What Are the Best Biomarkers and Definitions for Chronic Kidney Disease and How Well Do They Relate to Cardiovascular Risk?

Abstract

Generic chronic kidney disease (CKD) can be defined by a lowered estimated glomerular filtration rate (eGFR) and/or “kidney damage,” the latter by abnormal albuminuria (>30 mg/d), imaging, urinalysis, or renal pathology, that persists for at least 3 months. According to current schema, any adult with an eGFR <60 mL/min/1.73 m2 for 3 months or longer can be regarded as having CKD. This definition may be to all-encompassing and lead to over-diagnosis in some groups (particularly the elderly). It is currently undergoing a refinement. Although eGFR and albuminuria are principally used to define CKD and stratify its prognosis, a number of new biomarkers, such as NGAL, FGF-23, Cystatin C, uric acid, and ADMA are emerging that may have utility in enhancing the accuracy of predicting cardiovascular risk in CKD. As currently defined, CKD has important implications for the future risk of cardiovascular events. Albuminuria and lowered eGFR both contribute independently to the associations with cardiovascular risk. Albuminuria does so in a continuous log-linear manner whereas eGFR demonstrates a threshold effect (at around 45–60 mL/min/1.73 m2). The precise mechanisms underlying these associations are complex and poorly understood, but enhanced atherogenesis, diffuse endothelial injury, and left ventricular hypertrophy are important factors. Left ventricular hypertrophy is a major risk factor for congestive heart failure and sudden cardiac death in advanced CKD and it may become a specific target for interventions in the future, especially as the role of elevation in serum FGF-23 levels in the genesis of left ventricular hypertrophy are better understood.