An update on proteinuric chronic kidney disease : the dual goal aproach

REVIEW
SHELDON HIRSCH, MD

CME CREDIT

Chief of Nephrology, Mercy Hospital and Michael Reese Hospital, Chicago, IL

An update on proteinuric chronic kidney disease: The dual-goal approach
■ ■ABSTRACT
Lowering both blood pressure and urinary albumin excretion to specific goals may slow the progression of proteinuric chronic kidney disease. However, this dualgoal approach needs to bevalidated prospectively.

W1hen angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type receptor blockers (ARBs) were intro-

■ ■KEY POINTS
Evidence is emerging that urinary albumin is toxic to the kidney. Lowering both blood pressure and urinary albumin excretion, as a means to prevent progressive renal disease, appears to require aggressive inhibition of therenin-angiotensin-aldosterone system, often with several complementary drugs, ie, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, aldosterone receptor antagonists, and possibly, direct renin inhibitors. Volume status and potassium levels may help suggest which of several available drugs could be added at different times. Serum potassium levels must be managed aggressively when usingrenin-angiotensin-aldosterone inhibitors in combination.

duced, we hoped that these drugs would slow or stop the inexorable progression of chronic kidney disease. This hasn’t come to pass: the incidence of end-stage renal disease continued to increase throughout the 1990s, and although it may have finally reached a plateau, it remains unacceptably high.1 One reason may be that, used singly,drugs that block the renin-angiotensin-aldosterone system are only moderately successful, as approximately 20% to 40% of patients still reach unfavorable renal end points such as doubling of the serum creatinine level or dialysis.2–7

See related editorial, page 699

In view of these disappointing results, some experts are advocating a new strategy in which they advise that both blood pressure andurinary albumin excretion be lowered to specific goals. To achieve these goals, we will generally have to give higher doses of ACE inhibitors and ARBs alone or use a combination of these and other drugs that block the renin-angiotensin-aldosterone system at various sites. This article describes how the dual-goal approach, with a focus on renin-angiotensinaldosterone system inhibition, may beapplied in the therapy of proteinuric chronic kidney disease. This appears to be a reasonable approach, based on current evidence, to address the epidemic of renal failure. However, further studies are needed to establish the effectiveness of this approach, and the risk of hyperV O L UM E 75 • NUM BE R 10 O CT O BE R 2008

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PROTEINURICCHRONIC KIDNEY DISEASE

TABLE 1

Renoprotective antihypertensive drugs
Angiotensin-converting enzyme inhibitors2–4,7 Benazepril (Lotensin) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil, Zestril) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Angiotensin II type 1 receptor blockers5,6 Candesartan (Atacand)Eprosartan (Teveten) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar) Telmisartan (Micardis) Valsartan (Diovan) Aldosterone receptor antagonists18–20 Eplerenone (Inspra) Spironolactone (Aldactone)

Proposed goals: Systolic pressure < 120–125 mm Hg Urinary protein < 300–500 mg/day Decline in GFR < 2 mL/min/year

Nondihydropyridine calcium channel blockers36 Diltiazem (Cardizem, others)Verapamil (Calan, others) renin inhibitors21 * Aliskiren (Tekturna)
*

baseline proteinuria was almost linearly related to worse renal outcomes. In RENAAL, patients who excreted more than about 3 g of albumin per day had an 8.1-fold higher risk of progressing to end-stage renal disease.8 Moreover, the more that protein excretion could be reduced, the better the renal outcomes, down to a level...