1 Institut for Psykologi, Department of Psychology, Faculty of Social Sciences, Københavns Universitet2 Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg3 Department of Pediatrics, University Hospital Rostock4 Division of Pediatric Nephrology, School of Medicine, Cukurova University5 Division of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine6 Division of Pediatric Nephrology, Dpt. of Pediatrics, Hacettepe University Faculty of Medicine7 Division of Pediatric Nephrology, Ege University Medical Faculty8 Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon9 Department of Pediatric Nephrology, University of Gaziantep10 Division of Pediatric Nephrology, University Children's Hospital11 Division of Pediatric Nephrology, Istanbul Medeniyet University, Göztepe Training and Research Hospital12 Diskapi Children's Hospital13 Division of Pediatric Nephrology, Uludag University Faculty of Medicine14 Pediatric Hospital, University Hospital Motol15 University Children's Hospital16 KfH Kidney Center for Children17 Department of Pediatric Nephrology, Sisli Educational and Research Hospital18 Division of Pediatric Nephrology, Great Ormond Street Hospital19 Dialysis and Transplantation Department of Pediatrics20 Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School21 Clinic of Pediatric Nephrology, Charite Children's Hospital22 Institut for Psykologi, Department of Psychology, Faculty of Social Sciences, Københavns Universitet
Objectives: The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods: Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/ 1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results: Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion: Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.