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Cardiovascular implications of proteinuria: an indicator of chronic kidney disease

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.

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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Figure 1: Relationship between CV and renal outcomes in patients with different baseline degrees of albuminuria in the RENAAL (Reduction in endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan) trial.13
Figure 2: Relationship between change in albuminuria after 6 months of losartan therapy and CV and heart failure end points in the RENAAL (Reduction in endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan) trial.13

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Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Agrawal, V., Marinescu, V., Agarwal, M. et al. Cardiovascular implications of proteinuria: an indicator of chronic kidney disease. Nat Rev Cardiol 6, 301–311 (2009). https://doi.org/10.1038/nrcardio.2009.11

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