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Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5.
Schön, Anne; Leifheit-Nestler, Maren; Deppe, Jennifer; Fischer, Dagmar-Christiane; Bayazit, Aysun K; Obrycki, Lukasz; Canpolat, Nur; Bulut, Ipek Kaplan; Azukaitis, Karolis; Yilmaz, Alev; Mir, Sevgi; Yalcinkaya, Fatos; Soylemezoglu, Oguz; Melk, Anette; Stangl, Gabriele I; Behnisch, Rouven; Shroff, Rukshana; Bacchetta, Justine; Querfeld, Uwe; Schaefer, Franz; Haffner, Dieter.
Afiliação
  • Schön A; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.
  • Leifheit-Nestler M; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.
  • Deppe J; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.
  • Fischer DC; Department of Pediatrics, Rostock University Medical Center, Rostock, Germany.
  • Bayazit AK; Department of Pediatric Nephrology, Cukurova University School of Medicine, Adana, Turkey.
  • Obrycki L; Department of Nephrology, Kidney Transplantation and Hypertension, The Children`s Memorial Health Institute, Warszawa, Poland.
  • Canpolat N; Department of Pediatric Nephrology, Istanbul University-Cerrahpasa, Faculty of Medicine, Istanbul, Turkey.
  • Bulut IK; Division of Pediatric Nephrology, Department of Pediatrics, Ege University, Faculty of Medicine, Izmir, Turkey.
  • Azukaitis K; Clinic of Pediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
  • Yilmaz A; Department of Pediatric Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • Mir S; Department of Pediatric Nephrology, Ege University, Izmir, Turkey.
  • Yalcinkaya F; Department of Pediatrics, Ankara University Medical School, Ankara, Turkey.
  • Soylemezoglu O; Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey.
  • Melk A; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.
  • Stangl GI; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle, Germany.
  • Behnisch R; Institute of Medical Biometry and Informatics, University Heidelberg, Heidelberg, Germany.
  • Shroff R; Department of Pediatric Nephrology, UCL Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.
  • Bacchetta J; Centre de Référence des Maladies Rénales Rares, Centre de Référence des Maladies Rares du Calcium et du Phosphate, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.
  • Querfeld U; Department of Pediatrics, Division of Gastroenterology, Nephrology, and Metabolic Medicine, Charité University Medicine Berlin, Berlin, Germany.
  • Schaefer F; Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
  • Haffner D; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.
Nephrol Dial Transplant ; 36(3): 442-451, 2021 02 20.
Article em En | MEDLINE | ID: mdl-33241290
BACKGROUND: Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin-angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear. METHODS: In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case-control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3-5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months. RESULTS: In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups. CONCLUSIONS: Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3-5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Uremia / Vitaminas / Calcitriol / Hipertrofia Ventricular Esquerda / Insuficiência Renal Crônica Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Animals / Child / Female / Humans / Male Idioma: En Revista: Nephrol Dial Transplant Assunto da revista: NEFROLOGIA / TRANSPLANTE Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Uremia / Vitaminas / Calcitriol / Hipertrofia Ventricular Esquerda / Insuficiência Renal Crônica Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Animals / Child / Female / Humans / Male Idioma: En Revista: Nephrol Dial Transplant Assunto da revista: NEFROLOGIA / TRANSPLANTE Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido