Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.
Dis Markers. 2013;35(6):811-8. doi: 10.1155/2013/369784. Epub 2013 Nov 27.
Novel markers of nephrotoxicity, including kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and beta-2 microglobulin, were used in the detection of acute renal injury. The aim of the study was to establish the frequency of postchemotherapy chronic kidney dysfunction in children and to assess the efficacy of IL-18, KIM-1, and beta-2 microglobulin in the detection of chronic nephropathy. We examined eighty-five patients after chemotherapy (median age of twelve years). The median age at the point of diagnosis was 4.2 years, and the median follow-up time was 4.6 years. We performed classic laboratory tests assessing kidney function and compared the results with novel markers (KIM-1, beta-2 microglobulin, and IL-18). Features of subclinical renal injury were identified in forty-eight children (56.3% of the examined group). Nephropathy, especially tubulopathy, appeared more frequently in patients treated with ifosfamide, cisplatin, and/or carboplatin, following nephrectomy or abdominal radiotherapy (P = 0.14, P = 0.11, and P = 0.08, resp.). Concentrations of IL-18 and beta-2 microglobulin were comparable with classic signs of tubulopathy (P = 0.0001 and P = 0.05). Concentrations of IL-18 were also significantly higher in children treated with highly nephrotoxic drugs (P = 0.0004) following nephrectomy (P = 0.0007) and abdominal radiotherapy (P = 0.01). Concentrations of beta-2 microglobulin were higher after highly toxic chemotherapy (P = 0.004) and after radiotherapy (P = 0.02). ROC curves created utilizing IL-18 data allowed us to distinguish between children with nephropathy (value 28.8 pg/mL) and tubulopathy (37.1 pg/mL). Beta-2 microglobulin and IL-18 seem to be promising markers of chronic renal injury in children after chemotherapy.
新型肾毒性标志物，包括肾损伤分子 1（KIM-1）、白细胞介素 18（IL-18）和β2-微球蛋白，用于急性肾损伤的检测。本研究旨在确定儿童化疗后慢性肾功能障碍的频率，并评估 IL-18、KIM-1 和β2-微球蛋白在慢性肾病检测中的疗效。我们检查了 85 名化疗后的患者（中位年龄 12 岁）。诊断时的中位年龄为 4.2 岁，中位随访时间为 4.6 年。我们进行了经典的肾功能实验室检查，并将结果与新型标志物（KIM-1、β2-微球蛋白和 IL-18）进行了比较。在 48 名儿童（检查组的 56.3%）中发现了亚临床肾损伤的特征。肾切除术或腹部放疗后，接受异环磷酰胺、顺铂和/或卡铂治疗的患者更常出现肾病，尤其是肾小管病（P = 0.14、P = 0.11 和 P = 0.08）。IL-18 和β2-微球蛋白的浓度与肾小管病的经典标志相当（P = 0.0001 和 P = 0.05）。肾切除术（P = 0.0007）和腹部放疗（P = 0.01）后，接受高肾毒性药物治疗的儿童的 IL-18 浓度也显著升高。化疗后（P = 0.004）和放疗后（P = 0.02）β2-微球蛋白浓度升高。利用 IL-18 数据绘制的 ROC 曲线可以区分有肾病（值为 28.8 pg/mL）和肾小管病（37.1 pg/mL）的儿童。β2-微球蛋白和 IL-18 似乎是儿童化疗后慢性肾损伤有前途的标志物。
