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Fibroblast growth factor 23 and Klotho as cardiovascular risk factors in heart transplant recipients
P Przybylowski1, G Wasilewski1, L Janik1
1Department of Cardiovascular Surgery and Transplantology, Medical College, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland.
Insights
Heart transplant recipients show higher Fibroblast Growth Factor (FGF) 23 and lower Klotho hormone levels. These imbalances are linked to cardiovascular issues and kidney problems, increasing disease risk.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Nephrology
Background:
- Fibroblast Growth Factor (FGF) 23 is a bone-derived hormone linked to cardiovascular disease risk.
- Klotho, an FGF23 co-receptor, is recognized as a "longevity" hormone.
- The roles of FGF23 and Klotho in heart transplant (HT) recipients remain largely unexplored.
Purpose of the Study:
- To investigate serum concentrations of FGF23 and Klotho in heart transplant recipients.
- To analyze the relationship between these hormones and immunosuppressive therapy.
- To assess the association with comorbidities in heart transplant recipients.
Main Methods:
- Eighty-four stable heart transplant recipients and 22 healthy controls were studied.
- Serum concentrations of FGF23 and Klotho protein were measured.
- Markers of renal function (cystatin C, NGAL), heart failure (copeptin, NT-proBNP), and other clinical parameters were evaluated.
Main Results:
- Heart transplant recipients exhibited significantly higher FGF23 and lower Klotho levels compared to controls.
- FGF23 levels correlated with markers of renal function, heart failure, and cardiovascular structure.
- Lower estimated glomerular filtration rate (eGFR) was associated with higher FGF23 and lower Klotho.
Conclusions:
- Disorders in the FGF23/Klotho system are prevalent in heart transplant recipients.
- These imbalances are associated with impaired cardiovascular function and kidney disease.
- The FGF23/Klotho system may play a role in the increased cardiovascular risk observed post-transplantation.
Background:
Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for FGF23 and at the same time it is known as a "longevity" hormone. There are no data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The aim of this study was to assess Klotho and FGF23 serum concentration in heart transplant recipients depending on immunosuppressive therapy regimen and comorbidities.
Methods:
Eighty-four stable heart transplant recipients were enrolled in the study; 22 healthy volunteers served as control subjects. FGF23 and Klotho protein concentration, markers of renal function, such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), and heart failure markers, such as copeptine and N-termiinal pro-B-type natriuretic peptide (NT-proBNP), were evaluated.
Results:
FGF23 concentration was significantly higher in the HT group whereas Klotho protein was significantly lower. FGF23 correlated with creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate (eGFR; r = -0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P < .001), hemoglobin (r = -0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high-density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05). Klotho protein correlated only with age (r = -0.21; P < .05), creatinine (r = -0.21; P < .05), and eGFR (r = -0.31; P < .01). FGF23 concentration was significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was significantly lower. FGF23 predictors were renal function (creatinine concentration; β = 0.45; P = .0001), HDL (β = 0.33; P = .003), intraventricular septum thickness (β = 0.38; P = .0003), and right ventricular systolic pressure (β = 0.34; P = .003), explaining 70% of FGF23 variability.
Conclusions:
FGF23/Klotho system disorders in HT recipients are related to cardiovascular system function and kidney failure and could cause increased risk of cardiovascular disease.
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