#5559 bone specific alkaline phosphatase as a potential biomarker of autosomal dominant polycystic kidney disease progression

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disease, resulting in a dysfunction of the primary cilium, a sensory organelle ubiquitously present in human cells. Ciliopathies are characterized by disorders of seemingly unrelated organs and functions, which depend on integrity of the primary cilium, among them the skeleton and the kidneys. A distinct bone phenotype has been reported in ADPKD patients in several cohort studies. Findings, however, were heterogenous. Present study aimed to measure bone turnover biomarkers in patients with ADPKD across disease severity measured by eGFR and height-adjusted total kidney volume (HtTKV). Method In this cross-sectional study, we included 80 ADPKD patients with different chronic kidney disease (CKD) stages (G1 and G2 (n = 39), and G3 and G4 (n = 41)) with median age 44.0 (33.5-50.5) years, 62.5% men, and BMI 25.1 (23.3-28.7) kg/m2. HtTKV was measured with magnetic resonance imaging. We measured biochemical parameters of mineral metabolism, including bone specific alkaline phosphatase (BALP) and total ALP, calcium (Ca), parathyroid hormone (PTH), and 25(OH) vitamin D (25(OH)D) and bone strength index (BSi) with microindentation, using an OsteoProbe® (Active Life Scientific, USA). Microindentation is minimally invasive technique assessing bone quality. The cortical bone at the mid-shaft of the tibia is penetrated with the indenter to measure bone resistance. Results Bone biomarkers expressed as median and interquartile range were as follow: Ca 9.6 (9.3-9.9) mg/dL, BALP 9.0 (7.0-12.5) ug/L, ALP 59.0 (46.0-72.0) U/L, PTH 43.5 (26.6-72.0) pg/mL and 25(OH)D 25.4 (16.6-33.5) ng/mL. Median BSi was 79.1(73.5-82.1) in men and 68.5 (62.1-78.6) in women (lower than the average score in healthy caucasians). Among analyzed bone markers only BALP significantly associated with severity of ADPKD. BALP - but not eGFR - associated with HtTKV and was different across HtTKV tertiles. BALP was also higher in the highest BSi group, but BSi did not associate with HtTKV (Figure 1). Conclusion In patients with ADPKD and different stages of CKD, BALP associates with bone strength and kidney volume, suggesting that it may be a sensitive marker of systemic ADPKD manifestations. Further studies should elucidate whether BALP may be a more sensitive marker for ADPKD progression than GFR.