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Sclerostin─A Debutant on the Autosomal Dominant Polycystic Kidney Disease Scene?

Magdalena Jankowska1,2, Mathias Haarhaus1, Abdul Rashid Qureshi1

  • 1Division of Renal Medicine and Baxter Novum, Karolinska University Hospital at Huddinge, Karolinska Institutet, Stockholm, Sweden.

Kidney International Reports
|November 17, 2017
PubMed
Abstract

Insights

Autosomal dominant polycystic kidney disease (ADPKD) is linked to elevated sclerostin levels, potentially indicating impaired bone cell mechanosensation. This finding highlights the importance of kidney disease etiology in understanding bone health in renal failure patients.

Area of Science:

  • Nephrology
  • Endocrinology
  • Bone Biology

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) involves mutations in polycystin genes, affecting mechanosensation in kidney and bone cells.
  • The Wnt/β-catenin pathway is crucial for osteocyte mechanotransduction, with mechanical unloading upregulating sclerostin.
  • Sclerostin is a key inhibitor of bone formation, influenced by mechanical forces.

Purpose of the Study:

  • To investigate the association between ADPKD and circulating sclerostin levels.
  • To determine if ADPKD is an independent determinant of sclerostin levels in patients with end-stage renal disease.

Main Methods:

  • Observational, cross-sectional study of 100 end-stage renal disease patients.
  • Assessed circulating sclerostin and other mineral and bone disease parameters (PTH, calcium, phosphate, etc.).
  • Utilized multivariate analysis to identify independent associations.

Main Results:

  • Patients with ADPKD exhibited significantly higher sclerostin levels compared to non-ADPKD patients.
  • ADPKD was independently associated with increased sclerostin levels, irrespective of other factors.
  • Lower bone specific alkaline phosphatase (BALP) levels were observed in ADPKD patients.

Conclusions:

  • Circulating sclerostin levels are elevated in ADPKD, suggesting potential impaired mechanosensation in bone.
  • The findings underscore the significance of kidney disease etiology in confounding the relationship between renal failure and mineral and bone disease.
  • Further research is needed to clarify the clinical implications for bone health in ADPKD patients.
Keywords:
autosomal dominant polycystic kidney diseasebone mechanosensorskidney disease−mineral and bone disorderpolycystinsclerostin

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