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Abstract: TH-OR34

Noninvasive Method to Diagnose Renal Osteodystrophy: A Study on 19 Circulating MicroRNAs

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Vachey, Clement, Centre de recherche du CHU de Québec-Université Laval Site Hôtel Dieu, Quebec, Quebec, Canada
  • Ung, Roth-Visal, Centre de recherche du CHU de Québec-Université Laval Site Hôtel Dieu, Quebec, Quebec, Canada
  • Picard, Sylvain, Centre de recherche du CHU de Québec-Université Laval Site Hôtel Dieu, Quebec, Quebec, Canada
  • Dupuis, Marie-Eve, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Nickolas, Thomas, Columbia University Irving Medical Center, New York, New York, United States
  • Mac-Way, Fabrice, Centre de recherche du CHU de Québec-Université Laval Site Hôtel Dieu, Quebec, Quebec, Canada
Background

Current approach to manage bone fragility in chronic kidney disease (CKD) is in part based on assessment of bone turnover (BT) and mineralization. Prior work suggests that circulating microRNAs (miRNAs) identify low vs non-low cortical BT in CKD. We aimed to assess whether 19 miRNAs discriminate BT and biopsy proven contraindications (CI) to antiresorptive therapies (ART) in CKD patients .

Methods

Single-site cross-sectional study. Patients with stage 4-5 CKD having a high fracture risk underwent iliac crest bone biopsy for assessment of BT and mineralization levels according to ASBMR guidelines. Absolute CI to ART were defined by the presence of adynamic bone disease or osteomalacia. Relative CI were defined by the presence of mineralization defects without osteomalacia and low BT without adynamic bone. At the time of the biopsy, blood test were drawn for assessment of mineral biochemistry as per local standard and for measurement of 19 circulating miRNAs using the osteomiR kit (TAmiRNA, Austria). Each miRNA was compared between low vs high/normal BT, low/normal vs high BT, patients with absolute CI vs relative or no-CI to ART. Diagnostic accuracy was tested using the median and lowest tertile of each miRNA.

Results

Fourty four patients were included (women 56.8%, mean age 69.6±9.2, 45.4% dialysis). 19 had low BT, 16 normal, and 9 high BT; 7 patients had absolute CI to ART (2 osteomalacia, 5 adynamic bone). miRNA levels did not differ between low and normal/high BT groups. However, miRNA-31-5p was higher in patients with high BT (p=0,02), a value above the lowest tertile being associated with high BT status (sensitivity 100%, specificity 57,1% (95%CI: 40,8-73,5%), negative predicted value (NPV) 100%). We found 7 miRNAs (let7b5p, miRNA-141-3p, 143-3p, 17-5p, 19b-3p, 29b-3p, 550a-3p) with a very good capability to rule out CI to ART. A value above the median being associated with absolute CI to ART (sensitivity 85,7% (95%CI: 59,8-100%), specificity<60%, NPV 95.5% (95%CI: 86.8-100%)). A value above the lowest tertile was even more discriminant (NPV 100% for 5/7).

Conclusion

Circulating miRNAs can help clinical decision in the approach of bone fragility in CKD. Large studies in heterogeneous cohorts are needed to validate these results.