Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities

J Clin Endocrinol Metab. 2020 Aug 1;105(8):dgaa267. doi: 10.1210/clinem/dgaa267.

Abstract

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); however, 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.

Design: Cross-sectional multicenter study.

Setting: Hospital clinics.

Patients: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage.

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 with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate.

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

Keywords: FGF23; Klotho; OPG; TRAP5b; children; chronic kidney disease; cystinosis; rickets; sclerostin.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Resorption / diagnosis*
  • Bone Resorption / etiology
  • Bone Resorption / physiopathology
  • Calcification, Physiologic / physiology
  • Child
  • Chronic Kidney Disease-Mineral and Bone Disorder / diagnosis*
  • Chronic Kidney Disease-Mineral and Bone Disorder / etiology
  • Chronic Kidney Disease-Mineral and Bone Disorder / physiopathology
  • Cross-Sectional Studies
  • Cystinosis / complications*
  • Cystinosis / physiopathology
  • Cystinosis / surgery
  • Fanconi Syndrome / etiology*
  • Fanconi Syndrome / physiopathology
  • Fanconi Syndrome / surgery
  • Female
  • Fibroblast Growth Factor-23
  • Humans
  • Kidney Transplantation
  • Male
  • Prospective Studies
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / etiology*
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / surgery
  • Severity of Illness Index