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.

Figure 1

(a) Concentrations of beta-2 microglobulin depending on treatment modality. (b) Concentrations of beta-2 microglobulin depending on clinical evidence of nephrotoxicity. (c) Concentrations of IL-18 depending on treatment modality. (d) Concentrations of IL-18 depending on clinical evidence of nephrotoxicity.

Figure 2

(a) Receiver operating characteristic (ROC) curve of IL-18 for the detection of nephropathy. The best cut-off threshold of >28.8 pg/mL allowed for a sensitivity of 51% and specificity of 88%. Area under the curve equaled (0.65; 95% Confidence Interval 0.53–0.77). (b) ROC curves for tubulopathy (solid line) and glomerulopathy (dashed line). The optimal cut-off value for diagnosing tubulopathy using IL-18 equaled 37.1 pg/mL which showed sensitivity of 66% and specificity of 86%; AUC equaled 0.78 (95% CI 0.69–0.88).