Improved blood sugar control, smoking cessation and aggressive blood pressure treatment are mainstays for preventing or treating the development of kidney disease in people with diabetes. Increasingly, physicians are also turning to a class of drugs called ACE inhibitors to slow the progression of kidney disease in their patients.

As a result of diabetes, the kidneys may start to overwork, attempting to filter out excess sugar and eventually damaging the small blood vessels in the kidney. The earliest clinical evidence of kidney disease is the appearance of between 18 and 92 µg/mg* of albumin (or protein) within a 24-hour period. This condition is known as microalbuminuria and is easily detected through a 24-hour urine test. (see What A Few Yearly Tests Can Tell You).

What are ACE Inhibitors?

Peter Lodewick, MD, medical director of the Diabetes Care Center in Birmingham, Alabama, says that as microalbuminuria increases, so do the risks. "If microalbuminuria can be reduced with the use of ACE inhibitors, a therapeutic benefit can be expected," says Lodewick.

The use of angiotensin-converting enzyme (ACE) inhibitors is a popular therapy used to slow the rate of progression of kidney disease. ACE is an enzyme in our bodies that activates a hormone called angiotensin. Once activated, this causes blood vessels to constrict, resulting in higher blood pressure which puts a strain on the heart. ACE inhibitors prevent the activation of angiotensin, resulting in lower blood pressure.

"It is well established that even in the absence of high blood pressure or abnormal creatinine, ACE inhibitors prevent progression of microalbuminuria to overt proteinuria (excessive protein in the urine) and ultimately, diabetic renal failure," says Daniel Einhorn, MD, FACP, FACE, of the University of California at San Diego School of Medicine, who adds that ACE inhibitors have few side effects, and are generally safe if monitored.

End-stage Renal Disease (ESRD)

Microalbuminuria can progress to end-stage renal disease (ESRD) if left untreated. Diabetes is the most common single cause of ESRD in the United States and Europe. In the United States, diabetic nephropathy (kidney disease) accounts for about one-third of all cases of ESRD. Patients with ESRD usually go on dialysis or require a kidney transplant to survive. Kidney disease is a significant cause of death in patients with diabetes. Approximately 20 to 40 percent of patients with type 1 diabetes, and 10 to 15 percent of patients with type 2 diabetes, have diabetic kidney disease. Native Americans, Hispanics and African-Americans are at much higher risk.

How do ACE Inhibitors Help People With Diabetes?

Currently, doctors are unable to distinguish people who will develop serious complications from those whose kidney function will remain normal. Researchers do know, however, that ACE inhibitors can help people with diabetes by lowering their blood pressure, thereby protecting the kidneys from damage. ACE inhibitors are generally prescribed in lower doses initially to prevent any precipitous drops in blood pressure.

Other Possibilities Under Study

Einhorn mentions that other agents are also being tested for the prevention of kidney disease, including angiotensin receptor blockers, calcium channel blockers, and other antihypertensive agents.

ACE Inhibitors may Help Other Diseases

"The current consensus is that there is a unique benefit to the ACE inhibitors," says Einhorn. "This important area of vascular protection is rapidly evolving, and the effort to prevent kidney disease may become indistinguishable from the effort to prevent all vascular disease, including heart attack, stroke, and peripheral vascular disease in the legs."

Disagreements Over When to Start ACE Inhibitors

According to a 1995 issue of Lancet, researchers issued a consensus statement recommending the use of ACE inhibitors, irrespective of a patient's blood pressure, once microalbuminuria has been documented. "Some physicians feel that having diabetes is reason enough to use ACE inhibitors, while others wait until certain levels of proteinuria are reached," says Alan Marcus, MD, with South Orange County Endocrinology in Laguna Hills, CA.

The ADA recommends the use of ACE inhibitors in patients with diabetic kidney disease only if they have high blood pressure. The National Kidney Foundation (NKF), on the other hand, recommends the use of ACE inhibitors in diabetic patients at risk for kidney disease who have normal blood pressure.

Leonard G. Feld, MD, a renal disease expert at the Atlantic Health System, agrees with the NKF. "Waiting for these patients with kidney disease to develop high blood pressure and then loading them with the ACE inhibitors would be a bad idea, as most of the patients would be in the advanced stage of the disease by then," says Feld.

Studies Support the Efficacy of ACE Inhibitors

Numerous studies have shown that ACE inhibitors prevent an increase, and may even reduce microalbuminuria in patients with type 2 diabetes and hypertension. Other studies have shown that in type 1 hypertensive patients, ACE inhibitors can also slow the rate of progression of kidney disease to a greater degree than other antihypertensive agents.

Research presented recently at the Annual Meeting of the European Association for the Study of Diabetes in Brussels, Belgium, indicated that implementation of ACE inhibitor therapy in type 1 patients with microalbuminuria reduced progression to kidney disease and enhanced regression to normal albuminuria levels. Researchers evaluated 217 type 1s with persistent microalbuminuria between 30 and 300 µg/mg per 24-hour period.

"The key to success in the treatment with ACE inhibitors is early detection and prompt intervention at this correctable phase," says Feld.

ACE Inhibitors can Help Reduce the National Debt!

A study published in the October 1996 issue of Diabetes Care determined that using the ACE inhibitor captopril could slow progression to ESRD and save the country about $2.4 billion in cumulative health care costs from 1994 to 2004 alone. The report focuses on the fact that captopril therapy "can prolong life and save money at the same time because of its clinically significant positive effects on diabetic renal disease and because ESRD is so expensive."

Risks of Kidney Disease are Similar for Types 1 and 2

According to the U.S. Renal Data System, in the past two decades there has been a continual increase in the incidence of ESRD among patients with type 2 diabetes. In the past, the risk of kidney complications was thought to be considerably lower in patients with type 2 diabetes, however, there is now evidence that the risk of kidney disease is similar in both type 1 and 2 diabetes.

ESRD Comes with Increased Longevity

In the October 7 issue of The New England Journal of Medicine, Eberhard Ritz, MD, and Stephan Reinhold Orth, MD, of the Department of Internal Medicine, Renal Unit, at Ruperto Carola University in Heidelberg, Germany, wrote a review article about kidney disease in patients with type 2 diabetes. The authors speculate that the increased incidence of kidney failure in type 2s can be attributed to better treatment of hypertension and heart disease.

"This allows them to live long enough to see kidney disease and end-stage renal disease develop," write Ritz and Orth. "Hence, end-stage renal disease in patients with type 2 diabetes may be viewed as a disease of medical progress."

Make Your Check List and Read It Twice

To prevent or slow progression to ESRD, Ritz and Orth and other experts recommend taking the following steps:

• maintaining an HbA1c near 7%;
• maintaining blood pressure at 125/75 mm Hg, as recommended by the NKF;
• smoking cessation;
• reducing the level of microalbuminuria in the urine;
• restricting dietary intake of animal protein to 0.8 gm. per kilogram of body weight;**
• have a yearly 24-hour urine test to check for microalbuminuria;
• treat urinary tract and bladder infections promptly.

ACE Inhibitors are not for Everyone

Edelman cautions that some patients should not take ACE inhibitors, including people with:

• a predisposition for high potassium levels in the blood;
• Renal Artery Stenosis, or clogging of the arteries that deliver blood to the kidneys; and
• pregnant women.

According to R. Keith Campbell, RPh, CDE, professor of the pharmacy department at Washington State University, there are no vitamins or minerals which can specifically help people with diabetic nephropathy. He does warn that high doses of magnesium and potassium should not be used by patients with kidney problems.

For more information on diabetic types who should not be prescribed ACE inhibitors, check out www.tcoyd.com.

Minor Side-Effects

Many patients on ACE inhibitors do complain of minor side-effects initially, but these usually dissipate with time. Leichter says the only side-effect from the ACE inhibitor Quinapril, for example, is an "annoying cough."

* µg/mg: micrograms per milligram. 1 microgram=1/10,000th of a gram.

* *Or the equivalent of 61 grams of protein for a person who weighs 170 lbs. An egg contains 8 gm. of protein.