Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease

NCT03626246 | Completed DMC

• 2 other identifiers: AAAQ77781R01DK110871-01
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney disease patients have a variety of bone disorders that result in bone loss and fractures. The mechanisms of these bone disorders are not clear but may be related to abnormal modification of a bone protein known as collagen. Therefore, the investigators are conducting this research study to identify underlying mechanisms that are responsible for the disruption of bone collagen and determining whether the abnormal bone collagen impairs bone strength. The investigators intend to identify these mechanisms through studying relationships between kidney disease and bone strength via bone imaging, bone biopsy and non-invasive measures from blood and skin.

Conditions

Chronic Kidney Disease; End Stage Kidney Disease; Chronic Kidney Disease Mineral and Bone Disorder; Renal Osteodystrophy; Secondary Hyperparathyroidism

Keywords

Bone loss; Bone fracture; Bone biopsy; Kidney

Outcome Measures

Primary Outcomes (3)

• Determine amounts of abnormal collagen present in the bone of CKD patients

  In patients with CKD stage 3-5, the investigators will obtain transiliac crest bone biopsies and determine the amount of advanced glycation end-products that are present in bone collagen

  2.5 years

• Determine if greater amounts of abnormal collagen in the bone of CKD patients decreases bone strength

  In patients with CKD stage 3-5, the investigators will perform biomechanical testing of bone biopsy specimens and determine if greater degree of advanced glycation end-product modification of bone collagen changes bone strength.

  1 year

• To identify non-invasive biomarkers of advanced glycation end-products in bone collagen

  In patients with CKD stage 3-5, to obtain blood and skeletal imaging with high resolution peripheral computed tomography and to determine if the concentration of advanced glycation end-products in bone collagen can be identified by non-invasive methods.

  1 year

Study Arms (1)

Kidney disease

Patients who participate in our study are 40 years old or older and have a Chronic kidney disease stage 3, 4 or 5.

Other: Kidney disease

Interventions

Kidney disease OTHER

Being part of this study you agree to participate in all these interventions: Genetic: • Blood sample Procedure/Surgery: • Bone and muscle biopsies. Radiation: * Bone density (DXA) * Thoracic and lumbar spine plain films. * HRpQCT: high-resolution peripheral quantitative computed tomography Other: * Completing medical history, physical activity level, and dietary questionnaires for calcium and vitamin D. * Measure levels of Advanced Glycation End products (AGEs) in the skin.

Kidney disease

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from the general nephrology clinics at Columbia University Medical Center. Subjects referred for both clinical biopsy and those only participating in the research protocol will be eligible. The main clinical indication for bone biopsy in CKD patients is to determine turnover status for selection of type of bone active agent.

You may qualify if:

• Chronic kidney disease stage 3, 4 or 5
• Stable dose of vitamin D for 2-months

You may not qualify if:

• Dialysis
• Current use or treatment in the past one year with oral or inhaled glucocorticoids for more than 90 days.
• Current use or treatment in the past one year with sex hormone/SERM therapy for more than 30 days.
• Any use of bisphosphonates.
• Use of anti-osteoporosis therapies (denosumab, teriparatide, calcitonin or anti-sclerostin antibodies) in last 2 years.
• Any solid organ transplant or bone marrow transplant (Not including skin or cornea).
• Patients on non-aspirin anticoagulants that cannot be reasonably held for biopsy.
• Any cancers within 5-yrs of diagnosis that were metastatic to bone, and that are not in complete remission
• Any history of leukemia, multiple myeloma, lymphoma, amyloid or paraproteinemias.
• Any congenital or acquired collagen of bone diseases other than osteoporosis or renal osteodystrophy (Including but not limited to: Osteogenesis Imperfecta, X-Linked Hypophosphatemic Rickets, Pagets or Cushings Disease).
• History of Primary Hyperparathyroidism within 2-years of Parathyroidectomy.
• Hypoparathyroidism - primary or post-surgical
• Hyperthyroidism - if untreated and not on stable dose of medication for 6 months
• Hypothyroidism - if untreated and not on stable dose of medication for 6 months
• Non-ambulatory

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Columbia/CUMC

New York, New York, 10032, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

We would like to store the biological samples that you agreed to provide as part of this study: Blood, bone, urine and muscle. DNA taken from these samples and/or the data obtained from the study and possibly use them for future research. They will be stored at CUMC either with the researchers on this study or in a central storage facility called a repository.

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Kidney Failure, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder; Hyperparathyroidism, Secondary; Bone Diseases, Metabolic; Fractures, Bone

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Rickets; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Wounds and Injuries

Study Officials

• Thomas Nickolas, MD,MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 10, 2018
• Study Start: July 1, 2016
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: July 13, 2021

Record last verified: 2021-07

Locations

US (1)