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

Abstract

The high incidence of cardiovascular events in chronic kidney disease (CKD) warrants an accurate evaluation of risk aimed at reducing the burden of disease and its consequences. The use of biomarkers to identify patients at high risk has been in use in the general population for several decades and has received mixed reactions in the medical community. Some practitioners have become staunch supporters and users while others doubt the utility of biomarkers and rarely measure them. In CKD patients numerous markers similar to those used in the general population and others more specific to the uremic population have emerged; however their utility for routine clinical application remains to be fully elucidated. The reproducibility and standardization of the serum assays are serious limitations to the broad implementation of these tests. The lack of focused research and validation in randomized trials rather than ad hoc measurement of multiple serum markers in observational studies is also cause for concern related to the clinical applicability of these markers. We review the current literature on biomarkers that may have a relevant role in field of nephrology.

Traditional, Nontraditional, and Uremia-Related Threats for Cardiovascular Disease in Chronic Kidney Disease

“…In the study by Furuya et al, elevated levels of serum NGAL were independent risk factors for de novo CVD in HD patients [94]. Furthermore, hemodialysis patients with high NGAL levels in combination with high BNP levels had the greatest risk of CVD [86].…”

“…Low plasma APN levels were predictive of CV events among nondiabetic patients with mild to moderate CKD. Furthermore, low APN levels were found among the dialysis patients who developed CV complications [86].…”

“…Elevated FGF23 has been associated with LVH, and it has been suggested that FGF23 may induce myocardial hypertrophy through a direct effect on cardiac myocytes [102]. FGF-23 has been independently associated with risk of all-cause death in dialysis and CKD patients, heart failure, CV events and death in the general population [86].…”

Incidence and Risk Factors of Cardio-Cerebrovascular Event, Hospitalization, and Mortality in Patients Undergoing Regular Hemodialysis

“…This is due to the majority of these patients having both traditional and non-traditional risk factors for cardiovascular diseas- overload, and sympathetic over-reactivity. 6,7,8 Other than increasing the risk of cardiovascular disease, the impaired glomerular filtration caused retention of toxic molecules known as the uremic toxins. These molecules induce both activation and deficien cy of the immune system.…”

Free Radicals and Biomarkers Related to the Diagnosis of Cardiorenal Syndrome

“…Considering renal biomarkers of oxidative stress as part of the pathophysiology, the pool includes oxidized low-density lipoproteins (Ox-LDL), advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), plasma and urinary F2-isoprostanes, malondialdehyde (MDA), protein reduced thiols, total antioxidant status (TAS), protein carbonyls, advanced glycation end products (AGE), rinary 8-hydroxydeoxy guanosine (8-OHdG), 4-hydroxy-nonenal, antioxidant enzyme activities (e.g., superoxide dismutase, glutathione peroxidase, and catalase) [195,[224][225][226][227][228][229]. It is important to highlight that these biomarkers could indicate the possible correlated diseases, and not strictly renal injuries from CRS.…”