Cardiorenal Syndrome Type 3: Pathophysiologic and Epidemiologic Considerations [chapter]

Sean M. Bagshaw, Eric A. Hoste, Branko Braam, Carlo Briguori, John A. Kellum, Peter A. McCullough, Claudio Ronco
2013 Contributions to Nephrology  
Cardiorenal syndrome (CRS) type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) precipitates and contributes to the development of acute cardiac injury. There is limited understanding of the pathophysiologic mechanisms of how AKI contributes to acute cardiac injury and/or dysfunction. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Moreover, baseline
more » ... susceptibility will modify the subsequent risk for cardiac events associated with AKI. Experimental data suggest cardiac injury may be directly induced by inflammatory mediators, oxidative stress, apoptosis and activation of neuroendocrine systems early after AKI. Likewise, AKI may be associated with physiologic derangements (i.e. volume overload; metabolic acidosis, retention of uremic toxins, hyperkalemia; hypocalcemia), alterations to coronary vasoreactivity, and ventricular remodeling and fibrosis that indirectly exert negative effects on cardiac function. AKI may also adversely impact cardiac function by contributing to alternations in drug pharmacokinetics and pharmacodynamics. Additional experimental and transla-ADQI 11 Workshop members are listed in Appendix 2. Bagshaw et al. tional investigations coupled with epidemiologic surveys are needed to better explore that pathophysiologic mechanisms underpinning acute cardiac events associated with AKI and their impact on outcomes. Cardiorenal syndrome (CRS) type 3 (acute renocardiac syndrome) is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) precipitates and contributes to the development of acute cardiac injury and/or dysfunction [1] . There are a number of potential contributing causes for AKI that may predispose to the development of CRS type 3 and which are relevant for the susceptibility, etiology, severity and duration of the type 3 CRS (table 1) . In general, there is limited understanding of the pathophysiologic mechanisms whereby AKI contributes to acute cardiac injury and/or dysfunction. An episode of AKI may have severity and duration-dependent effects that both directly and indirectly predispose to an acute cardiac event. There is some experimental data to suggest that cardiac injury may be directly induced by inflammatory mediators, oxidative stress, and upregulation of neuroendocrine systems early after AKI [2] [3] [4] [5] . Likewise, AKI may be associated with physiologic derangements (i.e. volume overload; metabolic acidosis, retention of uremic toxins, hyperkalemia; hypocalcemia), alterations to coronary vasoreactivity, and ventricular remodeling and fibrosis that indirectly exert negative effects on cardiac function [6] [7] [8] [9] [10] . The development of AKI may also adversely impact cardiac function, through both direct and indirect mechanisms, by contributing to alternations in drug pharmacokinetics and pharmacodynamics. The relationship between these direct and indirect mechanisms remains poorly understood. There is a paucity of data describing the epidemiology of acute cardiac events (i.e. arrhythmia, myocardial ischemia, heart failure, cardiac arrest) occurring after an episode of AKI. There is also a lack of data specifically describing the temporal sequence of cardiac events after onset of AKI, including the dose-response effects related to AKI severity and duration on short-and long-term cardiac function [11, 12] . Moreover, there are challenges when trying to extrapolate on the epidemiology of CRS type 3 from the available literature due to: (1) variability in the methods for defining AKI and heterogeneity in the contributing causes for AKI; (2) variability in the populations at risk being studied and their susceptibility for development of either AKI or acute cardiac events; (3) difficulty in clarifying the temporal association between AKI and acute cardiac events, in particular from observational data, and (4) failure of many observational studies and clinical trials focused on AKI to specifically capture and/or describe the occurrence of acute cardiac events as key outcomes of interest. Accordingly, the objectives of this review were to: (1) to design a pathophysiologic model of CRS type 3 supported by evidence; (2) identify from this Downloaded by: 54.
doi:10.1159/000349971 pmid:23689660 fatcat:o5j4gnna7ngkpkpdwcvcq42yri