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.

Context High levels of the phosphate regulating hormone, fibroblast growth factor 23 (FGF23), associate with mortality in patients with end-stage renal disease (ESRD), but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease (CKD). Objective Evaluate FGF23 as a risk factor for adverse outcomes in patients with CKD. Design, Setting and Participants A prospective study of 3,879 participants with CKD stages 2 – 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008. Main Outcome Measures All-cause mortality and ESRD. Results At enrollment, mean estimated glomerular filtration rate (eGFR) was 42.8 ± 13.5 ml/min/1.73m2, and median FGF23 was 145 (interquartile range [IQR] 96 – 239) reference units/ml (RU/ml). During a median follow-up of 3.5 (IQR 2.5 – 4.4) years, 266 participants died (20.3/1000 person-years) and 410 reached ESRD (33.0/1000 person-years). Higher FGF23 levels independently associated with a greater risk of death in adjusted analyses of FGF23 on a continuous scale (hazard ratio [HR] per SD of lnFGF23, 1.5; 95%CI 1.3 – 1.7) or in quartiles (quartile 1, reference; quartile 2, HR 1.3; 95%CI 0.8 – 2.2; quartile 3, HR 2.0; 95%CI 1.2 – 3.3; quartile 4, HR 3.0; 95%CI 1.8 – 5.1). FGF23 was not independently associated with ESRD in adjusted analyses of the entire cohort, however, the effect was modified by eGFR (P for interaction = 0.005), which was the strongest predictor for ESRD. FGF23 independently associated with significantly greater risk of ESRD among participants with eGFR 30 – 44 (HR 1.3 per SD of lnFGF23; 95%CI 1.04 – 1.6) and ≥ 45 (HR 1.7; 95%CI 1.1 – 2.4), but not < 30 ml/min/1.73m2. Conclusion Elevated FGF23 is an independent risk factor for ESRD in patients with relatively preserved kidney function and for mortality across the spectrum of CKD.

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.

Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores.

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