Treatment of renal osteodystrophy is impeded by the lack of practical and accurate tools to determine underlying bone turnover. Gold standard bone biopsy is not practical in the clinic for the vast majority of kidney disease patients and parathyroid hormone and bone alkaline phosphatase have insufficient accuracy for turnover type to safely and confidently guide treatment of renal osteodystrophy. In the present investigation, the investigators will study a microRNA approach as a novel non-invasive biomarker of turnover for renal osteodystrophy.
Study participant has provided informed consent
Age ≥ 18 years
CKD Stages 3-5D regardless of kidney transplantation status
CKD5D patients receiving maintenance hemodialysis for at least 3 months
Currently receiving treatment in an investigational device or drug study, or less than 30 days since ending treatment on an investigational device or drug study(s)
Currently receiving investigational procedures/drugs from another study while participating in this study
Use of etelcalcetide, bisphosphonate, denosumab, teriparatide, abaloparatide or romosozumab during the 6 months prior to study enrollment; however, participant can be included if being treated with bone active agent but will have class change to an agent that will result in a change in bone turnover from low to high or high to low
New use of cinacalcet over the prior 6 months
This study will enroll forty adults with moderate to end stage kidney disease, including kidney transplant recipients, who have bone disease in need of treatment.
Other
Prospective
miRNAseq analysis
Procedure/SurgeryIdentify miRNA in serum and prepare a miRNA sequencing library for novel analysis.
Standard treatment for bone disorder
DrugParticipants will be prescribed a clinically indicated bone-targeted treatment for osteoporosis or bone disorder related to CKD. (non-experimental)
Correlation between miRNA panel to discriminate changes in bone turnover.
To determine the utility of a miRNA panel to discriminate changes in bone turnover. miRNA sequencing libraries will be prepared using the QIASeq miRNA Library Kit (Qiagen). Total RNA extracted from human serum will be used as the starting material. After a final library cleanup, the miRNA libraries will be QC and quantified using an Agilent Bioanalyzer 2100 and Invitrogen Qubit Fluorometer. The resulting miRNA libraries will be sequenced on an Illumina NextSeq 500 (Illumina, San Diego, CA) with single-end 75 bp read length. The study will then confirm any novel or other miRNA that are present in serum from RNAseq by PCR using TaqMan miRNA Assays (TaqMan MGP probes, FAM dye-labeled) with Applied Biosystems ViiA 7 Real-Time PCR systems. The ΔΔCT method will be used to analyze relative changes in miRNA expression.
Correlation between a miRNA panel that identifies bone turnover type is able to also identify with bone quality.
To utilize the circulating miRNA panel to fully assess bone quality in patients with renal osteodystrophy; whether there is evidence that bone turnover directly affects bone strength through alterations in bone quality.
Number of instances where miRNAs in circulation reflect miRNAs in bone-tissue.
The miRNA panel that identifies turnover type in blood will be compared to the miRNAs that are expressed in bone tissue derived from iliac crest bone biopsy.
Number of instances where miRNAs in circulation reflect changes in bone, based on bone imaging.
Pre- and post-treatment changes in the circulating miRNA profile will be compared to changes in bone imaging by HR-pQCT.
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Thomas Nickolas
Lead sponsor
Washington University School of Medicine
Sponsor institution
Indiana University
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
