부산대학교 도서관

Background. Down-regulation of the enzymes involved in tryptophan-derived nicotinamide (NAM) adenine dinucleotide ([NAD.sup.+]) production was identified after acute kidney injury (AKI), leading to the hypothesis that supplementation with NAM may increase the kidney [NAD.sup.+] content, rescuing tryptophan pathways and subsequently improving kidney outcomes. Methods. Urinary measurement of tryptophan and kynurenin using liquid chromatography-mass spectrometry metabolomics was used in a cohort of 167 cardiac bypass surgery patients along with tests for correlation to the development of postoperative AKI. A mouse model of ischaemic AKI using ischaemia-reperfusion injury (bilateral clamping of renal arteries for 25 min) was also used. Results. We identified a significant decrease in urinary tryptophan and kynurenin in patients developing AKI, irrespective of the Kidney Disease: Improving Global Outcomes (KDIGO) stage. Although a significant difference was observed, tryptophan and kynurenin moderately discriminated for the development of all AKI KDIGO stages {area under the curve [AUC] 0.82 [95% confidence interval (CI) 0.75-0.88] and 0.75 [0.68-0.83], respectively} and severe KDIGO Stages 2-3 AKI [AUC 0.71 (95% CI 0.6-0.81) and 0.66 (0.55-0.77), respectively]. Sparked by this confirmation in humans, we aimed to confirm the potential preventive effect of NAM supplementation in wild-type male and female C57BL/6 mice subjected to ischaemic AKI. NAM supplementation had no effect on renal function (blood urea nitrogen at Day 1, sinistrin-fluorescein isothiocyanate glomerular filtration rate), architecture (periodic acid-Schiff staining) and injury or inflammation (kidney injury molecule 1 and IL18 messenger RNA expression). In addition, NAM supplementation did not increase post-AKI [NAD.sup.+] kidney content. Conclusion. Notwithstanding the potential role of NAM supplementation in the setting of basal [NAD.sup.+] deficiency, our findings in mice and the reanalysis of published data do not confirm that NAM supplementation can actually improve renal outcomes after ischaemic AKI in unselected animals and probably patients. Keywords: acute tubular necrosis, AKI, biomarkers, cardiac surgery, ischaemia-reperfusion injury
INTRODUCTION Acute kidney injury (AKI) is a frequent and life-threatening condition. Despite extensive in vitro and in vivo research, translation of candidate drugs that positively affect renal outcomes in humans [...]