TABLE 3.

Pathophysiological factors of CRS

Mechanisms	Mediators	Heart effects	Renal effects
Central venous and intra‐abdominal pressures	Water and sodium retention Activation of RAAS/SNS	Acute/chronic HF Remodeling heart	Renal venous congestion GFR
Cardiac output and cardiac index	Vascular resistance Perfusion pressure Peripheral vasodilatation	RAAS/SNS activation, detrimental to the heart Cardiac ischemia from reduced perfusion	Reduced renal perfusion Renal ischemia
Neurohormonal dysregulation: RAAS activation, SNS activation, AVP	Impaired baroreceptor reflexes Renin, ang II and aldosterone secretion ET‐1 expression Oxidative stress	Ventricular hypertrophy Ventricular disfunction Infiammation with fibrotic effect Hypertension	Arteriolar vasoconstriction GFR Water and sodium reabsorption Infiammation with fibrotic effect
Oxidative stress	ROS production NADPH oxidase activity Uremic toxin‐mediated cytokines release	Ventricular hypertrophy Accelerated atherosclerosis Endothelial dysfunction Infiammation and fibrosis	Endothelial dysfunction Accelerated atherosclerosis Fibrosis Infiammation and interstitial fibrosis
Infiammatory mediators	TNF‐alpha, IL‐1 family, IL‐6, PCR	Accelerated atherosclerosis Infiammation and fibrosis Left ventricular dysfunction and hypertrophy Myocardial cells apoptosis	Infiammation and fibrosis Atherosclerosis Glomerular damage by mesangial cells apoptosis
Renal failure related disturbances	PBUTs Chronic infiammatory cytokines Oxidative stress FGF23 and Ca‐P abnormalities Anemia (EPO resistance) Acidemia Electrolyte disturbances Coagulation imbalances	Endothelial dysfunction Atherosclerosis and vascular calcification Left ventricular dysfuncion and hypertrophy Ischemia Arrythmias	Atherosclerosis Infiammation Interstitial and perivascular fibrosis
Iatrogenic factors	Drugs (ACE‐I, ARBs, ARNI, diuretics) Contrast agents	Hypotension	GFR Nephrotoxicity

Abbreviations: ACEi, angiotensin‐converting enzyme inhibitor; ang II, angiotensin II; ARBs, angiotensin receptor blockers; ARNI, angiotensin receptor‐neprilysin inhibitor; FGF‐23, fibroblast growth factor 23; GRF, glomerular filtration rate; HF, heart failure; PBUTs, protein‐bound uremic toxins; PCR, protein C‐reactive; RAAS, renin‐angiotensin‐aldosterone system; ROS, reactive oxygen species; SNS, sympathetic nervous system.