Thursday, November 21, 2024 11/21/2024

Understanding the role of the Complement Proteome in progressive Diabetic Kidney Disease

Award Number: R01DK123459
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY / ABSTRACT There is a critical need to identify novel mechanisms of diabetic kidney disease (DKD) that will provide targets for new interventions. Chronic inflammation is one plausible mechanism. Using untargeted high-throughput aptamer proteomics, our recently published study has shed new light on specific, key inflammatory drivers of DKD. This was a large prospective three-cohort study that identified a novel and extremely robust circulating signature (KRIS) associated with risk of ESRD in diabetes. Our pilot study points to the data-driven connection between circulating KRIS and urinary profiles of the Complement pathway. Our hypothesis is that the Complement involvement in the kidney is a downstream effect of the systemic inflammatory processes mediating an increased DKD risk. The overarching goal of this proposal is to provide a high-resolution view of the involvement of the Complement proteome in progressive diabetic kidney disease. Aim 1 will comprehensively evaluate the etiological role of the urinary Complement proteome in progressive DKD leading to ESRD. This evaluation will leverage a prospective two-cohort population of Joslin Kidney Study (JKS) participants with an overt DKD at baseline followed for 10 years (primary outcome – incident ESRD). Measurements will utilize an aptamer proteomic technology (SOMAscan). Aim 2 will extend generalizability of the urinary Complement proteome to earlier DKD stages. The proposed study will be conducted in participants of the Preventing Early Renal Loss (PERL) clinical trial with predominantly normal renal function at baseline followed for 3 years (primary outcome - renal slope). Aim 3 proposes to gain direct insight into the intra-renal Complement proteome by targeted and untargeted protein studies in diabetic kidney tissue (Susztaklab Biobank). This project focuses on a significant public health problem, leverages the progressiveness of the disease, employs an innovative proteomic technology and stems from strong preliminary data. Advances in this project will pinpoint missing key components of DKD etiology, thereby accelerating drug development strategies for patients with diabetes.


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: 2024 ( Subtotal = $351,902 )
2024	2024	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/16/2024	NON-COMPETING CONTINUATION	$351,902
														Subtotal = $351,902

Issue Date FY: 2023 ( Subtotal = $407,463 )
2023	2023	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/15/2023	NON-COMPETING CONTINUATION	$407,463
														Subtotal = $407,463

Issue Date FY: 2022 ( Subtotal = $516,658 )
2022	2022	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/22/2022	NON-COMPETING CONTINUATION	$51,668
2022	2022	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/23/2022	NON-COMPETING CONTINUATION	$464,990
														Subtotal = $516,658

Issue Date FY: 2021 ( Subtotal = $394,703 )
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	3/11/2021	NON-COMPETING CONTINUATION	$478,789
2021	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/5/2021	NEW	-$84,086
														Subtotal = $394,703

Issue Date FY: 2020 ( Subtotal = $583,022 )
2020	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/30/2020	NEW	$583,022
														Subtotal = $583,022

Grand Total All Awards = $2,253,748

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Understanding the role of the Complement Proteome in progressive Diabetic Kidney Disease

Award Number: R01DK123459

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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