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CYTOKINE GENE POLYMORPHISMS IN ACUTE RENAL FAILURE

Award Number: K23DK065102
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/15/2003
PERIOD OF PERFORMANCE END DATE: 08/31/2008

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CYTOKINE GENE POLYMORPHISMS IN ACUTE RENAL FAILURE - DESCRIPTION (provided by applicant): Acute renal failure (ARF) is a serious complication in hospitalized patients, with an incidence of 5-10%, and mortality exceeding 50% among those who require dialysis. Pro- and anti-inflammatory cytokines play a pivotal role in the host inflammatory responses that mediate the severity of ARF. Yet, the importance of susceptibility genetic factors such as cytokine gene polymorphisms has remained largely unexplored. The principal investigator (PI) has designed a rigorous training program that will provide him with the necessary skills, experience, and opportunities to develop into an independent investigator in the field of inflammatory genetic markers and epidemiology of acute renal failure. He will obtain a Masters of Science in Clinical Care Research, participate in projects utilizing a broad range of study designs for clinical research, and carry out an original research project from its inception to completion. His mentors have extensive experience in clinical and laboratory investigation of ARF and clinical care research in Nephrology. Single nucleotide polymorphisms (SNP) in the promoter region of the human tumor necrosis factor-alpha (TNF-alpha) (position -308), interleukin-6 (IL-6) (position -174) and interleukin-10 (IL-10) (position -1082) genes affect transcriptional activity and have functional relevance. These genetically determined differences might influence variations in host inflammatory responses to stressful stimuli. The hypotheses to be investigated are that SNP involving these cytokines predetermine the severity of ARF, and are independent risk factors for adverse clinical outcomes. The specific aims are to: 1) characterize the frequency of these pro- (TNF-alpha and IL-6) and anti-inflammatory (IL-10) cytokine gene polymorphisms in a cohort of patients with ARF; 2) Examine their relationship to leukocyte production and plasma levels of cytokines as well as clinical and laboratory variables; and 3) Evaluate whether these genetic markers individually or in combinations, predict adverse clinical outcomes, mainly dialysis requirement and mortality. The research project is achievable and promises to provide new insights into the importance of genetic markers as novel susceptibility factors for severity of disease in ARF. The results may help identify target patients who may benefit from anti-cytokine therapies. The PI has assembled a team of scientists to assist in the conduct of the project, and convened and internal and external scientific advisory committee to monitor his progress. The proposed training program and research project will prepare him for a career as an independent investigator.


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: 2007 ( Subtotal = $125,334 )
2007	2007	CARITAS ST ELIZABETH`S MEDICAL CENTER OF BOSTON	736 CAMBRIDGE ST, BOX OLH-6BD	BOSTON	MA	02135	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	6	7/31/2007	NON-COMPETING CONTINUATION	$125,334
														Subtotal = $125,334

Issue Date FY: 2006 ( Subtotal = $125,334 )
2006	2006	CARITAS ST ELIZABETH`S MEDICAL CENTER OF BOSTON	736 CAMBRIDGE ST, BOX OLH-6BD	BOSTON	MA	02135	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	5	8/25/2006	NON-COMPETING CONTINUATION	$125,334
														Subtotal = $125,334

Issue Date FY: 2005 ( Subtotal = $125,334 )
2005	2005	ST ELIZABETH'S HOSPITAL OF BOSTON	736 CAMBRIDGE ST, BOX OLH-6BD	BOSTON	MA	02135	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	4	8/11/2005	NON-COMPETING CONTINUATION	$125,334
														Subtotal = $125,334

Issue Date FY: 2004 ( Subtotal = $125,334 )
2004	2004	ST ELIZABETH'S HOSPITAL OF BOSTON	736 CAMBRIDGE ST, BOX OLH-6BD	BOSTON	MA	02135	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	3	9/6/2004	NON-COMPETING CONTINUATION	$125,334
														Subtotal = $125,334

Issue Date FY: 2003 ( Subtotal = $129,870 )
2003	2003	NEW ENGLAND MEDICAL CENTER HOSPITALS, INC	750 WASHINGTON STREET	BOSTON	MA	02111	SUFFOLK	USA	Kidney Diseases, Urology and Hematology Research	000	1	9/11/2003	NEW	$129,870
														Subtotal = $129,870

Grand Total All Awards = $631,206

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CYTOKINE GENE POLYMORPHISMS IN ACUTE RENAL FAILURE

Award Number: K23DK065102

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/15/2003

PERIOD OF PERFORMANCE END DATE: 08/31/2008

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