Cardiovascular Biomarkers in Chronic Kidney Disease: State of Current Research and Clinical Applicability

Table 1

Summary of evidence on the use of serum biomarkers for CV risk prediction in CKD.

Biomarker	Metabolism			Prediction		Clinically useful for
	Production	Accumulation in CKD	Dialysis	Putative mechanism(s) involved	Outcome	Risk stratification	Guide therapy
Natriuretic peptides
Atrial natriuretic peptide (ANP)	Atrial myocardium	Yes	Dialyzable only to a small degree	Marker of left ventricular dysfunction, severity of CHF in both general and CKD populations	All-cause mortality in CKD and dialysis patients. Sudden cardiac death and MI in dialysis patients	Useful	Useful (for CHF)
B-type natriuretic peptide (BNP)	Ventricular myocardium
C-type natriuretic peptide (CNP)	Endothelial cells/myocardium
Cardiac troponins
Troponins T, I, and C	Striated muscle	Yes	Increased in dialysis patients	Released after cardiac injury (cTNT)	Predicts CAD and death in CKD and dialysis patients	Useful	No data
Cardiac troponin I (cTNI)	Cardiomyocytes
Cardiac troponin T (cTNT)	Cardiomyocytes
C-reactive protein
C-reactive protein (CRP)	Liver-acute phase reactant	?	Increases during dialysis	Marker of systemic inflammation	Predicts CAD, all-cause mortality	Not useful if used alone	Not useful
Adiponectin
Adiponectin (APN)	Adipocytes	Yes	? Influenced by nutritional status	Anti-inflammatory and antiatherogenic activities, enhances insulin-sensitivity. Associated with malnutrition	Cardiovascular events, all-cause mortality	Not useful, influenced by nutritional status	Not useful, influenced by nutritional status
Leptin
Leptin	Adipocytes	Yes, glomerular filtration and tubular degradation	Increased levels influenced by insulin resistance, metabolic acidosis, and uremic toxins	Anorectic agent associated with cIMT and arterial stiffness	Inverse association with cardiovascular events?	Not useful	Not useful
Fibroblast growth factor 23 (FGF-23)
Fibroblast growth factor 23	Osteocytes	Yes	Increased levels, though low molecular weight and dialysable	Suppresses renal tubular phosphate reabsorption, 1,25OH vitamin D activation and increases 1,25HO vitamin D degradation and possibly iPTH secretion	Associated with ESRD occurrence, CKD progression, LVH, CHF, and atherosclerotic events, all-cause mortality	Useful	No data
Klotho
Klotho	Produced in different tissues: endothelial cells, parathyroid glands, renal tubular cells, and VSMC	Not known	Not known	FGF-23 coreceptor (see FGF-23 actions); ROS and NO production	Oxidative stress, vascular calcification, and all-cause mortality	No data	No data
Fetuin A and Calciprotein Particles
Fetuin-A/Calciprotein Particles	Hepatocytes/serum	Yes	?	Fetuin A forms soluble complexes in the circulation with calcium and phosphate crystals to avoid their precipitation.	Mortality. CKD progression	May be useful	No data; may become useful
Wnt inhibitors
Sclerostin	Osteocytes	Yes	Increased in dialysis patients	Inhibitors of Wnt pathway. Increase bone mass and reduce bone turnover	Mortality? CKD-MBD?	No data	No data
Dickkopf-1; (DKK-1)	?	?	?
Neutrophil gelatinase-associated lipocalin (NGAL)
NGAL	Several tissues	Inversely associated with creatinine clearance	?	Suppresses gelatinase B inactivation leading to proteolytic activity and collagen degradation	Acute Kidney Injury, CKD progression, CV events, and mortality	Useful	No data
Plasma growth factor-15 (GDF-15)
GDF-15	?	?	?	Potential inhibitor of left ventricular hypertrophy, overexpressed in atherosclerotic disease	Incident CKD, all-cause and CV mortality	No data	No data
Asymmetric dimethylarginine (ADMA)
ADMA	?	Renal clearance	Increased in dialysis patients	Impairs endothelium dependent NO dilatation	cIMT, LVH, CV events, renal function decline, and mortality	Useful	No data
Paraoxonase 1 (PON1)
PON1	?	Inversely associated with creatinine clearance	Reduced in dialysis patients. Optimal RRT may produce an increase in PON1	HDL-associated enzyme and has been shown to reduce the susceptibility of LDL to peroxidation	cIMT, CV events	No data	No data

CHF: congestive heart failure; CAD: coronary artery Disease; cIMT: carotid intima media thickness; iPTH: intact parathyroid hormone; LVH: left ventricular hypertrophy; VSMC: vascular smooth cells; CKD-MBD: chronic kidney disease mineral bone disorder; Wnt: wingless pathway.