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Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation
Leandro C Baia1, Jelmer K Humalda, Marc G Vervloet
1Department 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.
Insights
Fibroblast growth factor 23 (FGF23) is linked to higher cardiovascular and overall mortality in kidney transplant recipients. This finding holds true even after accounting for mineral metabolism and cardiovascular risk factors.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Circulating fibroblast growth factor 23 (FGF23) is associated with adverse cardiovascular outcomes in chronic kidney disease (CKD).
- The predictive value of FGF23 for cardiovascular mortality post-kidney transplantation remains unclear.
- Understanding FGF23's role is crucial for managing cardiovascular risk in transplant patients.
Purpose of the Study:
- To investigate whether plasma FGF23 predicts cardiovascular mortality in kidney transplant recipients.
- To determine if FGF23's association with mortality is independent of established risk factors.
- To assess FGF23's utility in risk stratification after kidney transplantation.
Main Methods:
- A single-center prospective cohort study of 593 stable kidney transplant recipients.
- Plasma C-terminal FGF23 levels were measured.
- Multivariate Cox regression models were used, adjusting for renal function, mineral metabolism, Framingham risk factors, and cardiac biomarkers (MR-proANP, NT-proBNP, copeptin).
Main Results:
- Plasma FGF23 was independently associated with cardiovascular mortality (HR, 1.88; P=0.02).
- FGF23 was also independently associated with all-cause mortality (HR, 1.86; P=0.001).
- Net reclassification improved significantly for both cardiovascular and all-cause mortality, indicating FGF23 adds predictive value.
Conclusions:
- Plasma FGF23 is an independent predictor of cardiovascular and all-cause mortality after kidney transplantation.
- This association persists even after adjusting for mineral metabolism and cardiovascular risk factors.
- FGF23 may serve as a valuable biomarker for risk stratification in kidney transplant recipients.
Background And Objectives:
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.
Design, Setting, Participants, & Measurements:
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.
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