Hairlike structures on cells may play a role in a host of genetic disorders, including kidney degeneration, vision impairment and even some cancers
In a review article published in the December 1 BioScience, George B. Witman, a cellular biologist at the University of Massachusetts Medical School, highlighted the growing body of evidence that abnormal or absent cilia can cause a wide range of human disorders, dubbed “ciliopathies.”
“Kidney disease and blindness, multiple digits, shortened bones or extremities, obesity—all of these things, it turns out, are due to defects in cilia,” he says. Experts add that the discovery of a common thread between these disparate disorders may eventually help researchers develop gene-based therapies to combat those conditions.
At first blush, cilia seem relatively innocuous. As they beat back and forth outside the cell, coordinated brushes of so-called motile cilia regulate fluid flow nearby. But almost all human cells also have one primary, or nonmotile, cilium that functions more like a molecular antenna. The primary cilium is an internally dynamic structure, packed with proteins that detect and convey important messages to its cell about the local environment. “The signaling machinery is concentrated in the cilia,” Witman says. “All in this very tightly controlled, constrained space.”
Effective cellular communication is especially important for a developing embryo. If faulty molecular antennae cut off or warp a signal in these early stages, the resulting miscommunication can disrupt organ formation. For that reason, “when you have defects in these cilia, you get a lot of congenital diseases,” Witman says.
The most common ciliopathy is polycystic kidney disease (PKD), which affects about 12.5 million people worldwide. Almost all patients face renal failure as multiple fluid-filled sacs (cysts) clog their kidneys and prevent blood purification. In 2000 Witman was part of the team that identified a gene responsible for cilia growth in green algae and noticed that it was nearly identical to a mouse gene that, when defective, caused polycystic kidney disease.
Scientists later learned that defects in that same gene cause malformed or absent cilia, which contribute to the formation of dangerous cysts in human kidneys. As urine flows through the channels and chambers of the kidney it bends the primary cilia, which act like sensors for fluid flow. “If you don’t have those cilia, you get these cysts that come up in the kidney,” says Ketan Badani, director of the Comprehensive Kidney Cancer Program at Mount Sinai Hospital in New York City.
Although scientists had known about the existence of primary cilia since the late 1800s, Witman’s study prompted researchers to revisit the structures that they had once assumed served minimal purpose. “Suddenly there was this idea that the primary cilium was a signaling system and that you had to put specific receptors into the primary cilium to prevent a pathology—in this case, polycystic kidney disease,” says Peter Satir, professor of anatomy and structural biology at Albert Einstein College of Medicine who was not involved in the research. “But then it turned out that that wasn’t the only pathology related to receptors in the primary cilium.” [Read more]
Over the past several years, lead author John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine, Perelman School of Medicine at the University of Pennsylvania, and his colleagues have developed small molecule versions of the drug compstatin, which inhibits a component of the complement immune response called C3. Lambris explains that this next-generation compound, called Cp40, "is a small peptide similar to cyclosporine in many aspects, however it uses a different mechanism of action."
Previous studies by Lambris and his team, in which modern polymer-based hemodialysis filters were perfused with human blood, showed significant complement activation and an increase in inflammatory biomarkers. This response could be suppressed using compstatin, suggesting that it might be used in dialysis to decrease the inflammatory response side effect. [Read more]
Living With PKD
From WLTX, CBS Affiliate, Manning, SC
A year ago the mayor of Manning Julia Nelson learned she was in the fight for her life and she needed a kidney. In an effort to get one, she went public and received tremendous support.
Nelson is suffering from Polycystic Kidney Disease, which is a genetic disease that exempted anyone in her family from being a donor for her.
" Several of my friends and people I didn't know signed up to try to give me a kidney," said Nelson.
Henry Well with the National Kidney Foundation in Columbia says there are resources out there, like the "Living Organ Exchange", where people like Nelson can go for help.
"Some people may not have a brother or sister who can donate a kidney but their kidney may match somebody else in another state or another region in the country where they can literally exchange kidneys", said Well.
Which is exactly what's happened for Nelson, working through the Living Organ Exchange, she's found a match and soon she'll get a new kidney.
"I'll get a second chance at life", said Nelson.
From Nigerian Observer
At any stage of kidney disease, knowledge is power. Knowing the symptoms of kidney disease can help you get the treatment you need to feel your best. If you or someone you know has one or more of the following symptoms of CKD, or you worry about kidney problems, see a doctor for blood and urine tests. Remember, many of the symptoms can be caused by other health problems. The only way to known the cause of your symptoms is to see a doctor.
Symptom 1: Changes in urination
Kidneys make urine, so when the kidneys are failing, the urine may change. How?
You may have to get up at night to urinate
Urine may be foamy or bubbly
You may urinate more often, or in greater amounts than usual, with pale urine.
You may urinate less often or in smaller amounts than usual, with dark coloured urine.
Your urine may contain blood.
You may feel pressure or have difficulty urinating.
What patients said:
“When you go to use the restroom, you couldn’t get it all out. And it would still feel just like fightness down there, there was so much pressure”.
“My urine is what I had started noticing. Then I was frequently going to the bathroom and when I got there nothing’s happening. You think, they, I’ve got to go to John; and you get there, 2, 3 drops”.
“I was passing blood in my urine. It was so dark it looked like grape Cool-Aid. And when I went to the hospital they thought I was lying about what colour it was”.
Symptom 2: swelling
Failing kidneys don’t remove extra fluid, which builds up in your body causing swelling in the legs, ankles, feet, face, and/or hands.
What patients said:
“I remember a lot of swelling in my ankles. My ankles were so big I couldn’t get my shoes on”.
“My sister, her hair started to fall out, she was losing weight, but her face was really puffy, you know, and everything like that, before she found out what was going on with her”.
“Coving to work one morning, my left ankle was swollen, real swollen, and I was very exhausted just walking to the bus stop. And I knew then that I have to see a doctor”.
Symptom 3: Fatigue:
Healthy kidneys make a hormone called erythropoietin (a-rith-ro-po’-un-tin), or EPO, that tells your body to make oxygen carring red blood cells. As the kidneys fail, they make less EPO with fewer red blood cells to carry oxygen, your muscles and brain tire very quickly. This is anemia, and it can be treated.
What patients said:
“I was constantly exhausted and didn’t have any pep or anything”.
“I would sleep a lot. I’d come home from work and get right in that bed”.
“It’s just like when you’re extremely tired at the time. Fatigued, and you’re just drained, even if you didn’t do anything, just totally drained.
Symptom 4: Skin Rash/Itching
Kidneys, remove wastes from the blood stream. When the kidneys fail, the build-up of wastes in your blood can cause severe itching.
What patients said:
“It’s not really a skin itch or anything. It’s just right down to the bone. I had to get a brush and dig. My back was just bloody from scratching it so much”.
“My skin had broke out, I was itching and scratching a lost”.
Symptoms 5: Metallic taste in mouth/ammonia breath
A build-up of wastes in the blood (called uremia) can make food taste different and cause bad breath. You may also notice that you stop liking to eat meat, or that you are losing weight because you just don’t feel like eating.
What patients said:
“Foul taste in your mouth. Almost like you are drinking iron” “you don’t have the appetite you used name”.
“Before I started dialysis, I must have lost around 10 pounds.
Symptom 6: Nausea and vomiting
A severe build-up of wastes in the blood (uremia) can also cause nausea and vomiting loss of appetite can lead to weight loss.
What patients said:
“I had a lot of itching, and I was nauseated, throwing up all the time. I couldn’t keep anything down in my stomach”.
“When I got the nausea, I couldn’t eat and I had a hard time taking my blood pressure pills”.
Symptom 7: shortness of breath
Trouble catching your breath can be related to the kidneys in two ways. First, extra fluid in the body can build up in the lungs. And second, anemia (a shortage of oxygen-carrying red blood cells) can leave your body oxygen starved and short of breath.
What patients said:
“At the times when I get the shortness of breath, it’s alarming to me. It just fears me. I think may be I might fall or something so I usually go sit down for a while”.
“I couldn’t sleep at night. I couldn’t catch my breath, like I was drowning or something, and bloating, can’t breathe, can’t walk anywhere. It was bad”.
“You go up a set of stairs and you are out of breath, or you do work and you get tired and you have to stop”.
Symptom 8: feeling cold
Anemia can make you feel cold all the time, even in a warm room.
What patients said
I notice sometimes I get really cold, I get chills”.
“Sometimes I get really, really cold. It could be hot and I would be cold.”
Symptom 9: Dizziness and trouble concentrating
Anemia related to kidney failure means that your brain is not getting enough oxygen. This can lead to memory problems, trouble with concentration, and dizziness.
What patients said:
“I know I mentioned to my wife that my memory I couldn’t remember what I did last week, or maybe what I had 2 days ago. I couldn’t really concentrate, because I like to work crossword puzzles and read a lot”.
“I was always fired and dizzy”.
“It got to the point, like I used to be at work, and all of a sudden I’d start getting dizzy. So I was thinking may be it was my blood pressure or else diabefes was going bad. That’s what was on my mind”.
Symptom 10: leg/flank pain
The most common causes of CKD do not cause any pain. And, much of the pain that is near the kidneys is not cause by a kidney problem. But some people who have CKD do have pain some people with kidney problems may have pain in the upper back (where the kidneys are) or on the same side as the affected kidney.
Polycystic kidney disease (PKD), which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause pain.
Kidney infections and kidney stones can cause severe pain, often in spasms.
Bladder infections can cause burning when you urinate. People who have medullary sponse kidney say it is painful.
What patients said:
“About 2 years ago, I was constantly going to the bathroom all the time, my back was always hurting and I was woundering why and they diagnosed kidney problem.
“And then you’re having to get up all time through the night and then you have the side ache, a backache, and you can’t move”.
“At night, I would get a pain in my side. It was worse than labour pain. And I would be crying and my husband would get up, everybody, rubbing my legs”.
Risk factors for CKD
When you have a risk factors, it means you are more likely to have a problem than someone who does not have it. But it doesn’t mean that you will definitely have the problem.
Some risk factors like your age or family history, are out of your control. But you can control other risk factors and perhaps slow down or even prevent some diseases. For instance, keeping your blood pressure and sugar in their target ranges may help your kidneys work longer. First, know your risk factors for CKD, then work with your doctor to prevent or delay kidney failure.
Kidney disease risk factors you can change
Diabetes
Type 2 diabetes is the number one cause of kidney failure. There is no such thing as “a touch of the sugar 44% of new dialysis patients have diabetes.
What you can do
Kidney disease does not have to happen to people with diabetes. Good blood pressure and blood sugar control can help prevent it tight control can have big pay offs in reducing the risk for kidney disease. It can also help protect your blood vessels, limbs and eyes.
High blood pressure (hypertension)
High blood pressure puts extra stress on all of your blood vessels, including your tiny, fragile kidney filters (nephrons). Hypertension is the number two cause of kidney failure.
Normal blood pressure is less than 130/85 this is the target for the general public.
If you have diabetes or protein in your urine, the target is 125/75.
Weight control, exercise, and medications can control blood pressure keeping your blood pressure in the target range can help prevent or slow the rate of CKD.
What you can do:
Take blood pressure pills as they are prescribed so they will work properly. It is not true that you can “feel” high blood pressure it can have no symptoms at all. If you can’t afford your blood pressure pills or they have side effects you can’t live with, tell your doctor. He or she can give you samples, switch you to a less costly drug or suggest of the options for you.
Two classes of blood pressure medications can help protect the kidneys, especially if you have protein in your urine. These are:
(1) Angiotensin-converting enzyme (ACE) inhibitors generic names end in “pril”- catopril, ramipril, etc.
(2) Angiotensin receptor blockers (ARBs) generic names end in “sartain” – telmisartan, valsartan, I sartan, olmisartan.
If you have high blood pressure and are not taking one of these drugs, ask your doctor if it would be a good choice for you.
Other risk factors that we will consider subsequently are: block ages, over use of pain killers and allergic reactions to antibiotics (water out for drugs with these ingredients – Ibuprofen (Advil, motrin) Naproxen (Aleve), Acetaminophem (TylenoI), Drug abuse, inflammation, x-ray Dye tests, etc.
There are kidney disease risk factors you can’t change but should know about them, i.e a family history of kidney disease, premature birth, age, trauma or accident, certain diseases – diabetes, high blood pressure, systemiclupus, erythematosus (a connective tissue disease), sickle cell anemia, cancer, AIDS, Hepatitis c, congestive heart failure, etc.
Despite a record 11,163 kidneys transplanted from deceased donors in 2013, an ever-growing waiting list seems inevitable. With an aging population and increasing rates of diabetes -- the most common cause of kidney failure -- more and more people are developing kidney disease. Although transplant centers have gotten very good at persuading the bereaved families of deceased potential donors to give the “gift of life,” too few people die in ways that keep their organs healthy for transplant. The waiting list reflects an absolute physical shortfall.
Within a few years, new rules about allocating kidneys, which went into effect last week, could shrink the waiting list. But this apparent improvement will be an illusion -- an artifact of the incentives the new rules create, not genuine progress. Changing who gets priority for scarce kidneys will help some patients and hurt others, and it might squeeze out a few more total years of healthy living for the lucky recipients. But a different process for managing the existing supply of kidneys won’t make a serious difference for the skyrocketing number of patients who need transplants.
In the past, how long you’d been on the waiting list was the main factor that determined how close you were to getting a compatible kidney. (Some blood types are harder to match than others, so someone with less compatible type O blood would wait longer than someone with type A.) The longer you waited, the further you moved up the list. The clock started when your transplant center did the necessary tests and listed you as a transplant candidate.
The old system hurt those patients, most of whom were black, who had spent years on dialysis before they got referred for transplants, whether because of medical factors, insufficient health insurance or complacent nephrologists. (About a third of the patients, about 35,000 people, currently on the waiting list are black.) The new system instead starts the clock when a patient goes on dialysis.
“In the previous system, it would make sense to list somebody even if they weren’t quite ready to get a transplant, so they could accrue waiting time,” Benjamin E. Hippen, a transplant nephrologist at Carolinas Medical Center in Charlotte, North Carolina, explained in an interview. Now, since they won’t have a shot at a kidney for years, there’s no reason to put them on the waiting list so soon. “It’s going to look like the overall list has shrunk,” he predicted, “when really it’s just a strategic move by the transplant center.”
While arguably fairer, counting dialysis years creates much more uncertainty. Every time a new patient is added, that person’s dialysis history rejiggers the list. It’s like waiting for an airline upgrade: If you’re a lowly gold status member, you may start out at the head of the line, only to end up in coach as platinum and executive platinum travelers put in their requests and push you down the queue. In this case, there’s a lot more at stake than more legroom and better meals.
The new system also changes who qualifies for which kidney. Its primary goal is to get more years out of each organ, essentially by matching younger, healthier patients with younger, healthier organs. Assuming the statistical models are correct, better matching is supposed to give kidney recipients an additional 9,000 years of life -- a number that sounds huge but amounts to less than one additional year per transplant patient. (When potentially compatible organs come up, the system also gives high priority to hard-to-match “sensitized” patients, often previous transplant recipients, who have developed many antibodies that can cause their bodies to reject most transplants.) [Read more]
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