Department of Medicine, Washington University, St. Louis, Missouri.
Department of Medicine, Stanford University, Palo Alto, California.
Kidney360. 2020 Aug 27;1(8):724-730. doi: 10.34067/kid.0001632020.
Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.
Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS that bind to plasma proteins.
Fractional clearance values for PAG, HIPP, IS, and PCS were >1.0 in patients with AKI as well as controls, indicating that these solutes were still secreted by the tubules of the injured kidneys. Fractional clearance values were, however, significantly lower in patients with AKI than controls, indicating that kidney injury reduced tubular secretion more than glomerular filtration (AKI versus control: PAG, 2.1±0.7 versus 4.6±1.4, <0.001; HIPP, 10±5 versus 15±7, =0.02; IS, 10±6 versus 28±7, <0.001; PCS, 3.3±1.8 versus 10±3, <0.001). Free plasma levels rose out of proportion to total plasma levels for each of the bound solutes in AKI, so that calculating their fractional clearance in terms of their total plasma levels failed to reveal their impaired secretion.
Tubular secretion of organic solutes can be reduced out of proportion to glomerular filtration in AKI. Impaired secretion of protein-bound solutes may be more reliably detected when clearances are expressed in terms of their free, unbound levels in the plasma.
肾功能的损伤通常通过测量肌酐的积累来评估，肌酐是一种主要通过肾小球滤过清除的有机溶质。我们在急性肾损伤患者中检测了溶质的清除率是否与肌酐的清除率成比例降低，这些溶质通过肾小管分泌。
在 10 名急性肾损伤患者和 17 名对照者的随机尿液和血浆样本中，测量了 4 种内源性产生的有机溶质（苯乙酰谷氨酰胺[PAG]、马尿酸[HIPP]、吲哚硫酸[IS]和对甲酚硫酸盐[PCS]）。以肌酐为基准计算相对清除率，以评估肾小管分泌作用。根据 HIPP、IS 和 PCS 与血浆蛋白结合的游离、未结合水平，计算出相对清除率值。
急性肾损伤患者和对照组患者的 PAG、HIPP、IS 和 PCS 的相对清除率均大于 1.0，表明这些溶质仍由受损肾脏的肾小管分泌。然而，急性肾损伤患者的相对清除率明显低于对照组，表明肾损伤导致肾小管分泌减少的程度超过了肾小球滤过（急性肾损伤患者与对照组相比：PAG，2.1±0.7 对 4.6±1.4，<0.001；HIPP，10±5 对 15±7，=0.02；IS，10±6 对 28±7，<0.001；PCS，3.3±1.8 对 10±3，<0.001）。对于每种结合的溶质，在急性肾损伤中，其游离血浆水平相对于总血浆水平不成比例地升高，因此，以其总血浆水平为基准计算其相对清除率，未能发现其分泌受损。
在急性肾损伤中，有机溶质的肾小管分泌可不成比例地低于肾小球滤过。当以其在血浆中的游离、未结合水平表示清除率时，可能更可靠地检测到蛋白结合溶质的分泌受损。
