Dekker Shosha E I, Ruhaak L Renee, Romijn Fred P H T M, Meijer Esther, Cobbaert Christa M, de Fijter Johan W, Soonawala Darius
Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Kidney Int Rep. 2019 Mar 22;4(6):833-841. doi: 10.1016/j.ekir.2019.03.011. eCollection 2019 Jun.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and variable renal function decline that frequently leads to end-stage renal failure. With the advent of renoprotective treatment, there is renewed interest in noninvasive biomarkers to help identify patients at risk of rapid disease progression at early stages. Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated as early markers of acute kidney injury. Because these markers are associated with tubular damage, we studied the performance of both markers in a cohort with chronic tubular pathology. We investigated whether these biomarkers may be useful to evaluate disease severity in ADPKD.
In a cross-sectional analysis, we measured TIMP-2 and IGFBP7 in stored spot urine samples of patients with ADPKD with various stages of chronic kidney disease (CKD) and healthy controls by enzyme-linked immunosorbent assay. Renal function was estimated using the CKD-Epidemiology Collaboration equation. Patients were stratified according to the Kidney Disease Outcomes Quality Initiative classification for CKD. In a subset of patients, total kidney volume (TKV; using magnetic resonance imaging [MRI]) was measured.
In 296 patients with ADPKD (45.5 ± 11.5 years, 51.0% female, serum creatinine 106 [85-147] μmol/l), urine levels of TIMP-2 and IGFBP7 were not increased or tended to be lower as compared with 71 healthy controls (46.5 ± 18.5 years, 72.6% female). The levels did not differ across CKD stages, which remained so after correcting for urine creatinine or osmolality, and for age, sex, and urine protein in multivariable analyses.
Urinary levels of TIMP-2 and IGFBP7 were not higher in patients with ADPKD, and did not correlate with disease severity.
常染色体显性遗传性多囊肾病（ADPKD）的特征是囊肿进行性形成以及肾功能的不同程度下降，这常常导致终末期肾衰竭。随着肾脏保护治疗的出现，人们对非侵入性生物标志物重新产生兴趣，以帮助在疾病早期识别有快速疾病进展风险的患者。尿金属蛋白酶组织抑制剂-2（TIMP-2）和胰岛素样生长因子结合蛋白7（IGFBP7）已被确认为急性肾损伤的早期标志物。由于这些标志物与肾小管损伤相关，我们研究了这两种标志物在一组患有慢性肾小管病变的人群中的表现。我们调查了这些生物标志物是否有助于评估ADPKD的疾病严重程度。
在一项横断面分析中，我们通过酶联免疫吸附测定法测量了患有不同慢性肾脏病（CKD）阶段的ADPKD患者和健康对照者储存的随机尿样中的TIMP-2和IGFBP7。使用CKD-Epidemiology Collaboration方程估算肾功能。根据CKD的肾脏病预后质量倡议分类对患者进行分层。在一部分患者中，测量了总肾体积（TKV；使用磁共振成像[MRI]）。
在296例ADPKD患者（45.5±11.5岁，51.0%为女性，血清肌酐106[85-147]μmol/l）中，与71例健康对照者（46.5±18.5岁，72.6%为女性）相比，尿TIMP-2和IGFBP7水平未升高或有降低趋势。这些水平在CKD各阶段并无差异，在对尿肌酐或渗透压以及年龄、性别和尿蛋白进行多变量分析校正后仍无差异。
ADPKD患者的尿TIMP-2和IGFBP7水平并不更高，且与疾病严重程度无关。
