American Society of Nephrology

Research findings point to new therapeutic approach for common cause of kidney failure.

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New research has uncovered a process that is defective in patients with autosomal dominant polycystic kidney disease, a common cause of kidney failure. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), point to a new potential strategy for preventing and treating the disease.

Polycystic kidney disease (PKD), the fourth leading cause of kidney failure worldwide, comes in two forms: autosomal dominant polycystic kidney disease (ADPKD) develops in adulthood and is quite common, while autosomal recessive polycystic kidney disease (ARPKD) is rare but frequently fatal. ADPKD is caused by mutations in either of two proteins, polycystin-1 and polycystin-2, while ARPKD is caused by mutations in a protein called fibrocystin. There is no cure or widely adopted clinical therapy for either form of the disease.

Polycystin-1, polycystin-2, and fibrocystin are all found in a cell’s primary cilium, which acts as the cell’s antenna and is intimately involved in human embryonic development as well as the development of certain diseases, including PKD. “What we don’t know, and were hoping to better understand, is what goes wrong with these proteins in the cells of PKD patients and what kinds of therapies might help those cells,” said Joseph Bonventre, MD, PhD (Brigham and Women’s Hospital).

Dr. Bonventre and his colleagues Benjamin Freedman, PhD and Albert Lam, MD led a team of scientists at Brigham and Women’s Hospital, the Mayo Clinic, and the Harvard Stem Cell Institute as they studied cells obtained from five PKD patients: three with ADPKD and two with ARPKD. The investigators reprogrammed patients’ skin cells into induced pluripotent stem cells, which can give rise to many different cell types and tissues. When the researchers examined these cells under the microscope, they discovered that the polycystin-2 protein traveled normally to the antenna, or cilium, in cells from ARPKD patients, but it had trouble reaching the antenna in ADPKD patients. When they sequenced the DNA in these ADPKD patient cells, the investigators found mutations in the gene that encodes polycystin-1, suggesting that polycystin-1 helps shepherd polycystin-2 to the cilium.

“When we added back a healthy form of polycystin-1 to our patient cells, it traveled to thecilium and brought its partner polycystin-2 with it, suggesting a possible therapeutic approach for PKD,” explained Dr. Freedman. “This was the first time induced pluripotent stem cells have been used to study human kidney disease where a defect related to disease mechanisms has been found.”

The researchers noted that reprogrammed stem cells from patients with ADPKD may also be useful for testing new therapeutics before trying them out in humans.

In an accompanying editorial, Alexis Hofherr, MD and Michael Köttgen, MD (University Medical Centre, in Freiburg, Germany) stated that the study has “laid the groundwork for using induced pluripotent stem cells in PKD research. This important step forward will provide novel opportunities to model PKD pathogenesis with human cells with defined patient mutations.”

 

 

CKD: Lower Salt Intake May Reduce Heart Risks.

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A diet with restricted salt intake may help to reduce the risk for cardiovascular disease in patients with chronic kidney disease (CKD), as well as the risk for CKD progression, according to an article published online November 7 in the Journal of the American Society of Nephrology.

Emma J. McMahon, PhD candidate, University of Queensland, Australia, and colleagues conducted a double-blind, placebo-controlled randomized crossover trial involving 20 adult patients with stage 3 to 4 CKD. In the phase I portion of the LowSALT CKD study, the researchers evaluated the effects of high vs low sodium intake on several physiological measures, including ambulatory blood pressure, protein excretion, and body fluid status.

The researchers counseled patients to eat a low-sodium (1080 – 1440 mg/day) diet during the 1-week run-in period of the 6-week study, they then randomly assigned patients to either a high-sodium or low-sodium diet. Those on the high-sodium diet had a goal of 1080 to 1440 mg/day plus 2160 mg/day from a slow-release tablet. Those on the low-sodium diet had a goal of 1080 to 1440 mg/day plus a placebo capsule. Patients crossed over after an intermediate washout week.

The investigators found a mean reduction of 9.7/3.9 mm Hg in blood pressure in patients on the low-salt diet compared with the high-salt diet. The reductions were consistent during a 24-hour period with no significant difference between daytime and nighttime measurements. Researchers also found that patients had reductions in fluid volume, body weight, and protein in the urine while on the low-salt diet.

“If these findings are transferable to the larger CKD population and shown to be sustainable long-term, this could translate to markedly reduced risk of cardiovascular events and progression to end-stage kidney disease, and it could generate considerable health-care savings,” senior author Katrina J. Campbell, PhD, from Princess Alexandra Hospital, Queensland, said in a news release.

“These are clinically significant findings, with this magnitude of blood pressure reduction being comparable to that expected with the addition of an anti-hypertensive medication and larger than effects usually seen with sodium restriction in people without CKD,” McMahon noted in the release. “If maintained long-term, this could reduce risk of progression to end-stage kidney disease — where dialysis or transplant is required to survive — by 30%.”

“This study is salient because few intervention studies have evaluated dietary sodium reduction in patients with CKD, write Cheryl A.M. Anderson, PhD, MPH, and Joachim H. Ix, MD, both from the University of California San Diego School of Medicine, in an accompanying editorial. “The evaluation of other outcomes in addition to BP is an additional strength of the trial.”

Diet Soda, Aspartame Shown to Destroy Kidney Function.

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In an 11-year study by scientists at the Brigham and Women’s Hospital in Boston, there was a strong positive correlation found between degeneration of kidney function and consumption of aspartame-containing diet soda.

Diet Soda, Aspartame Shown to Destroy Kidney Function - Aspartame - Aspartate - Phenylalanine - Methanol
Published in the Clinical Journal of the American Society of Nephrology, the study followed 3,318 women for a number of years as they consumed diet soda containing artificial sweeteners like Aspartame.

cientists took into account each participant’s age, blood pressure, smoking habits (when applicable), and pre-existing conditions like heart disease or diabetes, and administered food frequency questionnaires in 1984, 1986, 1990, 1994, and 1998. Two or more diet drinks daily, it was found, led to a doubled risk in fast-paced kidney decline.

A separate study published in the American Journal of Clinical Nutrition showed that, contrary to safety claims made by the manufacturers of aspartame, health-related concerns including non-Hodgkin lymphoma and leukemia still abound. While study authors at Brigham and Women’s Hospital and Harvard Medical School admitted that there were other variables to consider, such as the sex of the consumer in that particular case, they remained troubled by the risks associated with diet soda.

It’s worth noting that diet soda is also high in sodium—and in greater amounts than found in sodas sweetened with sugar or corn starch (which were not examined in either study).

Corruption: a Brief History of Aspartame

Is diet soda really that bad for you? This is neither the first nor will it be the last time diet soda and artificially sweetened goods will come under fire from the scientific community. The Food and Drug Administration quickly approved aspartame, called “NutraSweet,” in 1974 in use for limited foods, but only after examining studies provided by G. D. Searle Co.. Yes, the inventor of aspartame.

It was only after a research psychiatrist concluded that aspartic acid—a key ingredient in aspartame—made holes in mice brains that the FDA rounded up a task force to investigate Searle’s claims. The investigation unveiled a series of falsified claims, corrupted study results, and information that simply wasn’t there. Although the FDA moved for further investigation of Searle by grand jury, US Attorney Thomas Sullivan and Assistant US Attorney William Conlon didn’t lift a finger to help. Conlon, however, found a job at the law firm representing Searle.

Since then, the genetically modified creation, aspartame, has been implicated in a number of studies aspotentially causing tumors, seizures, brain holes, and reproductive problems. But the mainstream media won’t report on the aspartame-cancer link.

Other Sweeteners, the Good and the Bad

Other artificial sweeteners, like sucralose (supposedly “made from sugar”), have been implicated in other health problems like changing the gut flora environment and preventing proper nutrient absorption, according to the January 2008 issue of the Journal of Toxicology and Environmental Health.

Thus far, Stevia has drawn little fire comparative to artificial sweeteners, although excessive use might be cautioned as with anything. Stevia is, however, safer to use than artificial or GMO sugar, especially for diabetics.

Source: Nature