Bone and mineral metabolism in children with nephropathic cystinosis compared to other CKD entities

Presented by Annika Ewert, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Children’s Hospital, Hannover, Germany

Authors:  Annika Ewert1, Maren Leifheit-Nestler1, Katharina Hohenfellner2, Anja Büscher3, Markus J  Kemper4, Jun Oh5, Heiko Billing6, Julia Thumfart7, Gabriele Stangl8, Anja C. Baur8, Michael Föller9, Martina Feger9, Lutz T Weber10, Birgit Acham-Roschitz11, Klaus Arbeiter12, Burkhard Tönshoff13, Miroslav Zivicnjak1, Dieter Haffner1

Context: Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD), but systematic analyses are lacking.

Objective: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD.

Methods: In this cross-sectional study we investigated markers of bone and mineral metabolism in children with Cys (n=49) before and after renal transplantation in comparison to patients with other causes of CKD (non-Cys, n=80) by use of age and gender-related SD scores (SDS). Main outcome measures: Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity.Results: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities and/or requirement for skeletal surgery compared to CKD-controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low PTH, metabolic acidosis and a specific CKD stage- dependent pattern of bone marker alterations. Pre-transplant NC patients in mild to moderate CKD showed a delayed or lacking increase in FGF23 and sclerostin, and increased BAP, TRAP5b and OPG concentrations compared to CKD-controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared to CKD-controls and associated with higher serum phosphate.

Conclusions: NC patients show a more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism compared to CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.


Authors’ Affiliations:

1Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School
Children’s Hospital, Hannover, Germany

2Division of Pediatric Nephrology, Children’s Hospital, Rosenheim, Rosenheim, Germany,

3Department of Pediatrics II, University Hospital Essen, Essen, Germany.

4Asklepius Hospital, Hamburg, Germany

5Division of Pediatric Nephrology, University Children’s Hospital Hamburg, Hamburg,

6Division of Pediatric Nephrology, University Children’s Hospital Tübingen, Tübingen,

7Department of Pediatric Gastroenterology, Nephrology and Metabolism, Charite Hospital,
Berlin, Germany.

8Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg,
Halle, Germany

9Institute of Physiology, University of Hohenheim, Stuttgart, Germany

10Division of Pediatric Nephrology, Children´s and Adolescents´ Hospital, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany

11Department of Pediatrics, Medical University Graz, Graz, Austria

12Division of Pediatric Nephrology and Gastroenterology, Medical University Vienna, Austria

13Department of Pediatrics I, University Children’s Hospital Heidelberg, Heidelberg, Germany