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Assessment of Donor Quality for Improving Kidney Transplant Outcomes

Award Number: R01DK109581
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Assessment of Donor Quality for Improving Kidney Transplant Outcomes - Kidney transplant (KT) short-term outcomes have steadily improved over the last several decades, however, similar progress in long-term allograft survival has not yet been reached largely due to chronic allograft injury (CAI). In our previous funding cycle, we identified a gene expression signature in deceased donor kidney biopsies at pre-KT that was predictive of graft function, measured by eGFR, at 24-months post-KT. Further, our single- cell/nucleus transcriptome profiles yielded several important findings including that KT recipients with acute kidney injury have increased fibroblasts and macrophages (both donor- and recipient-origin) with a macrophage subset characterized by fibroblast-like markers; donor-derived macrophages were present in functioning kidney grafts with interstitial fibrosis and tubular atrophy (IFTA) more than 24-mo post-KT; and paired single-cell peripheral blood mononuclear cells (PBMCs) showed immune cell type specific profiles reflecting graft injury. Thus, our results revealed the unappreciated role of donor kidney cells (immune and non-immune) on tissue repair and local immunomodulation, which plays a critical role in response to injury and determines graft function. Moreover, post-KT graft survival is determined by a complex interplay between donor and recipient factors. Thus, our findings guided the establishment of our new hypothesis that early measurable donor and donor-recipient cellular interactions and molecular profiles are strong indicators of chronic inflammatory responses and maladaptive repair circuits, shaping long-term graft outcomes. Therefore, in this funding cycle, we will elucidate the effects of donor cell type-specific drivers of injury that exacerbate the initial donor/recipient immune- and non-immune cell interactions in response to injury and determine how these events are reflected in the peripheral samples, allowing non-invasive graft monitoring by using cell type-specific markers of injury. This will be accomplished by leveraging our large unique available resource that includes donor biopsies (pre-KT) with paired longitudinal recipient biopsies and PBMCs (post-KT) along with KT recipient clinical outcomes to pursue the following specific aims: Aim 1. Assess donor and recipient cells' origin, function, and interactions that play a role in graft injury. Aim 2. Uncover cell type-specific molecular signatures from peripheral immune cells derived from KT recipients at pre-implantation and longitudinally post-KT, reflecting immune risk status and kidney graft function. Aim 3. Establish a novel statistical method for developing a composite score using high-dimensional donor/recipient molecular and clinical/demographic variables to predict graft function. This study will provide (i) cell type-specific gene signatures and regulatory regions that control the transition between healthy and diseased kidney graft states, eventually guiding efforts to reprogram cells to promote repair after injury, (ii) cell type specific gene profiles within recipient PBMCs that can longitudinally inform ongoing graft injury/repair and assist with better matching of patients and organs for improved long-term outcomes, and (iii) combined scores for pre-KT immune risk and post-KT graft function prediction using timely and cost-effective cell type-specific markers.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $618,786 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	1/28/2026	NON-COMPETING CONTINUATION	$618,786
														Subtotal = $618,786

Issue Date FY: 2025 ( Subtotal = $644,250 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	5/12/2025	NON-COMPETING CONTINUATION	$644,250
														Subtotal = $644,250

Issue Date FY: 2024 ( Subtotal = $672,483 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	3/4/2024	COMPETING CONTINUATION	$672,483
														Subtotal = $672,483

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/6/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	10/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	11/23/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$421,523
2021	2019	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/23/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$421,523
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $536,174 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	5	8/4/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2020	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	7/31/2020	NON-COMPETING CONTINUATION	-$464,582
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	5	8/3/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$536,174
2020	2020	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/26/2019	NON-COMPETING CONTINUATION	$418,123
2020	2020	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/28/2020	NON-COMPETING CONTINUATION	$46,459
														Subtotal = $536,174

Issue Date FY: 2019 ( Subtotal = $492,819 )
2019	2019	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	12/5/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$492,819
2019	2019	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	3	1/28/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$591,905
2019	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	1/28/2019	NON-COMPETING CONTINUATION	-$497,558
2019	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/4/2018	NON-COMPETING CONTINUATION	$0
2019	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	1/28/2019	NEW	-$94,347
														Subtotal = $492,819

Issue Date FY: 2018 ( Subtotal = $497,558 )
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/29/2017	NON-COMPETING CONTINUATION	$447,801
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/20/2018	NON-COMPETING CONTINUATION	$49,757
														Subtotal = $497,558

Issue Date FY: 2017 ( Subtotal = $536,803 )
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/19/2017	NEW	$536,803
														Subtotal = $536,803

Grand Total All Awards = $3,998,873

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Assessment of Donor Quality for Improving Kidney Transplant Outcomes

Award Number: R01DK109581

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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