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(Hypertension. 2004;43:e14.)
© 2004 American Heart Association, Inc.

Letters to the Editor

Letters to the Editor

The Cardiorenal Connection

Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

Branko Braam

Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands

To the Editor:

With much interest we have read the article by Sarnak et al¹ on the risk of kidney disease for the development of cardiovascular disease. Considering the rising prevalence of chronic kidney disease and heart failure, we propose to perceive the reciprocal relationship of heart and kidney failure as a separate disease entity. This severe cardiorenal syndrome (SCRS) can be defined as the accelerated and extensive cardiovascular disease exclusively related to the coexistence of renal failure and heart disease.

In agreement with Sarnak et al, we feel that many questions remain unanswered. However, we would like to underscore the lack of insight in how renal and heart failure-related risk factors interact to lead to the SCRS. This inspired us to attempt to develop a model of heart/kidney interaction. The legacy of the late professor Guyton is a solid model to explain heart/kidney interaction by cardiac output, regulation of the extracellular fluid volume, blood pressure, and renal sodium handling. Central in the model of Guyton is the renin–angiotensin system (RAS), with its corresponding extensions (aldosterone, endothelin), and its antagonists (natriuretic peptides). While the model seems appropriate to explain extracellular fluid volume, blood pressure, and cardiac output in combined heart and renal failure, can it also explain the accelerated atherosclerosis, cardiac hypertrophy, and remodeling and progression of renal disease?

To answer these questions, we propose an extension to the Guytonian model for volume and blood pressure control, the cardiorenal connection (CRC) (Figure). At the corners of this model are the RAS, the NO/ROS balance, the sympathetic nervous system, and inflammation. We envision that derangement of one component of the CRC leads to a vicious cycle, so that other factors become disturbed and synergize. Ultimately this induces (irreversible) functional and structural damage in the heart and kidneys, thereby forming a positive feedback loop. In renal failure, oxidative stress² and inflammation³ have been proposed as key factors, and some evidence exists on the interaction of the four corners of the CRC in promoting CVD. In heart failure, evidence is scarce, but recent investigations seem to support our view of the existence of the CRC. For example, increased NADPH-oxidase mediated ROS-release has been identified in both the kidney⁴ and the heart⁵ in heart failure.

View larger version (34K): [in this window] [in a new window]   Pathophysiological basis of the severe cardiorenal syndrome. The model of Guyton explains heart/kidney interaction with respect to blood pressure (BP) and extracellular fluid volume (ECFV). When one of the organs fails, a vicious cycle develops in which the renin-angiotensin system, the NO/ROS balance, the sympathetic nervous system and inflammation interact and synergize, called the cardiorenal connection.

We strongly feel that unraveling the nature of the interactions between the primary forces of the cardiorenal connection will help to understand the severe cardiorenal syndrome. The statement by the American Heart Association strongly stimulates the commencement of a vivid debate by clinical and basic scientists on this intriguing part of pathophysiology.

References

1. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; Am 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 Am Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension. 2003; 42: 1050–1065.[Free Full Text]

2. Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002; 62: 1524–1538.[CrossRef][Medline] [Order article via Infotrieve]

3. Arici M, Walls J. End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link? Kidney Int. 2001; 59: 407–414.[CrossRef][Medline] [Order article via Infotrieve]

4. Tojo A, Onozato ML, Kobayashi N, Goto A, Matsuoka H, Fujita T. Angiotensin II and oxidative stress in Dahl salt-sensitive rat with heart failure. Hypertension. 2002; 40: 834–839.[Abstract/Free Full Text]

5. Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, Shah AM. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol. 2003; 41: 2164–2171.[Abstract/Free Full Text]

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This Article Extract Full Text (PDF) All Versions of this Article: 43/4/e14    most recent 01.HYP.0000118521.06245.b8v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bongartz, L. G. Articles by Braam, B. Search for Related Content PubMed PubMed Citation Articles by Bongartz, L. G. Articles by Braam, B. Pubmed/NCBI databases Medline Plus Health Information Heart Failure Related Collections Cardio-renal physiology/pathophysiology Pathophysiology