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.

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Abstract. Insights into end-stage renal disease have emerged from many investigations but less is known about the epidemiology of chronic renal insufficiency (CRI) and its relationship to cardiovascular disease (CVD). The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for progression of CRI and CVD among CRI patients and develop models to identify high-risk subgroups, informing future treatment trials, and increasing application of preventive therapies. CRIC will enroll approximately 3000 individuals at seven sites and follow participants for up to 5 yr. CRIC will include a racially and ethnically diverse group of adults aged 21 to 74 yr with a broad spectrum of renal disease severity, half of whom have diagnosed diabetes mellitus. CRIC will exclude subjects with polycystic kidney disease and those on active immunosuppression for glomerulonephritis. Subjects will undergo extensive clinical evaluation at baseline and at annual clinic visits and via telephone at 6 mo intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens will be collected annually.125 I-iothalamate clearances and CVD evaluations including a 12-lead surface electrocardiogram, an echocardiogram, and coronary electron beam or spiral CT will be performed serially. Analyses planned in CRIC will provide important information on potential risk factors for progressive CRI and CVD. Insights from CRIC should lead to the formulation of hypotheses regarding therapy that will serve as the basis for targeted interventional trials focused on reducing the burden of CRI and CVD.The rate of ESRD has increased steadily in the United States over the past three decades. Insights into the epidemiology and treatment of ESRD have emerged from many investigations including those conducted by the United States Renal Disease System. Much less is known about the epidemiology of pre-ESRD chronic renal insufficiency (CRI), especially the relationship between CRI and cardiovascular disease (CVD).CRI has been recognized as a silent epidemic (1) affecting more than ten million Americans. The burden of morbidity and mortality from CRI derives from the progression of CRI to ESRD and the disproportionate risk of CVD in the setting of CRI. CRI is strongly and independently associated with CVD, even after adjustment for traditional CVD risk factors. These findings led to the hypothesis that specific "uremia-related risk factors" augment the rate of CVD (2) and cause many patients with CRI to succumb to fatal cardiovascular events before needing renal replacement therapy.The National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) established the Chronic Renal Insufficiency Cohort (CRIC) Study in 2001 to improve understanding of the relationship between CRI and CVD. The CRIC Study goals are to examine risk factors for progression of CRI and CVD among patients with CRI and develop predictive mo...

Background The MDRD Study equation underestimates measured GFR at levels greater than 60 ml/min per 1.73 m2, with variable accuracy among subgroups; consequently estimated GFR (eGFR) ≥ 60 ml/min/1.73 m2 is not reported by clinical laboratories. Here, the performance of a more accurate GFR estimating equation, the CKD-EPI equation, is reported by level of GFR and clinical characteristics. Study Design Test of diagnostic accuracy Setting and Participants Pooled dataset of 3896 people from 16 studies with measured GFR (not used for development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid organ transplant, and body mass index. Index Tests eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine Reference Test Measured GFR using urinary or plasma clearance of exogenous filtration markers Results Mean (SD) measured GFR was 68 (36) ml/min/1.73 m2. For eGFR less than 30 ml/min/1.73 m2, both equations have similar bias (median difference compared to measured GFR). For eGFR between 30-59 ml/min/1.73 m2, bias was reduced from 4.9 to 2.1 ml/min/1.73 m2 (57% improvement). For eGFR between 60-89 ml/min/1.73 m2, bias was reduced from 11.9 to 4.2 ml/min/1.73 m2 (61 % improvement). For eGFR between 90-119 ml/min/1.73 m2, bias was reduced from 10.0 to 1.9 ml/min/1.73 m2 (75% improvement). Similar or improved performance was noted for most subgroups with eGFR < 90 ml/min/1.73 m2, other than BMI less than 20 kg/m2, with greater variation noted for some subgroups with eGFR ≥ 90 ml/min/1.73 m2. Limitations Limited number of elderly people and racial and ethnic minorities with measured GFR. Conclusions The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR ≥ 60 ml/min/1.73 m2 can be reported using the CKD-EPI equation.