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Hypertensive Renal Injury

Award Number: R01DK081866
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: 09/25/2009
PERIOD OF PERFORMANCE END DATE: 07/31/2011

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Hypertensive Renal Injury - DESCRIPTION (provided by applicant): In the prior funding period we have introduced a new approach to genetic mapping in inbred rodent strains that exploits closely related lines differing in traits of interest. Using a 10K SNP map, we have shown that two SHR lines differ at only 13% of their genomes, but that these differences have a profound effect on susceptibility to hypertensive renal disease. The close genetic similarity has allowed us to perform fine mapping that has resulted in the identification of three highly resolved quantitative trait loci (QTL) affecting blood pressure and renal injury. Because of the similarity between the lines, each of these QTL maps to a small, isolated block where the two SHR lines have descended from different ancestors. These blocks are surrounded by extensive regions that are identical-by-descent (IBD) and thus help to narrowly define the QTL's, down to a small number of genes. In the present study we propose to identify the genes in each QTL that contribute to increased hypertensive renal disease and to understand the mechanisms by which they act. One QTL has effects on both blood pressure and renal injury. We seek to identify the causative variation and determine whether it acts first on blood pressure with secondary effects on injury or whether it lies in a pathway that produces injury that then leads to reduced renal function and increased blood pressure. Another QTL has no effect on blood pressure and appears to lead to glomerular damage directly. We have also identified the immunoglobulin heavy chain as a locus containing extensive variation across our lines. We have shown that this includes variation with important effects on IgG function including the inability to transfer IgG from mother to offspring. This variation associates with increased albuminuria. We propose to investigate whether alterations in immune function that are encoded by differences in the heavy chain of immunoglobulin contribute to the emergence of renal disease in the susceptible SHR line and whether maternal-offspring IgG transfer is involved in the transmission of risk. We have identified allelic variatio in IgG in humans that is widespread and ancient and that is functionally homologous to the variation we detected across SHR lines. We will perform a large-scale human population genetic study to determine the association of this variation with renal function in humans.


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: 2021 ( Subtotal = -$1 )
2021	2009	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Trans-NIH Recovery Act Research Support	000	1	6/21/2021	NEW	-$1
														Subtotal = -$1

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	2/5/2020	NON-COMPETING CONTINUATION	-$1
2020	2009	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Trans-NIH Recovery Act Research Support	000	1	2/5/2020	NEW	$1
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $393,955 )
2017	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	7	8/23/2017	NON-COMPETING CONTINUATION	$393,955
2017	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	2/10/2017	EXTENSION WITH OR WITHOUT FUNDS	$10,672
2017	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/10/2017	NON-COMPETING CONTINUATION	-$10,672
														Subtotal = $393,955

Issue Date FY: 2016 ( Subtotal = $403,212 )
2016	2016	UNIVERSITY OF TEXAS, GRADUATE SCHOOL BIOMEDICAL SCIENCE	POST OFFICE BOX 20367	HOUSTON	TX	77225	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	8/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$403,212
														Subtotal = $403,212

Issue Date FY: 2015 ( Subtotal = $445,553 )
2015	2015	UNIVERSITY OF TEXAS, GRADUATE SCHOOL BIOMEDICAL SCIENCE	POST OFFICE BOX 20367	HOUSTON	TX	77225	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	8/18/2015	NON-COMPETING CONTINUATION	$445,553
														Subtotal = $445,553

Issue Date FY: 2014 ( Subtotal = $458,658 )
2014	2014	UNIVERSITY OF TEXAS, GRADUATE SCHOOL BIOMEDICAL SCIENCE	POST OFFICE BOX 20367	HOUSTON	TX	77225	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/27/2014	NON-COMPETING CONTINUATION	$458,658
														Subtotal = $458,658

Issue Date FY: 2013 ( Subtotal = $493,055 )
2013	2013	UNIVERSITY OF TEXAS, GRADUATE SCHOOL BIOMEDICAL SCIENCE	POST OFFICE BOX 20367	HOUSTON	TX	77225	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/1/2013	COMPETING CONTINUATION	$493,055
														Subtotal = $493,055

Issue Date FY: 2010 ( Subtotal = $349,971 )
2010	2010	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Trans-NIH Recovery Act Research Support	000	2	8/12/2010	NON-COMPETING CONTINUATION	$349,971
														Subtotal = $349,971

Issue Date FY: 2009 ( Subtotal = $349,979 )
2009	2009	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Trans-NIH Recovery Act Research Support	000	1	9/23/2009	NEW	$349,979
														Subtotal = $349,979

Grand Total All Awards = $2,894,382

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Hypertensive Renal Injury

Award Number: R01DK081866

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: 09/25/2009

PERIOD OF PERFORMANCE END DATE: 07/31/2011

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