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Mechanisms involved in the early development of renal disease associated with prepubertal obesity

Award Number: R01DK109133
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 Abstract Prepubertal childhood obesity has emerged as an epidemic and major health problem in the United States. Recent studies suggest that that childhood obesity is associated with increased risk of renal injury in children. Although the link between obesity and the development of type II diabetic nephropathy is well-documented, the consequences of childhood obesity as an independent risk factor in the absence of diabetes in the development of renal disease has received less attention. Currently, there are several obese animal models that develop renal disease, but these models have limited use in the investigation of the early mechanisms responsible for the development of renal injury prior to hypertension, diabetes, and/or puberty. As most of these obese models do not develop progressive proteinuria and chronic kidney disease (CKD). Recently, we observed our obese rat model (prepubertal obese - PPO) develops podocyte injury and 3-fold increase in proteinuria prior to the development of hypertension and diabetes at 6 weeks of age (childhood), which progresses to severe hypertension, CKD by 18 weeks of age (adulthood). In the current proposal, we will use our model of prepubertal obesity to explore several mechanisms that may contribute to the development of renal disease. The proposed studies will test whether glomerular hyperfiltration and lipid accumulation stimulate podocyte injury and macrophage inflitration leading to proteinuria and renal injury during prepubertal obesity. We will compare early changes in glomerular capillary pressure (Pgc) between the PPO model and their control-lean counterparts and determine whether there is a direct effect of mechanical strain/cyclic stretch on lipid accumulation in podocytes isolated from both strains. We also will evaluate the role of macrophages on the early development of proteinuria in the PPO model. These results should provide the scientific community with an obese animal model system that develops proteinuria, prior to puberty, to study mechanisms involved in renal injury and provide information critical to develop new treatments for the prevention of renal disease associated with prepubertal childhood obesity.


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 = $348,750 )
2021	2021	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/27/2021	NON-COMPETING CONTINUATION	$348,750
														Subtotal = $348,750

Issue Date FY: 2020 ( Subtotal = $348,750 )
2020	2020	UNIVERISTY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/27/2020	NON-COMPETING CONTINUATION	$348,750
														Subtotal = $348,750

Issue Date FY: 2019 ( Subtotal = $348,750 )
2019	2019	UNIVERISTY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/18/2019	NON-COMPETING CONTINUATION	$348,750
														Subtotal = $348,750

Issue Date FY: 2018 ( Subtotal = $348,750 )
2018	2018	UNIVERISTY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/25/2018	NON-COMPETING CONTINUATION	$348,750
														Subtotal = $348,750

Issue Date FY: 2017 ( Subtotal = $347,813 )
2017	2017	UNIVERISTY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/13/2017	NEW	$347,813
														Subtotal = $347,813

Grand Total All Awards = $1,742,813

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Mechanisms involved in the early development of renal disease associated with prepubertal obesity

Award Number: R01DK109133

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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