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Preserving physical function in patients with kidney disease

Award Number: R01AR077042
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/03/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Preserving physical function in patients with kidney disease - Project Summary/Abstract Skeletal muscle dysfunction contributes to frailty, disability, and mortality in patients with chronic kidney disease (CKD). This proposal seeks to determine if muscle dysfunction in CKD can be alleviated by dialysis (blood filtration for kidney failure). We recently discovered that patients with CKD experience progressively worsening muscle fibrosis, and that greater severity of fibrosis is associated with reduced muscle strength and physical function. In patients with severe CKD, fibrotic changes are extensive. However, despite the seemingly advanced nature of this fibrotic transformation, patients starting dialysis experienced marked improvement in fibrosis. This suggests that, in patients with severe CKD and muscle fibrosis, the initiation of dialysis could improve physical function. Therefore, this proposal tests the highly innovative hypothesis that the initiation of dialysis in patients with severe CKD reverses muscle fibrosis and improves physical function. We will accomplish this objective using a translational approach that integrates clinically relevant functional endpoints with state-of-the-art methods including muscle tissue mechanics, quantitative magnetic resonance imaging (qMR), and transcriptomic and proteomic studies of human skeletal muscle. The proposed human studies will (1) define the effect of dialysis initiation on muscle fibrosis by examining changes in muscle collagen content, collagen cross-linking, tissue passive stiffness, and qMR measures; (2) determine the extent to which regression of fibrosis after dialysis initiation translates into functional improvements by testing the association of alterations in the structural parameters from Aim 1 with changes in muscle strength, endurance, and lower extremity performance; and (3) identify molecular and cellular predictors of the resolution of fibrosis using transcriptomic and proteomic analyses of skeletal muscle. If our hypotheses are correct: (1) muscle fibrosis could be an indicator for physicians to start dialysis therapy; and (2) this proposal will identify an intervention to alleviate muscle dysfunction in patients with CKD.


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 = $594,000 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	7/14/2025	NON-COMPETING CONTINUATION	$594,000
														Subtotal = $594,000

Issue Date FY: 2024 ( Subtotal = $658,966 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	6/25/2024	NON-COMPETING CONTINUATION	$658,966
														Subtotal = $658,966

Issue Date FY: 2023 ( Subtotal = $692,343 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	6/2/2023	NON-COMPETING CONTINUATION	$692,343
														Subtotal = $692,343

Issue Date FY: 2022 ( Subtotal = $704,336 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	7/14/2022	NON-COMPETING CONTINUATION	$704,336
														Subtotal = $704,336

Issue Date FY: 2021 ( Subtotal = $778,679 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/2/2021	NEW	$778,679
														Subtotal = $778,679

Grand Total All Awards = $3,428,324

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Preserving physical function in patients with kidney disease

Award Number: R01AR077042

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/03/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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