Basturk Taner, Sari Ozlem, Koc Yener, Eren Nezaket, Isleem Mahmoud, Kara Ekrem, Sevinc Mustafa, Sakaci Tamer, Ahbap Elbis, Hasbal Nuri B, Bayrakdar Caglayan Feyza, Unsal Abdulkadir
Department of Nephrology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey -
Department of Biochemistry, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
Minerva Urol Nefrol. 2017 Jun;69(3):307-312. doi: 10.23736/S0393-2249.16.02770-3. Epub 2016 Oct 21.
Neutrophilgelatinase-associated lipocalin (NGAL) has been proven to be a useful biomarker for early detection of acute kidney injury, but it is not known whether adding NGAL measurements to conventional risk factors will improve the risk assessment in the setting of chronic kidney disease (CKD). The aim of the present study was to examine the correlation of NGAL with early stage renal impairment in CKD and to evaluate its prognostic value in these subjects.
This is a prospective observational cohort study of 54 patients with early stage (stage 1-2) CKD. Patients aged between 18 and 65 years with stable disease were enrolled in this study. Patients with a history of primary glomerulonephritis, diabetes mellitus, acute kidney injury, systemic diseases and stage 3-4-5 CKD were excluded from the study group. Estimated glomerular filtration (eGFR) rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The patients were followed for two years to determine the ability of baseline NGAL for prediction of renal outcome. In our study disease progression was defined as changes in eGFR (ΔeGFR) and proteinuria (Δproteinuria). Patients divided into two groups according to NGAL cut-off value as group 1 (N.=23, NGAL ≤98.71 ng/mL) and group 2 (N.=31, NGAL >98.71 ng/mL).
Out of 54 patients (mean age: 45.6±7.6 years, 64.8% female, baseline eGFR: 84.6±16.8 mL/min/1.73 m2, baseline NGAL level: 157.47±121.52 ng/mL); 18 patients were stage 1 and 36 patients were stage 2 CKD. In the ROC analysis, we found that the optimal cut-off value of NGAL for predicting stage 2 CKD was 98.71ng/mL (P=0.005) with the 72.2% sensitivity and 72.2% specificity. In correlation analysis, we evaluated significantly positive correlations between NGAL and CKD stage (r=0.389, P=0.004), baseline/last serum creatinine level (r=0.530, P<0.001 and r=0.439, P=0.003; respectively), last proteinuria level (r=0.359, P=0.043). There were significantly negative correlation between NGAL and baseline/last eGFR (r=-0.498, P<0.001 and r=-0.462, P=0.002; respectively). Compared to the group 1, we determined that group 2 patients had further deterioration in renal functions regarding ΔeGFR (-1.12±12.6 mL/min vs. -1.46±12.4 mL/min: respectively, P=0.930) and Δproteinuria (98.1±569.3 mg/day vs. 339±701.6 mg/day; respectively, P=0.305); however these differences were not statistically significant at the end of the two years follow-up period.
Altough NGAL has a positive correlation with disease severity, it does not seem to be a marker of disease progression in patients with early stage CKD. But further studies stated in different patient groups may also explain the usability of NGAL in clinical practice.
中性粒细胞明胶酶相关脂质运载蛋白(NGAL)已被证明是急性肾损伤早期检测的有用生物标志物,但在慢性肾脏病(CKD)患者中,将NGAL检测结果添加到传统风险因素中是否会改善风险评估尚不清楚。本研究的目的是探讨NGAL与CKD早期肾功能损害的相关性,并评估其在这些患者中的预后价值。
这是一项对54例CKD早期(1-2期)患者进行的前瞻性观察队列研究。纳入年龄在18至65岁之间、病情稳定的患者。研究组排除有原发性肾小球肾炎、糖尿病、急性肾损伤、全身性疾病及CKD 3-4-5期病史的患者。采用慢性肾脏病流行病学协作组(CKD-EPI)公式计算估算肾小球滤过率(eGFR)。对患者进行为期两年的随访,以确定基线NGAL预测肾脏结局的能力。在本研究中,疾病进展定义为eGFR(ΔeGFR)和蛋白尿(Δ蛋白尿)的变化。根据NGAL临界值将患者分为两组,即第1组(n=23,NGAL≤98.71 ng/mL)和第2组(n=31,NGAL>98.71 ng/mL)。
54例患者(平均年龄:45.6±7.6岁,64.8%为女性,基线eGFR:84.6±16.8 mL/min/1.73 m2,基线NGAL水平:157.47±121.52 ng/mL)中,18例为1期CKD,36例为2期CKD。在ROC分析中,我们发现预测2期CKD的NGAL最佳临界值为98.71 ng/mL(P=0.005),敏感性为72.2%,特异性为72.2%。在相关性分析中,我们评估了NGAL与CKD分期(r=0.389,P=0.004)、基线/末次血清肌酐水平(分别为r=0.530,P<0.001和r=0.439,P=0.003)、末次蛋白尿水平(r=0.359,P=0.043)之间存在显著正相关。NGAL与基线/末次eGFR之间存在显著负相关(分别为r=-0.498,P<0.001和r=-0.462,P=0.002)。与第1组相比,我们发现第2组患者在ΔeGFR(分别为-1.12±12.6 mL/min对-1.46±12.4 mL/min:P=0.930)和Δ蛋白尿(分别为98.1±569.3 mg/天对339±701.6 mg/天;P=0.305)方面肾功能进一步恶化;然而,在两年随访期结束时,这些差异无统计学意义。
尽管NGAL与疾病严重程度呈正相关,但它似乎不是CKD早期患者疾病进展的标志物。但在不同患者群体中进行的进一步研究可能也会解释NGAL在临床实践中的可用性。