Raines Nathan H, Leone Dominic A, Amador Juan Jose, Lopez-Pilarte Damaris, Ramírez-Rubio Oriana, Delgado Iris S, Francey Lauren J, Leibler Jessica H, Asara John M, Scammell Madeleine K, Parikh Samir M, Brooks Daniel R, Friedman David J
Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Kidney Int Rep. 2024 Apr 18;9(7):2250-2259. doi: 10.1016/j.ekir.2024.04.027. eCollection 2024 Jul.
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.
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.
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], < 0.0001) and marginally higher than in workers with CKD (0.086 [0.063-0.142], = 0.059). Urine levels of the NAD+ precursor nicotinamide were lower in the AKI group than in comparison groups.
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.
中美洲肾病（MeN）是一种慢性肾病（CKD），可能由反复急性肾损伤（AKI）引起。我们在尼加拉瓜甘蔗种植工人中调查了尿喹啉酸与色氨酸比值（Q/T），这是一种已验证的烟酰胺腺嘌呤二核苷酸（NAD+）生物合成标志物，在缺血性和炎症性AKI期间会升高，该人群中MeN发病率较高。
在研究的693名男性甘蔗种植工人中，我们确定了45名在收获季节发生AKI的工人。我们根据年龄和工作类别将他们与两个对照组进行1:1匹配：（i）“无肾损伤”，即血清肌酐（sCr）<1.1mg/dl的在职甘蔗种植工人；（ii）“CKD”，即因CKD不再从事甘蔗种植工作的个体，这些个体还根据sCr进行了1:1匹配。我们使用液相色谱串联质谱（LC-MS/MS）测量尿液代谢物，并比较AKI组与对照组之间的Q/T和其他代谢特征。
AKI工人的尿Q/T显著高于无肾损伤工人（中位数四分位间距[IQR]：0.104[0.074 - 0.167]对0.060[0.045 - 0.091]，P<0.0001），略高于CKD工人（0.086[0.063 - 0.142]，P = 0.059）。AKI组中NAD+前体烟酰胺的尿液水平低于对照组。
发生AKI的MeN高危工人表现出NAD+生物合成受损的特征，从而为该人群的损伤代谢机制提供了新见解。应研究口服烟酰胺的治疗用途，其可能改善NAD+生物合成紊乱并预防肾损伤，以防止在此情况下发生AKI。
