Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA,
Nephron. 2019;143(3):184-187. doi: 10.1159/000500168. Epub 2019 May 3.
Acute kidney injury (AKI) is estimated to affect 3-10% of all hospitalized adults in the United States, making it one of the most common inpatient diagnoses. Despite this staggering incidence, most individuals exposed to AKI stressors, such as intravenous radiocontrast or cardiopulmonary bypass, do not develop AKI. In fact, whereas animal models of ischemia, sepsis, or nephrotoxicity suggest near-uniform responses to stressors, the natural history of stressed patients is highly heterogeneous. Recent studies of mitochondrial perturbations underlying experimental and human AKI suggest a conserved metabolic contribution to this variance. The renal tubule is only second to the heart in terms of mitochondrial abundance, reflecting the exquisite need for fuel combustion to generate the energy for active solute transport. The homeostasis of nicotinamide adenine dinucleotide (NAD+), a requisite coenzyme in oxidative metabolism, may be an important determinant of the renal response to AKI stressors. This mini-review highlights recent studies implicating NAD+ dysregulation in experimental and human AKI and summarizes findings from a pilot randomized trial to augment NAD+ among at-risk individuals.
急性肾损伤（AKI）估计影响美国所有住院成年患者的 3-10%，是最常见的住院诊断之一。尽管发病率如此之高，但大多数接触 AKI 应激源的个体，如静脉内放射性对比剂或体外循环，并未发展为 AKI。事实上，尽管缺血、脓毒症或肾毒性的动物模型提示对应激源的反应几乎一致，但应激患者的自然病程高度异质。最近对实验和人类 AKI 基础的线粒体扰动的研究表明，代谢对这种差异有保守的贡献。肾小管在其线粒体丰度方面仅次于心脏，反映了对燃料燃烧以产生主动溶质转运所需能量的极高需求。烟酰胺腺嘌呤二核苷酸（NAD+）的稳态，氧化代谢所必需的辅酶，可能是肾脏对 AKI 应激源反应的一个重要决定因素。这篇迷你综述强调了最近的研究表明 NAD+失调与实验和人类 AKI 有关，并总结了一项在高危人群中补充 NAD+的试点随机试验的结果。
