Vessel Drug Slows Kidney Damage in Diabetics
Studies show major gains against end-stage disease
WEDNESDAY, Sept. 19, 2001 (HealthDayNews) -- Drugs that relax constricted blood vessels can greatly slow the advance of kidney failure in patients with non-insulin dependent diabetes, new studies show.
Two studies in this week's issue of The New England Journal of Medicine have found that a family of medicines that ease vessel contraction relieves kidney failure in people with adult-onset diabetes and lowers the odds that their condition will lead to end-stage renal disease.
A third report in the journal shows that the drugs can also keep early kidney damage linked to the blood sugar disorder from becoming more serious.
Dr. Barry Brenner, director emeritus of the kidney division at Harvard's Brigham and Women's Hospital in Boston, and lead author of one of the papers, says the findings should have an immediate impact on patient care. "I would use my results to say this is a drug that we should" be using right now, says Brenner, who studied a compound called losartan.
Kidney failure is a major global health problem, particularly in the United States, where more than 90,000 patients were diagnosed with the condition last year. That figure is double that of a decade ago, because of a surge in Type II diabetes, which leads to renal damage.
Type II diabetes -- also called adult-onset or non-insulin dependent -- accounts for as many as 40 percent of all cases in this country and almost all of the recent increase in prevalence, experts say. During any given week, 300,000 Americans undergo dialysis, which takes over for failed kidneys and scrubs their blood of impurities. The procedure costs billions of dollars and sorely taxes health care resources.
Earlier studies had found that compounds called angiotensin-converting enzyme (ACE) inhibitors can reduce the risk of kidney failure in diabetics with the early-onset, or Type I, form of the condition. Type I diabetics make no insulin at all and must inject themselves with the hormone to control their blood sugar.
What was less clear, however, is how well the inhibitors work in people with Type II diabetes. Type II diabetics make some insulin but their bodies don't use it well; mostly they control the disease with diet and exercise.
The latest research focuses on a class of drugs called angiotensin-II-receptor antagonists. Like the ACE inhibitors, they are used to control high blood pressure and they act on the angiotensin system.
But rather than muzzle the production of angiotensin-converting enzyme, they prevent certain molecules, or receptors, in the blood vessel lining from binding with the chemical.
Brenner and his colleagues, a group that covered 28 countries and 250 medical centers worldwide, studied losartan in 1,513 men and women with Type II diabetes and kidney failure.
The result: Patients who didn't take the losartan were 25 percent more likely to see their kidneys' filtering power cut in half. For those who did take the losartan, their risk of end-stage disease was 28 percent lower than that of untreated patients.
The patients were taking high blood pressure drugs, too, but the effect on kidney improvement was above and beyond that from controlling hypertension, the researchers say.
Although each group had about the same odds of dying from cardiovascular complications, the patients taking losartan were almost a third less likely than the others to be hospitalized for the first time with heart failure.
In fact, says Brenner, cardiovascular deaths and heart attacks did appear to be lower in the patients taking losartan, but the study wasn't large enough to prove that effect statistically significant.
"If you ease the kidney disease progression, the component that kidney disease brings to bear on cardiovascular mortality" is reduced, Brenner says.
In the second study, a group of scientists led by Dr. Edmund Lewis, of Rush-Presbyterian-St. Luke's Medical Center in Chicago, showed that a different ARB, irbesartan, also stalled the progression of kidney failure in Type II diabetics.
Lewis, who did the first study of kidney failure and an ACE inhibitor, says irbesartan was "very well tolerated, given how sick this patient population was."
In the last trial, European researchers found that irbesartan could prevent early-stage kidney disease from developing into full-blown renal failure in diabetics. The scientists also showed that higher doses of the drug worked better than lower ones, and that the effect is due not simply to its impact on blood pressure.
Lewis says the lesson from that study is that doctors should screen diabetic patients for the first signs of failing kidneys.
"The earlier you treat them, the better will be your results," he says.
Taken together, the three trials show that ARBs do indeed protect the kidneys in patients with Type II diabetes, more convincingly even than ACE inhibitors, Lewis and Brenner say.
Indeed, Lewis says that the results are probably conservative, and that tracking patients for more than two or three years will show more dramatic improvement -- perhaps leading to "remission" of kidney disease is some people.
The looming question, experts say, is whether ARBs work as well as ACE inhibitors in improving heart and vessel health, which is an important standard for many doctors because such conditions are the leading cause of death among diabetes patients.
"I don't think that we have done enough analysis of our data to convincingly show that ARBs are equivalent [to ACE inhibitors] in this situation," Lewis says. But he thinks in the long run that they will prove to be.
Doctors will doubtless also like to know how well ACE inhibitor and ARBs fare in a head-to-head trial against kidney damage in diabetics, Lewis adds. Such a study would be costly and time consuming, he says.
The drug maker Merck & Co., which makes forms of losartan, sponsored one of the studies. Bristol-Myers Squibb and Sanofi-Synthelabo funded the two trials of irbesartan, which they are marketing jointly.
What To Do
For more on diabetes, visit the American Diabetes Association. To read more about kidney failure, try the Kidney Patient Guide or Columbia University. The National Institute of Diabetes & Digestive & Kidney Diseases is a good source for information about both conditions.