Tubular Secretion in CKD
Tubular Secretion in CKD
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DOI：
10.1681/asn.2014121193
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发表时间：
2016-07-01
影响因子：
13.6
通讯作者：
Kestenbaum, Bryan R.
中科院分区：
文献类型：
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作者：
Suchy-Dicey, Astrid M.;Laha, Thomas;Kestenbaum, Bryan R.
肾功能一般是通过测量GFR和尿白蛋白排泄来评估的。其他肾脏固有功能，如近端肾小管分泌，通常不能量化。小管分泌溶质比肾小球滤过更有效，是肾脏药物消除的主要机制，提示分泌功能障碍的重要临床后果。测量肾小管分泌作为肾脏功能的独立标志物可能有助于了解肾脏疾病的病因并改善不良后果的预测。在一项298例肾病患者的前瞻性队列研究中，我们使用液相色谱-串联质谱法测定血清和定时尿液样本的分泌溶质（马来酸盐、肉桂酰甘氨酸、对甲酚硫酸盐和吲哚酚硫酸盐）清除率，以估计分泌功能。我们通过相同样本中肌酐和尿素的平均清除率来估计GFR，并评估肾脏分泌与参与者特征、死亡率和CKD进展到透析的关系。小管分泌率与eGFR适度相关，并与参与者的一些特征相关，尤其是电解质的少量排泄。与eGFR无关的低清除率与较高的死亡风险相关（风险比为2.3；95%可信区间为1.1 - 4.7；风险比为2.5；95%可信区间分别为1.0 - 6.1）。危害模型也表明低肉桂酰甘氨酸清除率与透析风险之间存在关联，但统计分析并未排除零假设。因此，近端小管分泌功能的估计与肾小球滤过有关，但净分泌的实质性变化仍然存在。观察到的净分泌与死亡率和CKD进展的关系需要证实。
Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.