Titze Jens, Rakova Natalia, Kopp Christoph, Dahlmann Anke, Jantsch Jonathan, Luft Friedrich C
Interdisciplinary Center for Clinical Research and Department for Nephrology and Hypertension, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Interdisciplinary Center for Clinical Research and Department for Nephrology and Hypertension, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Nephrol Dial Transplant. 2016 Jul;31(7):1078-81. doi: 10.1093/ndt/gfv343. Epub 2015 Sep 25.
Sodium balance is achieved within a matter of days and everything that enters should come out; sodium stores are of questionable relevance and sodium accumulation is accompanied by weight gain. Careful balance studies oftentimes conflicted with this view, and long-term studies suggested that total body sodium (TBNa) fluctuates independent of intake or body weight. We recently performed the opposite experiment in that we fixed sodium intake for weeks at three levels of sodium intake and collected all urine made. We found weekly (circaseptan) patterns in sodium excretion that were inversely related to aldosterone and directly related to cortisol. TBNa was not dependent on sodium intake, but instead exhibited far longer (greater than or equal to monthly) infradian rhythms independent of extracellular water, body weight or blood pressure. To discern the mechanisms further, we delved into sodium magnetic resonance imaging (Na-MRI) to identify sodium storage clinically. We found that sodium stores are greater in men than in women, increase with age and are higher in hypertensive than normotensive persons. We have suggestive evidence that these sodium stores can be mobilized, also in dialysis patients. The observations are in accordance with our findings that immune cells regulate a hypertonic interface in the skin interstitium that could serve as a protective barrier. Returning to our balance studies, we found that due to biological variability in 24-h sodium excretion, collecting urine for a day could not separate 12, 9 or 6 g/day sodium intakes with the precision of tossing a coin. Every other daily urine sampling correctly classified a 3-g difference in salt intake less than half the time, making the gold standard 24-h urine collection of little value in predicting salt intake. We suggest that wobbles in expected outcomes can lead to novel clinical insights even with respect to banal salt questions.
钠平衡在数天内即可实现,所有摄入的物质都应排出体外;钠储备的相关性存疑,钠蓄积会伴随体重增加。细致的平衡研究常常与这一观点相矛盾,长期研究表明,总体钠(TBNa)的波动与摄入量或体重无关。我们最近进行了相反的实验,即我们将钠摄入量固定在三个水平数周,并收集所有产生的尿液。我们发现钠排泄存在每周(约七天周期)的模式,与醛固酮呈负相关,与皮质醇呈正相关。TBNa并不依赖于钠摄入量,而是呈现出长得多(大于或等于每月)的超日节律,与细胞外液、体重或血压无关。为了进一步探究其机制,我们深入研究了钠磁共振成像(Na-MRI)以在临床上识别钠储备。我们发现男性的钠储备比女性多,随年龄增长而增加,高血压患者比血压正常者更高。我们有提示性证据表明,这些钠储备也可以在透析患者中被调动。这些观察结果与我们的发现一致,即免疫细胞调节皮肤间质中的高渗界面,该界面可作为一种保护屏障。回到我们的平衡研究,我们发现由于24小时钠排泄存在生物学变异性,收集一天的尿液无法以抛硬币的精度区分每天12克、9克或6克的钠摄入量。每隔一天进行尿液采样正确分类盐摄入量3克差异的时间不到一半,这使得预测盐摄入量的金标准24小时尿液收集几乎没有价值。我们认为,即使是关于平凡的盐问题,预期结果的波动也可能带来新的临床见解。