Cardiorenal syndrome

1. What does cardiorenal syndrome (CRS) mean?

The term CRS has been used to define different clinical conditions in which heart and kidney dysfunction overlap. A consensus classification of CRS is outlined in Table 9.1 .

2. What is CRS type 1?

CRS type 1 (CRS-1) is when patients have acute worsening of cardiac function that leads to acute kidney injury (AKI). This is usually seen with acute decompensated heart failure (ADHF) that follow ischemic (acute coronary syndrome, cardiac surgery complications) or non-ischemic (valvular disease, pulmonary embolism) heart disease.

3. Which pathophysiologic pathways are involved in the development of CRS-1?

Hemodynamic mechanisms probably play a major role. With ADHF, decreases in kidney artery blood flow result in decreased glomerular filtration rate (GFR). Two patterns have been described for CRS-1: cold and warm patients.

• 1.

  In cold patients, severe vasoconstriction from activation of the renin angiotensin-aldosterone system (RAAS) and the systemic nervous system, or reduced effective circulating volume compromise kidney artery blood flow.

• 2.

  In warm (also described as “wet”) patients, marked increases in central venous pressure (CVP) decreases perfusion pressure throughout the kidney. Increased CVP also increases interstitial pressure, collapsing the tubules and further lowering GFR.

Patients with a warm hemodynamic profile have pulmonary and/or systemic congestion. The warm profile is the most frequent profile in acute and chronic advanced heart failure (HF). The cold hemodynamic profile may also have an increased CVP, but kidney perfusion pressure is better maintained due to higher arterial blood pressures.

4. Are there any non-hemodynamic mechanisms for CRS-1?

Non-hemodynamic mechanisms may also be involved in CRS-1, specifically increased reactive oxygen species and impaired of nitric oxide production.

5. What is the prevalence of CRS-1?

Type 1 CRS occurs in about 25% of patients hospitalized for ADHF; among these patients, chronic kidney disease (CKD) is quite common and contributes to AKI in 60% of cases. Developing AKI is an independent risk factor for death in ADHF.

6. Could biomarkers be helpful in type 1CRS diagnosis?

Many biomarkers have been proposed for the early diagnosis of kidney injury in CRS-1. Cystatin C represents a valid surrogate to test kidney function and it has been recognized as more predictive of long-term mortality and rehospitalization for ADHF than serum creatinine or serum brain natriutetic peptide (BNP). Neutrophil gelatinase-associated lipocalin (NGAL) correlates with kidney function markers, adverse cardiovascular outcomes, or death in ADHF patients. Type 1 CRS also can be diagnosed by bioimpedance electrical devices that track total body water. The use of bioimpedance has demonstrated an association between increased body fluid volume and rehospitalization and death.

7. Is there a diagnostic role for ultrasound?

Echocardiography could show abnormal heart function including:

• Abnormal myocardial kinetics (indicating an ischemic condition)

• Left ventricular hypertrophy

• Valvular stenosis

• Valvular regurgitation

• Pericardial effusions

• Aortic aneurysm

• Aortic dissection

The echocardiogram should show normal inspiratory collapse of the inferior vena cava to exclude severe hypervolemia. Kidney ultrasound usually shows normal or slightly increased kidney size and increased cortical-to-medullary ratio, and Doppler evaluation will show regular intraparenchymal blood flow, often with an increased resistance index (>0.8 cm/s)

8. What are the main treatment approaches in CRS-1 patients?

Diuretics, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers should be started or maximized in the setting of ADHF. The management of patients with cardiogenic shock can be challenging because of the limited effectiveness of pharmacological therapy. Among patients requiring emergency coronary artery bypass graft (CABG) surgery, the in-hospital mortality rate in Europe and the United States is about 20%, with a high incidence of stroke (8%), kidney failure requiring dialysis (8.3%), and bleeding (63.3%). Inotropic support remains the central therapy for depressed myocardium, and correction of the underlying cause, such as ischemia, will improve outcomes and produce less kidney injury.

9. How is type 2 cardiorenal syndrome (CRS-2) defined?

CRS-2 is characterized by chronic abnormalities in cardiac function leading to kidney injury or dysfunction. CKD has been observed in 45% to 63% of congestive heart failure (CHF) patients.

10. What are the main pathophysiologic pathways involved in CRS-2?

Intrinsic to its definition, CRS-2 is characterized by CKD onset or progression in HF patients, but two fundamental features are proposed: CHF and CKD are found simultaneously, and CHF is the cause of the CKD or responsible for its progression. Examples of CRS-2 include cyanotic nephropathy occurring in patients with congenital heart disease, when heart disease clearly precedes kidney involvement or acute coronary syndrome leading to left ventricular dysfunction and the onset or progression of coexisting CKD. The pathophysiological mechanisms of CRS-2 include:

• Neurohormonal activation

• Kidney hypoperfusion

• Venous congestion

• Inflammation

• Atherosclerosis

• Oxidative stress

These mechanisms are operative in recurrent episodes of acute heart and kidney decompensation associated with HF and CKD progression.

11. Is there a pathophysiological role for the RAAS?

Patients with decompensated HF and venous congestion often have significant RAAS activation without decreased circulating volume. Kidneys of HF patients release renin, which increases angiotensin II production. Persistent RAAS and sympathetic nervous system (SNS) activation could contribute to CKD progression.

Angiotensin II production and aldosterone release increase sodium reabsorption leading to increased blood pressure and volume overload. Increased aldosterone levels also contribute to glomerular fibrosis due to the up-regulation of transforming growth factor-β (TGF-β) and increased fibronectin.

Persistent inflammation triggered by cardiac decompensation also promotes CKD progression in CHF.