Sunday, July 6, 2025 7/6/2025

Renal electrolyte handling in females vs. males over life cycle

Award Number: R01DK083785
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: 08/01/2010
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Renal electrolyte handling in females vs. males over life cycle - PROJECT SUMMARY Kidney function is critical to maintaining effective circulating volume (ECV), electrolyte homeostasis and blood pressure (BP). Dysregulation of fluid and electrolyte transport in the kidney is central to hypertension (HTN) and cardiovascular disease (CVD) progression. Na+, K+, and volume homeostasis are maintained by regulation of renal ion and water transporters expressed in tubule specific patterns; K+ balance also depends on regulation of muscle transporters. HTN and CVD are a function of sex, age and lifestyle; less frequent in females than males below 65 yr and more common in post-menopausal females vs males over 65 yr; salt sensitivity of BP increases in both sexes with age. We have reported sex differences in the abundance of transporters along the nephron in both Sprague Dawley rats (SDR) and C57BL/6J mice, and used computational models to establish the functional implications of the dimorphisms, e.g. more robust natriuretic responses in young female vs male SDR. How kidney and muscle transporter profiles respond to life cycle transitions from development through aging and menopause is not known. Our overarching goal is to combine experimental and computational approaches to determine how kidney (and muscle) functions adapt to maintain ECV, electrolyte and fluid homeostasis in response to life cycle challenges in both male and female rats and mice: from development to aging, through the female-specific challenges of lactation and menopause, and the common challenges of dietary Na+ and K+. Aim 1. Test the hypothesis that baseline kidney function adapts during life cycle in a sex-specific manner to maintain fluid and electrolyte homeostasis. When do transporter sex differences appear? Is the more robust natriuresis in young females vs males still evident at 12 mo? Do muscle K+ transporters exhibit sex dimorphisms that impact K+ adaptation with age? We will utilize the Four Core Genotype mouse model to attribute dimorphisms along life cycle to gonadal hormones vs sex chromosome complement. Aim 2. Describe mechanisms of female kidney adaptation to lactation. Do kidney and nephron function adapt to maintain maternal homeostasis during peak lactation at minimal cost? Do kidney function, ECV and electrolyte homeostasis return to baseline after lactation cessation? Does extrarenal K+ homeostasis (skeletal muscle K+ transporters and [K+]) adapt during/after lactation? Aim 3. Test the hypothesis that menopause and age reduce sex differences and increase salt-sensitivity. Does ovotoxin-induced menopause change female kidney and muscle transporter profiles and function? Is salt-sensitive hypertension sex dependent? Exacerbated after menopause? Accomplishing these aims will fill important gaps in knowledge about sex-specific mechanisms of Na+, K+, and volume homeostasis and physiology throughout life cycle, thus, providing a better understanding of the female advantage in CVD and guiding therapeutic targets in both sexes across life cycle.


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 = $511,876 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	6/21/2024	NON-COMPETING CONTINUATION	$511,876
														Subtotal = $511,876

Issue Date FY: 2023 ( Subtotal = $552,572 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	5/31/2023	NON-COMPETING CONTINUATION	$552,572
														Subtotal = $552,572

Issue Date FY: 2022 ( Subtotal = $604,503 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	8/29/2022	COMPETING CONTINUATION	$604,503
														Subtotal = $604,503

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	8/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $437,456 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	3/21/2019	NON-COMPETING CONTINUATION	$437,456
														Subtotal = $437,456

Issue Date FY: 2018 ( Subtotal = $400,937 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	9/6/2018	SUPPLEMENT FOR EXPANSION	$29,687
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	4/30/2018	NON-COMPETING CONTINUATION	$371,250
														Subtotal = $400,937

Issue Date FY: 2017 ( Subtotal = $371,250 )
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	3/23/2017	NON-COMPETING CONTINUATION	$334,125
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	6/22/2017	NON-COMPETING CONTINUATION	$37,125
														Subtotal = $371,250

Issue Date FY: 2016 ( Subtotal = $371,250 )
2016	2016	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	2/23/2016	COMPETING CONTINUATION	$371,250
2016	2014	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	900898001	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/18/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $371,250

Issue Date FY: 2014 ( Subtotal = $357,606 )
2014	2014	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/30/2014	NON-COMPETING CONTINUATION	$357,606
														Subtotal = $357,606

Issue Date FY: 2013 ( Subtotal = $344,216 )
2013	2013	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/16/2013	NON-COMPETING CONTINUATION	$344,216
														Subtotal = $344,216

Issue Date FY: 2012 ( Subtotal = $356,338 )
2012	2012	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/17/2012	NON-COMPETING CONTINUATION	$356,338
														Subtotal = $356,338

Issue Date FY: 2011 ( Subtotal = $407,500 )
2011	2011	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/11/2011	COMPETING CONTINUATION	$407,500
														Subtotal = $407,500

Grand Total All Awards = $4,715,504

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Renal electrolyte handling in females vs. males over life cycle

Award Number: R01DK083785

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: 08/01/2010

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer