Cardiorenal syndrome type 2: from diagnosis to optimal management

Figures & data

Table 1 Five-part classification system for CRSs proposed by Ronco et al

Type	Inciting event	Secondary disturbance	Example
Type 1 (acute CRS)	Rapid worsening of cardiac function	Acute kidney injury or dysfunction	Acute cardiogenic shock or acute decompensation of chronic heart failure
Type 2 (chronic CRS)	Chronic abnormalities in cardiac function	Progressive chronic kidney injury or dysfunction	Chronic heart failure
Type 3 (acute reno-cardiac syndrome)	Abrupt worsening of kidney function	Acute heart injury and/or dysfunction (eg, heart failure, arrhythmia, or pulmonary edema)	Acute kidney injury or glomerulonephritis
Type 4 (chronic reno-cardiac syndrome)	Chronic kidney disease	Decreased cardiac function, ventricular hypertrophy, diastolic dysfunction and/or increased risk of adverse cardiovascular events	Chronic glomerular disease
Type 5 (secondary CRS)	Acute or chronic systemic disorder	Combined cardiac and renal dysfunction	Diabetes mellitus, sepsis, systemic lupus erythematosus, vasculitis, sarcoidosis

Note: Data from Ronco et al.¹

Abbreviation: CRS, cardiorenal syndrome.

Table 2 Diuretic dosing for acute HF according to the ASCEND-HF model

Creatinine clearance*	Patient	Initial IV dose§	Maintenance dose
>60 mL/min/1.73 m^2	New-onset HF or no maintenance diuretic therapy Established HF or chronic oral diuretic therapy	Furosemide 20–40 mg 2–3 times daily Furosemide bolus equivalent to oral dose	Lowest diuretic dose that allows for clinical stability is the ideal dose
<60 mL/min/1.73 m^2	New-onset HF or no maintenance diuretic therapy Established HF or chronic oral diuretic therapy	Furosemide 20–80 mg 2–3 times daily Furosemide bolus equivalent to oral dose

Notes:

* Creatinine clearance is calculated from the Cockroft–Gault or Modified Diet in Renal Disease formula.

§ Intravenous continuous furosemide at doses of 5–20 mg/hour is also an option. Data from Ezekowitz et al.³³

Abbreviations: HF, heart failure; IV, intravenous.

Figure 1 Water and solute transport in IUF.

Notes: Water molecules cross semipermeable membranes by IUF, which is a fluid shift driven by a hydrostatic pressure difference. (A) The principle of ultrafiltration; (B) the pressure gradient across the filter membrane during ultrafiltration.
Abbreviations: IUF, isolated ultrafiltration; TMP, transmembrane pressure.

Table 3 Rationale and therapeutic targets of IUF in heart failure

Rationale	Therapeutic target	Comments
Fluid balance regulation	More rapid relief of systemic and pulmonary congestion as compared to usual therapy with diuretics	The main component of the rationale for IUF in heart failure^Citation38,Citation63^–^Citation66,Citation68
Solute regulation	Correction of hyponatremia, hyperkalemia, and metabolic acidosis Reduced incidence of hypokalemia Correction of azotemia Higher clearance of sodium, with more effective reduction of sodium pool in comparison with diuretics	Because of its operational characteristics, IUF is unable to correct serum electrolyte/acid-base derangements^Citation40,Citation44,Citation45 IUF leaves serum potassium levels unchanged and does not correct the azotemia.^Citation40,Citation44,Citation45 The ultrafiltrate has a higher sodium concentration if compared to urine after loop diuretics; the former is isotonic whereas the latter is hypotonic compared with the plasma^Citation68
Homeostasis control	Restoring sensitivity to diuretics Osmoceptor resetting Decreased neurohormonal activation (reduced activation of the macula densa mechanisms and tubuloglomerular feedback mechanism, reduced stimulation of sympathetic nervous system, and RAAS axis)	Scarce evidence Not demonstrated An important determinant of the favorable therapeutic profile of IUF in heart failure^Citation45,Citation68
Reduced costs	Shortened hospital length of stay Decreased rate of readmission	Partially supported by the cost-effectiveness analyses available so far^Citation38,Citation68,^69

Abbreviations: IUF, isolated ultrafiltration; RAAS, renin–angiotensin–aldosterone axis.

Table 4 Baseline characteristics of the renal parameters found in the UNLOAD trial and CARRESS-HF trial

		Basal serum creatinine (mg/dL)		Basal blood urea nitrogen (mg/dL)
UNLOAD	Mean ± SD	IV diuretics arm (n=100 patients) 1.5±0.5	IUF arm (n=100 patients) 1.5±0.5	IV diuretics arm (n=100 patients) 33±20	IUF arm (n=100 patients) 32±16
CARRESS-HF	Median (IQR)	IV diuretics arm (n=94 patients) 2.09 (1.71–2.65)	IUF arm (n=94 patients) 1.90 (1.57–2.37)	IV diuretics arm (n=94 patients) 50.5 (39–64)	IUF arm (n=94 patients) 48.7 (39.5–66)

Note: The table denotes that basal renal function is substantially worse in CARRESS-HF trial patients compared with those enrolled by UNLOAD.

Abbreviations: IV, intravenous; n, number; IUF, isolated ultrafiltration; SD, standard deviation; IQR, interquartile range.

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