Rivara Matthew B, Zelnick Leila R, Hoofnagle Andrew N, Newitt Rick, Tracy Russell P, Kratz Mario, Weigle David S, Kestenbaum Bryan R
Kidney Research Institute, Seattle, WA.
Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA.
Clin Chem. 2017 Apr;63(4):915-923. doi: 10.1373/clinchem.2016.260117. Epub 2017 Feb 10.
The renal proximal tubule is essential for removing organic solutes and exogenous medications from the circulation. We evaluated diurnal, prandial, and long-term biological variation of 4 candidate endogenous markers of proximal tubular secretion.
We used LC-MS to measure plasma and urine concentrations of hippurate (HA), cinnamoylglycine (CMG), indoxyl sulfate (IS), and -cresol sulfate (PCS) in 25 healthy adults. We measured plasma concentrations of secreted solutes at 13 time points over a 24-h period, and again after 2 weeks and 14 weeks of follow-up. We further measured 24-h renal clearances of secreted solutes at baseline, 2 weeks, and 14 weeks.
Plasma concentrations of secreted solutes varied over the 24-h baseline period. Diurnal variation was greatest for HA, followed by CMG, IS, and PCS. Plasma concentrations of HA ( = 0.002) and IS ( = 0.02), but not CMG and PCS, increased significantly following meals. Long-term intraindividual biological variation (CV) in plasma concentrations of secreted solutes over 14 weeks varied from 21.8% for IS to 67.3% for PCS, and exceeded that for plasma creatinine (CV, 7.1%). Variation in 24-h renal clearances was similar among the secreted solutes [intraindividual variation (CV), 33.6%-47.3%] and was lower using pooled plasma samples from each study visit.
Plasma concentrations of HA, CMG, IS, and PCS fluctuate within individuals throughout the day and over weeks. Renal clearances of these secreted solutes, which serve as estimates of renal proximal tubule secretion, are also subject to intraindividual biological variation that can be improved by additional plasma measurements.
肾近端小管对于从循环中清除有机溶质和外源性药物至关重要。我们评估了近端小管分泌的4种候选内源性标志物的昼夜、餐时和长期生物学变异。
我们使用液相色谱-质谱法测量了25名健康成年人血浆和尿液中马尿酸盐（HA）、肉桂酰甘氨酸（CMG）、硫酸吲哚酚（IS）和对甲酚硫酸盐（PCS）的浓度。我们在24小时内的13个时间点测量了分泌溶质的血浆浓度，并在随访2周和14周后再次测量。我们还在基线、2周和14周时测量了分泌溶质的24小时肾清除率。
在24小时基线期内，分泌溶质的血浆浓度有所变化。HA的昼夜变化最大，其次是CMG、IS和PCS。进食后，HA（P = 0.002）和IS（P = 0.02）的血浆浓度显著升高，但CMG和PCS没有。14周内分泌溶质血浆浓度的长期个体内生物学变异（CV）从IS的21.8%到PCS的67.3%不等，超过了血浆肌酐的变异（CV，7.1%）。分泌溶质的24小时肾清除率变异相似[个体内变异（CV），33.6%-47.3%]，并且使用每次研究访视的混合血浆样本时变异更低。
HA、CMG、IS和PCS的血浆浓度在个体内全天和数周内都会波动。这些分泌溶质的肾清除率作为肾近端小管分泌的估计值，也存在个体内生物学变异，通过额外的血浆测量可以改善这种变异。
