Ohashi Naro, Ishigaki Sayaka, Isobe Shinsuke, Matsuyama Takashi, Sato Taichi, Fujikura Tomoyuki, Tsuji Takayuki, Kato Akihiko, Yasuda Hideo
Internal Medicine 1, Hamamatsu University School of Medicine, Japan.
Blood Purification Unit, Hamamatsu University School of Medicine, Japan.
Intern Med. 2019 Jun 1;58(11):1557-1564. doi: 10.2169/internalmedicine.1929-18. Epub 2019 Feb 1.
Objective Salt loading induces renal damage independently of blood pressure (BP) elevation via reactive oxygen species and sympathetic activity. Melatonin, a hormone that regulates the circadian rhythm, has multiple functions, including anti-oxidant effects and the inhibition of sympathetic activity. We have shown that impaired melatonin secretion is associated with renal damage in chronic kidney disease (CKD) patients. However, the associations between salt loading, melatonin secretion, and urinary albumin and protein have not been clarified. Methods We recruited 32 CKD patients, conducted 24-hour ambulatory BP monitoring and collected daytime and nighttime urine while the patients were consuming a standard salt (10 g/day) or low salt (6 g/day) diet. The excretion levels of albumin, protein and 6-sulfatoxymelatonin (aMT6s), a metabolite of melatonin, in daytime and nighttime urine were investigated in patients consuming standard salt and low salt diets. Results The urinary aMT6s levels in daytime and nighttime of the patients consuming standard salt and low salt diets did not differ to a statistically significant extent. However, the urinary aMT6s levels in patients consuming a standard salt diet-but not patients consuming a low salt diet-were significantly and negatively correlated with the daytime and nighttime urinary albumin and protein levels. Contrarily, no significant correlations were found between the urinary aMT6s levels and the BP levels, renal function, and plasma angiotensin II levels in patients consuming either a standard salt or low salt diet. A multiple regression analysis adjusted for age, sex, and body mass index revealed that the urinary albumin and protein levels were significantly and negatively associated with the urinary aMT6s levels in patients consuming a standard salt diet, but not in patients consuming a low salt diet. Conclusion Salt loading aggravates the relationship between melatonin secretion and albuminuria or proteinuria.
目的 盐负荷通过活性氧和交感神经活动独立于血压升高诱导肾损伤。褪黑素是一种调节昼夜节律的激素，具有多种功能，包括抗氧化作用和抑制交感神经活动。我们已经表明，褪黑素分泌受损与慢性肾脏病（CKD）患者的肾损伤有关。然而，盐负荷、褪黑素分泌与尿白蛋白和蛋白质之间的关联尚未阐明。方法 我们招募了32例CKD患者，进行24小时动态血压监测，并在患者食用标准盐（10克/天）或低盐（6克/天）饮食时收集白天和夜间尿液。研究食用标准盐和低盐饮食患者白天和夜间尿液中白蛋白、蛋白质和褪黑素代谢物6-硫酸氧褪黑素（aMT6s）的排泄水平。结果 食用标准盐和低盐饮食患者白天和夜间的尿aMT6s水平在统计学上没有显著差异。然而，食用标准盐饮食患者的尿aMT6s水平（而非食用低盐饮食患者）与白天和夜间尿白蛋白和蛋白质水平显著负相关。相反，在食用标准盐或低盐饮食的患者中，尿aMT6s水平与血压水平、肾功能和血浆血管紧张素II水平之间未发现显著相关性。对年龄、性别和体重指数进行校正的多元回归分析显示，食用标准盐饮食患者的尿白蛋白和蛋白质水平与尿aMT6s水平显著负相关，而食用低盐饮食患者则不然。结论 盐负荷加剧了褪黑素分泌与蛋白尿或白蛋白尿之间的关系。
