Segarra-Medrano Alfons, Martin Marisa, Agraz Irene, Vilaprinyó Mercè, Chamoun Betty, Jatem Elias, Molina Maria, Colàs-Campàs Laura, Garcia-Carrasco Alicia, Roche Sarai
Servicio de Nefrologia, Hospital Arnau de Vilanova, Lleida, Spain.
Institut de Recerca Biomèdica, Lleida, Spain.
Clin Kidney J. 2019 Aug 1;13(4):607-612. doi: 10.1093/ckj/sfz105. eCollection 2020 Aug.
Height-adjusted total kidney volume (htTKV) is considered as the best predictor of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), but its limited predictive capacity stresses the need to find new biomarkers of ADPKD progression. The aim of this study was to investigate urinary biomarkers of ADPKD progression.
This observational study included ADPKD patients, and two comparator groups of ischaemic and non-ischaemic kidney injury: benign nephroangiosclerosis patients and non-ischaemic chronic kidney disease (CKD) patients. Proteinuria, htTKV and urinary levels of molecules are associated with ischaemia and/or tubular injury. The slope of estimated glomerular filtration rate (eGFR) was used as a dependent variable in univariate and multivariate models of kidney function decline.
The study included 130 patients with ADPKD, 55 with nephroangiosclerosis and 40 with non-ischaemic CKD. All patients had increased urinary concentrations of biomarkers associated with tubular lesions (liver fatty acid-binding protein, kidney injury molecule-1, β2-microglobulin) and molecules overexpressed under ischaemic conditions [hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)]. These biomarkers correlated positively with htTKV and negatively with the eGFR slope. htTKV was the single best predictor of the eGFR slope variability in univariate analyses. However, a multivariate model including urinary levels of β2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone.
The urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (β2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.
身高校正后的总肾体积（htTKV）被认为是常染色体显性多囊肾病（ADPKD）患者肾功能的最佳预测指标，但其有限的预测能力凸显了寻找ADPKD进展新生物标志物的必要性。本研究旨在探究ADPKD进展的尿液生物标志物。
这项观察性研究纳入了ADPKD患者，以及缺血性和非缺血性肾损伤的两个对照群体：良性肾血管硬化患者和非缺血性慢性肾脏病（CKD）患者。蛋白尿、htTKV以及与缺血和/或肾小管损伤相关分子的尿液水平。估计肾小球滤过率（eGFR）的斜率在肾功能下降的单变量和多变量模型中用作因变量。
该研究纳入了130例ADPKD患者、55例肾血管硬化患者和40例非缺血性CKD患者。所有患者尿液中与肾小管病变相关的生物标志物（肝脂肪酸结合蛋白、肾损伤分子-1、β2-微球蛋白）以及在缺血条件下过表达的分子（缺氧诱导因子-1α、血管内皮生长因子（VEGF）和单核细胞趋化蛋白-1（MCP-1））的浓度均升高。这些生物标志物与htTKV呈正相关，与eGFR斜率呈负相关。在单变量分析中，htTKV是eGFR斜率变异性的最佳单一预测指标。然而，与单独使用htTKV相比，包含β2-微球蛋白、MCP-1和VEGF尿液水平的多变量模型提高了预测ADPKD患者eGFR下降的能力。
与肾脏缺血（VEGF和MCP-1）或肾小管损伤（β2-微球蛋白）相关分子的尿液水平与ADPKD患者的肾功能恶化相关，因此，有望作为ADPKD进展的生物标志物。
