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Kidney Tubule Dysfunction and Future Risk of Acute Kidney Injury

Award Number: R01DK128803
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: 08/19/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Kidney Tubule Dysfunction and Future Risk of Acute Kidney Injury - PROJECT SUMMARY Acute kidney injury (AKI) is common in hospitalized patients, costly, and strongly associated with mortality. It is also now widely recognized to be a driver of progressive chronic kidney disease (CKD). AKI occurs frequently in common clinical scenarios including sepsis, heart failure, and after coronary artery bypass graft (CABG) surgery, but it is unclear why some individuals develop AKI in these settings while others do not. We hypothesize that abnormalities in kidney function that are not captured by creatinine or proteinuria may identify those predisposed to AKI risk. In preliminary studies in the SPRINT trial, we have shown that abnormalities in kidney tubule function at baseline predict future development of AKI, independent of creatinine, proteinuria, or other AKI risk factors. If confirmed, this finding could provide a paradigm shift as it would allow identification of apparently healthy individuals who are at risk of AKI before the event occurs, enabling strategies to minimize AKI risk such as alterations in medications, hydration protocols, and surgical approaches. This knowledge may also give critical new insights into potential pathological mechanisms driving AKI events. By leveraging the large 30,239 subject Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, this application seeks to utilize blood and urine specimens collected when REGARDS participants were clinically stable outpatients to characterize their kidney tubule health. We will identify REGARDS participants who subsequently experience sepsis, heart failure, or CABG, and will abstract daily in-patient hospital creatinine data during these admissions to ascertain AKI presence and severity. We will then determine whether tubule dysfunction at times of relative health predicts AKI in these clinical scenarios (Aim 1). Next, we will build a parsimonious biomarker panel that will predict AKI in these settings, setting the stage for future clinical implementation (Aim 2). Finally, we will re-examine changes in these biomarkers after 10 years of follow-up, and determine whether tubule injury or dysfunction is differentially altered in survivors of AKI versus controls. This biomarker signature may allow clinicians to determine whether outpatient (unwitnessed) AKI episodes may underlie the development or progression of CKD (Aim 3). Our efforts will directly link baseline tubule function with future AKI risk, setting the stage for innovative therapies to mitigate or prevent AKI.


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 = $621,154 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/9/2024	NON-COMPETING CONTINUATION	$621,154
														Subtotal = $621,154

Issue Date FY: 2023 ( Subtotal = $682,173 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/21/2023	NON-COMPETING CONTINUATION	$682,173
														Subtotal = $682,173

Issue Date FY: 2022 ( Subtotal = $694,270 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/15/2022	NON-COMPETING CONTINUATION	$694,270
2022	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	7/20/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2022	2021	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	7/20/2022	NEW	-$1
														Subtotal = $694,270

Issue Date FY: 2021 ( Subtotal = $753,625 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	8/19/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$753,624
2021	2021	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/23/2021	NEW	$732,909
2021	2021	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	8/17/2021	NEW	-$732,908
														Subtotal = $753,625

Grand Total All Awards = $2,751,222

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Kidney Tubule Dysfunction and Future Risk of Acute Kidney Injury

Award Number: R01DK128803

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: 08/19/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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