Kidney disease is a significant public health problem in the United States. Approximately 20 million Americans have kidney disease. Of these, more than 8 million have seriously reduced kidney function, and 10 million have proteinuria. In 2001, about 400,000 people had end-stage renal disease (ESRD), requiring dialysis or a kidney transplant to stay alive. That figure had doubled in a 10-year period.1 In 2000, the same number of people died from kidney failure as from breast cancer and prostate cancer combined. This burden of disease is paralleled by the enormous cost of treating patients with ESRD, which is more than $20 billion annually.1
Chronic kidney disease (CKD) has been defined as an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m2. Microalbuminuria of >30 mg of urinary albumin/1 g of urinary creatinine also defines CKD in diabetes, but a higher value of 300 mg/1 g is used conventionally in other renal diseases.2
Yet, effective therapeutic approaches exist that could, in some cases, prevent ESRD and, in many others, slow progression of CKD to ESRD. Diabetes and hypertension are the leading causes of kidney disease. Over the last decade, multiple studies have demonstrated the benefits of blood pressure control in patients with kidney disease of both type 2 and type 1 diabetes. Treatment of such patients with angiotensinconverting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) slows the progression of their disease.3,4 The same has been shown to occur in other progressive renal diseases, including hypertensive nephrosclerosis.
The recent release of the Seventh Report of the Joint National Committee for the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines CKD as a "compelling indication" for aggressive antihypertensive therapy that includes ACE inhibitors and a lower blood pressure goal in patients with decreased renal function to <130/80 mm Hg.6 To reach this goal, many patients with CKD probably will need more than one drug. A diuretic should almost always be a part of the regimen. If the estimated GFR is <40 mL/min/1.73 m2, loop diuretics are preferred.
The major safety concerns with ACE-inhibitor or ARB therapy in the CKD patient are hyperkalemia and a rapid decline in GFR. These drugs should not be used in patients with baseline hyperkalemia. A limited rise in serum creatinine of as much as 35% above baseline with ACE inhibitors or ARBs is acceptable and is not a reason to withhold treatment unless hyperkalemia develops. To avoid these complications, follow- up measures of creatinine and potassium should be obtained 7 to 10 days after the initiation of therapy.
Cough occurs in about 10% of those taking ACE inhibitors, and angioneurotic edema, a lifethreatening condition, occurs in <1%. ARBs do not seem to cause cough. Some cases of angioneurotic edema have been reported with ARBs, and many clinicians have begun to forgo even ARBs if the patient has suffered angioneurotic edema with an ACE inhibitor.7
Because of the success in treating CKD with drugs blocking the renin-angiotensin system, some investigators have begun to study combination therapies in hopes of achieving yet more complete blockade. The combination of an ACE inhibitor and an ARB has not yet been proven more effective than either alone for patients with CKD. The possibility of antagonizing the most distal component of this hormonal pathway, aldosterone, also is being entertained. The present use of such drugs as spironolactone in conjunction with ACE inhibitors in the CKD population is entirely investigational.