Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA, USA.
Kidney Research Institute, Seattle, WA, USA.
Nephrol Dial Transplant. 2020 Nov 1;35(11):1916-1923. doi: 10.1093/ndt/gfz144.
Laboratory measures of glomerular function such as the glomerular filtration rate (GFR) contribute toward clinical evaluation of chronic kidney disease (CKD). However, diverse CKD etiologies have distinct pathological mechanisms that may differentially impact the kidney tubules. Little is known regarding how tubular function changes with varying kidney disease types.
We used targeted mass spectrometry to quantify paired serum and urine concentration of 11 solutes of proximal tubular secretion in 223 patients from an outpatient CKD cohort. We reviewed clinic notes to ascertain the primary CKD diagnosis and categorized these as vascular, diabetic, glomerular or tubulointerstitial. We used one-way analysis of variance to compare secretory solute clearance across diagnoses setting a false discovery threshold of ≤5% and used linear regression to compare differences after adjustments for estimated GFR, age, race, sex, body mass index and urine albumin excretion.
After full adjustment, glomerular disease was associated with higher clearances of three tubular secretory solutes compared with vascular disease: 48% higher isovalerylglycine clearance [95% confidence interval (CI) 18-87%], 28% higher kynurenic acid clearance (95% CI 3-59%) and 33% higher tiglylglycine clearance (95% CI 7-67%). Diabetic kidney disease (DKD) was associated with 39% higher isovalerylglycine clearance compared with vascular disease (95% CI 13-72%).
Glomerular disorders and DKD are associated with higher net clearances of several secretory solutes compared with vascular causes of kidney disease. These findings suggest that different underlying etiologies of CKD may differentially impact proximal tubular secretory pathways.
肾小球滤过率（GFR）等肾小球功能的实验室检测有助于对慢性肾脏病（CKD）进行临床评估。然而，不同的 CKD 病因具有不同的病理机制，这些机制可能会对肾小管产生不同的影响。目前尚不清楚肾小管功能随不同类型的肾病如何变化。
我们使用靶向质谱法对来自门诊 CKD 队列的 223 名患者的血清和尿液中 11 种近端肾小管分泌物的浓度进行了配对检测。我们查阅了临床记录，以确定主要的 CKD 诊断，并将这些诊断归类为血管性、糖尿病性、肾小球性或肾小管间质性。我们使用单向方差分析比较了不同诊断组之间的分泌溶质清除率，设定了 5%的错误发现率阈值，并使用线性回归比较了在调整了估计的肾小球滤过率、年龄、种族、性别、体重指数和尿白蛋白排泄量后，差异。
经过全面调整，与血管疾病相比，肾小球疾病与三种肾小管分泌溶质的清除率更高相关：异缬氨酸清除率高 48%（95%CI 18-87%），犬尿氨酸清除率高 28%（95%CI 3-59%），以及丁羟甘氨酸清除率高 33%（95%CI 7-67%）。与血管疾病相比，糖尿病肾病（DKD）的异缬氨酸清除率高 39%（95%CI 13-72%）。
与血管性肾病病因相比，肾小球疾病和 DKD 与几种分泌性溶质的更高净清除率相关。这些发现表明，CKD 的不同潜在病因可能对近端肾小管分泌途径产生不同的影响。
