1] MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark [2] Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Kidney Int. 2014 Jul;86(1):67-74. doi: 10.1038/ki.2013.504. Epub 2013 Dec 18.
The kidneys account for about 10% of the whole body oxygen consumption, whereas only 0.5% of the total body mass. It is known that intrarenal hypoxia is present in several diseases associated with development of kidney disease, including diabetes, and when renal blood flow is unaffected. The importance of deranged oxygen metabolism is further supported by deterioration of kidney function in patients with diabetes living at high altitude. Thus, we argue that reduced oxygen availability alters renal energy metabolism. Here, we introduce a novel magnetic resonance imaging (MRI) approach to monitor metabolic changes associated with diabetes and oxygen availability. Streptozotocin diabetic and control rats were given reduced, normal, or increased inspired oxygen in order to alter tissue oxygenation. The effects on kidney oxygen metabolism were studied using hyperpolarized [1-(13)C]pyruvate MRI. Reduced inspired oxygen did not alter renal metabolism in the control group. Reduced oxygen availability in the diabetic kidney altered energy metabolism by increasing lactate and alanine formation by 23% and 34%, respectively, whereas the bicarbonate flux was unchanged. Thus, the increased prevalence and severity of nephropathy in patients with diabetes at high altitudes may originate from the increased sensitivity toward inspired oxygen. This increased lactate production shifts the metabolic routs toward hypoxic pathways.
肾脏约占全身耗氧量的 10%，而其占体重的比例仅为 0.5%。众所周知，在与肾脏疾病发展相关的几种疾病中，包括糖尿病，当肾血流量不受影响时，也会出现局部肾缺氧。氧代谢紊乱的重要性还得到了以下事实的进一步支持：在高海拔地区生活的糖尿病患者肾功能恶化。因此，我们认为氧气供应减少会改变肾脏的能量代谢。在这里，我们介绍了一种新的磁共振成像（MRI）方法，用于监测与糖尿病和氧气供应相关的代谢变化。链脲佐菌素诱导的糖尿病大鼠和对照组大鼠分别接受低氧、常氧或高氧吸入，以改变组织氧合。使用 1-(13)C]丙酮酸的极化 MRI 研究了这些处理对肾脏氧代谢的影响。低氧吸入并未改变对照组大鼠的肾脏代谢。糖尿病大鼠的氧供应减少通过分别增加 23%和 34%的乳酸和丙氨酸形成来改变能量代谢，而碳酸氢盐通量保持不变。因此，高原地区糖尿病患者中肾病的发病率和严重程度增加可能源于对吸入氧的敏感性增加。这种增加的乳酸生成使代谢途径转向缺氧途径。
