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Biomarker-Based Diagnostic Algorithms To Prevent, Detect And Guide Treatment Of Kidney Disease In Persons Living With HIV

Award Number: R01AG034853
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Our strategies for preventing, detecting, and monitoring kidney disease in people living with HIV (PLWH) have lagged far behind the incredible advances in HIV treatment and management over the past decades. Despite their proven limitations for diagnosing chronic kidney disease (CKD), the serum creatinine and the urine protein concentration remain the mainstays of kidney health monitoring for PLWH. While clinical kidney diagnostic testing has stagnated, PLWH face an increasing myriad of insults to the kidneys, including metabolic and vascular risk factors, chronic inflammation, direct viral toxicity, and potentially nephrotoxic medications. Consequently, CKD has accelerated as a cause of morbidity and mortality in PLWH. Over the past decade, our pioneering work in PLWH has shown that biomarkers of tubule health yield significantly more diagnostic and prognostic information than could be obtained by conventional kidney health assessments. This competitive renewal application will build upon this prior work to fulfill our mission of fundamentally changing how kidney disease is detected, diagnosed and monitored. This proposal strategically addresses the most challenging aspects of CKD diagnosis and treatment, and will provide the evidence needed to advance kidney biomarker-based diagnostic algorithms into clinical practice. Successful completion and clinical translation of our Aims will allow clinicians to achieve the following major goals. 1) Among PLWH with acute elevations of the serum creatinine, we will be able to distinguish whether or not the individual has true kidney injury and to identify the patterns of injury that forecast the likelihood of kidney function recovering or worsening during subsequent follow-up (Aim 1). 2) For each modifiable kidney disease risk factor in PLWH, we will be able to monitor the impact of improvements and deteriorations in risk factor control on the kidney, using a tailored set of surrogate biomarkers (Aim 2a). 3) We will use a time- updated algorithm that will integrate dynamic changes in risk factors and kidney biomarkers to prognosticate longitudinal changes in risk for rapidly progressive kidney disease, for each individual PLWH (Aim 2b). 4) For the many PLWH with myriad exposures that threaten or lower risk for progressive kidney disease, we will utilize a novel biomarker-based monitoring algorithm to identify and prioritize each risk factor based on its Bayesian probability of causing the observed pattern and severity of kidney damage. Despite these ambitious goals, this proposal is both feasible and efficient as we will use biospecimens and clinical data that have been or will be collected among PLWH in the Multicenter AIDS Cohort Study (MACS), the Women’s Interagency HIV Study (WIHS), the MACS-WIHS Combined Cohort Study (MWCCS), and the Predictors of Acute Renal Injury Study (PARIS) cohorts. The study investigators are a multi-disciplinary team of experts who bring enormous enthusiasm, experience and commitment to the proposal and will guarantee its success.


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: 2023 ( Subtotal = $746,192 )
2023	2023	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	003	13	8/29/2023	NON-COMPETING CONTINUATION	$746,193
2023	2022	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	002	12	8/17/2023	NON-COMPETING CONTINUATION	$0
2023	2022	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	001	12	7/31/2023	NON-COMPETING CONTINUATION	$0
2023	2019	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST # 151	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	10	11/21/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $746,192

Issue Date FY: 2022 ( Subtotal = $763,684 )
2022	2022	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	002	12	7/15/2022	NON-COMPETING CONTINUATION	$763,684
2022	2021	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	001	11	3/10/2022	COMPETING CONTINUATION	$100,032
2022	2019	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	10	3/10/2022	NON-COMPETING CONTINUATION	-$100,032
														Subtotal = $763,684

Issue Date FY: 2021 ( Subtotal = $799,447 )
2021	2021	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	002	11	8/20/2021	COMPETING CONTINUATION	$799,447
2021	2019	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	10	3/1/2021	NON-COMPETING CONTINUATION	$0
2021	2019	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	001	10	8/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $799,447

Issue Date FY: 2019 ( Subtotal = $610,991 )
2019	2019	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	10	5/6/2019	NON-COMPETING CONTINUATION	$610,991
														Subtotal = $610,991

Issue Date FY: 2018 ( Subtotal = $617,711 )
2018	2018	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	9	5/22/2018	NON-COMPETING CONTINUATION	$617,711
														Subtotal = $617,711

Issue Date FY: 2017 ( Subtotal = $624,242 )
2017	2017	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION, INC.	4150 CLEMENT ST 151 NC	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	8	6/30/2017	NON-COMPETING CONTINUATION	$624,242
														Subtotal = $624,242

Issue Date FY: 2016 ( Subtotal = $628,604 )
2016	2016	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	7	5/3/2016	NON-COMPETING CONTINUATION	$628,604
														Subtotal = $628,604

Issue Date FY: 2015 ( Subtotal = $651,898 )
2015	2015	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	6	9/15/2015	COMPETING CONTINUATION	$651,898
2015	2014	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	001	5	9/16/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $651,898

Issue Date FY: 2014 ( Subtotal = $451,139 )
2014	2014	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	5	6/11/2014	NON-COMPETING CONTINUATION	$451,139
														Subtotal = $451,139

Issue Date FY: 2013 ( Subtotal = $451,564 )
2013	2013	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	4	5/21/2013	NON-COMPETING CONTINUATION	$451,564
														Subtotal = $451,564

Issue Date FY: 2012 ( Subtotal = $552,666 )
2012	2012	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	3	4/26/2012	NON-COMPETING CONTINUATION	$552,666
														Subtotal = $552,666

Issue Date FY: 2011 ( Subtotal = $576,020 )
2011	2011	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	2	6/9/2011	NON-COMPETING CONTINUATION	$576,020
														Subtotal = $576,020

Issue Date FY: 2010 ( Subtotal = $640,984 )
2010	2010	NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH & EDUCATION	4150 CLEMENT STREET	SAN FRANCISCO	CA	94121	SAN FRANCISCO	USA	Aging Research	000	1	4/22/2010	NEW	$640,984
														Subtotal = $640,984

Grand Total All Awards = $8,115,142

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Biomarker-Based Diagnostic Algorithms To Prevent, Detect And Guide Treatment Of Kidney Disease In Persons Living With HIV

Award Number: R01AG034853

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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