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

Author:

Michon-Colin Arthur1234ORCID,Metzger Marie5,Bankir Lise67ORCID,Gauci Cédric25,Brunel Mélanie1234,Baron Stéphanie12634,Prot-Bertoye Caroline26734,Stengel Bénédicte5,Thervet Eric18,Haymann Jean-Philippe910,Boffa Jean-Jacques911,Vrtovsnik François112,Flamant Martin113,Houillier Pascal12634,Prie Dominique11415,Courbebaisse Marie121434,Flamant Martin,Houillier Pascal,Haymann Jean Philippe,Boffa Jean-Jacques,Thervet Eric,Vrtovsnik François,Stengel Benedicte,Vrtovsnik François,Daugas Eric,Flamant Martin,Vidal-Petiot Emmanuelle,Tabibzadeh Nahid,Jacquot Christian,Karras Alexandre,Roueff Stéphane,Thervet Eric,Houillier Pascal,Courbebaisse Marie,Bertocchio Jean-Philippe,Prot-Bretoye Caroline,Boffa Jean-Jacques,Ronco Pierre,Fessi H,Rondeau Eric,Letavernier Emmanuel,Haymann Jean-Philippe,Metzger Marie,Urena-Torres Pablo,

Affiliation:

1. Université Paris Cité , Paris , France

2. Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris , Paris , France

3. Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte , Paris , France

4. Centre de Référence des Maladies Rares du Calcium et du Phosphate , Paris , France

5. INSERM UMRS 1018, Equipe d'Epidémiologie Clinique, CESP, Université Paris-Saclay , Villejuif , France

6. Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité , Paris , France

7. CNRS, ERL 8228, Laboratory of Kidney Physiology and Tubulopathies , Paris , France

8. Néphrologie et Hémodialyse, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris , Paris , France

9. Explorations Fonctionnelles Multidisciplinaires, Sorbonne Université Paris , France

10. Explorations Fonctionnelles Multidisciplinaires, Hôpital Tenon, Assistance Publique – Hôpitaux de Paris , Paris , France

11. Néphrologie et Dialyse, Hôpital Tenon, Assistance Publique – Hôpitaux de Paris , Paris , France

12. Néphrologie, Hôpital Bichat, Assistance Publique – Hôpitaux de Paris , Paris , France

13. Explorations Fonctionnelles Multidisciplinaires, Hôpital Bichat, Assistance Publique – Hôpitaux de Paris , Paris , France

14. INSERM U1151, Institut Necker Enfants Malades , Paris , France

15. Département de Physiologie, Hôpital Necker, Assistance Publique – Hôpitaux de Paris , Paris , France

Abstract

ABSTRACT 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 m2 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.

Funder

Inserm GIS-IReSP

French Ministry of Health

Inserm

Agence de la Biomédecine

AURA

Roche

F. Hoffmann-La Roche

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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