Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease

Abstract

Fibroblast growth factor 23 (FGF23) regulates phosphorus metabolism and is a strong predictor of mortality in dialysis patients. FGF23 has been proposed as an early biomarker of disordered phosphorus metabolism in earlier stages of chronic kidney disease (CKD), but data from large, well-characterized CKD cohorts are lacking. We measured FGF23 in baseline samples from 3,879 participants in the Chronic Renal Insufficiency Cohort study, a nationally representative, diverse CKD cohort with mean (± sd) estimated glomerular filtration rate (eGFR) of 42.8 ± 13.5 ml/min/1.73m2. Serum phosphate (3.7 ± 0.7 mg/dl) and parathyroid hormone (PTH; median 54, interquartile range [IQR] 35 – 89 pg/ml) levels were in the normal range, but FGF23 (median 145, IQR 96 – 239 RU/ml) was markedly greater than in healthy populations and increased significantly with decreasing eGFR. FGF23 excess, defined as ≥ 100 RU/ml, was more common than secondary hyperparathyroidism (≥ 65 pg/ml) and hyperphosphatemia (≥ 4.6 mg/dl) in all strata of eGFR, and the eGFR threshold at which the slope of FGF23 increased (57.8; 95%CI: 55.4 – 60.8 ml/min/1.73m2) was higher than the corresponding threshold for PTH (46.9; 95%CI: 45.5 – 51.4 ml/min/1.73m2). Thus, increased FGF23 is a common manifestation of CKD that develops earlier than increases in phosphate or PTH. These findings provide additional support for use of FGF23 as a sensitive early screening test to identify disordered phosphorus metabolism in CKD patients with normal serum phosphate levels.

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

“…Other mechanisms by which FGF‐23 could lead to adverse cardiovascular consequences include calcitriol deficiency, altered phosphorus homeostasis, systemic inflammation and oxidative stress, and sodium retention 31, 32, 33. Additionally, FGF‐23 may downregulate soluble α‐klotho,34 an enzyme with anti‐aging effects that was shown to protect the heart against cardiac hypertrophy and cardiac remodeling 35, 36. In a study by Reindl et al, FGF‐23 was significantly higher in patients who developed LV remodeling post ST‐segment–elevation myocardial infarction even after adjustment for biomarkers of myocardial necrosis, myocardial stress, and inflammation 37.…”

Bone disease after transplantation: osteoporosis and fractures risk

“…Gradually failing allografts lead to post-transplantation CKD stage 3-5 leading to increased risk of worsening or de novo development of hyperparathyroidism with active vitamin D deficiency and metabolic disorders similar to those observed before transplantation (22).…”

Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease

“…Previous studies in adult and pediatric patients have demonstrated that FGF-23 levels are elevated in early CKD and increase with CKD progression, suggesting that renal injury affects the skeleton in even very early stages of CKD (7)(8)(9). However, the skeletal changes associated with circulating FGF-23 levels in predialysis CKD are unknown, and it remains uncertain whether FGF-23 levels increase before PTH elevations become detectable or whether an increase in PTH, which has been shown in some studies to increase FGF-23 levels (10), precedes the increase in FGF-23.…”