Mark M Mitsnefes1, Aisha Betoko2, Michael F Schneider2, Isidro B Salusky3, Myles Selig Wolf4, Harald Jüppner5, Bradley A Warady6, Susan L Furth7, Anthony A Portale8. 1. Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 3. Division of Nephrology, Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 4. Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. 5. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 6. Section of Nephrology, Children's Mercy Hospital, Kansas City, Missouri. 7. Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and. 8. Division of Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, California anthony.portale@ucsf.edu.
Abstract
BACKGROUND AND OBJECTIVES: High plasma concentration of fibroblast growth factor 23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that high FGF23 levels associate with a higher prevalence of LVH in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed echocardiograms and measured plasma C-terminal FGF23 concentrations in 587 children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We used linear and logistic regression to analyze the association of plasma FGF23 with left ventricular mass index (LVMI) and LVH (LVMI ≥95th percentile), adjusted for demographics, body mass index, eGFR, and CKD-specific factors. We also examined the relationship between FGF23 and LVH by eGFR level. RESULTS: Median age was 12 years (interquartile range, 8-15) and eGFR was 50 ml/min per 1.73 m2 (interquartile range, 38-64). Overall prevalence of LVH was 11%. After adjustment for demographics and body mass index, the odds of having LVH was higher by 2.53 (95% confidence interval, 1.28 to 4.97; P<0.01) in participants with FGF23 concentrations ≥170 RU/ml compared with those with FGF23<100 RU/ml, but this association was attenuated after full adjustment. Among participants with eGFR≥45 ml/min per 1.73 m2, the prevalence of LVH was 5.4%, 11.2%, and 15.3% for those with FGF23 <100 RU/ml, 100-169 RU/ml, and ≥170 RU/ml, respectively (Ptrend=0.01). When eGFR was ≥45 ml/min per 1.73 m2, higher FGF23 concentrations were independently associated with LVH (fully adjusted odds ratio, 3.08 in the highest versus lowest FGF23 category; 95% confidence interval, 1.02 to 9.24; P<0.05; fully adjusted odds ratio, 2.02 per doubling of FGF23; 95% confidence interval, 1.29 to 3.17; P<0.01). By contrast, in participants with eGFR<45 ml/min per 1.73 m2, FGF23 did not associate with LVH. CONCLUSIONS: Plasma FGF23 concentration ≥170 RU/ml is an independent predictor of LVH in children with eGFR≥45 ml/min per 1.73 m2.
BACKGROUND AND OBJECTIVES: High plasma concentration of fibroblast growth factor 23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that high FGF23 levels associate with a higher prevalence of LVH in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed echocardiograms and measured plasma C-terminal FGF23 concentrations in 587 children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We used linear and logistic regression to analyze the association of plasma FGF23 with left ventricular mass index (LVMI) and LVH (LVMI ≥95th percentile), adjusted for demographics, body mass index, eGFR, and CKD-specific factors. We also examined the relationship between FGF23 and LVH by eGFR level. RESULTS: Median age was 12 years (interquartile range, 8-15) and eGFR was 50 ml/min per 1.73 m2 (interquartile range, 38-64). Overall prevalence of LVH was 11%. After adjustment for demographics and body mass index, the odds of having LVH was higher by 2.53 (95% confidence interval, 1.28 to 4.97; P<0.01) in participants with FGF23 concentrations ≥170 RU/ml compared with those with FGF23<100 RU/ml, but this association was attenuated after full adjustment. Among participants with eGFR≥45 ml/min per 1.73 m2, the prevalence of LVH was 5.4%, 11.2%, and 15.3% for those with FGF23 <100 RU/ml, 100-169 RU/ml, and ≥170 RU/ml, respectively (Ptrend=0.01). When eGFR was ≥45 ml/min per 1.73 m2, higher FGF23 concentrations were independently associated with LVH (fully adjusted odds ratio, 3.08 in the highest versus lowest FGF23 category; 95% confidence interval, 1.02 to 9.24; P<0.05; fully adjusted odds ratio, 2.02 per doubling of FGF23; 95% confidence interval, 1.29 to 3.17; P<0.01). By contrast, in participants with eGFR<45 ml/min per 1.73 m2, FGF23 did not associate with LVH. CONCLUSIONS: Plasma FGF23 concentration ≥170 RU/ml is an independent predictor of LVH in children with eGFR≥45 ml/min per 1.73 m2.
Authors: Maren Leifheit-Nestler; Robert Große Siemer; Kathrin Flasbart; Beatrice Richter; Felix Kirchhoff; Wolfgang H Ziegler; Michael Klintschar; Jan U Becker; Andreas Erbersdobler; Christoph Aufricht; Tomas Seeman; Dagmar-Christiane Fischer; Christian Faul; Dieter Haffner Journal: Nephrol Dial Transplant Date: 2015-12-17 Impact factor: 5.992
Authors: Manish D Sinha; Charles Turner; Caroline J Booth; Simon Waller; Pernille Rasmussen; David J A Goldsmith; John M Simpson Journal: Pediatr Nephrol Date: 2015-05-15 Impact factor: 3.714
Authors: Songcang Chen; Christopher S Law; Christopher L Grigsby; Keith Olsen; Ting-Ting Hong; Yan Zhang; Yerem Yeghiazarians; David G Gardner Journal: Circulation Date: 2011-09-26 Impact factor: 29.690
Authors: Sarah Seiler; Kyrill S Rogacev; Heinz J Roth; Pagah Shafein; Insa Emrich; Stefan Neuhaus; Jürgen Floege; Danilo Fliser; Gunnar H Heine Journal: Clin J Am Soc Nephrol Date: 2014-03-27 Impact factor: 8.237
Authors: Edward R Smith; Martin L Ford; Laurie A Tomlinson; Gary Weaving; Bernard F Rocks; Chakravarthi Rajkumar; Stephen G Holt Journal: Clin Chim Acta Date: 2011-02-12 Impact factor: 3.786
Authors: G de Simone; S R Daniels; R B Devereux; R A Meyer; M J Roman; O de Divitiis; M H Alderman Journal: J Am Coll Cardiol Date: 1992-11-01 Impact factor: 24.094
Authors: Joseph T Flynn; Mark Mitsnefes; Christopher Pierce; Steven R Cole; Rulan S Parekh; Susan L Furth; Bradley A Warady Journal: Hypertension Date: 2008-08-25 Impact factor: 10.190
Authors: Kristen Sgambat; Jennifer Roem; Mark Mitsnefes; Anthony A Portale; Susan Furth; Bradley Warady; Asha Moudgil Journal: Pediatr Nephrol Date: 2018-06-05 Impact factor: 3.714
Authors: Linto Thomas; Jianxiang Xue; Viktor N Tomilin; Oleh M Pochynyuk; Jessica A Dominguez Rieg; Timo Rieg Journal: Am J Physiol Renal Physiol Date: 2020-08-03
Authors: Tae-Hwi Schwantes-An; Sai Liu; Margaret Stedman; Brian S Decker; Leah Wetherill; Howard J Edenberg; Matteo Vatta; Tatiana M Foroud; Glenn M Chertow; Sharon M Moe Journal: Am J Nephrol Date: 2019-01-22 Impact factor: 3.754
Authors: Meredith A Atkinson; Derek K Ng; Bradley A Warady; Susan L Furth; Joseph T Flynn Journal: Pediatr Nephrol Date: 2020-02-03 Impact factor: 3.714