Table 1.

Studies Evaluating the Association Between Proteinuria and Cardiovascular Disease

Table 2.

Therapeutic Strategies for Reduction of Cardiovascular and Renal Risk in Patients With Proteinuria Based on the KDOQI Guidelines

Box 1.

Classification of Proteinuria

Box 2.

Screening for Proteinuria

Sarnak, M. J. et al. American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure research, Clinical Cardiology, and epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure research, Clinical Cardiology, and epidemiology and Prevention. Circulation 108, 2154–2169 (2003).
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Segura, J., Campo, C. & Ruilope, L. M. effect of proteinuria and glomerular filtration rate on cardiovascular risk in essential hypertension. Kidney Int. Suppl. 92, s45–s49 (2004).
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de Zeeuw, D. et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 110, 921–927 (2004).
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Eddy, A. A. Proteinuria and interstitial injury. Nephrol. Dial. Transplant. 19, 277–281 (2004).
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Caglar, K. et al. ADMA, proteinuria, and insulin resistance in non-diabetic stage i chronic kidney disease. Kidney Int. 70, 781–787 (2006).
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Stehouwer, C. D. et al. increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes 51, 1157–1165 (2002).
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Hirano, T., Kashiwazaki, K., Moritomo, Y., Nagano, s. & Adachi, M. Albuminuria is directly associated with increased plasma PAi-1 and factor vii levels in NiDDM patients. Diabetes Res. Clin. Pract. 36, 11–18 (1997).
Zimmermann, J. et al. Hemorheology, plasma protein composition and von willebrand factor in type i diabetic nephropathy. Clin. Nephrol. 46, 230–236 (1996).
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Paisley, K. E. et al. endothelial dysfunction and inflammation in asymptomatic proteinuria. Kidney Int. 63, 624–633 (2003).
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Kougias, P. et al. Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease: mediators of endothelial dysfunction and atherosclerosis. Med. Sci. Monit. 12, rA5–rA16 (2006).
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Yang, J. C. et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med. 349, 427–434 (2003).
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Anavekar, N. S. et al. Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. Kidney Int. Suppl. 92, s50–s55 (2004).
Halbesma, N. et al. Macroalbuminuria is a better risk marker than low estimated GFR to identify individuals at risk for accelerated GFR loss in population screening. J. Am. Soc. Nephrol. 17, 2582–2590 (2006).
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Cardoso, C. R. & Salles, G. F. Gross proteinuria is a strong risk predictor for cardiovascular mortality in Brazilian type 2 diabetic patients. Braz. J. Med. Biol. Res. 41, 674–680 (2008).
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Howard, B. V. et al. rising tide of cardiovascular disease in American indians. The strong Heart study. Circulation 99, 2389–2395 (1999).
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Irie, F. et al. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int. 69, 1264–1271 (2006).
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Varun Agrawal, MD

Department of Internal Medicine, William Beaumont Hospital, Royal Oak, Michigan

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Disclosure: Varun Agrawal, MD, has disclosed no relevant financial relationships.

Victor Marinescu, MD, PhD

Department of Internal Medicine, William Beaumont Hospital, Royal Oak, Michigan

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Disclosure: Victor Marinescu, MD, PhD, has disclosed no relevant financial relationships.

Mohit Agarwal, MD

Department of Hospitalist Medicine, Marion General Hospital, Marion, Ohio

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Disclosure: Mohit Agarwal, MD, has disclosed no relevant financial relationships.

Peter A. McCullough, MD, MPH, FACC, FACP, FCCP

Divisions of Cardiology, Nutrition, and Preventive Medicine, William Beaumont Hospital, Royal Oak, Michigan

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Disclosure: Peter A. McCullough, MD, MPH, FACC, FACP, FCCP, has disclosed no relevant financial relationships.

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Charles P. Vega, MD

Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine

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Disclosure: Charles P. Vega, MD, FAAFP, has disclosed that he has served as an advisor or consultant to Novartis, Inc.

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Bryony Mearns, PhD

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CME

Cardiovascular Implications of Proteinuria: An Indicator of Chronic Kidney Disease

Authors: Varun Agrawal, MD; Victor Marinescu, MD, PhD; Mohit Agarwal, MD; Peter A. McCullough, MD, MPH, FACC, FACP, FCCP
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Target Audience and Goal Statement

This activity is intended for primary care physicians, nephrologists, endocrinologists, cardiologists, and other physicians who care for patients with proteinuria.

The goal of this activity is to describe the relationship between proteinuria and cardiovascular disease.

Upon completion of this activity, participants will be able to:

Describe the procedure of screening for proteinuria
Identify the effect of inhibitors of the renin-angiotensin-aldosterone system on cardiovascular outcomes among patients with proteinuria
Describe the relationship between proteinuria and dyslipidemia
List treatment goals for patients with proteinuria

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Author(s)

Varun Agrawal, MD

Department of Internal Medicine, William Beaumont Hospital, Royal Oak, Michigan

Disclosures

Disclosure: Varun Agrawal, MD, has disclosed no relevant financial relationships.

Victor Marinescu, MD, PhD

Department of Internal Medicine, William Beaumont Hospital, Royal Oak, Michigan

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Disclosure: Victor Marinescu, MD, PhD, has disclosed no relevant financial relationships.

Mohit Agarwal, MD

Department of Hospitalist Medicine, Marion General Hospital, Marion, Ohio

Disclosures

Disclosure: Mohit Agarwal, MD, has disclosed no relevant financial relationships.

Peter A. McCullough, MD, MPH, FACC, FACP, FCCP

Divisions of Cardiology, Nutrition, and Preventive Medicine, William Beaumont Hospital, Royal Oak, Michigan

Disclosures

Disclosure: Peter A. McCullough, MD, MPH, FACC, FACP, FCCP, has disclosed no relevant financial relationships.

CME Author(s)

Charles P. Vega, MD

Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine

Disclosures

Disclosure: Charles P. Vega, MD, FAAFP, has disclosed that he has served as an advisor or consultant to Novartis, Inc.

Editor

Bryony Mearns, PhD

Editor, Nature Reviews Cardiology

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Disclosure: Bryony Mearns, PhD, has disclosed no relevant financial relationships.

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Sidebar: Key Points

Proteinuria is associated with an increased risk for all-cause and cardiovascular mortality
Factors associating proteinuria with increased cardiovascular risk include chronic kidney disease, hypertension, hyperlipidemia, systemic inflammation, thrombotic factors, coronary artery calcification and vascular endothelial growth factor
identifying proteinuria in high-risk individuals allows risk stratification and initiation of therapies to reduce the risk for progression to end-stage renal disease and cardiovascular disease
Future studies need to evaluate if proteinuria reduction should be a therapeutic target to achieve renal and cardiovascular protection

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Sidebar: Key Points

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Table 1.

Table 2.

Box 1.

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References

Faculty and Disclosures

Author(s)

Varun Agrawal, MD

Victor Marinescu, MD, PhD

Mohit Agarwal, MD

Peter A. McCullough, MD, MPH, FACC, FACP, FCCP

CME Author(s)

Charles P. Vega, MD

Editor

Bryony Mearns, PhD

CME

Cardiovascular Implications of Proteinuria: An Indicator of Chronic Kidney Disease

Target Audience and Goal Statement

Disclosures

Author(s)

Varun Agrawal, MD

Victor Marinescu, MD, PhD

Mohit Agarwal, MD

Peter A. McCullough, MD, MPH, FACC, FACP, FCCP

CME Author(s)

Charles P. Vega, MD

Editor

Bryony Mearns, PhD

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Cardiovascular Implications of Proteinuria: An Indicator of Chronic Kidney Disease

Sidebar: Key Points

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