Independent associations of other indices of phosphorus metabolism, such as phosphorus intake, urinary phosphate excretion, or hormones that regulate these systems, like fibroblast growth factor 23 (FGF23), with markers of cardiovascular disease in CKD, have been studied in less detail.
High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD).
Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown.
Higher levels of fibroblast growth factor 23 were significantly associated with prevalent anemia (odds ratio per 1-SD increase in natural log-transformed fibroblast growth factor 23, 1.39; 95% confidence interval, 1.26 to 1.52), decline in hemoglobin over 4 years, and risk of incident anemia (hazard ratio per 1-SD increase in natural log-transformed fibroblast growth factor 23, 1.13; 95% confidence interval, 1.04 to 1.24; quartile 4 versus quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.19 to 2.11) independent of demographic characteristics, cardiovascular disease risk factors, CKD-specific factors, and other mineral metabolism markers.
Elevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD.
In Cox proportional hazards models adjusted for age, sex, race, clinical site, education level, physical activity, total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, use of antihypertensive treatment, current cigarette smoking, diabetes status, body mass index, C-reactive protein level, hemoglobin A1c level, phosphorus level, troponin T level, log N-terminal pro-B-type natriuretic peptide level, fibroblast growth factor 23 level, estimated glomerular filtration rate, and proteinuria, the hazard ratios associated with per 1 SD log of CAC were 1.40 (95% CI, 1.16-1.69; P < .001) for cardiovascular disease, 1.44 (95% CI, 1.02-2.02; P = .04) for myocardial infarction, 1.39 (95% CI, 1.10-1.76; P = .006) for heart failure, and 1.19 (95% CI, 0.94-1.51; P = .15) for all-cause mortality.
Despite the important physiological effect of FGF23 in maintaining phosphate homeostasis, there is increasing evidence that higher FGF23 levels are a risk factor for mortality and cardiovascular disease.
This review article will discuss the current experimental and clinical evidence regarding the role of FGF23 in physiology and pathophysiology of CKD and its associated complications with an emphasis on CVD.
Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function.
A high FGF23 level was associated with increased risks of all-cause mortality (RR 1.46, 95% CI 1.38-1.55, p < 0.001), CVD (RR 1.37, 95% CI 1.15-1.63, p < 0.001), and renal events (RR 1.31, 95% CI 1.07-1.59, p = 0.008), respectively.
Nontraditional risk factors for cardiovascular disease (CVD), including mineral disorder, high fibroblast growth factor 23 (FGF23), low klotho, and low soluble TWEAK could predict the incipient risk of CVD in chronic kidney disease (CKD).
Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there are no data on fibroblast growth factor 23 (FGF23) perturbations in nephrotic syndrome.
Two biomarkers, growth differentiation factor 15 (GDF-15) and fibroblast growth factor 23 (FGF-23)), reflecting different aspects of renal pathophysiology, were evaluated as determinants of decline in estimated glomerular filtration rate (eGFR), incident cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D) and microalbuminuria, but without clinical cardiac disease.
The independent associations between the presence of abdominal obesity and the increase in serum FGF23 levels in specific groups suggest that serum FGF23 levels may indicate the risk of metabolic and cardiovascular disease in men and postmenopausal women.