Cardiorenal syndrome

As early as 1844, Rayer (1793 - 1867) pointed out that even previously healthy kidneys can develop insufficiency in the presence of significant heart disease (Rayer 1844).

The term "cardiorenal syndrome" was first defined at a consensus conference in 2004 (Dovjak 2024).

A cardiorenal system (CRS / KRS) is a functional disorder of the heart that has an unfavorable effect on kidney function and vice versa (Herold 2023). Kasper (2017) describes cardiorenal syndrome as a complication of ADHF (acute decompensated heart failure).

The national care guideline "Chronic heart failure" deliberately does not use the term cardiorenal syndrome, as in its opinion the term is still partly controversial and not clearly defined (Bundesärztekammer 2023).

The classification according to Ronco (2008) differentiates on the basis of the time course and pathogenetic aspects (Scurt 2019) between:

• Type 1 Acute cardiorenal syndrome:

Acute cardiorenal syndrome is triggered by acute heart failure. This results in acute kidney injury (AKI) with the following symptoms:

- Acute decompensated chronic heart failure

- Hypertensive pulmonary edema

- Acute right heart failure

- Cardiogenic shock

The volume status should be monitored diagnostically, e.g. by sonography of the vena cava (venous congestion).

Therapeutically, the focus is on therapy with diuretics (Herold 2023).

• Type 2 Chronic cardiorenal syndrome:

This is characterized by chronic congestive heart failure leading to chronic kidney disease. The following symptoms may occur:

- Peripheral underperfusion, so-called "low output ischemia"

- Macrovasculopathy

- Microvasculopathy

Therapeutically, it is difficult to ensure a balanced fluid balance in type 2 because, on the one hand, too forced treatment with diuretics can lead to a further deterioration in kidney function and, on the other hand, volume overload due to increased venous backflow into the renal venous system can have a negative impact on kidney function (Herold 2023).

• Type 3 Acute renocardial syndrome:

Here, acute kidney injury (AKI) can cause cardiac dysfunction with the following symptoms:

- Electrolyte imbalances, in particular hyperkalemia with arrhythmias and cardiac arrest

- Hyperhydration with subsequent pulmonary edema

- Uremia with pericarditis, which reduces myocardial contractility

Only very rarely can CRS type 3 be caused by bilateral renal artery stenosis or by renal artery stenosis in a single kidney (Herold 2023).

• Type 4 Chronic renocardial syndrome:

In type 4, CKD worsens cardiac function. The following clinical symptoms occur:

- Accelerated atherosclerosis

- left ventricular hypertrophy and dysfunction

- Cardiovascular events (Herold 2023)

• Type 5 Secondary cardiorenal syndrome:

In this case, systemic diseases lead to damage to both the heart and the kidneys, such as:

- Autoimmune diseases

- Diabetes mellitus

- sepsis

- Septic shock (Herold 2023)

• Type 6 of chronic secondary cardiorenal syndrome:

Type 6 was first described in 2021 by Zhang et al. Typical causes are a combination of:

- Arterial hypertension

- Metabolic syndrome

- Diabetes mellitus (Schwenger 2023)

Almost 50% of the approximately 4 million patients with heart failure (CHF) in Germany also have chronic kidney disease (CKD). And of the approximately 9 million patients with chronic kidney disease, at least 15% have an increased cardiovascular risk (Schwenger 2022).

In CRS, the central pathophysiological mechanism is neurohumoral activation with increased sympathetic tone and system-wide activation of tissue-bound renin-angiotensin-aldosterone systems, the so-called RAAS. This causes activation of the innate immune system with systemic inflammation and the triggering of insulin resistance. This results in remodeling processes in the lungs, heart and kidneys, which ultimately lead to functional impairment of the organs through fibrosis (Schwenger 2023).

Hemodynamically, a distinction can be made between:

• Functional forward failure (low cardiac output)

This results in renal hypoperfusion due to prerenal renal damage in the presence of HFrEF (heart failure with reduced ejection fraction).

• Functional reverse failure

In functional reverse failure, there is an increased central venous filling pressure (renal venous congestion in heart failure with preserved ejection fraction) with accompanying pulmonary hypertension (Schwenger 2023).

Patients with a cardiorenal syndrome are characterized by:

- Recurrent hydropic decompensation (Schwenger 2023)

- Pulmonary hypertension (Schwenger 2023)

The disease is one of the most common causes of hospitalization (Schwenger 2023).

Initially, the focus is on the etiological clarification of cardiac and renal insufficiency (Herold 2023).

The degree of kidney damage is classified into so-called RIFLE stages (Risk Injury Failure Loss) by monitoring serum creatinine and urine excretion, an initial classification system divided into 5 stages (Schwenger 2024).

Echocardiography

Echocardiographic assessment of the ejection fraction is now only of limited use as a prognostic marker. They are increasingly being replaced by innovative echo and MRI markers such as the global longitudinal strain (GLS) (Schwenger 2023).

Right and left heart catheterization

This invasive diagnostic procedure is indicated to rule out both CHD and pulmonary hypertension or, if pulmonary hypertension is present, to be able to phenotype it further (Schwenger 2023).

Cardiac biomarkers

Cardiac biomarkers such as troponin and NT-proBNP represent an important individual progression parameter, but are difficult to interpret in individual cases due to the altered serum half-life (Schwenger 2023).

Blood gas analysis

Blood gas analyses should be carried out at regular intervals, particularly with regard to possible:

- Hyperkalemia

- Renal acidosis with bicarbonate levels < 22mmol / l

- Hypercapnia with bicarbonate values > 32 mmol / l (Schwenger 2023)

• Independent kidney disease
• Haemato-oncological diseases such as amyloidosis or multiple myeloma
• Autoimmune diseases such as sarcoidosis, systemic lupus erythematosus, vasculitis (Schwenger 2023)

The therapeutic measures for CRS consist of treating heart failure and hypervolemia with pleural effusions, ascites and pulmonary edema (Herold 2023).

The focus here is on avoiding hypervolemia and life-threatening hyperkalemia (Schwenger 2023).

In order to avoid frequent hydropic decompensation, regular weight checks, determination of the amount to drink and dietary salt intake should be carried out (Schwenger 2023).

Ultrafiltration therapy (Herold 2023) or dialysis therapy can be used as a last resort (Schwenger 2023).

Treatment options depending on the type:

• Type I: Ultrafiltration and continuous venovenous hemofiltration are recommended. Hemodialysis is only recommended to a limited extent.
• Type II: Ultrafiltration, hemodialysis, peritoneal dialysis are recommended. Continuous venovenous hemofiltration is recommended to a limited extent.
• Type III: Continuous venovenous hemofiltration and hemodialysis are recommended.
• Type IV: Only hemodialysis and peritoneal dialysis are recommended.
• Type V: Hemodialysis and peritoneal dialysis are recommended. Continuous venovenous hemofiltration and ultrafiltration are recommended to a limited extent.

The following medications can be used:

• Diuretics

The therapeutic pathway for diuretics is narrow. If the dosage is too high, kidney function can deteriorate further and there may be an increase in the urea/creatinine ratio, uric acid, pH value and bicarbonate (Schwenger 2022). No increase in diuresis can be achieved by the additional administration of diuretics anyway, as the arterial intravascular filling volume is reduced (Schwenger 2023).

• Inhibitors of the renin-angiotensin-aldosterone system

These are of considerable therapeutic importance in cardiorenal syndrome, as they are effective in reducing inflammation and fibrosis in both cardiac and renal insufficiency (Schwenger 2023).

• Mineral corticoid receptor antagonists (MRAs)

MRAs such as spironolactone and finerenone are available. Recommended dosage: 25 mg spironolactone, 10 mg finerenone. Due to the risk of hyperkalemia, potassium levels should be checked regularly (Schwenger 2023).

• Angiotensin receptor neprilysin inhibitor (ARNI)

ARNIs such as sacubitril / valsartan have been recommended for the treatment of HFrEF since 2016 (Schwenger 2023).

• SGLT-2 inhibitors

The innovative SGLT-2 inhibitors are now an integral part of the treatment of heart failure and increasingly also for renal failure, particularly in the presence of albuminuria (Schwenger 2023).

Every hospitalization due to cardiorenal decompensation is associated with a worsening of the prognosis. Both the hospitalization rate and mortality of patients are high and lie between 40 - 50 % in the first year (Schwenger 2023).

The guideline published in 2011 by the European Society of Cardiology recommends that all patients with left heart failure (HFrEF) should initially receive:

• ACE inhibitor or angiotensin receptor neprilysin inhibitor
• beta-blocker
• Mineral corticoid receptor antagonists
• SGLT2 inhibitor (Schwenger 2022)

In addition, kidney function should be monitored, the volume balance should be controlled by restricting the amount of fluids consumed with daily weight monitoring and dietary salt reduction to below 6 g / d (Schwenger 2022).

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