Heart Drug Can Limit Diabetics’ Kidney Disease
A commonly used heart drug can halve the risk of death, dialysis or kidney transplants resulting from kidney disease among diabetics, dramatically improving their quality of life and significantly reducing the cost of medical care, researchers reported Wednesday.
An estimated 30% of the 14 million diabetic Americans will develop kidney disease, so the new treatment has the potential to significantly alter the treatment of tens of thousands of patients every year, said Dr. Edmund J. Lewis of the Rush-Presbyterian-St. Luke’s Medical Center in Chicago. Lewis headed the tests, conducted with 409 patients at 30 U.S. medical centers.
“We are very excited about these results, which have far exceeded our expectations,” Lewis said at a news conference marking publication of their report today in the New England Journal of Medicine. In a later interview, he urged physicians to begin using the drug, captopril, immediately.
“Unless there is some very good reason to the contrary, the stakes are so high that, in my opinion, diabetic patients who show any evidence of renal involvement should get the drug,” he said. He would even recommend it for diabetics who have not yet developed kidney problems, even though such patients were not studied in the trial. “If my kid had diabetes, I wouldn’t wait to find out if he was going to be in the 30% who develop kidney disease. I would give him captopril.”
Others were equally enthusiastic. “For everyone with diabetes, these are striking and important findings . . . that are expected to establish a new standard of care for these patients and offer hope for a longer and better quality of life,” said Dr. James R. Gavin III, president of the American Diabetes Assn.
“This study provides the first solid evidence that we now have the means to slow the progression of the most dreaded complication of insulin-dependent diabetes,” Dr. Gary Striker of the National Institute of Diabetes and Digestive and Kidney Diseases said.
Diabetes results when the pancreas does not produce enough insulin to regulate the use and storage of sugars by body tissues. Up to 1 million Americans have Type 1 diabetes, also known as insulin-dependent diabetes, in which daily insulin shots are necessary to control blood sugar levels. The remaining 13 million have Type 2 diabetes, which can often be controlled by diet and exercise, or by the use of drugs that stimulate the pancreas to produce more insulin.
Both types of diabetics suffer a variety of complications that are thought to be caused by poor control of blood sugar levels. These include blindness, nerve damage in the arms and legs and kidney damage--also known as end-stage renal disease, or ESRD--which is often the most devastating. There are currently no drugs available to delay or prevent the onset of kidney damage.
An estimated 210,000 Americans have ESRD. Diabetes is the leading cause, accounting for about 35% of new cases annually. In ESRD, the kidneys fail and either dialysis or a kidney transplant is required for survival. The cost of caring for such patients in the United States totals $7.2 billion annually, according to the National Kidney Foundation.
Captopril is a member of a family of drugs called angiotensin-converting enzyme, or ACE, inhibitors. The drug relaxes capillaries, including those in the kidney, so that blood can flow more freely. It is widely used for controlling high blood pressure and has been shown to have some benefit in prolonging life after a heart attack. Other ACE inhibitors are used in reducing blood pressure but have not yet been tested for their effect in preventing kidney damage in diabetes.
Initial tests in diabetic animals showed that captopril could reduce kidney damage. The current trial, sponsored by the National Institutes of Health and Bristol-Myers Squibb, which manufactures captopril, was begun in December, 1987. The subjects were between the ages of 18 and 49, had Type 1 diabetes and already had evidence of kidney disease. About 75% also had high blood pressure.
In the study, 207 of the patients received captopril three times daily and 202 got placebo pills. Patients also received other medication to control their blood pressure when necessary.
During the trial, 68 patients suffered a 50% loss of kidney function, 25 in the captopril group and 43 in the placebo group.
Another 65 patients either died or required dialysis or transplantation, 23 in the captopril group and 42 in the placebo group. The chances that these improvements arose by chance are less than 1 in 1,000, Lewis said.
Remarkably few side effects were observed. The most important was an increase in blood potassium levels, which can lead to heart attacks. Three patients on captopril had significant “but not alarming” increases in blood potassium levels and were dropped from the study, Lewis said.
Three others had smaller increases and were removed from the study by their personal physicians, even though the researchers did not believe it to be necessary. There were no differences in other side effects between the treated and control groups.
“That surprised us a little bit,” Lewis said. “In diabetics who were sick to begin with, we expected to see more (side effects).”
Because captopril has already been approved by the Food and Drug Administration for the control of blood pressure, physicians are free to prescribe it for any use they deem reasonable.
