Clin J Am Soc Nephrol 3: S1-S2, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.03240807
Managing CKD: Key Therapeutic Issues Introduction
Stuart L. Linas
Department of Internal Medicine, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, Colorado
Correspondence: Dr. Stuart L. Linas, University of Colorado Health Sciences Center, 660 Bannock Street, Denver, CO 80204. Phone: 303-436-5905; Fax: 303-436-7249; E-mail: stuart.linas{at}uchsc.edu
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Introduction
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The content is based on an official American Society of Nephrology continuing medical education luncheon symposium held November 16, 2006, in San Diego, California.
Faculty:
George L. Bakris, MD, Hypertensive Diseases Unit, Section of Endocrinology, Diabetes and Metabolism, Pritzker School of Medicine, University of Chicago, Chicago, Illinois
Stuart L. Linas, MD, Department of Internal Medicine, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, Colorado
Raymond R. Townsend, MD, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Credit Designation Statement: The American Society of Nephrology designates this educational activity (entire supplement) for a maximum of 2.0 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Learning Objectives:
- To examine the epidemiology and pathophysiology of stroke and cardiovascular disease in the chronic kidney disease population
- To evaluate the efficacy of current therapies for the treatment of cardiovascular risk in patients with renal disease
- To apply new clinical insights for the identification and treatment of cardiovascular risk to improve outcomes for patients with chronic kidney disease
Categories: Chronic kidney disease, cardiovascular disease in the context of renal dysfunction
Patients with chronic kidney disease (CKD) face elevated risk for stroke (1,2). Both CKD and reduced kidney function have been associated with higher risk for cardiovascular disease (CVD) (1–4). Traditional risk factors such as hypertension, diabetes, and dyslipidemia seem to account for only some of the excess stroke and cardiovascular risk in CKD. This has led to the proposal that the environment of renal impairment itself increases susceptibility to stroke and, potentially, to CVD.
Recent pathophysiologic evidence suggests that actions of the renin-angiotensin system (RAS) may offer a biologic rationale for the associations among these conditions. Ritz (5) suggested that minor reductions in renal function, as manifested by microalbuminuria or reduced GFR, increase oxidative stress and initiate the cycle of effects the lead to vascular disease well described by Dzau (6).
Cardiovascular risk factors such as dyslipidemia, smoking, hypertension, and diabetes cause oxidative stress in the vessel wall. This stress leads to endothelial dysfunction and vascular inflammation, which in turn increase local production of angiotensin-converting enzyme (ACE) and angiotensin II, thereby perpetuating the deleterious cycle and promoting vascular complications (6). This scenario suggests consideration of a role for RAS-blocking agents.
Controlling BP with antihypertensive agents that block the RAS not only reduces risk for stroke but also slows decline of kidney function (7–9). This supplement reviews evidence for effects of ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in CKD beyond those attributable to BP lowering.
Proteinuria is a recognized risk factor for renal disease progression (10–13). ACEI and ARB seem to offer renoprotection to a degree not accounted for by BP lowering. George L. Bakris, MD, summarizes the growing body of data suggesting that the antiproteinuria activity of RAS inhibition explains this effect.
Stroke prevention is an issue in the treatment of people with CKD because of the association of stroke risk with reduced kidney function. BP lowering is the single most important factor in stroke prevention. Raymond R. Townsend, MD, summarizes recent evidence for addressing other risk factors as well and reviews physiologic evidence for stroke reduction with ARB beyond that attributable to BP lowering.
Neither ACEI nor do ARB fully block the RAS. It has been suggested that a combination of both agents may inhibit the RAS more effectively than either treatment alone. Stuart L. Linas, MD, discusses this theory, the evidence for dual RAS blockade on proteinuria and BP, and the safety of this option.
We hope that this supplement facilitates clinicians’ efforts to reduce risk for renal deterioration, stroke, and other CVD in patients with renal impairment.
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Disclosures
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S.L.L. has served as a consultant to Merck, AstraZeneca, and Gilead and has received honoraria from Merck, AstraZeneca, Pfizer, and Novartis; he also serves as chair of the American Society of Nephrology Hypertension Advisory Group.
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Acknowledgments
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This activity is supported by an independent educational grant from Boehringer Ingelheim.
Eileen A. McCaffrey, MA, Clarus Health, provided writing support.
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Footnotes
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Activity Production: Each author was provided with the final edited manuscript, which was transcribed by a medical writer from the author's original presentation, for final approval. The posttest questions were written on the basis of the supplement content and reviewed by the continuing medical education accreditor.
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References
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Introduction
Disclosures
