Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation.
OBJECTIVE
Circulating fibroblast growth factor 23 (FGF23) is associated with adverse cardiovascular outcomes in CKD. Whether FGF23 predicts cardiovascular mortality after kidney transplantation, independent of measures of mineral metabolism and cardiovascular risk factors, is unknown.


METHODS
The association between plasma C-terminal FGF23 and cardiovascular mortality was analyzed in a single-center prospective cohort of 593 stable kidney transplant recipients (mean age ± SD, 52 ± 12 years; 54% male; estimated GFR, 47 ± 16 ml/min per 1.73 m(2)), at a median of 6.1 (interquartile range, 2.7-11.7) years after transplantation. Multivariate Cox regression models were built, adjusting for measures of renal function and mineral metabolism; Framingham risk factors; the left ventricular wall strain markers midregional fragment of pro-A-type natriuretic peptide (MR-proANP) and N-terminal-pro brain natriuretic peptide (NT-proBNP); and copeptin, the stable C-terminal portion of the precursor of vasopressin.


RESULTS
In multivariate linear regression analysis, MR-proANP (β=0.20, P<0.001), NT-proBNP (β=0.18, P<0.001), and copeptin (β=0.26, P<0.001) were independently associated with FGF23. During follow-up for 7.0 (interquartile range, 6.2-7.5) years, 128 patients (22%) died, of whom 66 (11%) died due to cardiovascular disease; 54 (9%) had graft failure. FGF23 was associated with an higher risk of cardiovascular mortality in a fully adjusted multivariate Cox regression model (hazard ratio [HR], 1.88 [95% confidence interval (CI), 1.11 to 3.19]; P=0.02). FGF23 was also independently associated with all-cause mortality (full model HR, 1.86 [95% CI, 1.27 to 2.73]; P=0.001). Net reclassification improved for both cardiovascular mortality (HR, 0.07 [95% CI, 0.01 to 0.14]; P<0.05) and all-cause mortality (HR, 0.11 [95% CI, 0.05 to 0.18]; P<0.001).


CONCLUSIONS
Plasma FGF23 is independently associated with cardiovascular and all-cause mortality after kidney transplantation. The association remained significant after adjustment for measures of mineral metabolism and cardiovascular risk factors.
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands;, †Department of Nephrology, UNIFESP, Sao Paolo, Brazil, ‡Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
Leandro C
LC
Baia
Jelmer K
JK
Humalda
Marc G
MG
Vervloet
Gerjan
G
Navis
Stephan J L
SJ
Bakker
Martin H
MH
de Borst
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000401:mortality*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009426:Netherlands; D010446:Peptide Fragments / Q000097:blood; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; C000717427:FGF23 protein, human; D006020:Glycopeptides; D010446:Peptide Fragments; C048197:copeptins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D009320:Atrial Natriuretic Factor