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Drug Treatment for Kidney Disease and Diabetes

Question: How should clinicians use ACE inhibitors and ARBs to manage kidney disease?

Answer: In over half of diabetes patients who develop kidney disease, the first manifestation is the development of albuminuria—abnormally high albumin protein in the urine—which should be measured annually. Levels of 30–299 mg/g creatinine (or mg/24h) are designated as microalbuminuria, and levels >300 are designated clinical albuminuria or just albuminuria. Other causes of elevated urinary albumin, such as menstrual blood, infection, or recent intense exercise, must be excluded.

Over the years, albumin levels gradually climb, and eventually the glomerular filtration rate (GFR) falls. In some individuals, the GFR falls without any prior abnormalities of albumin excretion. The GFR should be assessed annually, using one of the estimating equations that are based on the serum creatinine, age, sex, and race of the patient. Interestingly, the rate of GFR decline appears to be more rapid in those who have albuminuria. At some point in the course of developing kidney disease, over 90% of individuals will also develop hypertension.

Over and above their blood pressure (BP) lowering effects, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor-blockers (ARBs) have been shown to reduce the rate of progression from microalbuminuria to albuminuria and the rate of decline of GFR, although ARBs have not been studied in people with type 1 diabetes.¹ Given their similarities in mechanism of action, ARBs likely would also work in those with type 1.

Since less than one-third of people with diabetes ever develop chronic kidney disease, I do not treat all people with diabetes with these drugs but restrict their use to those with evidence of kidney disease or hypertension. These drugs should be started in those who develop urine albumin levels >30 mg/g creatinine (repeated at least once) or those who develop hypertension. I prefer ACE inhibitors to ARBs in those with type 1 diabetes, and either can be used in type 2. If a person does not tolerate one class, then switching to the other class is indicated.²

Some clinicians prefer to titrate the dosing of these drugs to urine albumin levels, but there are few data to support this. The benefits appear to be class effects, so other ACE inhibitors or ARBs can be used in equivalent doses. Maintaining BP level <130/80 mmHg is important, and salt restriction is helpful in augmenting the effects of these drugs. If BP control cannot be obtained with higher doses of these drugs plus salt restriction, a diuretic should be added. Often three or more drugs may be needed.²

Both classes commonly cause a mild fall in GFR, and this should be checked after 2–6 weeks; as long as this fall is <35%, the drugs should be continued. If the early fall is greater than this, there may be underlying bilateral renal artery stenosis and the drugs should be stopped. If a cough occurs with an ACE inhibitor, the physician should switch the patient to an ARB, which rarely causes coughs.²

As the kidney disease progresses, hyperkalemia may occur. This is not an indication for patients to stop these drugs, as they appear to be beneficial right up to the time patients progress to kidney failure. If potassium levels rise to >5 mEq/L, patients should be instructed in dietary potassium restriction by a dietitian and told to avoid salt substitutes. As the GFR falls to <40–50 ml/min/1.73 m², thiazide diuretics no longer work, and transition to a loop diuretic is in order to improve not only blood pressure control but also potassium control. In some patients, cation exchange resin (Kayexalate, Sanofi-Aventis) may be necessary to control potassium levels.²

Footnotes

Mark E. Molitch, MD, is professor of medicine in the Division of Endocrinology, Metabolism, and Molecular Medicine at Northwestern University's Feinberg School of Medicine in Chicago.

References

1. Karalliedde J, Viberti G.: Evidence for renoprotection by blockade of the renin-angiotensin-aldosterone system in hypertension and diabetes. J Human Hypertension 20:239–253, 2006.[Medline]

2. Nelson RG, Tuttle KR, Aschner P, et al.: Clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). Am J Kidney Dis 49 (Suppl. 2):S1 –S179, 2007.

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Services Email this article to a friend Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                What's this?