Table 2.
Biomarkers in Cardiorenal Syndrome.
| Biomarkers | Characteristics | Clinical Utility |
|---|---|---|
| Cardiac Biomarkers | CRS Type | |
| cTn | Marker of myocardial injury that correlates with ventricular remodeling in HF. | 1, 2 |
| Natriuretic peptides | Markers of myocardial increased wall stretch. They are the most used and recognized biomarkers in chronic and acute HF and are also raised in patients with CKD. | 1, 2, 3, 4, 5 |
| sST2 | sST2 is a member of the IL-1 receptor family that affects the activation of Th2 cells and the production of Th2-related cytokines. sST2 correlates with cardiovascular events and mortality in patients with AHF and CHF. Moreover, sST2 correlates with the development of CKD, as well as to the risk of CV events and HF development in patients with renal dysfunction. | 2, 5 |
| Galectin-3 | It is a component of the beta-galactosidase-binding lectin family, it is released by activated macrophages and induces the activation and deposition of collagen in the extracellular matrix promoting fibrosis at renal and cardiac level. Patients with elevated Galectin-3 levels showed an accelerated decline of GFR. | 2, 4, 5 |
| VEGF | Involved in the regulation of endothelial function and angiopoiesis; it may affect myocardial afterload. It is elevated in patients with HF. | 2, 4, 5 |
| PDGF | Involved in regulation of myocardial and kidney fibrosis. It is elevated in patients with HF. | 2, 4, 5 |
| sFlt-1 | Soluble VEGF receptor associated with microvascular disease and impaired angiopoiesis. It is elevated in patients with HF. | 2, 4, 5 |
| Copeptin | It is considered a marker of activated hypothalamus pituitary-adrenals axis. There is evidence that copeptin could be associated with CVD in patients with CKD, as well as it could be considered as a marker of AHF and AKI. | 1, 2, 3 4, 5 |
| MR-proadrenomedullin | Involved in regulation of vascular leakage; it predicts the decline of renal function and morbidity in patients with HF. | 2, 4, 5 |
| Kidney biomarkers | ||
| Serum creatinine | Produced by skeletal muscle, its clearance its representative of renal function. | 1, 2, 3, 4, 5 |
| CysC | Cysteine proteinase inhibitor filtered through the glomerulus and then reabsorbed by tubular cells. It is an accurate surrogate marker of GFR. | 1, 2, 3, 4, 5 |
| Albuminuria | Marker of glomerular integrity/PCT function. | 2, 4 |
| TIMP/IGFBP7 | Involved in G1 cell cycle arrest; it increases in tubular cell injury as an early marker. | 1, 3, 5 |
| NGAL | Small protein freely filtered through the glomerulus and reabsorbed in the proximal tubule. It increases in case of tubular damage 24 h before the rise of creatinine. | 1, 3, 5 |
| NAG | NAG is a lysosomal protein excreted into urine in case of tubular damage. NAG is increased in patients with AKI, CKD, or HF and may predict prognosis in these patients. | 1, 3, 5 |
| KIM1 | KIM1 is expressed in proximal tubule cells after hypoxic injury and may identify the development of AKI or CKD in patients with HF. KIM1 is associated with HF, cardiovascular events, and deaths in patients with AKI and CKD. | 1, 3, 5 |
| IL-18 | It is a component of NLEP3 inflammasome, and it is elevated in AKI. IL-18 levels are also increased in HF. | 1, 3, 5 |
| L-FABP | L-FABP is expressed in tubular epithelial cells and is excreted into urine with cytotoxic lipids. Urinary L-FABP has been associated with ischemic tubular injury and risk for acute kidney failure in type 1 CRS. | 1, 3 |
| α-1 Microglobulin | It is filtered by glomerulus and is completely reabsorbed by the renal tubule. It can be found in urine in case of tubule damage. | 2, 4, 5 |
ACS, acute coronary syndrome; AHF, acute heart failure; AKI, acute kidney injury; CKD, chronic kidney disease; CRS, cardiorenal syndrome; cTn, cardiac troponin; CysC, cystatin C; GFR, glomerular filtration rate; HF, heart failure; H-FABP, heart-type fatty acid–binding protein; IGFBP7, insulin-like growth factor protein 7; IL, interleukin; KIM-1, kidney injury molecule-1; L-FABP, liver-type fatty acid–binding protein; MR-adrenomedullin, Mid-Regional- adrenomedullin; NAG, N-acetyl-κ-d-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; PCT, proximal convoluted tubule; PDGF, Platelet Derived Growth Factor; sFlt-1, soluble fms-like tyrosine kinase 1; sST2, soluble suppressor of tumorigenicity; Th2, T-helper type 2; TIMP, tissue inhibitor of metalloproteinase; VEGF, Vascular Endothelial Growth Factor.