J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Review

Volume 14, Number 1, January 2022, pages 22-27

Experimental Cardiorenal Syndrome Type 3: What Is Known so Far?

Figure 2. Molecular mechanisms involved in myocardial dysfunction in CRS type 3. The figure summarizes the essential findings described in the article. Acute kidney injury of various origin triggers mitochondrial dysfunction in cardiomyocytes, an aberrant (systemic and local) immune response, and systemic vasomodulatory disturbances. CRS: cardiorenal syndrome.

**Table 1.** Characteristics, Pathophysiological Hallmarks, and Treatment Strategies of CRS Types 1-4
CRS type	Characteristics	Pathophysiological hallmarks	Treatment strategy
The table exclusively summarizes the most important information. CRS: cardiorenal syndrome; AHF: acute heart failure; AKI: acute kidney injury; CHF: chronic heart failure; CKD: chronic kidney disease; FGF-23: fibroblast growth factor-23; RAS: renin-angiotensin system.
I	AHF induces AKI	Cardiac output ↓, venous congestion, activation of renin-angiotensin-aldosterone and sympathetic nervous system → impaired renal perfusion	Treatment of respective cause, anti-congestive therapy, vasopressors if mandatory, fluid removal by hemodialysis/hemodiafiltration/slow extended daily dialysis/peritoneal dialysis if mandatory
II	CHF aggravates progression of CKD	Low cardiac output and prolonged venous congestion → renal ischemia and subsequent endothelial cell dysfunction	Treatment of respective cause, management of CHF according the current recommendations (beta-blocker, mineralocorticoid antagonist, gliflozine, RAS inhibitor or sacubitril/valsartan), anti-progressive CKD treatment according to current recommendations, kidney replacement therapy if mandatory
III	AKI induces acute cardiac complications (e.g., arrhythmias, left ventricular insufficiency, myocardial ischemia)	Hyperhydration due to oligo-anuria, hyperkalemia, metabolic acidosis, intrarenal inflammation with subsequent systemic inflammation	Treatment of respective cause, treatment of electrolyte disturbances if mandatory, treatment of infections, avoidance of nephrotoxic substances, kidney replacement therapy if mandatory
IV	CKD aggravates CHF	Retention of sodium and water, retention of phosphorus, increase of blood FGF-23, renal anemia, CKD-associated endothelial cell dysfunction	Treatment of respective cause, anti-progressive CKD treatment according to current recommendations, particularly: blood pressure control, phosphorus-lowering therapy, bicarbonate supplementation, control of renal anemia, kidney replacement therapy if mandatory

Table 1. Characteristics, Pathophysiological Hallmarks, and Treatment Strategies of CRS Types 1-4

CRS type

Characteristics

Pathophysiological hallmarks

Treatment strategy

The table exclusively summarizes the most important information. CRS: cardiorenal syndrome; AHF: acute heart failure; AKI: acute kidney injury; CHF: chronic heart failure; CKD: chronic kidney disease; FGF-23: fibroblast growth factor-23; RAS: renin-angiotensin system.

AHF induces AKI

Cardiac output ↓, venous congestion, activation of renin-angiotensin-aldosterone and sympathetic nervous system → impaired renal perfusion

Treatment of respective cause, anti-congestive therapy, vasopressors if mandatory, fluid removal by hemodialysis/hemodiafiltration/slow extended daily dialysis/peritoneal dialysis if mandatory

CHF aggravates progression of CKD

Low cardiac output and prolonged venous congestion → renal ischemia and subsequent endothelial cell dysfunction

Treatment of respective cause, management of CHF according the current recommendations (beta-blocker, mineralocorticoid antagonist, gliflozine, RAS inhibitor or sacubitril/valsartan), anti-progressive CKD treatment according to current recommendations, kidney replacement therapy if mandatory

III

AKI induces acute cardiac complications (e.g., arrhythmias, left ventricular insufficiency, myocardial ischemia)

Hyperhydration due to oligo-anuria, hyperkalemia, metabolic acidosis, intrarenal inflammation with subsequent systemic inflammation

Treatment of respective cause, treatment of electrolyte disturbances if mandatory, treatment of infections, avoidance of nephrotoxic substances, kidney replacement therapy if mandatory

CKD aggravates CHF

Retention of sodium and water, retention of phosphorus, increase of blood FGF-23, renal anemia, CKD-associated endothelial cell dysfunction

Treatment of respective cause, anti-progressive CKD treatment according to current recommendations, particularly: blood pressure control, phosphorus-lowering therapy, bicarbonate supplementation, control of renal anemia, kidney replacement therapy if mandatory