Cardiorenal syndrome: long road between kidney and heart

Abstract

Almost 200 years ago, the first evidence described by Robert Bright (1836) showed the strong interaction between the kidneys and heart and, since then, the scientific community has dedicated itself to better understanding the mechanisms involved in the kidney-heart relationship, known in recent decades as cardiorenal syndrome (CRS). This syndrome includes a wide clinical variety that affects the kidneys and heart, in an acute or chronic manner. Moreover, it is well established in the literature that the immune system, the sympathetic nervous system, the renin-angiotensin-aldosterone, and the oxidative stress actively play a strong role in the cellular and molecular processes present in CRS. More recently, uremic molecules and epigenetic factors have been also shown to be key mediators in the development of syndrome. The present review intends to present the state of the art regarding CRS and to show the paths known, until now, in the long road between the kidneys and heart.

Cardiovascular Alterations and Structural Changes in the Setting of Chronic Kidney Disease: a Review of Cardiorenal Syndrome Type 4

“…In addition to the net effect of sodium and water retention, elevated levels of aldosterone, and angiotensin II have numerous downstream implications within the inflammatory cascade and cardiac myocytes. Angiotensin II, a powerful vasoconstrictor, reduces coronary blood flow, and ensuing ischemia triggers an inflammatory cascade which then facilitates myocardial injury and necrosis, that then stimulates myocardial fibrosis and causes maladaptive remodeling and hypertrophy on the macrovascular level [ 21 , 22 ]. Interestingly, in vivo studies on mice also suggested that circulating levels of angiotensin II may be cardioprotective following ischemic reperfusion injury [ 23 ], with one proposed mechanism stipulating that reduced coronary blood flow reduces the arrival of inflammatory mediators and thus limits inflammation; a hypothesis that will need validation in other models.…”

“…Neurohormonal activation, angiotensin II, catecholamines, uremic toxins activate pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), interleukin-6 (IL-6), and transforming growth factor beta (TGFβ) [ 1 , 15 , 21 , 24 , 25 ]. Renal impairment causes a systemic imbalance of superoxide and reactive oxygen species, which also contributes [ 22 ]. Such molecules trigger endothelial dysfunction and disrupt the delicate homeostasis of cellular membranes and mitochondria, leading to premature apoptosis and necrosis.…”

“…In particular, IL-6, a pro-inflammatory cytokine that has received significant attention as a result of its deleterious effects associated with severe COVID-19 infection, is also involved in regulating gene transcription among inflammatory, metabolic, and cell death pathways, and can have such deleterious effects on cardiac myocytes if left unregulated. Decreased nitric oxide availability due to endothelial dysfunction further propagates the above changes [ 15 , 22 ].…”

“…Immune cells including macrophages, mast cells, neutrophils, and fibroblasts subsequently infiltrate the area of injured myocardium, remove the debris, and activate anti-inflammatory cytokines and fibroblasts, which, in mechanisms mediated by toll-like receptors (TLRs), damage-associated molecular patterns (DAMPs) among others, deposit collagen matrix, leading to fibrosis, reduced contractility, and hypertrophy [ 22 ]. While several molecules and mechanisms have been identified, the nuanced complexity carried among these systems remains an active area of research and must be further delineated before being effectively carried over to clinical treatments.…”

Association between the risk of heart failure hospitalization and end-stage renal disease with digoxin usage in patients with cardiorenal syndrome: A population-based study

“…Overactivation of the sympathetic nervous system will exacerbate the heart failure progression ( 11 ). Third, the other factors that contribute to the worsening of the heart and the kidney include the immune system, metabolic disorders (including diabetes, metabolic syndrome, and obesity), oxidative stress, uremic molecules, and epigenetic factors ( 12 ). Based on the initial pathology, there are two main CRS groups: cardiorenal and reno-cardiac, which are further split into five forms of CRS, and the majority are type 2 and type 4 CRS ( 13 ).…”