Cardiorenal syndrome: pathophysiology and potential targets for clinical management

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.

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

“…Cardiorenal syndrome is the complex bidirectional relationship between HF and kidney disease (45). Many mechanisms have been proposed to explain cardiorenal syndrome, including altered hemodynamics (from both poor cardiac output and venous congestion) (46), alterations in the sympathetic nervous system and the renin-angiotensin-aldosterone system, inflammation, oxidative stress, and atherosclerosis (47,48). Although we cannot determine the mechanism leading to elevations in NT-proBNP and/or TnT in our study population, it is plausible that elevations in these biomarkers reflect early changes in volume and cardiac stretch, venous congestion, subclinical atherosclerosis, or myocardial ischemia, which may contribute to decline in kidney function.…”

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome

“…29 Already in this first publication, a relation with endothelial dysfunction was proposed. 29 Endothelial injury is implicated in CRS, 20 whereas in HFpEF patients, vascular changes represented by endothelial dysfunction have been reported. 30 A direct link between heart failure, vascular activation, metabolic comorbidities, and CKD was presented by Shestakova et al, 19 who demonstrated a correlation between endothelial dysfunction and the hallmarks of HF in CRS patients with type 1 diabetes mellitus.…”

“…15,16 Vascular oxidative stress leading to endothelial dysfunction and inflammation has been proposed as one of the key pathways in HFpEF 17 and CRS, [18][19][20] and it is strongly linked to metabolic risk factors. 19,21 However, details of the cardiac and renal microvasculature response in CRMS remain to be investigated.…”

Multiple Beneficial Effects of Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension

“…30 Although the pathophysiology of this relationship appears to be complex, hemodynamic impairment might play a major role in CHF-induced organ dysfunctions. Mechanical circulatory support devices, such as left ventricular assist device and intra-aortic balloon pump, improve endorgan dysfunction including dysglycemia in patients with advanced CHF.…”