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

Abstract

IntroductionMesoamerican 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 elevated during ischemic and inflammatory AKI, in a sugarcane worker population with high rates of MeN in Nicaragua. MethodsAmong 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 two comparison groups: (1) “no kidney injury,” active sugarcane workers with serum creatinine <1.1mg/dL; and (2) “CKD,” individuals no longer working in sugarcane due to their CKD, who had additional 1:1 matching for serum creatinine. We measured urine metabolites using liquid chromatography-coupled tandem mass spectrometry, and compared Q/T and other metabolic features between the AKI and comparison groups. ResultsUrine Q/T was significantly higher in workers with AKI than in those with no kidney injury (median [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. ConclusionWorkers at risk for MeN who develop AKI demonstrate features of impaired NAD+ biosynthesis, 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.