Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease

Background. Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. Methods. We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. Results. A total of 329 CKD patients (243 men, mean age 60.3 +/- 14.6 years) were included. Among them, 301 with an mGFR >15 ml/min/1.73 m(2) were included in survival and mGFR slope analyses. During a median follow-up of 4.61 years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Conclusion. Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD. LAY SUMMARY Copeptin and intact fibroblast growth factor 23 (iFGF23) are circulating proteins that increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. We included 301 CKD patients before end-stage renal disease from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and direct measurement of glomerular filtration rate (GFR). Baseline iFGF23 concentrations but not those of copeptin were associated after multiple adjustments with a composite outcome reflecting an unfavourable renal or vital evolution: kidney failure (KF) (dialysis initiation, pre-emptive transplantation or 57% decrease of mGFR) or death before KF. Neither copeptin nor iFGF23 were associated with measured GFR slope over time in additional analyses. It is the first time that these two potential biomarkers have been tested in a population of well-phenotyped CKD patients. Our study encourages the integration of iFGF23 measurement into the follow-up of CKD patients, whatever the CKD cause.