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Automated detection of microstructural features that have unique protein markers and are prognostic for chronic kidney disease

Award Number: R01DK090358
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: 02/10/2011
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Automated detection of microstructural features that have unique protein markers and are prognostic for chronic kidney disease - The primary microstructural attributes seen in “normal” kidneys are nephrosclerosis (arteriosclerosis, global glomerulosclerosis, and interstitial fibrosis/tubular atrophy), nephron number, and nephron size. However manual measures of these microstructures are impractical. Further, understanding their pathophysiology may lead to new interventions for kidney disease. Automated morphometry with deep learning (DL) networks may be able to rapidly measure nephrosclerosis, nephron number, and nephron size. Novel morphometry of structures impacted by glomerular hyperfiltration (podocyte and parietal epithelial cell (PEC) density, Bowman’s space, and the diameter of proximal and distal tubule) and of microvasculature are needed to better understand the pathophysiology of early disease. Proteomic analysis of specific microstructures that differ between kidneys that do versus do not develop CKD outcomes has the potential to identify prognostic or even pathogenic proteins for early kidney disease. The multi-discipline multi-site Aging Kidney Anatomy study has unique resources for the study of microstructure in “normal” kidneys. This includes data and specimens on living kidney donors including needle core biopsies at donation with digitized whole slide images (WSI) and long-term CKD outcomes in the donor and recipient. This also includes data and specimens on patients who had a radical nephrectomy for tumor including digitized WSI of kidney wedge sections and annual eGFR testing for CKD outcomes during follow-up. Aim 1 will determine if automated morphometry of nephrosclerosis, nephron number, and nephron size predicts CKD outcomes to test the hypothesis that DL tools allows for efficient quantification of these clinically relevant microstructural attributes. This aim will use both previously developed and new DL networks, develop models to predict CKD outcomes from automated morphometry, and compare prediction of CKD outcomes between automated and manual morphometry. Aim 2 will characterize novel microstructural attributes that associate with kidney function, CKD risk factors, and CKD outcomes to test the hypothesis that encoded in the kidney tissue are unexplored structural attributes that reflect the glomerular hyperfiltration and interstitial microvascular status that are prognostic for CKD. This aim will automatically quantify podocytes, PECs, peritubular capillaries (PTC), Bowman’s space (volume), and proximal and distal tubules (diameter) on WSI using previously developed and newly developed DL tools and associate these structures with kidney function, CKD risk factors, and CKD outcomes. Aim 3 will discover protein markers linked to the microstructural attributes that are prognostic for CKD outcomes to test the hypothesis that differentially expressed proteins contained within kidney microstructures predict CKD outcomes. This aim will use laser capture microdissection, mass spectroscopy-based proteomics (both discovery and targeted validation approaches), and immunohistochemistry to identify proteins on kidney biopsy sections that predict CKD outcomes and to determine their association with microstructural attributes.


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: 2025 ( Subtotal = $687,548 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	4/14/2025	NON-COMPETING CONTINUATION	$687,548
														Subtotal = $687,548

Issue Date FY: 2024 ( Subtotal = $665,277 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	1/5/2024	NON-COMPETING CONTINUATION	$623,698
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	5/15/2024	NON-COMPETING CONTINUATION	$41,579
														Subtotal = $665,277

Issue Date FY: 2023 ( Subtotal = $692,998 )
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	1/31/2023	NON-COMPETING CONTINUATION	$692,998
2023	2020	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	6/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $692,998

Issue Date FY: 2022 ( Subtotal = $693,291 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	4/1/2022	COMPETING CONTINUATION	$693,291
														Subtotal = $693,291

Issue Date FY: 2020 ( Subtotal = $676,255 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	1/8/2020	NON-COMPETING CONTINUATION	$608,629
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	2/10/2020	NON-COMPETING CONTINUATION	$67,626
														Subtotal = $676,255

Issue Date FY: 2019 ( Subtotal = $701,410 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	1/16/2019	NON-COMPETING CONTINUATION	$701,410
														Subtotal = $701,410

Issue Date FY: 2018 ( Subtotal = $701,410 )
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	12/12/2017	NON-COMPETING CONTINUATION	$631,269
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	4/26/2018	NON-COMPETING CONTINUATION	$70,141
														Subtotal = $701,410

Issue Date FY: 2017 ( Subtotal = $701,410 )
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	12/8/2016	NON-COMPETING CONTINUATION	$631,269
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	6/15/2017	NON-COMPETING CONTINUATION	$70,141
														Subtotal = $701,410

Issue Date FY: 2016 ( Subtotal = $739,434 )
2016	2016	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	3/14/2016	COMPETING CONTINUATION	$739,434
2016	2015	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	3/10/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $739,434

Issue Date FY: 2015 ( Subtotal = $434,042 )
2015	2015	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/3/2015	NON-COMPETING CONTINUATION	$434,042
														Subtotal = $434,042

Issue Date FY: 2014 ( Subtotal = $596,261 )
2014	2014	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/4/2014	NON-COMPETING CONTINUATION	$596,261
														Subtotal = $596,261

Issue Date FY: 2013 ( Subtotal = $630,768 )
2013	2013	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/3/2013	NON-COMPETING CONTINUATION	$588,281
2013	2013	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/21/2013	NON-COMPETING CONTINUATION	$42,487
														Subtotal = $630,768

Issue Date FY: 2012 ( Subtotal = $590,664 )
2012	2012	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/13/2012	NON-COMPETING CONTINUATION	$590,664
														Subtotal = $590,664

Issue Date FY: 2011 ( Subtotal = $706,523 )
2011	2011	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	6/7/2011	NEW	$89,970
2011	2011	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/4/2011	NEW	$594,114
2011	2011	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	3/1/2011	NEW	$22,439
														Subtotal = $706,523

Grand Total All Awards = $9,217,291

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Automated detection of microstructural features that have unique protein markers and are prognostic for chronic kidney disease

Award Number: R01DK090358

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: 02/10/2011

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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