions. The researchers estimate that 1636 hospital admissions with acute kidney injury – which has a mortality rate in the UK of around 25-30 per cent of patients – could potentially have been avoided if the prescribing rate had remained at the 2007/8 levels. They estimate that one in seven cases of acute kidney injury could be due to increased prescriptions for these drugs.

This is the first time that a study has been able to assess the extent to which these medications are linked to acute kidney injury. However, the researchers emphasise that we cannot assume that the medication was a direct cause of the acute kidney injury in this study, and no one should stop taking these medications unless advised by their doctor to do so.

Dr Rupert Payne, senior author of the study from the University of Cambridge’s Institute of Public Health, said: “There has been lots of anecdotal evidence suggesting these drugs may be a contributory factor in patients developing acute kidney injury, and this work gives us an opportunity to estimate the size of the problem, as well as making clinicians and patients more aware of the importance of using these drugs in accordance with current clinical guidelines.

“As both a GP and clinical pharmacologist, it also highlights to me the importance of improving our understanding of the risks and benefits of drugs more generally in the real world of clinical practice, away from the artificial setting of clinical trials.”

Dr Laurie Tomlinson, co-author of the study, added: “As a kidney doctor I have looked after many patients with acute kidney injury who were taking these medications prior to becoming unwell and have often worried that the drugs were doing more harm than good. These results are the first to estimate to what extent these drugs may be contributing to the growing incidence of acute kidney injury. Therefore, they represent the first step of research needed to better define when they can be prescribed safely, which should reduce the growing burden of acute kidney injury and save NHS costs and ultimately lives.”

The researchers will next use large primary care databases to examine the association between the drugs and acute kidney injury for individual patients and, in particular, the role of other medication, patient factors (such as the existence of chronic kidney disease) and infections in causing acute kidney injury.

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For additional information please contact:

Genevieve Maul, Office of Communications, University of Cambridge Tel: direct, +44 (0) 1223 765542, +44 (0) 1223 332300 Mob: +44 (0) 7774 017464 Email: Genevieve.maul@admin.cam.ac.uk

Notes to editors:

The paper ‘ACE Inhibitor and Angiotensin Receptor-II Antagonist prescribing and hospital admissions with acute kidney injury: A longitudinal ecological study’ will be published in the 06 November edition of PLOS ONE.

The live article will be available at http://dx.plos.org/10.1371/journal.pone.0078465

Current Black Market Prices for People and Organs

EEV: This list helps brings the reality of human exploitation a little closer to home. These are generalized estimates, based on few sources.

Click dollar figure to see original post and source information. Last update: October 9, 2013.

  • TRANSPLANT PRICE in U.S. DOLLARS

Click dollar figure to see original post and source information.

  • PRICE per PERSON

http://www.havocscope.com/blackmarket/

Component of citrus fruits found to block the formation of kidney cysts

Contact: Tanya Gubbay tanya.gubbay@rhul.ac.uk 01-784-443-552 Royal Holloway, University of London

A new study published today in British Journal of Pharmacology has identified that a component of grapefruit and other citrus fruits, naringenin, successfully blocks the formation of kidney cysts.

Known as polycystic kidney disease, this is an inherited disorder which leads to the loss of kidney function, high blood pressure and the need for dialysis. Few treatment options are currently available.

The team of scientists from Royal Holloway University, St George’s, University of London and Kingston University London used a simple, single-celled amoeba to identify that naringenin regulates the PKD2 protein responsible for polycystic kidney disease and as a result, blocks formation of cysts.

“This discovery provides an important step forward in understanding how polycystic kidney disease may be controlled,” said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.

“In the study, we have demonstrated how effective the amoeba Dictyostelium is in the discovery of new treatments and their targets. Having previously applied the same method of testing in our work into epilepsy and bipolar treatments, it is clear that this new approach could help us reduce reliance on animal testing and provide major improvements.”

To test how this discovery could apply in treatments, the team used a mammalian kidney cell-line, and triggered the formation of cysts in these cells. They were then able to block the formation of the cysts by adding naringenin and saw that when levels of the PKD2 protein were reduced in the kidney cells, so was the block in cyst formation, confirming that the effect was connected.

Dr Mark Carew, from the School of Pharmacy and Chemistry at Kingston University, said: “Further investigation is underway to understand the action of naringenin at the molecular level. This work will entail looking at the function of the PKD2 protein as a cell growth regulator.”

“Indeed, this study provides a good example of how chemicals identified in plants can help us develop new drugs for the treatment of disease,” added Professor Debbie Baines from St George’s, University of London.

“Autosomal dominant polycystic kidney disease affects between 1 in 10 people on dialysis and 1 in 8 with a kidney transplant. Kidney Research UK welcomes this publication that may provide hope for a future new treatment for polycystic kidney disease, alongside its own on-going research focusing on tackling this common genetic kidney disease,” said Elaine Davies, Head of Research Operations at Kidney Research UK.

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The research was funded by a SWan (SouthWest London Academic Network) research grant.

Chinese man kept alive for 13 years with homemade dialysis machine

Monday, Jan 28, 2013 The New Paper

CHINA – A man in China suffering from kidney disease has been using a homemade dialysis machine for the last 13 years.

Mr Hu Songwen, from Nantong, Jiangsu province, was diagnosed with uraemia in 1993, reported the Guangzhou-based Southern Weekly.

For six years, he received 13 dialysis treatments a month and this used up his family’s savings, the paper reported.

Mr Hu began experimenting with the machine in 1996, buying the necessary parts and solutions to conduct blood-filtering treatment at home.

He said the process costs only 60 yuan (S$12) each time, eight times cheaper than the cost of haemodialysis in a hospital.

Mr Hu built his own haemodialysis machine with medical equipment, such as a blood pump and plastic tubing bought from a local market, reported Xinhua news agency.

Three times a week, Mr Hu sits on a small toilet in his home and fires up his homemade dialysis machine.

Mr Hu mixes potassium chloride, sodium chloride and sodium hydrogen carbonate into purified water to make dialysis fluid before undergoing the procedure.

“Most people who suffer from kidney disease are unaware of the theory behind the machines,” he said.

Common anti-fever medications pose kidney injury risk for children

Contact: Eric Schoch eschoch@iu.edu 317-274-8205 Indiana University

Sick children, especially those with some dehydration from flu or other illnesses, risk significant kidney injury if given drugs such as ibuprofen and naproxen, Indiana University School of Medicine researchers said Friday.

In an article published online Jan. 25 by the Journal of Pediatrics, Jason Misurac, M.D., and colleagues from IU and Butler University reported that nearly 3 percent of cases of pediatric acute kidney injury over a decade could be traced directly to having taken the common nonsteroidal anti-inflammatory drugs, or NSAIDs.

Although relatively few in terms of percentage of total kidney damage cases, the children with problems associated with NSAIDs included four young patients who needed dialysis, and at least seven who may have suffered permanent kidney damage, the researchers said.

“These cases, including some in which patients’ kidney function will need to be monitored for years, as well as the cost of treatment, are quite significant, especially when you consider that alternatives are available and acute kidney injury from NSAIDs is avoidable,” Dr. Misurac, a fellow in pediatric nephrology, said.

Although such drugs have been linked to kidney damage in small, anecdotal reports, the study reported Thursday is believed to be the first large-scale study of the incidence and impact of acute kidney injury caused by NSAIDs.

The research team evaluated medical records at Riley Hospital for Children at IU Health in Indianapolis from January 1999 through June 2010 and found 1,015 cases in which patients had been treated for acute kidney injury from any cause.

After excluding cases in which the acute kidney injuries could possibly be explained by other factors, such as diseases affecting kidney function, the researchers found 27 cases, or 2.7 percent, in which the only factors were the administration of NSAIDs. In nearly all cases, the NSAIDs were administered before the children were admitted to the hospital. Because many of the 1,015 cases involved multiple potential causes of acute kidney injury, the researchers said the 27 cases are likely an underestimate of the number of cases in which NSAIDs contributed to the kidney damage.

Among the researchers’ findings:

  • Most of the children had been treated with recommended dosages.
  • All of the children under the age of 5 needed to undergo dialysis temporarily, were more likely than the older children to be placed in an intensive care unit and needed longer hospital stays.
  • The average cost for hospital and kidney specialist fees in the 27 cases was nearly $13,500, and the costs were much higher for younger children. At least $375,000 was spent on the NSAID-associated kidney injury cases at Riley Hospital over the study period, the researchers said, but billing data for other specialists were not available in the database, suggesting that the actual costs were likely much higher.

 

NSAIDs affect kidney function by restricting blood flow to the blood-filtering components of the kidneys, which suggests the risks from the drugs are greater among children who are dehydrated due to the effects of their illness, such as vomiting or diarrhea, Dr. Misurac said.

Fever is normal during an infection and not in itself dangerous, he noted, so “one alternative to NSAIDs would be acetaminophen, but another alternative would be no medication at all, at least for a while, to let the body fight the infection.”

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In addition to Dr. Misurac, authors of the paper are Sharon P. Andreoli, M.D., Jeffrey D. Leiser, M.D., Ph.D., Corina Nailescu, M.D., and Amy C. Wilson, M.D., of the IU School of Medicine, and Chad A. Knoderer, Pharm.D., of the Butler University College of Pharmacy and Health Sciences.

Baking soda appears to slow progression of chronic kidney disease

2009 study posted for filing

Contact: Shari Leventhal
sleventhal@asn-online.org
202-416-0658
American Society of Nephrology

Baking soda: For cooking, cleaning and kidney health?

Sodium bicarbonate appears to slow progression of chronic kidney disease

 

A daily dose of sodium bicarbonate—baking soda, already used for baking, cleaning, acid indigestion, sunburn, and more—slows the decline of kidney function in some patients with advanced chronic kidney disease (CKD), reports an upcoming study in the Journal of the American Society of Nephrology (JASN). “This cheap and simple strategy also improves patients’ nutritional status, and has the potential of translating into significant economic, quality of life, and clinical outcome benefits,” comments Magdi Yaqoob, MD (Royal London Hospital).

The study included 134 patients with advanced CKD and low bicarbonate levels, also called metabolic acidosis. One group received a small daily dose of sodium bicarbonate in tablet form, in addition to their usual care. For this group, the rate of decline in kidney function was greatly reduced—about two-thirds slower than in patients. “In fact, in patients taking sodium bicarbonate, the rate of decline in kidney function was similar to the normal age-related decline,” says Yaqoob.

Rapid progression of kidney disease occurred in just nine percent of patients taking sodium bicarbonate, compared to 45 percent of the other group. Patients taking sodium bicarbonate were also less likely to develop end-stage renal disease (ESRD) requiring dialysis.

Patients taking sodium bicarbonate also had improvement in several measures of nutrition. Although their sodium levels went up, this didn’t lead to any problems with increased blood pressure.

Low bicarbonate levels are common in patients with CKD and can lead to a wide range of other problems. “This is the first randomized controlled study of its kind,” says Yaqoob. “A simple remedy like sodium bicarbonate (baking soda), when used appropriately, can be very effective.”

The researchers note some important limitations of their study—there was no placebo group and the researchers were aware of which patients were receiving sodium bicarbonate. “Our results will need validation in a multicenter study,” says Yaqoob.

 

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Other authors were Ione de Brito-Ashurst, RD, Mira Varaganum, PhD, and Martin J. Raftery, MD (William Harvey Research Institute and Barts and the London NHS Trust, London). The authors reported no financial disclosures.

The study entitled, Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status will appear online at http://jasn.asnjournals.org/ on July 16, 2009, doi 10.1681/ASN.2008111205.

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

Founded in 1966, ASN is the world’s largest professional society devoted to the study of kidney disease. Comprised of 11,000 physicians and scientists, ASN continues to promote expert patient care, to advance medical research, and to educate the renal community. ASN also informs policymakers about issues of importance to kidney doctors and their patients. ASN funds research, and through its world-renowned meetings and first-class publications, disseminates information and educational tools that empower physicians.

Kidney damage from medical imaging procedures can cause long-term health problems: Most patients are told that injury is only temporary

2009 study posted for filing

Contact: Shari Leventhal sleventhal@asn-online.org 202-416-0658 American Society of Nephrology

 

Kidney injury that can arise after undergoing certain medical imaging procedures increases a patient’s risk of having a stroke or heart attack over the next year or two, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN). The findings indicate that seemingly minor and reversible kidney damage from these common clinical procedures is a serious health threat.

Medical imaging often uses contrast agents, substances such as iodine and barium that enhance the contrast of structures or fluids within the body. For example, contrast agents may be used during cardiac angiography and computed tomography procedures to visualize blood vessels and changes in tissues. Exposure to contrast agents can injure the kidneys, but patients are often told that this is only a temporary side effect. Recent research has suggested that such contrast-induced kidney damage may actually be more serious, although no thorough studies have looked into the hypothesis.

To investigate the issue, Richard Solomon, MD (University of Vermont), and his colleagues studied 294 patients with kidney disease who were exposed to contrast agents during cardiac angiography. Patients in the CARE (Cardiac Angiography in REnally Impaired Patients) trial were randomly divided to receive one of two contrast agents: iopamidol or iodixanol. After following patients for at least one year, the researchers found that 92 (31%) of the patients experienced negative health effects. Thirty-eight (13%) of the patients experienced a major event, such as death, stroke, heart attack, or end-stage renal disease. Individuals who developed contrast-induced kidney injuries had twice as many long-term negative health effects compared with patients whose kidneys were not damaged. In the absence of contrast-induced kidney injury, there was no difference in the incidence of long-term negative health effects between patients taking iopamidol or iodixanol. However, the investigators found that patients taking iopamidol had reduced incidences of both kidney damage and long-term negative effects. These parallel decreased incidences support the theory that contrast-induced kidney injury causes long-term negative effects.

The CARE trial findings should prompt investigators to design additional studies on the long-term negative health effects of contrast-induced kidney damage.

###

 

This work was supported by Bracco Diagnostics, Inc., which manufactures iopamidol. Dr. Solomon serves as a consultant for Bracco Diagnostics, Inc. Study co-authors who received research funding from Bracco Diagnostics, Inc. include Madhu Natarajan, MD (Hamilton Health Sciences, Canada), Serge Doucet, MD (Montreal Heart Institute, Canada), Richard Katholi, MD (Prairie Educational and Research Cooperative), Cezar Staniloae, MD (St. Vincent’s Hospital Manhattan and Medical Center), Samin Sharma, MD (Mt. Sinai Medical Center), Marino Labinaz, MD (University of Ottawa Heart Institute, Canada), and Joseph Gelormini, MD (Buffalo Heart Group). Co-authors Roxana Mehran, MD (New York-Presbyterian Hospital/Columbia University Medical Center) and Brendan Barrett, MD (Memorial University of Newfoundland, Canada) report no financial disclosures.

The article, entitled “The Relationship of Contrast-Induced Nephropathy to Long-Term Adverse Events: Is it Cause and Effect?” will appear online at http://cjasn.asnjournals.org/ on June 25, 2009, doi 10.2215/CJN.00550109.

Founded in 1966, the American Society of Nephrology (ASN) is the world’s largest professional society devoted to the study of kidney disease. Comprised of 11,000 physicians and scientists, ASN continues to promote expert patient care, to advance medical research, and to educate the renal community. ASN also informs policymakers about issues of importance to kidney doctors and their patients. ASN funds research, and through its world-renowned meetings and first-class publications, disseminates information and educational tools that empower physicians

60th Health Research Report 07 JUL 2009 – Reconstruction

Editors Top Five:

1.Your Arteries on Wonder Bread

2.Report: Prostate cancer screening has yet to prove its worth

3. Doubts cast on credibility of some published clinical trials

4. Health food supplement may curb compulsive hair pulling

5. Acid-reducing medicines may lead to dependency

In this issue:

1.Irritability should be considered when diagnosing bipolar disorder in children

2. Kidney damage from medical imaging procedures can cause long-term health problems

3. Chemicals in common consumer products may play a role in pre-term births

4. Vitamin A derivative provides clues to better breast cancer drugs

5.Your Arteries on Wonder Bread

6. Tryptophan deficiency may underlie quinine side effects

7. Mice run faster on high-grade oil

8.Report: Prostate cancer screening has yet to prove its worth

9. Magic ingredient in breast milk protects babies’ intestines

10.K-STATE RESEARCHER STUDIES THE ANTI-CANCER CAPABILITIES OF A SPECIAL PURPLE SWEET POTATO

11.Triggering muscle development — a therapeutic cure for muscle wastage?

12.Acid-reducing medicines may lead to dependency

13.Doubts cast on credibility of some published clinical trials

14.. Caffeine reverses memory impairment in Alzheimer’s mice

15.Researchers find possible environmental causes for Alzheimer’s, diabetes

16.Muscle damage may be present in some patients taking statins

17. Health food supplement may curb compulsive hair pulling

18.Sugar substitute appears to prevent early childhood cavities

Health Research Report

60th Issue Date 07 JUL 2009

Compiled By Ralph Turchiano

www.healthresearchreport.me www.vit.bz

www.youtube.com/vhfilm www.facebook.com/engineeringevil

www.engineeringevil.com

Study finds bacteria may reduce risk for kidney stones: 70 percent reduction in the risk of recurrent kidney stones

Contact: Gina Digravio gina.digravio@bmc.org 617-638-8491 Boston University

Boston, MA—Researchers from Boston University’s Slone Epidemiology Center have found that the bacteria Oxalobacter formigenes (O. formigenes), a naturally occurring bacterium that has no known side effects, is associated with a 70 percent reduction in the risk of recurrent kidney stones.  These findings appear online in the March issue Journal of the American Society of Nephrology.

Kidney stones are an important health problem in many countries.  In the United States, the lifetime risk for developing a stone is five to 15 percent, and a five-year risk for recurrence is 30 to 50 percent.  The economic impact of hospital admissions for this condition is $2 billion per year.

According to the researchers, up to 80 percent of kidney stones are predominately composed on calcium oxalate (CaOx) and urinary oxalate is a major risk factor for CaOx stone formation. O. formigenes metabolizes oxalate in the intestinal tract and is present in a large proportion of the normal adult population.

Data was collected in the Boston, Massachusetts and Durham, North Carolina areas from 247 adult patients with recurrent CaOx stones and compared with 259 age, sex, and region-matched controls.  O. formigenes colonization was determined by culture of stool samples.  Information was obtained by interview and self-administered dietary questionnaire.  24-hour oxalate excretion and other urinary risk factors were measured in a subset of 139 cases and 138 controls.  The prevalence of O. formigenes was 17 percent among cases and 38 percent among controls, giving an odds ration of 0.3.  The finding was consistent in subgroups defined according to age, sex, race, region and antibiotic use.

“We observed a strong inverse association between colonization with O. formigenes and recurrent CaOx kidney stones, with a 70 percent reduction in overall risk,” said lead researcher David Kaufman, ScD, a professor of epidemiology at Boston University School of Public Health.  “Our findings are of potential clinical importance.  The possibility of using the bacterium as a probiotic is currently in the early stages of  investigation,” added Kaufman.

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This study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

Study targets key molecule to reverse kidney damage in mice

Test likely to proceed to clinical trials

BOSTON — In findings that may lead to clinical trials of a promising new drug for kidney disease, researchers at Beth Israel Deaconess Medical Center (BIDMC) and their colleagues have identified a key molecular player and shown how a targeted experimental drug can reverse kidney damage in mouse models of diabetes, high blood pressure, genetic kidney disease, and other kidney injuries.

The study builds on a discovery that, in mice, a key protein can repair and reverse renal fibrosis, the critical damage caused by different kidney diseases in humans. The new paper details 10 years of methodical follow-up experiments to understand, verify and harness the protective molecular process with a new drug that can be tested in people. The paper appears in the March 2012 issue of Nature Medicine.

“This paper reports the discovery of one of the first targeted drugs specifically developed to reverse fibrosis and regenerate the kidney,” said senior author Raghu Kalluri, MD, PhD, Chief of the Division of Matrix Biology at BIDMC and Professor of Medicine at Harvard Medical School (HMS). “We’re optimistic about the benefits, but the real proof will come from clinical testing.”

Chronic kidney disease is becoming a major public health problem, partly due to the increase in obesity, diabetes, hypertension and an aging population. It affects one out of every 10 people older than 20, and is most prevalent in those over 60. Most people with impaired kidney function are in the early stages and have no symptoms, but deteriorating kidneys significantly raise the risk of death by cardiovascular disease. Those who survive heart attacks and strokes can progress to end-stage renal disease, which requires dialysis in most cases or transplants when donor kidneys are available.

“The field is desperate for new interventions that can halt or slow the progression of renal failure,” said nephrologist Qais Al-Awqati, MB, ChB, a professor of medicine and physiology at Columbia University and immediate past editor of the journal Kidney International. Al-Awqati, who was not involved in the study, notes that kidney disease is the third leading cause of death in the U.S.

In the kidneys and other organs, fibrosis develops from normal repair mechanisms that do not stop. Scar tissue slowly builds up and replaces the working cells of the organ. In 2003, Kalluri’s lab reported that the destructive fibrosis in mice can be countered by the human protein BMP-7, originally named for its ability to spur bone growth. A manmade version of BMP-7 is approved by the U.S. Food & Drug Administration (FDA) to help repair long bones and vertebrate disks. However, the large protein needs to be injected or surgically implanted and, therefore, is not useful for long-term treatment protocols.

Kalluri and his colleagues continued their studies, seeking a smaller molecule that could be taken by mouth in a pill form in order to more specifically exert its protective effect on the kidney. Probing deeper into the biology of the kidney, they identified the protein Alk3, which is not the protein’s primary partner in bone.

Soon after the BIDMC team identified the key receptor Alk3 in the lab, they collaborated with a Canadian biotechnology company, Thrasos Therapeutics, interested in developing targeted therapies for the prevention and treatment of severe organ failure, especially kidney disease. Based on the details about the molecular interaction between the BMP protein and the ALK receptor, company scientists developed a class of small functional peptides, including THR-123, which then underwent further testing.

Researchers in the Kalluri lab used the experimental compound to document the role of the receptor in reversing the fibrosis and allowing normal tissue to regenerate in one mouse model after another. “This receptor must be present for the new molecule to function,” said Kalluri. Working through the receptor, the molecule suppressed inflammation, cell death and fibrosis formation, as well as reversing established fibrosis and allowing kidneys to regenerate functional cells, he adds.

Further experiments showed that the test drug worked even better in the mice when given in combination with ACE inhibitors, the anti-hypertensive drugs now considered a standard therapy for chronic kidney disease which work by targeting another molecular process.

“Targeting the receptor not only stops fibrosis, it removes established fibrosis, and it works in combination with an existing drug used in patients,” Kalluri notes. “The next step is to test this molecule in the clinic.”

The mice studies are “a good first step,” said Al-Awqati. “It will be interesting to pin down the role of the BMP-7 pathway in kidney fibrosis in people.”

Going forward, Kalluri’s group will continue to study these molecular players and their roles in fibrosis in other organs, including the liver, lung, intestine and heart in the hopes of expanding the experimental-drug pipeline. “If you don’t have a pipeline of experimental drugs, how will you succeed in coming up with new drugs?” he asks.

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This study was supported by several project and training grants from the National Institutes of Health, and the Else Kroner-Memorial-Stipend. Kalluri discloses that in the past he has held stock options (subsequently returned to the company unexercised) and received de minimus payments for consulting for Thrasos Therapeutics, Inc.

Study coauthors include BIDMC investigators Hikaru Sugimoto, Valerie S. LeBleu, Gangadhar Taduri, Wibke Bechtel, Hirokazu Okada, Keizo Kanasaki and Michael Zeisberg; Thrasos Therapeutic investigators Dattatreyamurty Basukonda, and Peter Keck; William Carlson Jr. of Thrasos Therapeutics and Massachusetts General Hospital; Mary Rusckowski of the University of Massachusetts Medical College; and Bjorn Tampe and Desiree Tampe of Goettingen University Medical Center, Goettingen, Germany.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Phosphate additives pose a risk to health

Excessive consumption of phosphate is damaging to health. Therefore, food that contains phosphate additives should be labeled, as recommended by Eberhard Ritz and coauthors in their article in the current issue of Deutsches Ärzteblatt International [Dtsch Arztebl Int 2012; (109 (4): 49-55].

Ritz et al. selectively review the literature on the subject, which documents the fact that ex-cessive phosphate consumption elevates mortality in patients with renal disease. Recent stud-ies have also shown that phosphate apparently damages blood vessels and induces aging pro-cesses. Free phosphate (the type found in food additives) is entirely resorbed in the gastroin-testinal tract. Persons with renal disease have been found to have a markedly elevated serum phosphate concentration.

Phosphate additives are present in many types of fast food, which are eaten mainly by persons of lower socioeconomic status. It seems likely that excessive phosphate consumption is linked to the increased prevalence of cardiovascular diseases in the general population.

The authors conclude that physicians and the public need to be educated about the role of phosphate additives as a risk factor for disease.

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http://www.aerzteblatt.de/pdf.asp?id=119592