There is currently a worldwide shortage of kidneys for transplantation due mainly to the fact that there is no reliable means to determine their viability (i.e., kidneys stored for long periods of time, etc.). Also, following transplantation, kidneys oftn do not function immediately and their status is unclear. Previously, we have shown that the histopathology of living, superficial, kidney proximal convoluted tubules is a good indicator of kidney viability and post-transplant renal function. Indeed, the histopathology of superficial proximal tubules reflects the status of the proximal convoluted kidneys throughout the entire kidney cortex. It is important, however, that proximal convoluted tubules are imaged in a non-invasive and living state because of their well- established dramatic sensitivity to ischemia (i.e. such as associated with excision biopsies). Optical coherence tomography (OCT) is an emerging imaging technology that can obtain high resolution, non-invasive, cross- sectional images of biological tissues in situ and in real time. In our recently published papers, we have demonstrated that OCT will provide novel non-invasive, real-time histopathological information of the kidney that is impossible to obtain using any other known procedure. In a preliminary clinical trial (27 patients) of living human donor kidneys, we have demonstrated that OCT imaging of human kidney histopathology both prior to and following their transplant can be used to predict post-transplant renal function. Furthermore, these preliminary trials have demonstrated that OCT imaging of human donor kidneys with a hand-held unit in the operating room is safe and that the entire kidney can be evaluated within a short period of time. Finally, we have recently demonstrated that OCT can be used in a Doppler mode (DOCT) to image renal blood flow, even in individual glomeruli (i.e., glomerular blood flow). These DOCT images provide an additional measure of renal/glomerular function and pathology. In this proposal, we will develop an advanced ultrahigh-speed swept- source OCT/DOCT imaging system to evaluate the histopathology of human donor kidneys prior to and following renal transplant. These OCT/DOCT imaging studies will be correlated with post-transplant renal function in order to develop imaging guidelines and associated algorithms for OCT evaluation of kidney viability for transplant. The proposed studies will increase the number of healthy kidneys available for transplantation by making the most efficient use of available donor kidneys, eliminating the possible use of bad donor kidneys (i.e., excessively damaged ischemic or diseased kidneys), providing a measure of expected post-transplant renal function, and allowing better distinction between post-transplant immunological rejection and ischemic- induced acute renal failure.

Public Health Relevance

Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can function as a type of optical biopsy, providing non-invasive cross-sectional images of tissue architectural morphology in situ and in real-time. This proposal will demonstrate that OCT has the ability to provide novel and valuable histopathological information regarding donor kidneys that can be used to predict post-transplant renal function. These investigations will result in a major breakthrough in increasing the number of healthy kidneys available for transplantation by making the most efficient use of available donor kidneys, eliminating the possible use of bad donor kidneys, providing an accurate measure of expected post-transplant renal function, and allowing better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01DK094877-01A1
Application #
8696002
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kusek, John W
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Georgetown University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20057
Andrews, Peter M; Cooper, Matthew; Verbesey, Jennifer et al. (2014) Mannitol infusion within 15 min of cross-clamp improves living donor kidney preservation. Transplantation 98:893-7