Cardiorenal Syndrome: New Pathways and Novel Biomarkers
Abstract
:1. Introduction
Definition of Cardiorenal Syndrome
2. Pathophysiology of Cardiorenal Syndrome
2.1. Hemodynamic Mechanism
2.2. Current AKI Biomarkers and New Standpoints
2.3. Neurohormonal Dysregulation
2.4. Endothelial Dysfunction and Atherosclerosis
2.5. Oxidative Stress and Inflammation
3. Biomarkers Connecting the Heart and Kidney
3.1. A New Look at an “Old” Biomarker: NT-proBNP
3.2. Biomarkers of CKD-Related Bone and Mineral Metabolism and CRS
3.3. Promising Biomarkers for Monitoring and Identifying Cardiorenal Syndrome
3.4. The Future Is Now: The Use of microRNAs for Cardiorenal Syndrome
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Biomarker | Description | References |
---|---|---|
Renal Biomarkers | ||
Serum creatinine (SCr), albuminuria, cystatin C (CysC), potassium, eGFR | Classical biomarkers for the assessment of kidney function. Evidence for several indicators in CRS, especially when combined, has increased in recent years. For example, reduced albuminuria and potassemia indicate early renal repair processes after resynchronization therapy in CRS2. | Gala-Błądzińska et al. [16] |
TIMP2•IGFBP7 | Urinary tissue inhibitor of metalloproteinase-2 • Insulin-like growth factor–binding protein 7 (TIMP2•IGFBP7). This is a combined marker of acute kidney damage. It can predict the onset of moderate to severe AKI, and is elevated in CRS patients. | Gunnerson et al. [22] |
Urinary angiotensinogen | A marker of acute kidney damage and a strong predictor of worsening of AKI, with death in acute decompensated heart failure. The urinary angiotensinogen measured at the time of CRS diagnosis shows improved risk stratification. | Chen et al. [13] |
NAG | Urinary enzyme N-acetyl-β-d-glucosaminidase (NAG). Measured at the time of CRS diagnosis, it shows improved risk stratification in determining which patients will experience adverse outcomes. | Chen et al. [13] |
KIM-1 | Urinary kidney injury molecule 1 (KIM-1). Measured at the time of CRS diagnosis, it shows improved risk stratification in determining which patients will experience adverse outcomes. | Chen et al. [13] |
NGAL | Urinary and serum neutrophil gelatinase associated lipocalin (NGAL). It is primarily used (especially its urinary determination) as early marker of renal damage. | Chen et al. [13] Cernaro et al. [15] |
L-FABP | Liver fatty acid-binding protein (L-FABP). This is a marker of acute kidney damage in acute decompensated heart failure. | Hishikari et al. [23] |
b2M and TIMP1 | β2-microglobulin (b2M) and tissue inhibitor of metalloproteinases 1 (TIMP1). Their values have been demonstrated to be potentially linked to severity of CRS. | Vianello et al. [21] |
UP/Cr | Urine podocin/creatinine ratio (UP/Cr) is an emerging biomarker of CRS. In a study conducted in dogs, the UP/Cr in the CVD and CKD groups was significantly higher than in the control group. | Szczepankiewicz et al. [89] |
Cardiac Biomarkers | ||
hs-cTnI | High sensitivity troponin I (hs-cTnI). Marker of myocardial injury, which increases with declining eGFR. Sustained elevation is associated with a higher mortality risk. | Chen et al. [13] |
Galectin-3 | A marker of cardiac fibrosis, stress and remodeling. It is associated with the progression of renal dysfunction in patients with heart disease. | Iacoviello et al. [90] |
Neurohormones and hormones | ||
BNP; NT-proBNP; emBNP | B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are the gold standard biomarkers for heart failure. The elevation of the NT-proBNP/estimated mature BNP (emBNP) ratio precedes the worsening of renal function in patients with acute HF, and has been strongly associated with decreases in eGRF. | Kociol et al. [45] |
AVP and copeptin | Copeptin is the C-terminal part of the arginine vasopressin (AVP), and is an easily measurable and stable molecule in plasma. Copeptin could be correlated with CVD in patients with CKD or ERSD. | Yalta et al. [33] |
Oxidative stress and inflammatory biomarkers | ||
XOA | The increased xanthine oxidoreductase activity (XOA), the elevated CysC value and reduced eGFR are significantly related to risk of acute CRS. | Tasić et al. [17] |
IL-18 | Interleukin 18 (IL-18) is a cytokin used as a marker in acute kidney damage. Measured at the time of CRS diagnosis, it shows improved risk stratification in determining which patients will experience adverse outcomes. | Chen et al. [13] |
Mineral and bone disorder biomarkers | ||
FGF-23 | Fibroblast growth factor 23 (FGF-23) is involved in phosphate homeostasis. It could be used as marker of renal and heart failure. | Jean et al. [71] Scialla et al. [74] |
Vitamin D | Vitamin D has pleiotropic effects and, as a marker, has a significant impact on the cardiovascular, nervous, endocrine and immune systems. However, its role in CRS patients is not clear. | Mann et al. [81] Binanay et al. [10] |
MicroRNAs | ||
MiR-21; miR-122-5p, miR-222-3p, miR-21-5p, miR-146a-5p, miR-29b-3p | MicroRNAs (miR) in clinical practice also involves CRS. MiR-122-5p, miR-222-3p, miR-21-5p, miR-146a-5p, and miR-29b-3p, correlated with CRS. MiR-21 has been shown to be an independent influencing factor for CRS. | Yan et al. [78] Keller et al. [85] Wang et al. [84] |
Other biomarkers | ||
MPV | Mean platelet volume (MPV). This might be a useful predictor of acute CRS prognosis. | Li et al. [67] |
Hepcidin | There is a link between elevated serum hepcidin (high in anemia of inflammation that is hyporesponsive to erythropoiesis-stimulating agents) and cardiac geometry (relative wall thickness and left ventricular mass index). It is correlated with prognosis in patients with heart failure. | Kim et al. [88] |
suPAR | Soluble urokinase-type plasminogen activator receptor (suPAR) might represent a valuable biomarker for risk estimation in coronary artery disease and HF. Its prognostic value remains valid also after adjusting for eGFR. | Nikorowitsch et al. [91] |
PlGF | Placental growth factor (PIGF) is a key molecule in CRS and a predictor of adverse events in chronic kidney disease patients. | Nakada et al. [92] |
Urinary cofilin-1 | Acts as a modulator of epithelial-mesenchymal transition or de-differentiated renal tubular cells, which are essential for AKI and renal function recovery, and is related to severity of HF. It is a highly potential biomarker for predicting CRS among coronary care unit patients. | Rastaldi et al. [91] Huntley et al. [72] Chen et al. [73] |
ADX, ECP, FETUB, GDF15, GUAD, NOTCH1 | Urinary adrenodoxin (ADX), eosinophil cationic protein (ECP), fetuin B (FETUB), growth differentiation factor 15 (GDF15), guanine deaminase (GUAD) and neurogenic locus notch homolog protein 1 (NOTCH1) are a panel of urinary proteins, already used for CV risk, that might be useful in foreseeing and preventing CRS features. | Martinez et al. [74] |
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Gembillo, G.; Visconti, L.; Giusti, M.A.; Siligato, R.; Gallo, A.; Santoro, D.; Mattina, A. Cardiorenal Syndrome: New Pathways and Novel Biomarkers. Biomolecules 2021, 11, 1581. https://doi.org/10.3390/biom11111581
Gembillo G, Visconti L, Giusti MA, Siligato R, Gallo A, Santoro D, Mattina A. Cardiorenal Syndrome: New Pathways and Novel Biomarkers. Biomolecules. 2021; 11(11):1581. https://doi.org/10.3390/biom11111581
Chicago/Turabian StyleGembillo, Guido, Luca Visconti, Maria Ausilia Giusti, Rossella Siligato, Alessia Gallo, Domenico Santoro, and Alessandro Mattina. 2021. "Cardiorenal Syndrome: New Pathways and Novel Biomarkers" Biomolecules 11, no. 11: 1581. https://doi.org/10.3390/biom11111581
APA StyleGembillo, G., Visconti, L., Giusti, M. A., Siligato, R., Gallo, A., Santoro, D., & Mattina, A. (2021). Cardiorenal Syndrome: New Pathways and Novel Biomarkers. Biomolecules, 11(11), 1581. https://doi.org/10.3390/biom11111581