Miloševski-Lomić Gordana, Kotur-Stevuljević Jelena, Paripović Dušan, Nikolovski Srdjan, Lazić Jelena, Rodić Predrag, Milošević Goran, Mitrović Jadranka, Vukmir Biljana, Petrović Ana, Peco-Antić Amira
Faculty of Medicine, University of Belgrade, Belgrade, 11000, Serbia.
Nephrology Department, University Children's Hospital, Tiršova 10, Belgrade, 11000, Serbia.
BMC Nephrol. 2025 Mar 28;26(1):159. doi: 10.1186/s12882-025-04085-4.
Acute kidney injury (AKI) is a common complication in pediatric oncology patients, most often caused by nephrotoxic drugs. We aimed to assess whether levels of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), liver fatty acid binding protein (uL-FABP) and Vanin-1 (uVNN-1), individually and in combination-integrated could be early markers for cytotoxic treatment induced AKI.
Children with different malignant diseases treated with cisplatin (CIS) or ifosfamide (IFO) were included. AKI was defined using pediatric KDIGO (Kidney Disease Improving Global Outcomes) criteria by comparing pretreatment serum creatinine (sCr) values with those acquired at 48 h after the first or second chemotherapy cycle. Five serum (at baseline, 2, 6, 24 and 48 h after treatment) and four urine samples (at baseline, 2, 6 and 24 h after treatment) were obtained. Urinary biomarkers (uBm) were normalized to urine creatinine.
Thirty-eight patients were assessed. Within 48 h following chemotherapy 6 (15.79%) patients experienced AKI. Patients with AKI were younger and tend to have lower baseline sCr values than patients without AKI, but these differences were not statistically significant. Compared to baselines, all uBm were significantly increased during the first 6 h while sCr concentrations did not change significantly during the study period. The median increases in uBm during the first 6 h after treatment were 529.8% (interquartile range - IQR, 63.9-1835.2%) - 2194.0% (IQR, 255.3-4695.5%) in AKI vs. 302.2% (IQR 114.6-561.2%) -429.8% (156.5-1467.0%) in non-AKI group depending of tested uBm. The magnitude of these changes over time didn't differ significantly between groups. The area under receiver operator curve (AUC) for uL-FABP and uNGAL at 24 h after chemotherapy were 0.81 and 0.72, respectively. The ROC analysis revealed that the other individual biomarkers' performance at any time-point wasn't statistically significant (AUC < 0.7). A model of integrated-combined uBm, 2 h (AUC 0.78), 6 h (AUC 0.85) and 24 h after (AUC 0.92) treatment with CIS and/or IFO showed good utility for early AKI prediction.
The results of this study support that the use of the uBm to improves early AKI prediction in patients receiving CIS and/or IFO containing chemotherapy. Further studies on larger comparable groups of patients are needed.
急性肾损伤（AKI）是儿科肿瘤患者常见的并发症，最常见的原因是肾毒性药物。我们旨在评估尿肾损伤分子-1（uKIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）、肝脏脂肪酸结合蛋白（uL-FABP）和血管生成素-1（uVNN-1）的水平，单独及联合检测是否可作为细胞毒性治疗诱导AKI的早期标志物。
纳入接受顺铂（CIS）或异环磷酰胺（IFO）治疗的不同恶性疾病患儿。根据儿科改善全球肾脏病预后组织（KDIGO）标准，通过比较化疗前血清肌酐（sCr）值与首个或第二个化疗周期后48小时测得的值来定义AKI。采集5份血清样本（基线、治疗后2、6、24和48小时）和4份尿液样本（基线、治疗后2、6和24小时）。尿生物标志物（uBm）以尿肌酐进行标准化。
共评估了38例患者。化疗后48小时内，6例（15.79%）患者发生AKI。与未发生AKI的患者相比，发生AKI的患者年龄更小，基线sCr值往往更低，但这些差异无统计学意义。与基线相比，所有uBm在最初6小时内均显著升高，而sCr浓度在研究期间无显著变化。治疗后最初6小时内，AKI组uBm的中位数升高幅度为529.8%（四分位间距-IQR，63.9-1835.2%）-2194.0%（IQR，255.3-4695.5%），而非AKI组为302.2%（IQR 114.6-561.2%）-429.8%（156.5-1467.0%），具体取决于所检测的uBm。两组间这些变化随时间的幅度无显著差异。化疗后24小时，uL-FABP和uNGAL的受试者工作特征曲线下面积（AUC）分别为0.81和0.72。ROC分析显示，其他单个生物标志物在任何时间点的表现均无统计学意义（AUC＜0.7）。CIS和/或IFO治疗后2小时（AUC 0.78）、6小时（AUC 0.85）和24小时（AUC 0.92）的联合uBm模型对早期AKI预测具有良好的效用。
本研究结果支持使用uBm改善接受含CIS和/或IFO化疗患者的早期AKI预测。需要对更大规模的可比患者群体进行进一步研究。
