Kee Youn Kyung, Shin Dong Ho, Oh Jieun, Park Ji Young, Kim Dong Hyun, Ko Kyungjai, Lee Samuel, Jeon Hee Jung
Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
Department of Laboratory Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Koreas.
PLoS One. 2025 May 21;20(5):e0324529. doi: 10.1371/journal.pone.0324529. eCollection 2025.
Chronic renal allograft injury (CRAI) is a major cause of allograft loss in kidney transplant recipients (KTRs). The aim of this study was to evaluate the associations of urinary apolipoprotein A4 (ApoA-IV) levels with renal function and rapid renal function decline in KTRs. This study included 50 KTRs. Proteomic analysis via liquid chromatography‒mass spectrometry and tandem mass spectrometry (LC-MS/MS) was performed to identify potential urinary biomarkers. The SWATH (sequential window acquisition of all theoretical mass spectra) method was used for protein quantification. Urinary ApoA-IV levels were validated by enzyme-linked immunosorbent assay (ELISA). Rapid renal function decline was defined as an estimated glomerular filtration rate (GFR) decrease of >3 mL/min/1.73 m2 per year or initiation of dialysis. The log-transformed urinary ApoA-IV levels measured by ELISA had a significantly inverse correlation with the estimated GFR (r = -0.72, P < 0.001). Moreover, urinary ApoA-IV levels were higher in patients with rapid renal function decline than in those with stable renal function (215.4 ± 181.8 μg/mL vs. 42.5 ± 72.4 μg/mL, P = 0.001). Univariate logistic regression analysis revealed that log-transformed urinary ApoA-IV levels were significantly associated with rapid renal function decline (odds ratio [OR] 6.70, 95% confidence interval [CI] 2.56-22.83; P < 0.001). Multiple logistic regression showed urinary ApoA-IV levels remained a significant risk factor for rapid renal function decline (OR 4.10, 95% CI 1.10-19.55; P = 0.047). ROC curve analysis revealed the area under the curve (AUC) of 0.834 (95% CI 0.722-0.945, P < 0.001) for urinary ApoA-IV levels in predicting rapid renal function decline. Our results suggest that urinary ApoA-IV levels might be a potential biomarker for renal allograft function and could be used as a predictor for rapid renal function decline in KTRs.
慢性肾移植损伤(CRAI)是肾移植受者(KTRs)移植肾丢失的主要原因。本研究旨在评估尿载脂蛋白A4(ApoA-IV)水平与KTRs肾功能及肾功能快速下降之间的关联。本研究纳入了50名KTRs。通过液相色谱-质谱联用和串联质谱(LC-MS/MS)进行蛋白质组学分析,以鉴定潜在的尿生物标志物。采用SWATH(所有理论质谱的顺序窗口采集)方法进行蛋白质定量。尿ApoA-IV水平通过酶联免疫吸附测定(ELISA)进行验证。肾功能快速下降定义为估计肾小球滤过率(GFR)每年下降>3 mL/min/1.73 m2或开始透析。ELISA测定的经对数转换的尿ApoA-IV水平与估计的GFR呈显著负相关(r = -0.72,P < 0.001)。此外,肾功能快速下降患者的尿ApoA-IV水平高于肾功能稳定患者(215.4±181.8 μg/mL对42.5±72.4 μg/mL,P = 0.001)。单因素逻辑回归分析显示,经对数转换的尿ApoA-IV水平与肾功能快速下降显著相关(比值比[OR] 6.70,95%置信区间[CI] 2.56 - 22.83;P < 0.001)。多因素逻辑回归显示,尿ApoA-IV水平仍然是肾功能快速下降的显著危险因素(OR 4.10,95% CI 1.10 - 19.55;P =