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Abstract: TH-OR027

A MicroRNA Approach to Diagnosing Renal Osteodystrophy

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Nickolas, Tom, Columbia University Medical Center, New York, New York, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Mcmahon, Donald J., Columbia University, New York, New York, United States
  • Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium
  • D'Haese, Patrick C., University Antwerp, Edegem, Belgium
  • Mac-Way, Fabrice, CHU de Quebec, Hotel-Dieu de Quebec Hospital, Quebec, Quebec, Canada
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

The primary goal of treating renal osteodystrophy (ROD) is reducing high bone turnover with calcitriol and/or calcimimetics while avoiding the development of low turnover. A main obstacle in managing ROD is identifying the underlying bone turnover-type. Bone biopsy, the gold standard to define turnover, is impractical for routine clinical use. Therefore, KDIGO recommends that clinical use (starting/stopping) of these agents is guided by parathyroid hormone (PTH) and bone specific alkaline phosphatase (BSAP). However, bone biopsy studies demonstrated that PTH and BSAP are poor guides for ROD treatment. We hypothesized that 4 circulating microRNAs (miRs) that regulate osteoblast (30b, 30c, 125b) and osteoclast development (155) would provide superior discrimination of low and high turnover than PTH and BSAP.

Methods

In 24 patients with CKD 3-5D, we obtained tetracycline double-labeled iliac crest bone biopsy and measured levels of intact PTH, BSAP and circulating miR-30b, 30c, 125b and 155 (evaluated independently and together as a panel). Spearman correlations assessed relationships between miRs, dynamic parameters of bone biopsy, and PTH and BSAP. Discrimination of low / high turnover were determined by receiver operator curve analysis; areas under curve were compared by χ2.

Results

miRs moderately correlated with bone formation and adjusted apposition rate (ρ 0.43-0.51; p<0.05) by biopsy but were not correlated with PTH or BSAP. Discrimination of low vs. non-low and high vs. non-high turnover for PTH, BSAP and miRs (both individually and as a panel) are shown in the Table.

Conclusion

These data suggest that a panel of circulating miRs provide accurate non-invasive identification of low and high turnover and individually identified low turnover. Future work will discover and validate additional miR biomarkers of turnover and determine their impact on clinical decision making and outcomes.

Areas under the curve for diagnosis turnover by bone biopsy
 Low vs. Non-LowHigh vs. Non-High
 AUC95% CIAUC95% CI
PTH0.4790.209-0.7530.5930.296-0.901
BSAP0.7810.571-0.9910.9560.862-1.000
miR-30b0.8750.733-1.0000.6500.408-0.892
miR-30c0.8250.645-1.0000.6080.362-0.855
miR-125b0.8000.613-0.9870.6580.365-0.951
miR-1550.7670.559-0.9740.5580.310-0.807
miR Panel0.9830.944-1.0000.8000.576-1.000

Funding

  • NIDDK Support