From Nature Genetics, via MedicalXpress.com
Surprising mechanism discovered in polycystic kidney disease
A study by Yale researchers has uncovered a new and unexpected molecular mechanism in the development of polycystic kidney disease, or PKD. The study appears in Nature Genetics.
Cilia are the hair-like structures on the surface of many human cells that can either move things along – dirt out of the lungs, or an egg from the ovary to the uterus – or sense the environment, such as vision in the retina or smell in the nose. Recent research has implicated defects in the sensory cilia—often caused by genetic mutations—in many human diseases, including cancer, cardiac disease, blindness, and kidney disease. In the kidney, disruption of sensory cilia cause kidney cysts.
The polycystin-1 and -2 (also known as PC1 and PC2) proteins are key players in the normal functioning of the kidneys. Earlier research has shown that when they are lost or mutated, cysts grow in the kidneys and cause almost all cases of PKD in humans.
Working in mice, the Yale team found that cysts grew when the cilia were intact but lacked polycystin—but, surprisingly, cysts stopped growing despite the absence of polycystins when the cilia were disrupted or eliminated.
The activity of this pathway, and the timing of the loss of polycystin proteins and the cilia, determined the severity of both early- and adult-onset PKD, the researchers found.
"None of the other pathways discovered so far have proven as universal as the cilia dependent pathway in explaining polycystic kidney disease," said corresponding author Dr. Stefan Somlo, professor of internal medicine (nephrology) and genetics at Yale School of Medicine. "We found to our surprise that elimination of cilia suppresses cyst growth in all of the genetic models of human PKD." [Read more]
Cilia are the hair-like structures on the surface of many human cells that can either move things along – dirt out of the lungs, or an egg from the ovary to the uterus – or sense the environment, such as vision in the retina or smell in the nose. Recent research has implicated defects in the sensory cilia—often caused by genetic mutations—in many human diseases, including cancer, cardiac disease, blindness, and kidney disease. In the kidney, disruption of sensory cilia cause kidney cysts.
The polycystin-1 and -2 (also known as PC1 and PC2) proteins are key players in the normal functioning of the kidneys. Earlier research has shown that when they are lost or mutated, cysts grow in the kidneys and cause almost all cases of PKD in humans.
Working in mice, the Yale team found that cysts grew when the cilia were intact but lacked polycystin—but, surprisingly, cysts stopped growing despite the absence of polycystins when the cilia were disrupted or eliminated.
The activity of this pathway, and the timing of the loss of polycystin proteins and the cilia, determined the severity of both early- and adult-onset PKD, the researchers found.
"None of the other pathways discovered so far have proven as universal as the cilia dependent pathway in explaining polycystic kidney disease," said corresponding author Dr. Stefan Somlo, professor of internal medicine (nephrology) and genetics at Yale School of Medicine. "We found to our surprise that elimination of cilia suppresses cyst growth in all of the genetic models of human PKD." [Read more]
PKD Treatment
From MedPageToday.com, by David Pittman, Washington Correspondent, MedPageToday
FDA Reviewers Pan Tolvaptan Trial ResultsWASHINGTON -- FDA reviewers aren't ready to endorse tolvaptan (Samsca) to treat autosomal dominant polycystic kidney disease (ADPKD), citing missing clinical trial data, they said ahead of an advisory committee meeting to consider the drug.
A single phase III trial showed the drug slowed the loss of renal function in patients with relatively healthy kidneys but deemed at high risk of failure, FDA reviewers noted in briefing documents prepared for the agency's Cardiovascular and Renal Drugs Advisory Committee.
"However, because of missing data in a sizeable portion of the study population and particularly so in the tolvaptan arm, the size of the treatment effect is unclear," staff stated in the documents for Monday's meeting. "Treatment effects on other endpoints -- kidney volume and renal pain events requiring medical intervention -- were supportive of the drug's activity."
The committee will meet to discuss the trial results and vote on recommending approval for slowing kidney disease in adults at risk of rapidly progressing ADPKD. [Read more]
Save a Life
From Herald-Mail.com, Fredeirick, Maryland
Kindness of a stranger: Woman donates kidney to her customerFREDERICK, Md. — It can be called a bank withdrawal and deposit of a different kind for two Frederick women.
Deanna Henderson, assistant branch manager of M&T Bank’s Worman’s Mill Branch in Frederick, recently donated a kidney to a bank customer, Carla Watts of Frederick.
Henderson, of Frederick and a Boonsboro native, said she only knew Watts in passing from coming into the bank. She said they didn’t have any other relationship than a friendly hello when Watts banked. That changed in March 2012.
Living with PKD
From Tele-Management.ca
Will a healthy diet help my kidneys?
I am a 45-year-old male with polycystic kidney disease. I have changed my diet and eat mostly vegetarian. Will this type of diet help my kidneys? Is there anything I can do as far as dieting or exercise that will preserve my kidney function?
...There is no specific treatment for the condition, but measures should be taken to avoid damaging the kidneys further. Contact sports are inadvisable, since trauma can cause bleeding in the cysts. Kidney infections, which usually follow catheterization or cystoscopy, must be avoided. Medications that damage the kidneys, including some antibiotics (not penicillin, cephalosporin or erythromycin), phenacetin (a component of some pain meds), and nonsteroidal anti-inflammatories such as ibuprofen and others, should be avoided.
Hypertension must be aggressively treated. Dehydration and salt restriction should be avoided.
Your letter raises an interesting question regarding eating meat. When someone with polycystic renal disease develops actual kidney failure, then protein must be limited, and meat of course is rich in protein. However, this does not mean that avoiding protein before the development of kidney failure will prevent it. Research in normal laboratory animals seems to indicate that eating a high-protein diet may help cause kidney failure, but I don’t believe that this has been shown in humans, and standard texts do not advise restricting meat in this condition until the kidney failure actually develops. If you are happy with your vegetarian diet, which can be perfectly healthy if it is balanced, then perhaps you may slow the progression to kidney failure, but I am not aware of any strong evidence in favor of this treatment. [Read more] Medical Disclaimer...
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