Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Epidemiology and Biostatistics

Supervisor

Amit Garg

Abstract

Fractures are a global health concern, leading to morbidity and mortality. Individuals with reduced kidney function experience bone mineral metabolism changes which can increase fracture risk. Yet, there is little consensus on the fundamentals: prediction, incidence, risk factors, and screening of fractures in kidney disease patients. This thesis addressed these critical areas helping decrease the health burden of fracture in this unique population.

This research used data from the Canadian Multicentre Osteoporosis Study (CaMos) to examine individuals with chronic kidney disease (CKD) (n=320). CaMos is a national longitudinal study designed to collect information on fractures. To examine kidney transplant recipients data from Ontario administrative healthcare databases was used (n=4821). The predictive ability of the Fracture Risk Assessment Tool (FRAX) in individuals with CKD was evaluated using area under the receiver operator characteristic curves and survival analyses. The incidence and risk factors for fracture in kidney transplant recipients were assessed using incidence rates and Cox hazard regression analysis.

The first manuscript systematically summarized the incidence and risk factors for fracture in kidney transplant recipients; fracture incidence and risk factors were variable across studies.

The second manuscript examined the predictive value of FRAX in individuals with CKD compared to individuals with normal kidney function. The discriminative ability of FRAX for fracture prediction was comparable in both groups.

The third manuscript examined the incidence of fracture in kidney transplant recipients. The cumulative incidence of fracture was low with approximately 2% sustaining a hip fracture over 10-years.

The fourth manuscript examined risk factors for fracture in kidney transplant recipients. Transplant-specific risk factors (i.e., diabetes or cystic kidney disease as the cause of end-stage renal disease and donor age) and general risk factors (i.e., older recipient age and female sex) were significantly associated with fractures.

The fifth manuscript examined the frequency and variability in bone mineral density (BMD) testing across Ontario transplant centres. Over half of kidney transplant recipients received at least one BMD and the ordering of BMD tests varied widely by centre – from 15% to 92%.

Results can be used to improve prognostication, advance clinical guidelines, clarify fracture incidence, and guide informed consent.

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