Danger to Kidneys May Lurk in Some Preparations for Colonoscopies
By DEBORAH FRANKLIN

The New York Times
December 27, 2005

No one disputes that colonoscopies save lives. But recent research has prompted concern that in rare instances certain popular bowel-cleansing preparations that patients gulp down the day before a procedure can severely damage the kidneys.

The products are oral preparations made with sodium phosphate and they include Visicol tablets, sold by prescription, and over-the-counter solutions like Fleet-Phosphosoda and store-brand versions that contain the same active ingredients.

A team of doctors from the Columbia College of Physicians and Surgeons recently reported 21 cases of acute kidney failure from such products, including three that led to permanent dialysis and one to a kidney transplant. The study appeared in the November issue of The Journal of the American Society of Nephrology.

Previously, just a few groups of patients, notably those with impaired kidneys or congestive heart failure, had been advised to avoid phosphate-based bowel preparations.

The new findings lengthen the list of people who may be especially vulnerable to kidney damage. Among the dozen or so groups now thought to have a slightly elevated risk are healthy elderly people, patients with unstable angina or who have had heart attacks and anyone who is especially likely to become dehydrated, including people who take certain hypertension drugs and people who do not drink enough fluid to replenish that lost in bowel cleansing.

While experts agree that the likelihood of severe kidney damage is very small, some say that any added risk is unnecessary, and that people in these risk groups should avoid phosphate-based bowel preparations.

Others argue that such cleansers have benefits over other types and can be used safely by most people. To provide an extra margin of safety, those experts say, all patients should drink extra fluid when taking the treatments.

In addition, doctors should consider lowering the dose for some people or taking blood samples before and after to monitor electrolytes and the kidneys.

The kidney damage has been found only among patients who used the solutions as a preparation. The same products given as a mild laxative, in much smaller doses and according to directions, do not carry the same risk. Neither do Fleet enemas or store-brand equivalents, which amount to a different dilution of the same ingredients administered rectally.

The manufacturer of Fleet-Phosphosoda, C. B. Fleet of Lynchburg, Va., has posted updated guidelines on its Web site and sent letters to doctors. "We take these side effects very seriously and believe our safety record is extraordinarily good," said Sarah S. Post, senior vice president for global scientific affairs for Fleet.

No one condones using the recent findings as an excuse to put off a colonoscopy. "Your risk of colon cancer is much greater than your risk of this side effect, no question," said Dr. Glen S. Markowitz, a Columbia renal pathologist.

Some commonly prescribed bowel cleansers, including GoLytely and Colyte, are phosphate free and are not known to pose risk of kidney damage.

In the new study, Dr. Markowitz and his colleagues described medical sleuthing that began at a microscope in 2003. The Columbia renal pathology lab is a specialty center run by Dr. Vivette D. D'Agati, senior author on the paper. Each day, the laboratory receives kidney tissue samples from 80 or 90 hospitals in 12 states.

"We see rare things commonly," Dr. Markowitz said.

That vantage may have helped detect a pattern that other eyes missed. One day, Dr. Markowitz was scrutinizing a biopsy slide from a patient with nephrocalcinosis, a type of damage caused by a chalky tissue-inflaming buildup of calcium phosphate sediment in the kidney.

He mentioned the finding to Dr. D'Agati, who said she had seen a similar sample that day. When they checked the patients' medical histories, they found that in each case the damage had developed abruptly, soon after a colonoscopy.

Looking for a source of the phosphate, the doctors noticed the patients had been prescribed a sodium phosphate solution to drink the night before the exam. Guessing the link might not be coincidental, the doctors decided to search all 7,349 kidney biopsy samples received by the laboratory since 2000, hunting for cases of nephrocalcinosis. "The answer was alarming," Dr. Markowitz said.

Among the 31 cases they turned up and followed for an average of 16.7 months, at least 21 fit the pattern:acute kidney failure, normal blood levels of calcium and recent colonoscopy or bowel surgery preceded by a phosphate-based preparation.

Six of the 21 patients were in their 60's, with most others spread from ages 43 to 82. One was 39.

"Starting at age 50, kidney function drops about a half percent a year, as a part of normal aging," said Dr. Jai Radhakrishnan, a Columbia nephrologist who contributed to the study. "A 90-year-old typically has 60 percent of the kidney function he had at 50."

Older people, in particular, Dr. Radhakrishnan figured, could ill afford another hit.

Sixteen of the 21 patients had histories of high blood pressure, and 14 of those were taking one of two types of medication to treat it: angiotensin receptor blockers or an angiotensin-converting enzyme inhibtors, known a ACE inhibitors.In May, Dr. Charles Ganley, director of the Food and Drug Administration's office of nonprescription drug products, invited Dr. Markowitz to present his data at a conference for some members of the drug agency's review staff.

"We were clearly interested in the information that he had," Dr. Ganley said, but he stopped short of giving details about any agency action. "Even if it turns out that the effect only occurs in 1 in 10,000 or 1 in 50,000 applications, if you're that one person, it can be devastating," Dr. Ganley said.

Still, many experts are not convinced that switching from phosphates is necessary or even best for many patients.

The treatment schedules for such cleansers usually call for dividing the treatment into two doses, to be taken 10 to 12 hours apart, each diluted in a glass or two of water or other clear fluid, and chased with several more glasses of plain liquid.

Some gastroenterologists say they have found that under the divided dosing, sodium phosphate cleansers produce a cleaner, more effectively scanned bowel than other preps. Even many doctors who deem all cleansers to be equally effective agree that some patients will balk if told to avoid phosphate-based solutions.

The phosphate-based treatments tend to be less daunting than other types because they require drinking only a glass or two of foul-tasting fluid in a single sitting, instead of a gallon of polyethylene glycol solutions like GoLytely.

Patients who choose the sodium phosphate solutions are supposed to make up much of the difference in fluid volume by consuming a clear beverage.

But some patients are likely to skimp on the extra fluid.

Dr. Markowitz, who has seen the medical records of people who were healthy before swallowing a phosphate-based bowel cleanser and are now limping along on dialysis, does not think this risk is worth it and wants to make sure every patient understands that the risk exists.

He and Dr. Radhakrishnan have each been hired as consultants by lawyers representing clients who claim that their loss of kidney function can be traced to phosphate-based bowel cleansing products.

Dr. Markowitz said he was just 37 years old, so had not yet experienced his first colonoscopy. "But I can safely tell you," he said, "that neither of my parents, will be getting a phosphate-based prep."