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Pathobiology of autoimmune-mediated diffuse podocytopathy

Award Number: R01DK135667
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: 09/05/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Pathobiology of autoimmune-mediated diffuse podocytopathy - Project Summary/Abstract Minimal change disease and primary focal and segmental glomerulosclerosis are morphologic expressions of a diffuse podocytopathy of to date unknown cause, and all present with acute onset Nephrotic Syndrome. Although the majority of patients achieve clinical remission, relapse and treatment failure is common, and when progressing to end stage kidney disease, the disease frequently and vigorously recurs in the allograft. We recently published a groundbreaking study that identified circulating autoantibodies against the extracellular domain of nephrin in a subset of adults and children with non-genetic Minimal Change Disease and in a single patient with recurrent disease in the allograft, which correlate with disease activity. Our findings underpin the paradigm-shifting hypothesis that at least a subset of these diseases are mediated by an organ- specific, antibody-mediated autoimmune disease of B cell origin which causes an acquired diffuse podocytopathy by means of direct action of the autoantibodies on the podocyte, an essential component of the kidney filter. The current proposal now aims at proving this concept by 1) establishing pathogenic autoimmunity in anti-nephrin mediated podocytopathy by means of analyzing immunophenotypes and immunological signatures, and by 2) identifying direct downstream pathomechanistic effects by nephrin autoantibodies that cause changes in podocyte structure and function. Altogether, results from these studies will serve as critical basis for the development of novel, personalized and targeted treatment strategies for our patients with minimal change disease, primary focal and segmental glomerulosclerosis as well as those patients with recurrent disease in the transplant.


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 = $708,681 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/20/2025	NON-COMPETING CONTINUATION	$708,681
														Subtotal = $708,681

Issue Date FY: 2024 ( Subtotal = $796,293 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/5/2024	NEW	$796,293
														Subtotal = $796,293

Grand Total All Awards = $1,504,974

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Pathobiology of autoimmune-mediated diffuse podocytopathy

Award Number: R01DK135667

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: 09/05/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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