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

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease originating from a mutation in genes encoding polycystin 1 and 2. Recent evidence suggests that these polycystins mediate mechanosensation not only in the primary cilium of kidney cells but also in bone cells. The Wnt/β-catenin signaling pathway plays a central role in mechanotransduction in osteocytes. Mechanical unloading causes the upregulation of the Wnt inhibitor sclerostin. We tested the hypothesis that ADPKD associates with higher circulating sclerostin levels. METHODS: In this observational, cross-sectional study, circulating levels of sclerostin and other laboratory parameters of mineral and bone disease, including intact parathyroid hormone (PTH), calcium, phosphate, magnesium, 25(OH) D-vitamin, 1,25 (OH)(2) D-vitamin, and bone specific alkaline phosphatase (BALP) were assessed in 100 patients with end-stage renal disease recruited from an ongoing longitudinal cohort study in Stockholm, Sweden. RESULTS: Patients with ADPKD had higher sclerostin levels and lower BALP levels as compared to patients with other primary renal disease. In multivariate analysis, ADPKD associated with circulating sclerostin levels, independent of the established determinants including age, gender, body mass index, diabetes, phosphate, PTH, and 1,25 (OH)(2) D-vitamin. DISCUSSION: Circulating sclerostin levels are increased in ADPKD, possibly reflecting impaired mechanosensation. The clinical relevance of this finding, especially with regard to bone health, remains to be investigated. Our finding draws attention to the etiology of kidney disease as an important, yet neglected, confounder of the association between renal failure and mineral and bone disease.