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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

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:

  1. Describe the procedure of screening for proteinuria
  2. Identify the effect of inhibitors of the renin-angiotensin-aldosterone system on cardiovascular outcomes among patients with proteinuria
  3. Describe the relationship between proteinuria and dyslipidemia
  4. 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

    Disclosures

    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

    Disclosures

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


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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, FCCPFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

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Abstract and Introduction

Abstract

Proteinuria, defined as urine protein excretion greater than 300 mg over 24 h, is a strong and independent predictor of increased risk for all-cause and cardiovascular mortality in patients with and without diabetes. Proteinuria is a sign of persistent dysfunction of the glomerular barrier and often precedes any detectable decline in renal filtration function. Measurement of proteinuria is important in stratifying the risk for cardiovascular disease and chronic kidney disease progression. A variety of basic pathophysiologic mechanisms that can partially explain simultaneous renal and cardiac disease will be discussed in this review. In addition to being a prognostic marker, proteinuria is being considered as a therapeutic target in cardiovascular medicine. Therapeutic strategies for amelioration of proteinuria by achieving blood pressure targets, glycemic control in diabetes, treatment of hyperlipidemia, and reducing dietary salt and protein intake are also reviewed in this paper. Future clinical studies are needed to assess if proteinuria reduction should be a target of treatment to reduce the burden of end-stage renal disease, cardiovascular disease, and improve survival in this high-risk population.

Introduction

AHA guidelines recommend that patients with chronic kidney disease (CKD) be considered at very high risk for cardiovascular disease (CVD).[1] CKD is defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, or presence of markers of kidney damage for ≥3 months.[2] Proteinuria and microalbuminuria are markers of renal injury that can be detected in early stages of CKD and predict rapid decline in renal filtration function. The NHANES III (Third National Health AND Nutrition Examination Survey study 1988-1994)[3] showed proteinuria to be present in 1% of the general population, 3.3% of patients with eGFR 30.60 ml/min/1.73 m2, and 26.0% of patients with eGFR <30 ml/min/1.73 m2. Another study found the prevalence of proteinuria to be 10.2% in patients with hypertension and eGFR <60 ml/min/1.73 m2.[4]

Proteinuria usually refers to the presence of an abnormal amount of protein (albumin and nonselective proteins) in the urine, owing to defects in the glomerular barrier; urine measurements that define proteinuria are described in Box 1 . Macroalbuminuria is defined as more than 300 mg urine albumin over 24 h and will be referred to as proteinuria in this paper. Microalbuminuria—urine albumin secretion of 30–300 mg over 24 h—has been extensively reviewed elsewhere,[5] and will not be discussed in this paper unless there are inferences relevant to proteinuria.

In this review, we will present the current data that shows an association of proteinuria with CVD, and highlight the probable mechanisms responsible for this association. Finally, we will present practical strategies for management of patients with proteinuria to decrease their risk of CVD.

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