Department of Medicine, Stanford University, Palo Alto, California.
Department of Medicine, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California.
J Am Soc Nephrol. 2021 Nov;32(11):2877-2884. doi: 10.1681/ASN.2021030336. Epub 2021 Aug 18.
The clearance of solutes removed by tubular secretion may be altered out of proportion to the GFR in CKD. Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD.
To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 patients with CKD and an eGFR of 7±2 ml/min per 1.73 m and 16 control participants. Fractional clearances were calculated as the ratios of urine to plasma levels of each solute relative to those of creatinine and urea in patients with CKD and to those of creatinine in controls.
Metabolomic analysis identified 39 secreted solutes with fractional clearance >3.0 in control participants. Fractional clearance values in patients with CKD were reduced on average to 65%±27% of those in controls. These values were significantly lower for 18 of 39 individual solutes and significantly higher for only one. Assays of the secreted anions phenylacetyl glutamine, -cresol sulfate, indoxyl sulfate, and hippurate confirmed variable impairment of secretory clearances in advanced CKD. Fractional clearances were markedly reduced for phenylacetylglutamine (4.2±0.6 for controls versus 2.3±0.6 for patients with CKD; <0.001), -cresol sulfate (8.6±2.6 for controls versus 4.1±1.5 for patients with CKD; <0.001), and indoxyl sulfate (23.0±7.3 versus 7.5±2.8; <0.001) but not for hippurate (10.2±3.8 versus 8.4±2.6; =0.13).
Secretory clearances for many solutes are reduced more than the GFR in advanced CKD. Impaired secretion of these solutes might contribute to uremic symptoms as patients approach dialysis.
在慢性肾脏病（CKD）中，经肾小管分泌清除的溶质的清除率可能与肾小球滤过率（GFR）不成比例地改变。最近的研究描述了 CKD 患者中相对于 GFR 的废物溶质分泌清除率存在相当大的变异性。
为了检验分泌清除率相对于 GFR 在接近透析的患者中降低的假设，我们使用代谢组学分析来鉴定 16 名 CKD 患者和 16 名对照参与者的同时尿液和血浆样本中的溶质，这些患者的 eGFR 为 7±2 ml/min/1.73 m，且他们的血清肌酐清除率为 7±2 ml/min/1.73 m。分数清除率计算为患者中每个溶质的尿液与血浆水平与肌酐和尿素的比值，以及对照中每个溶质的尿液与血浆水平与肌酐的比值。
代谢组学分析鉴定出 39 种在对照参与者中具有分数清除率>3.0 的分泌溶质。CKD 患者的分数清除率平均值降低至对照的 65%±27%。在 39 种单个溶质中，有 18 种的分数清除率显著降低，只有 1 种显著升高。对分泌阴离子苯乙酰谷氨酰胺、-对甲酚硫酸盐、吲哚硫酸和马尿酸的测定证实了晚期 CKD 中分泌清除率的不同程度的损害。苯乙酰谷氨酰胺（对照者为 4.2±0.6，CKD 患者为 2.3±0.6；<0.001）、-对甲酚硫酸盐（对照者为 8.6±2.6，CKD 患者为 4.1±1.5；<0.001）和吲哚硫酸（对照者为 23.0±7.3，CKD 患者为 7.5±2.8；<0.001）的分数清除率显著降低，但马尿酸（对照者为 10.2±3.8，CKD 患者为 8.4±2.6；=0.13）的分数清除率无显著降低。
在晚期 CKD 中，许多溶质的分泌清除率比 GFR 降低得更多。这些溶质的分泌受损可能导致尿毒症症状，因为患者接近透析。
