Fibroblast growth factor 23 and Klotho as cardiovascular risk factors in heart transplant recipients.
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.
Department of Cardiovascular Surgery and Transplantology, Medical College, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland. Electronic address: piotr.przybylowski@uj.edu.pl.
P
P
Przybylowski
Department of Cardiovascular Surgery and Transplantology, Medical College, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland.
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G
Wasilewski
Department of Cardiovascular Surgery and Transplantology, Medical College, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland.
L
L
Janik
Department of Cardiovascular Surgery and Transplantology, Medical College, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland.
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S
Kozlowska
Department of Internal Medicine and Angiology, Brothers Hospitallers' of St John of God Hospital, Cracow, Poland.
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E
Nowak
2nd Department of Nephrology, Medical University of Bialystok, Poland.
J
J
Malyszko
D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate / Q000502:physiology; D005966:Glucuronidase / Q000097:blood*; D006020:Glycopeptides / Q000097:blood; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000090265:Klotho Proteins; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000097:blood; D012307:Risk Factors; D066027:Transplant Recipients
D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; C000717427:FGF23 protein, human; D006020:Glycopeptides; D007166:Immunosuppressive Agents; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008075:Lipoproteins, HDL; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C048197:copeptins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine; D005966:Glucuronidase; D000090265:Klotho Proteins