Putting the Brakes on Diabetic Kidney Disease

Diabetes is the most common single cause of end-stage renal disease (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. Most patients with ESRD usually go on dialysis or require a kidney transplant to survive.

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 higher risk.

As a result of having diabetes, the kidney may start to overwork. The earliest clinical evidence of kidney disease is the appearance of greater than 30 milligrams of albumin (or protein) in a 24-hour collection period. This condition is known as microalbuminuria and is easily detected through a 24-hour urine test. Microalbuminuria can progress to ESRD if left untreated.

Increasingly, physicians are turning to a class of drugs called angiotensin-converting enzyme (ACE) inhibitors to slow the progression of kidney disease in their diabetic patients.

What are ACE Inhibitors and How do They Help People with Diabetes?

The use of ACE inhibitors is a popular therapy used to slow the rate of progression of kidney disease. The disease develops when the hormone angiotensin is activated, causing blood vessels to constrict. This results in higher blood pressure, which puts a strain on the heart.

“Angiotensin increases pressures inside the kidney, which leads to kidney damage,” says Robert Stanton, MD, chief of nephrology at Joslin Diabetes Center in Boston. “ACE inhibitors prevent the activation of angiotensin, resulting in lower blood pressure and lower pressure inside the kidney.”

Daniel Einhorn, MD, FACP, FACE, of the University of California at San Diego School of Medicine, says 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. ACE inhibitors are generally prescribed in lower doses initially to prevent any precipitous drops in blood pressure.

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

When to Start ACE Inhibitors

According to a 1995 issue of The 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, of South Orange County Endocrinology in Laguna Hills, California.

The American Diabetes Association and National Kidney Foundation (NKF) recommend that people with diabetes at risk for kidney disease should take ACE inhibitors regardless of having high blood pressure. Leonard G. Feld, MD, a renal disease expert at the Atlantic Health System, agrees.

“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

Studies have shown that ACE inhibitors prevent microalbuminuria from increasing, and may even reduce it, 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.

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

Minor Side-Effects

Many patients on ACE inhibitors complain of minor side effects initially, but these usually dissipate with time. Steven Leichter, MD, FACP, FACE, co-director of West Georgia Center for Metabolic Disorders in Columbus, Georgia, says the only side effect from the ACE inhibitor Quinapril, for example, is an “annoying cough.”

Stanton adds that any ACE inhibitor can cause a cough.

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