Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Biomolecules. 2023 Feb 9;13(2):338. doi: 10.3390/biom13020338.
Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) have been associated with acute kidney injury and the severity and progression of chronic kidney disease (CKD). This study investigated its potential utility as a biomarker for the risk of new-onset CKD in a population-based cohort study. Individuals without CKD at baseline (n = 4660) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma NGAL concentrations were investigated for their associations with new-onset CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m, urinary albumin excretion (UAE) > 30 mg/24-h, or both. Mean (±SD) plasma NGAL concentrations were 104.0 (±34.7) μg/L and median eGFR was 96 [IQR: 85.3-105.8] mL/min/1.73 m. After median follow-up of 8.3 [IQR: 7.8-8.9] years, 467 participants developed new-onset CKD. Plasma NGAL concentrations were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.35 [95% CI: 1.11-1.63], = 0.002), even after adjustment for potentially confounding factors (1.37 [1.09-1.73], = 0.007) except baseline eGFR (1.09 [0.86-1.37], = 0.490). In secondary analyses, plasma NGAL concentrations were significantly associated with new-onset CKD as defined by eGFR < 60 mL/min/1.73 m alone (adjusted HR per doubling 2.54 [1.69-3.80], < 0.001), which was abrogated after adjustment for eGFR (1.05 [0.69-1.59], = 0.828), also when UAE > 30 mg/24-h was set as individual outcome (1.05 [0.82-1.35], = 0.705). Higher plasma NGAL concentrations are associated with an increased risk of developing CKD in the general population. This association is dependent on renal function, and mainly driven by new-onset CKD as defined by renal function decline.
循环中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 的水平与急性肾损伤以及慢性肾脏病 (CKD) 的严重程度和进展相关。本研究在一项基于人群的队列研究中，调查了其作为新发生 CKD 风险的生物标志物的潜力。在荷兰进行的预防肾脏和血管终末期疾病 (PREVEND) 前瞻性基于人群的队列研究中，纳入了基线时无 CKD（n=4660）的个体。研究了基线时血浆 NGAL 浓度与新发生 CKD 的关系，新发生 CKD 定义为估算肾小球滤过率（eGFR）<60mL/min/1.73m、尿白蛋白排泄（UAE）>30mg/24h 或两者的复合结果。平均（±SD）血浆 NGAL 浓度为 104.0（±34.7）μg/L，中位 eGFR 为 96[IQR：85.3-105.8]mL/min/1.73m。中位随访 8.3[IQR：7.8-8.9]年后，467 名参与者出现新发生的 CKD。血浆 NGAL 浓度与新发生 CKD 的风险增加显著相关（每翻倍 HR 为 1.35[95%CI：1.11-1.63]， = 0.002），即使在调整了可能的混杂因素后（1.37[1.09-1.73]， = 0.007），但基线 eGFR 除外（1.09[0.86-1.37]， = 0.490）。在次要分析中，血浆 NGAL 浓度与仅以 eGFR<60mL/min/1.73m 定义的新发生 CKD 显著相关（每翻倍调整 HR 为 2.54[1.69-3.80]，<0.001），但在调整 eGFR 后则不相关（1.05[0.69-1.59]， = 0.828），当以 UAE>30mg/24-h 为单独结局时也不相关（1.05[0.82-1.35]， = 0.705）。较高的血浆 NGAL 浓度与普通人群中 CKD 发生风险的增加相关。这种相关性依赖于肾功能，主要由肾功能下降定义的新发生 CKD 驱动。
