NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Road, EX2 5AX, UK.
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Road, EX2 5AX, UK.
Nitric Oxide. 2020 Apr 1;97:16-19. doi: 10.1016/j.niox.2020.01.011. Epub 2020 Jan 30.
Nitric oxide (NO) is rapidly oxidised in humans to nitrite and nitrate, with nitrate being present in much greater abundance. These oxidation products can be recycled back into nitric oxide via a complex entero-salivary pathway, thus preserving NO activity. Approximately 65% of circulating nitrate is excreted in the urine in 48 h, with the excretory pathway of the remainder unknown. The effect of declining renal function on nitrate clearance is unknown METHODS: Forty five subjects, 21 M, 24F, median age 69 (range 27-75 years) with renal function assessed by CKD-EPI eGFR between 9 and 89 ml/min/1.73 m completed the study. Following a 24 h low nitrate diet a microplate spectrophotometric method was employed to measure plasma nitrate concentration and 24 h urinary nitrate excretion were measured to determine renal nitrate clearance.
There was a strong positive correlation between urinary nitrate clearance and eGFR, (Spearman R = 0.7665, p < 0.0001) with a moderate negative correlation between plasma nitrate concentration and CKD-EPI eGFR, (Spearman's R = -0.37, p = 0.012). There was a trend between fractional excretion of nitrate and CKD-EPI eGFR (ml/min/1.73 m) Spearman's R 0.27, p = 0.07 though this did not reach statistical significance. Plasma nitrate concentration and serum creatinine concentration were positively correlated, Spearman's R = 0.39, p = 0.008.
We have observed a strong positive association between renal nitrate clearance and renal function such that plasma nitrate rises as renal function falls. Fractional excretion of nitrate appears to decline as renal function falls. As such, urinary nitrate excretion is unlikely to be a reliable marker of endogenous NO synthesis in settings where renal function is altered.
一氧化氮（NO）在人体内迅速氧化为亚硝酸盐和硝酸盐，而硝酸盐的含量要高得多。这些氧化产物可以通过复杂的肠-唾液途径重新循环回一氧化氮，从而保持 NO 的活性。大约 65%的循环硝酸盐在 48 小时内从尿液中排出，其余部分的排泄途径未知。肾功能下降对硝酸盐清除率的影响尚不清楚。
45 名受试者，21 名男性，24 名女性，年龄中位数为 69 岁（范围 27-75 岁），通过 CKD-EPI eGFR 评估肾功能，范围为 9-89ml/min/1.73m2，完成了这项研究。在进行 24 小时低硝酸盐饮食后，采用微孔板分光光度法测量血浆硝酸盐浓度，测量 24 小时尿硝酸盐排泄量以确定肾脏硝酸盐清除率。
尿硝酸盐清除率与 eGFR 呈强正相关（Spearman R=0.7665，p<0.0001），而血浆硝酸盐浓度与 CKD-EPI eGFR 呈中度负相关（Spearman R=-0.37，p=0.012）。硝酸盐的分数排泄与 CKD-EPI eGFR（ml/min/1.73m2）之间存在趋势（Spearman R 0.27，p=0.07），但未达到统计学意义。血浆硝酸盐浓度与血清肌酐浓度呈正相关（Spearman R=0.39，p=0.008）。
我们观察到肾脏硝酸盐清除率与肾功能之间存在强烈的正相关，即随着肾功能下降，血浆硝酸盐水平升高。随着肾功能下降，硝酸盐的分数排泄似乎下降。因此，在肾功能改变的情况下，尿硝酸盐排泄不太可能成为内源性 NO 合成的可靠标志物。
