عنوان

Bone Perfusion Alterations in Chronic Kidney Disease

Number

TLpq2240082921

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Bone Perfusion Alterations in Chronic Kidney Disease

General Material Designation

[Thesis]

First Statement of Responsibility

Aref, Mohammad W.

Subsequent Statement of Responsibility

Allen, Matthew R.

Name of Publisher, Distributor, etc.

Indiana University - Purdue University Indianapolis

Date of Publication, Distribution, etc.

2019

Specific Material Designation and Extent of Item

138

Dissertation or thesis details and type of degree

Ph.D.

Body granting the degree

Indiana University - Purdue University Indianapolis

Text preceding or following the note

2019

Text of Note

Patients with chronic kidney disease (CKD) are at an alarming risk of fracture and cardiovascular disease-associated mortality. There is a critical need to better understand the underlying mechanism driving altered cardiovascular and skeletal homeostasis, as well as any connection between the two. CKD has been shown to have negative effects on many vascular properties including end-organ perfusion. Surprisingly, exploration of skeletal perfusion and vasculature has not been undertaken in CKD. Alterations in bone perfusion are linked to dysregulation of bone remodeling and mass in multiple conditions. An understanding of the detrimental impact of CKD on bone perfusion is a crucial step in understanding bone disease in these patients. The goal of this series of studies was to test the global hypothesis that skeletal perfusion is altered in CKD and that alterations can be modulated through treatments that affect metabolic dysfunction. These studies utilized a rat model of CKD to conduct metabolic assessments, bone perfusion measurements, bone imaging studies, and isolated vessel reactivity experiments. Our results showed that animals with CKD had higher levels of parathyroid hormone (PTH), leading to substantial bone resorption. Bone perfusion measurements showed CKD-induced elevations in cortical bone perfusion with levels progressing alongside CKD severity. Conversely we show that marrow perfusion was lower in advanced CKD. PTH suppression therapy in animals with CKD resulted in the normalization of cortical bone perfusion and cortical bone mass, but did not normalize marrow bone perfusion. These results show a clear association between bone deterioration and altered bone perfusion in CKD. While the relationship of altered bone perfusion and bone deterioration in CKD necessitates further work, these results indicate that determining the mechanisms of bone perfusion alterations and whether they are drivers, propagators, or consequences of skeletal deterioration in CKD could help untangle a key player in CKD-induced bone alterations.

Medicine

Allen, Matthew R.

Aref, Mohammad W.

Electronic name

p

[Thesis]

276903

a

Y