Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy

Introduction: Mesoamerican nephropathy (MeN) is a chronic kidney disease (CKD) which may be caused by recurrent acute kidney injury (AKI). We investigated urinary quinolinate-to-tryptophan ratio (Q/T), a validated marker of nicotinamide adenine dinucleotide (NAD+) biosynthesis that is elevated durin...

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Main Authors: Nathan H. Raines, Dominic A. Leone, Juan Jose Amador, Damaris Lopez-Pilarte, Oriana Ramírez-Rubio, Iris S. Delgado, Lauren J. Francey, Jessica H. Leibler, John M. Asara, Madeleine K. Scammell, Samir M. Parikh, Daniel R. Brooks, David J. Friedman
Format: Article
Language:English
Published: Elsevier 2024-07-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924016504
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author Nathan H. Raines
Dominic A. Leone
Juan Jose Amador
Damaris Lopez-Pilarte
Oriana Ramírez-Rubio
Iris S. Delgado
Lauren J. Francey
Jessica H. Leibler
John M. Asara
Madeleine K. Scammell
Samir M. Parikh
Daniel R. Brooks
David J. Friedman
author_facet Nathan H. Raines
Dominic A. Leone
Juan Jose Amador
Damaris Lopez-Pilarte
Oriana Ramírez-Rubio
Iris S. Delgado
Lauren J. Francey
Jessica H. Leibler
John M. Asara
Madeleine K. Scammell
Samir M. Parikh
Daniel R. Brooks
David J. Friedman
author_sort Nathan H. Raines
collection DOAJ
description Introduction: Mesoamerican nephropathy (MeN) is a chronic kidney disease (CKD) which may be caused by recurrent acute kidney injury (AKI). We investigated urinary quinolinate-to-tryptophan ratio (Q/T), a validated marker of nicotinamide adenine dinucleotide (NAD+) biosynthesis that is elevated during ischemic and inflammatory AKI, in a sugarcane worker population in Nicaragua with high rates of MeN. Methods: Among 693 male sugarcane workers studied, we identified 45 who developed AKI during the harvest season. We matched them 1:1 based on age and job category with 2 comparison groups: (i) “no kidney injury,” active sugarcane workers with serum creatinine (sCr) <1.1 mg/dl; and (ii) “CKD,” individuals no longer working in sugarcane due to their CKD, who had additional 1:1 matching for sCr. We measured urine metabolites using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) and compared Q/T and other metabolic features between the AKI and comparison groups. Results: Urine Q/T was significantly higher in workers with AKI than in those with no kidney injury (median interquartile Range [IQR]: 0.104 [0.074–0.167] vs. 0.060 [0.045–0.091], P < 0.0001) and marginally higher than in workers with CKD (0.086 [0.063–0.142], P = 0.059). Urine levels of the NAD+ precursor nicotinamide were lower in the AKI group than in comparison groups. Conclusion: Workers at risk for MeN who develop AKI demonstrate features of impaired NAD+ biosynthesis, thereby providing new insights into the metabolic mechanisms of injury in this population. Therapeutic use of oral nicotinamide, which may ameliorate NAD+ biosynthetic derangement and fortify against kidney injury, should be investigated to prevent AKI in this setting.
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spelling doaj-art-db74188090594e44b8db61b3191eb64b2025-08-20T02:06:12ZengElsevierKidney International Reports2468-02492024-07-01972250225910.1016/j.ekir.2024.04.027Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican NephropathyNathan H. Raines0Dominic A. Leone1Juan Jose Amador2Damaris Lopez-Pilarte3Oriana Ramírez-Rubio4Iris S. Delgado5Lauren J. Francey6Jessica H. Leibler7John M. Asara8Madeleine K. Scammell9Samir M. Parikh10Daniel R. Brooks11David J. Friedman12Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Correspondence: Nathan H. Raines, Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USADepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USADepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USADepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USADepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA; ISGlobal, Barcelona Institute for Global Health, Barcelona, SpainDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USADivision of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USADepartment of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USAHarvard Medical School, Boston, Massachusetts, USA; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USADepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USADivision of Nephrology, Department of Medicine, University of Texas Southwestern Medical School, Dallas, Texas, USADepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA; Daniel R. Brooks, Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts 02118, USADivision of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; David J. Friedman, Medicine/Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.Introduction: Mesoamerican nephropathy (MeN) is a chronic kidney disease (CKD) which may be caused by recurrent acute kidney injury (AKI). We investigated urinary quinolinate-to-tryptophan ratio (Q/T), a validated marker of nicotinamide adenine dinucleotide (NAD+) biosynthesis that is elevated during ischemic and inflammatory AKI, in a sugarcane worker population in Nicaragua with high rates of MeN. Methods: Among 693 male sugarcane workers studied, we identified 45 who developed AKI during the harvest season. We matched them 1:1 based on age and job category with 2 comparison groups: (i) “no kidney injury,” active sugarcane workers with serum creatinine (sCr) <1.1 mg/dl; and (ii) “CKD,” individuals no longer working in sugarcane due to their CKD, who had additional 1:1 matching for sCr. We measured urine metabolites using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) and compared Q/T and other metabolic features between the AKI and comparison groups. Results: Urine Q/T was significantly higher in workers with AKI than in those with no kidney injury (median interquartile Range [IQR]: 0.104 [0.074–0.167] vs. 0.060 [0.045–0.091], P < 0.0001) and marginally higher than in workers with CKD (0.086 [0.063–0.142], P = 0.059). Urine levels of the NAD+ precursor nicotinamide were lower in the AKI group than in comparison groups. Conclusion: Workers at risk for MeN who develop AKI demonstrate features of impaired NAD+ biosynthesis, thereby providing new insights into the metabolic mechanisms of injury in this population. Therapeutic use of oral nicotinamide, which may ameliorate NAD+ biosynthetic derangement and fortify against kidney injury, should be investigated to prevent AKI in this setting.http://www.sciencedirect.com/science/article/pii/S2468024924016504acute kidney injury (AKI)chronic kidney disease of unknown etiology (CKDu)chronic kidney disease of nontraditional cause (CKDnt)Mesoamerican nephropathymetabolomicsnicotinamide adenine dinucleotide (NAD+)
spellingShingle Nathan H. Raines
Dominic A. Leone
Juan Jose Amador
Damaris Lopez-Pilarte
Oriana Ramírez-Rubio
Iris S. Delgado
Lauren J. Francey
Jessica H. Leibler
John M. Asara
Madeleine K. Scammell
Samir M. Parikh
Daniel R. Brooks
David J. Friedman
Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy
Kidney International Reports
acute kidney injury (AKI)
chronic kidney disease of unknown etiology (CKDu)
chronic kidney disease of nontraditional cause (CKDnt)
Mesoamerican nephropathy
metabolomics
nicotinamide adenine dinucleotide (NAD+)
title Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy
title_full Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy
title_fullStr Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy
title_full_unstemmed Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy
title_short Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy
title_sort derangement in nicotinamide adenine dinucleotide metabolism is observed during acute kidney injury among male agricultural workers at risk for mesoamerican nephropathy
topic acute kidney injury (AKI)
chronic kidney disease of unknown etiology (CKDu)
chronic kidney disease of nontraditional cause (CKDnt)
Mesoamerican nephropathy
metabolomics
nicotinamide adenine dinucleotide (NAD+)
url http://www.sciencedirect.com/science/article/pii/S2468024924016504
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