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Cardiorenal syndrome: pathophysiology and potential targets for clinical management

Nature Reviews Nephrology volume 9, pages 99–111 (2013)Cite this article

Abstract

Combined dysfunction of the heart and the kidneys, which can be associated with haemodynamic impairment, is classically referred to as cardiorenal syndrome (CRS). Cardiac pump failure with resulting volume retention by the kidneys, once thought to be the major pathophysiologic mechanism of CRS, is now considered to be only a part of a much more complicated phenomenon. Multiple body systems may contribute to the development of this pathologic constellation in an interconnected network of events. These events include heart failure (systolic or diastolic), atherosclerosis and endothelial cell dysfunction, uraemia and kidney failure, neurohormonal dysregulation, anaemia and iron disorders, mineral metabolic derangements including fibroblast growth factor 23, phosphorus and vitamin D disorders, and inflammatory pathways that may lead to malnutrition–inflammation–cachexia complex and protein–energy wasting. Hence, a pathophysiologically and clinically relevant classification of CRS based on the above components would be prudent. With the existing medical knowledge, it is almost impossible to identify where the process has started in any given patient. Rather, the events involved are closely interrelated, so that once the process starts at a particular point, other pathways of the network are potentially activated. Current therapies for CRS as well as ongoing studies are mostly focused on haemodynamic adjustments. The timely targeting of different components of this complex network, which may eventually lead to haemodynamic and vascular compromise and cause refractoriness to conventional treatments, seems necessary. Future studies should focus on interventions targeting these components.

Key Points

  • The so-called cardiorenal syndrome is a complex phenomenon involving multiple organ systems; traditional understanding of the mechanisms involved forms only a small part of the big picture

  • Any overt or covert involvement of heart or kidney can affect the other organ and usually by the time of clinical manifestation, multiple components of the interconnected network of events are involved

  • It is not usually practically possible to specify whether kidney or heart was the initiator of the events

  • Besides haemodynamic interactions, many other components are involved in the pathophysiology of cardiorenal syndrome; these components can be potential targets for management

  • Most studies, particularly major clinical trials, have targeted and are still focusing on the 'haemodynamic' mechanisms of cardiorenal syndrome; future studies need to concentrate further on the other elements of this complex pathophysiology

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Figure 1: Putative pathophysiologic connections in cardiorenal syndrome.

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Authors and Affiliations

  1. Division of Nephrology, University of Michigan, 3914 Taubman Center, SPC 5364, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA

    Parta Hatamizadeh

  2. Ahmanson-UCLA Cardiomyopathy Center, 10833 Le Conte Avenue, Los Angeles, 90095-1679, CA, USA

    Gregg C. Fonarow

  3. St John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, 90509, CA, USA

    Matthew J. Budoff & Sirous Darabian

  4. Division of Nephrology, Salem Veterans Affairs Medical Center, 1970 Roanoke Boulevard, Salem, 24153, VA, USA

    Csaba P. Kovesdy

  5. Division of Nephrology and Hypertension, University of California Irvine Medical Center, 101 The City Drive South, City Tower, Suite 400 - ZOT: 4088

    Kamyar Kalantar-Zadeh

  6. Orange, 92868-3217, CA, USA

    Kamyar Kalantar-Zadeh

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  1. Parta Hatamizadeh
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Contributions

P. Hatamizadeh and K. Kalantar-Zadeh researched data for the article, contributed to the discussion of content, wrote the article and reviewed/edited the manuscript before submission. G. C. Fonarow, M. J. Budoff, S. Darabian and C. P. Kovesdy were involved in the review/editing of manuscript before submission.

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Correspondence to Kamyar Kalantar-Zadeh.

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Competing interests

G. C. Fonarow is a consultant for the following companies: Boston Scientific, Gambro, Johnson & Johnson, Novartis, Medtronic, Medicines Company, and Takeda. K. Kalantar-Zadeh has received honoraria and/or research grants from Abbott, Amgen, B. Braun, DaVita, Fresenius, Genzyme, Otsuka, Shire, and Vifor. The other authors declare no competing interests.

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Hatamizadeh, P., Fonarow, G., Budoff, M. et al. Cardiorenal syndrome: pathophysiology and potential targets for clinical management. Nat Rev Nephrol 9, 99–111 (2013). https://doi.org/10.1038/nrneph.2012.279

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