MINNEAPOLIS, Minn.— In an effort to provide an evidence base to guide recommendations coming from the U.S. Preventive Services Task Force and the American College of Physicians, Howard A. Fink, M.D., M.P.H., of the Minneapolis Veterans Affairs Medical Center, and colleagues reviewed randomized, controlled trials that evaluated screening, monitoring, or treatment of CKD; reported clinical outcomes; and discussed the benefits and harms of screening and monitoring.

The researchers found that 110 trials assessed treatments, and no trials evaluated screening or monitoring. Compared with placebo, angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers decreased end-stage renal disease (relative risk [RR], 0.65 and 0.77, respectively), mainly in patients with diabetes who had macroalbuminuria.

For patients with microalbuminuria and cardiovascular disease or high-risk diabetes, angiotensin-converting enzyme inhibitors reduced mortality compared to placebo (RR, 0.79). For patients with impaired estimated glomerular filtration rate and either hyperlipidemia or congestive heart failure, statins and ?-blockers reduced mortality and cardiovascular events, compared to placebo or control.

There was no difference in mortality, end-stage renal disease, or other clinical outcomes with strict or usual blood pressure control. For angiotensin II-receptor blockers and statins, the evidence was rated high; for angiotensin-converting enzyme inhibitors and ?-blockers, moderate; and for strict blood pressure control, low.

"We need more research to develop outcome measures that will comprehensively capture the effect of CKD treatments on the diverse and disparate outcomes encountered in this complex population," write the authors of an accompanying editorial.

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Love takes many forms.

In the home of Alvin and Joyce Ermel, love is a bright blue dialysis machine with looping tubes. It whirs as it draws blood from Joyce's arm and cleans it—a job her kidneys suddenly quit doing on July 3, 2010, thanks to a rare disease that strikes one in two million people.

Alvin, who turns 76 in May, now runs the home dialysis machine that keeps Joyce alive and the two of them living in Houston.

Every second day, or whenever Joyce needs it, Alvin installs new tubing, a new blood filter, and primes the machine with IV fluid.

Then, with a practiced hand, Alvin guides a needle to the "buttonhole" in Joyce's arm—a surgically-made passage between her artery and vein that he says is tricky to use but means less chance of infection.

"Even the doctors that come in here and see it—they just look at Alvin and say, 'I can't believe you're doing this,'" says Joyce.

But she knows better.

When he was a boy growing up in Bethune, Saskatchewan, she says Alvin told his parents that he wanted to be a doctor.

Money was tight though, and they needed him to work on the family farm.

Alvin stayed, and he did well—this summer, he and Joyce will fly back to Bethune for the town's centennial after farming there for 50 years.

Still, handy as Alvin was fixing farm equipment, Joyce says her husband always longed to fix people instead.

"He took a St. John's Ambulance course, and every time there was an accident in Regina he would be driving behind the ambulance to see if he couldn't do something," she says.

"So this was pre-ordained years ago."

Luckily for Alvin, even after he starts Joyce's dialysis, there is still plenty of work to do.

For the next four and a half hours, he stays close by while the machine runs and Joyce sleeps, does crosswords, listens to radio, or phones whoever she owes a call. Friends drop by, some after signing up to a visit list at church—a blessing Joyce says helps pass the time.

Meanwhile, the machine cycles through more than 80 litres of blood.

Alvin steps in regularly to check a screen and make sure Joyce's blood pressure and the machine's flow rate are okay.

"This is just like a monitor on a combine, actually," he said, taking down some numbers in the middle of a dialysis.

Once each session is over, Alvin disposes of the tubes and blood filter, then mixes one of three cleaning solutions to disinfect the machine. All in all, he says it's a five-hour job.

But that doesn't include the time Alvin and Joyce spend arranging supplies, swapping out water filters, or taking monthly blood samples that Alvin spins in a centrifuge and mails to a lab for nutrient testing.

"Both of them are up there among my star patients," says Angela Robinson, a home dialysis nurse who regularly visits the Ermels.

As well as Alvin's fine work on the dialysis machine, Robinson noted how well Joyce watches her diet.

Given how hard it is to process salt and potassium, dialysis patients are caught in the strange position of having to keep most healthy foods off their plate.

"White flour, white sugar, nothing whole wheat, no greens, no salt," Joyce says. "I tell them that my diet is worse than this dialysis machine."

But Joyce does follow her recommended diet, Robinson said, something she sees in regular reports from Joyce's dietician.

"I know things are going well there," she said.

Robinson says she has 15 home dialysis patients right now, scattered from Dawson Creek to Chetwynd and Quesnel.

Many people in the Northern Health area chose home dialysis to stay in their home town, she says. From Houston, the closest dialysis clinics are in Terrace or Prince George.

But since 2004, Robinson says the province has also stepped up home dialysis in more urban parts of the province because it often shows better results.

As Joyce says, compared to in-clinic dialysis, home dialysis is a Cadillac.

"You can do it when you want, for as long as you want," she says.

Robinson agrees, noting that even at independent clinics, where patients can hook up the machines themselves, patients have to follow a more limited schedule.

"If you want to do it, and you meet the criteria, we can get you home," she says.

But not everyone is capable of taking on as much as Alvin has.

"He needs a medal," Joyce says. "He doesn't have a chest big enough."

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WASHINGTON—Minorities face a disproportionately increased risk for developing kidney disease, which currently affects more than 26 million Americans. Millions more are in jeopardy of developing it.

In recognition of National Minority Health month, the American Society of Nephrology, Dialysis Patient Citizens, and the National Urban League, are hosting a Kidney Health Disparities Congressional Briefing.

Understanding and acknowledging that health disparities exist is a first step towards reducing these gaps and ultimately eliminating them.

The event will highlight aspects of research and clinical care that relate to minorities with kidney disease, while raising awareness about the condition and other important minority health concerns.

• African Americans with kidney disease are nearly four times more likely to progress to kidney failure than Caucasians, and six times more likely to develop kidney failure related to hypertension.
• Hispanics and Native Americans are approximately two times more likely to progress to kidney failure than Caucasians.
• Nearly 70,000 patients are on the waiting list for kidney transplants, with African Americans alone comprising 35 percent of those patients. Minorities are more likely spend more time on the waiting list.
• Medical research and patient education improve prevention and treatment of kidney disease for minority populations.

The event will be held in the Capitol Visitors Center North Congressional Meeting room on Thursday, April 19, from 1:30p.m. to 3 p.m.. Lunch and refreshments will be served.

Speakers include:

Kafui Agbemenu, MPH, MSN, RN
Health Advocate
Urban League of Greater Pittsburgh

Eric Edwards
Board of Directors
Dialysis Patient Citizens

Cristina M. Arce, MD
Division of Nephrology
Stanford University

Neil R. Powe, MD, MPH, MBA, FASN
Chief of Medicine, San Francisco General Hospital
Constance B. Wofsy Distinguished Professor
University of California San Francisco

Dana Atwater, MBA
Account Executive
Baxter Healthcare

To RSVP, please contact Dialysis Patient Citizens at This e-mail address is being protected from spambots. You need JavaScript enabled to view it or 202-789-6931.

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What is Hemolytic Uremic Syndrome?

Hemolytic uremic syndrome is a severe, life-threatening complication of an E. coli bacterial infection that was first described in 1955, and is now recognized as the most common cause of acute kidney failure in childhood. E. coli O157:H7 is responsible for over 90% of the cases of HUS that develop in North America. In fact, some researchers now believe that E. coli O157:H7 is the only cause of HUS in children. HUS develops when the toxin from E. coli bacteria, known as Shiga-like toxin (SLT) [1,2], enters cells lining the large intestine. The Shiga-toxin triggers a complex cascade of changes in the blood. Cellular debris accumulates within the body’s tiny blood vessels and there is a disruption of the inherent clot-breaking mechanisms. The formation of micro-clots in the blood vessel-rich kidneys leads to impaired kidney function and can cause damage to other major organs.

What are the Symptoms associated with Hemolytic Uremic Syndrome?

About ten percent of individuals with E. coli O157:H7 infections (mostly young children) goes on to develop Hemolytic Uremic Syndrome, a severe, potentially life-threatening complication. HUS is an extremely complex process that researchers are still trying to fully explain.

Its three central features describe the essence of Hemolytic Uremic Syndrome: destruction of red blood cells (hemolytic anemia), destruction of platelets (those blood cells responsible for clotting, resulting in low platelet counts, or thrombocytopenia), and acute renal failure. In HUS, renal failure is caused when the nephrons, or filtering units, become occluded (blocked) by micro-thrombi, which are tiny blood clots. In almost all cases, the filtering ability of the kidneys recovers as the body of the patient slowly dissolves the micro-thrombi within the microvessels.

A typical person is born with about one million filtering units, called nephrons, in each kidney. The core of the nephron is a bundle of tiny blood vessels, called a glomerulus, where osmotic exchange allows for the filtration of wastes that eventually collect in the urine and are excreted. During Hemolytic Uremic Syndrome, the lack of blood flow to the nephrons can cause them to die or be damaged, just as heart muscle can die as the result of coronary vessel occlusion during a heart attack. Dead nephrons do not regenerate.

In general, the longer a patient suffers kidney failure, the greater the loss of filtering units as a result. At some point, the damage to the kidneys’ filtering units can be so severe that the patient will, over a period of years, lose kidney function and suffer end-stage renal disease (ESRD), which requires chronic dialysis or transplantation.

HUS can also cause transient or permanent damage to other organs, which include the pancreas, liver, brain, and heart. The essential pathogenic process is the same regardless of the organ affected: microthrombi inhibit necessary blood flow and cause tissue death or damage. During the acute stage of Hemolytic Uremic Syndrome, patients must be carefully monitored for these extra-renal complications. It is very difficult to predict the severity and course of HUS once it initiates.

The active stage of Hemolytic Uremic Syndrome may be defined as that period of time during which there is evidence of hemolysis and the platelet count is less than 100,000. In HUS, the active stage usually lasts an average of six days (range, 2-16 days). It is during the active stage that the complications of HUS per se usually occur.

What are the complications and long-term risks associated with Hemolytic Uremic Syndrome?

Several studies have demonstrated that children with HUS who have apparently recovered will develop hypertension, urinary abnormalities and/or renal insufficiency during long-term follow-up.

End Stage Renal Disease, Dialysis and Kidney Transplantation

End Stage Renal Disease

Children and adolescents with chronic renal failure face a number of complications from the condition, including alterations in calcium and phosphate balance and renal osteodystrophy (softening of the bones, weak bones and bone pain), anemia (low blood cell count that leads to a lack of energy), growth failure (final height as an adult substantially below normal), hypertension (high blood pressure), and other complications.

Renal osteodystrophy (softening of the bones) is an important complication of chronic renal failure. Bone disease is nearly universal in patients with chronic renal failure; in some children, symptoms are minor to absent while others may develop bone pain, skeletal deformities and slipped epiphyses (abnormal shaped bones and abnormal hip bones) and have a propensity for fractures with minor trauma. Treatment of the bone disease associated with chronic renal failure includes control of serum phosphorus and calcium levels with restriction of phosphorus in the diet, supplementation of calcium, the need to take phosphorus binders, and the need to take medications for bone disease.

Anemia is a very common complication of chronic renal failure. The kidneys make a hormone that tells the bone marrow to make red blood cells and this hormone is not produced in sufficient amounts in children with chronic renal failure. Thus, children with chronic renal failure gradually become anemic while their chronic renal failure is slowly progressing. The anemia of chronic renal failure is treated with human recombinant erythropoietin (a shot given under the skin one to three times a week or once every few weeks with a longer acting human recombinant erythropoietin).

Growth failure ultimately leading to short height as an adult is a very common complication of chronic renal failure in children. The mechanisms of growth failure are complex and due to multiple causes. Poorly controlled renal osteodystrophy (bone disease), inadequate nutrition (insufficient intake of adequate calories), chronic acidosis (blood system too acid) and abnormalities of the growth hormone axis (growth hormone deficiency) are each major contributors to poor growth in the child with chronic renal failure. Growth hormone therapy with human recombinant growth hormone has been approved for use in children with chronic renal failure and such therapy has been shown to accelerate growth, induce persistent catch up growth and lead to normal adult height in children with chronic renal failure. Growth hormone therapy requires giving a shot under the skin once a day. Complications of growth hormone therapy are rare but may include glucose intolerance and exacerbation of poorly controlled renal osteodystrophy.

Dialysis and Kidney Transplantation

Renal replacement therapy can be in the form of dialysis (peritoneal dialysis or hemodialysis) or renal transplantation.

If the patient does not have a living related donor for their first kidney transplant and when they need a second kidney transplant after loss of the first transplant, they will need dialysis until a subsequent transplant can be performed. The patient can be on peritoneal dialysis or on hemodialysis.

Peritoneal dialysis has been a major modality of therapy for chronic renal failure for several years. Continuous Ambulatory Peritoneal Dialysis (CAPD) and automated peritoneal dialysis also called Continuous Cycling Peritoneal Dialysis (CCPD) are the most common forms of dialysis therapy used in children with chronic renal failure. In this form of dialysis, a catheter is placed in the peritoneal cavity (area around the stomach); dialysate (fluid to clean the blood) is placed into the abdomen and changed 4 to 6 times a day. Parents and adolescents are able to perform CAPD/CCPD at home. Peritonitis (infection of the fluid) is a major complication of peritoneal dialysis.

Hemodialysis has also been used for several years for the treatment of chronic renal failure during childhood. During hemodialysis, blood is taken out of the body by a catheter or fistula and circulated in an artificial kidney to clean the blood. Hemodialysis is usually performed three times a week for 3-4 hours each time in a dialysis unit.

Renal transplantation can be from a deceased or a living related donor (parent or sibling who is over the age of 18 who is compatible). Should the patient have a living related donor available to donate a kidney, they can undergo transplantation without the need for dialysis (preemptive transplantation). Should they not have a living related donor, they will likely need to undergo dialysis while on the waiting list for a deceased donor transplant. Fortunately, children have the shortest waiting time on the deceased donor transplant list. The average waiting time for children age 0-17 years is approximately 275-300 days while the average waiting time for patient’s age 18-44 years is approximately 700 days.

Following transplantation, the patient will need to take immunosuppressive medications for the remainder of their life to prevent rejection of the transplanted kidney. Medications used to prevent rejection have considerable side effects. Corticosteroids are commonly used following transplantation. The side effects of corticosteroids are Cushingnoid features (fat deposition around the cheeks and abdomen and back), weight gain, emotional liability, cataracts, decreased growth, osteomalacia and osteonecrosis (softening of the bones and bone pain), hypertension, acne and difficulty in controlling glucose levels. The steroid side effects, particularly the effects on appearance, are difficult for children, especially teenagers, and non compliance do to the side effects of medications is a risk in children; again, particularly teenagers.

Cyclosporine and/or tacrolimus are also commonly used as immunosuppressive medications following transplantation. Side effects of these drugs include hirsutism (increased hair growth), gum hypertrophy, interstitial fibrosis in the kidney (damage to the kidney), as well as other complications. Meclophenalate is also commonly used after transplantation (sometimes imuran is used); each of these drugs can cause a low white blood cell count and increased susceptibility to infection. Many other immunosuppressive medications and other medications (anti-hypertensive agents, anti-acids, etc) are prescribed in the postoperative period.

Life long immunosuppression, as used in patients with kidney transplants, is associated with several complications including an increased susceptibility to infection, accelerated atherosclerosis (hardening of the arteries), increased incidence of malignancy (cancer) and chronic rejection of the kidney.

United States Renal Data Systems (USRDS) report that the half-life (time at which 50% of the kidneys are still functioning and 50% have stopped functioning) is 10.5 years for a deceased transplant in children age 0-17 years and 15.5 years for a living related transplant in children 0-17 years. Similar data for a transplant at age 18 to 44 years is 10.1 years and 16.0 years for a deceased donor and a living related donor, respectively. Thus, depending upon the age when the patient receives their first transplant they may need 2-3 transplants over the course of their life.

Thus, the life expectancy of a person with a kidney transplant is significantly less than the general population and the life expectancy of a person on dialysis is markedly less than the general population.

Hemolytic uremic syndrome patient follow-up

Children who appear to have recovered from HUS may develop late complications. A precise determination of the risk of late complications is not likely. It is important to note that the risks of longer term (more than 20 years) complications are unknown and are likely to be higher than risks at 10 years, as many of the above studies describe.

A nephrologist—a kidney specialist—should formally evaluate all persons who have experienced HUSat a year following their acute illness. Kidneys injured by HUS may slowly recover function over at least a six-month period following the acute episode and perhaps longer. Even persons with “mild” HUS who did not require dialysis should be formally evaluated. Such an evaluation should include a routine physical, blood pressure measurement, and blood and urine analyses from which kidney filtration rate can be calculated.

Studies done to date on HUS outcomes have largely confirmed a positive correlation between more severe kidney involvement acutely, particularly the need for extended dialysis, and increased incidence of future renal complications. However, it has been shown in multiple studies that even moderate kidney compromise in the acute phase of HUS can result in long-term complications due to damage to the filtering units in the kidneys.

Among survivors of HUS, estimates are that about five percent will eventually develop end stage kidney disease, with the resultant need for dialysis or transplantation, and another five to ten percent experience neurological or pancreatic problems which significantly impair quality of life. Since the longest available follow-up studies of HUS are about twenty (20) years, an accurate lifetime prognosis is not available, and as such, medical follow-up is indicated for even the mildest affected cases.

[1] Recent research suggests that E. coli O157:H7 acquired its pathological character when a bacteriophage (virus that infects bacteria) transmitted genetic material for the creation of the toxin from a closely related Shigella bacterial species (hence the epithet, Shiga-like toxin) to a formerly benign species of E. coli.

[2] Verotoxin-globotriaosyl ceramide binding receptors.

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