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Theory of Solute and Water Transport Across Epithelia

Award Number: R01DK029857
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 The overall project objective has been mathematical modeling of renal fluid and electrolyte transport in health and disease. Prior to the last period, this project had produced a model library of all kidney tubule segments, and the first task of the last period was to concatenate these segmental models into a nephron. The major effort of the last period was adding the medullary microcirculation, to advance the nephron to a kidney model, in which medullary composition was calculated, rather than specified. Simulation of major metabolic derangements (e.g. hyperglycemia, hyperkalemia, alkalosis), diuretic use, and genetic transport defects require a model of this scope. While, the kidney model captured overall solute excretion, interstitial concentration profiles and intratubular hydrostatic pressures need additional work. Specifically, medullary Na+ and urea and NH4+ concentrations were lower than expected; and changes in distal flow distorted pressures along the entire nephron. In the next period, Aim 1 preserves current model structure, and addresses Na+ and urea and pressure. It is expected that adjusting juxtamedullary nephron transport parameters will improve interstitial composition, and that revising tubular compliance will mitigate pressure effects. Aim 2 addresses renal NH4+ concentrations and partitioning of NH4+ flow between renal vein and urine. This cannot be done with parameter adjustments, but requires cortical microvasculature. It is expected that countercurrent exchange within cortical blood vessels can enhance ammonia excretion, while limiting renal venous ammonia (as seen in acidosis and liver disease). Aim 3 will be introduce calcium as a new model solute. Renal calcium concentration is a regulator of sodium transport, and of translational importance (e.g. hypercalciuric disorders, stone formation). Aim 4 comprises model application in experimental collaborations. Work continues with Dr. Tong Wang, examining the role of flow-dependent sodium reabsorption in renal cystic disease. A polycystic kidney disease gene may mediate this flow-response, and we suspect that failure to match fluxes to flows elevates tubule pressures, exacerbating cyst formation. In this regard, attention in Aim 1 to tubule pressures and compliance will be foundational for this aim. Collaboration is continuing with Dr. Larry Palmer to apply segmental and nephron models to K+ excretion in Na+-avid states. These experiments typically document changes in specific transporter densities, and the models provide a means of capturing these defects and estimating impact on other segments.


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 = -$11,598 )
2025	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	36	11/13/2024	NON-COMPETING CONTINUATION	-$11,598
														Subtotal = -$11,598

Issue Date FY: 2022 ( Subtotal = $211,875 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	36	6/28/2022	NON-COMPETING CONTINUATION	$211,875
														Subtotal = $211,875

Issue Date FY: 2021 ( Subtotal = $211,875 )
2021	2021	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	35	6/9/2021	NON-COMPETING CONTINUATION	$211,875
														Subtotal = $211,875

Issue Date FY: 2020 ( Subtotal = $211,875 )
2020	2020	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	34	6/22/2020	NON-COMPETING CONTINUATION	$211,875
														Subtotal = $211,875

Issue Date FY: 2019 ( Subtotal = $211,875 )
2019	2019	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	33	6/13/2019	NON-COMPETING CONTINUATION	$211,875
2019	2018	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	32	11/16/2018	COMPETING CONTINUATION	$7,566
2019	2015	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	11/16/2018	NON-COMPETING CONTINUATION	-$7,566
														Subtotal = $211,875

Issue Date FY: 2018 ( Subtotal = $219,095 )
2018	2018	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	32	7/9/2018	COMPETING CONTINUATION	$8,409
2018	2018	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	32	6/19/2018	COMPETING CONTINUATION	$210,686
2018	2015	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	6/14/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $219,095

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	9/11/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $220,545 )
2015	2015	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	8/13/2015	NON-COMPETING CONTINUATION	$220,545
														Subtotal = $220,545

Issue Date FY: 2014 ( Subtotal = $220,545 )
2014	2014	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	30	7/24/2014	NON-COMPETING CONTINUATION	$220,545
														Subtotal = $220,545

Issue Date FY: 2013 ( Subtotal = $212,827 )
2013	2013	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	29	8/21/2013	NON-COMPETING CONTINUATION	$212,827
														Subtotal = $212,827

Issue Date FY: 2012 ( Subtotal = $180,027 )
2012	2012	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	28	9/11/2012	COMPETING CONTINUATION	$180,027
2012	2010	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	3/2/2012	NON-COMPETING CONTINUATION	$0
2012	2010	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	27	9/3/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $180,027

Issue Date FY: 2010 ( Subtotal = $194,668 )
2010	2010	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK	NY	10021	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	1/22/2010	NON-COMPETING CONTINUATION	$194,668
														Subtotal = $194,668

Issue Date FY: 2008 ( Subtotal = $196,634 )
2008	2008	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	26	7/3/2008	NON-COMPETING CONTINUATION	$196,634
														Subtotal = $196,634

Issue Date FY: 2007 ( Subtotal = $200,647 )
2007	2007	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	25	6/21/2007	NON-COMPETING CONTINUATION	$200,647
														Subtotal = $200,647

Issue Date FY: 2006 ( Subtotal = $227,140 )
2006	2006	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	24	6/19/2006	COMPETING CONTINUATION	$227,140
														Subtotal = $227,140

Issue Date FY: 2005 ( Subtotal = $211,875 )
2005	2005	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	23	1/27/2005	NON-COMPETING CONTINUATION	$211,875
														Subtotal = $211,875

Issue Date FY: 2004 ( Subtotal = $211,875 )
2004	2004	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	22	1/22/2004	NON-COMPETING CONTINUATION	$211,875
														Subtotal = $211,875

Issue Date FY: 2003 ( Subtotal = $211,875 )
2003	2003	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	21		NON-COMPETING CONTINUATION	$211,875
														Subtotal = $211,875

Issue Date FY: 2001 ( Subtotal = $243,893 )
2001	2001	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	20	7/30/2001	COMPETING CONTINUATION	$243,893
														Subtotal = $243,893

Issue Date FY: 2000 ( Subtotal = $164,670 )
2000	2000	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	19	8/7/2000	NON-COMPETING CONTINUATION	$164,670
														Subtotal = $164,670

Issue Date FY: 1999 ( Subtotal = $164,194 )
1999	1999	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	18	6/18/1999	NON-COMPETING CONTINUATION	$164,194
														Subtotal = $164,194

Issue Date FY: 1998 ( Subtotal = $163,730 )
1998	1998	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Kidney Diseases, Urology and Hematology Research	000	17	7/16/1998	NON-COMPETING CONTINUATION	$163,730
														Subtotal = $163,730

Grand Total All Awards = $4,080,142

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Theory of Solute and Water Transport Across Epithelia

Award Number: R01DK029857

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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