title: Interleukin 18 as a marker of chronic nephropathy in children after anticancer treatment.
abstract: 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.
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zubowska
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wyka
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Zalewska-Szewczyk
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use; D020382:Interleukin-18 / Q000097:blood*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000139:chemically induced; D009396:Wilms Tumor / Q000188:drug therapy; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D020382:Interleukin-18; D001613:beta 2-Microglobulin; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide