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Nicotinamide Adenine Dinucleotide (NAD+) Metabolism During Observational and Experimental Heat Stress and the Effect of Niacinamide Among Individuals at Risk for Mesoamerican Nephropathy

Award Number: K23DK138320
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/02/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Nicotinamide Adenine Dinucleotide (NAD+) Metabolism During Observational and Experimental Heat Stress and the Effect of Niacinamide Among Individuals at Risk for Mesoamerican Nephropathy - PROJECT SUMMARY Heat stress, arising from hot external temperatures and heat generation as a byproduct of metabolism, has myriad health effects. An index condition of its impact on the kidneys appears to be chronic kidney disease of nontraditional cause (CKDnt), a form of chronic kidney disease (CKD); epidemiologic evidence strongly connects heat stress and CKDnt development. A potential mechanism linking heat stress and CKDnt may be recurrent subclinical ischemic or inflammatory injury to the kidney. Prior research shows that nicotinamide adenine dinucleotide (NAD+) biosynthetic derangement is a diagnostic and pathophysiologic feature of ischemic and inflammatory kidney injury, and that administration of niacinamide boosts NAD+ biosynthesis and prevents injury. A key marker of NAD+ biosynthesis is the urine quinolinate to tryptophan (Q/T) ratio, which increases during injury. Across three parallel aims, this project will test the hypothesis that kidney injury and NAD+ biosynthetic derangement develop in individuals exposed to heat stress, and that both metabolic derangement and kidney injury may be mitigated by administration of niacinamide. Aim 1 will be observational, evaluating urinary Q/T ratio and kidney injury biomarkers in heat-stressed sugarcane cutters, a profession with very high rates of CKDnt. Aim 2 will define a dose-response curve between heat stress and biomarkers of stress to the kidney in a controlled human experimental setting, with parallel measurement of urine Q/T and other metabolic features to study the mechanisms connecting heat stress and kidney injury. Healthy volunteers will exercise in a heated environmental chamber under increasingly intense heat stress, modeling the spectrum experienced during sugarcane cutting. Aim 3 will be a randomized cross-over double-blind placebo-controlled trial of niacinamide during heat stress. Healthy volunteers will exercise in a heated environmental chamber, at heat stress levels determined to elicit kidney stress and a rise in urine Q/T in Aim 2. Kidney injury biomarkers and Q/T will be compared between niacinamide and placebo groups. This project will (1) help isolate the role of heat stress in driving kidney injury associated with CKDnt; (2) develop an experimental protocol to study the mechanisms of heat stress-related kidney injury; and (3) evaluate a potential therapy to mitigate injury. It will also permit my further training in metabolomics; enable me to refine my skills in experimental physiology, clinical trials, and provocative testing; and help me continue to develop my academic leadership within the supportive and well-resourced Beth Israel Deaconess Medical Center. The proposed research Aims and career development plan will help me establish a career as an independent investigator, with expertise in uniting human trials and provocative testing with metabolomics to explore mechanisms connecting environmental exposures, kidney disease, and therapeutic response.


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: 2026 ( Subtotal = $189,981 )
2026	2026	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/7/2026	NON-COMPETING CONTINUATION	$189,981
														Subtotal = $189,981

Issue Date FY: 2025 ( Subtotal = $190,700 )
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/17/2025	NON-COMPETING CONTINUATION	$190,700
														Subtotal = $190,700

Issue Date FY: 2024 ( Subtotal = $192,984 )
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/2/2024	NEW	$192,984
														Subtotal = $192,984

Grand Total All Awards = $573,665

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Nicotinamide Adenine Dinucleotide (NAD+) Metabolism During Observational and Experimental Heat Stress and the Effect of Niacinamide Among Individuals at Risk for Mesoamerican Nephropathy

Award Number: K23DK138320

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/02/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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