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Interleukin 18 as a marker of chronic nephropathy in children after anticancer treatment.

Zubowska M, Wyka K, Fendler W, Młynarski W, Zalewska-Szewczyk B - Dis. Markers (2013)

Bottom Line: 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).Beta-2 microglobulin and IL-18 seem to be promising markers of chronic renal injury in children after chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.

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.

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(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.
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fig1: (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.

Mentions: Assessments of beta-2 microglobulin, IL-18, and KIM-1 concentrations in urine showed significant differences between particular subgroups of patients. We found statistically significant connections between previously used treatments (without nephrotoxic drugs, with moderately nephrotoxic drugs, with highly nephrotoxic drugs, and nephrectomy) and concentrations of IL-18 (P = 0.0004) and beta-2 microglobulin (P = 0.004). Concentrations of IL-18 were lower in children treated with cyclophosphamide compared to children treated with ifosfamide/cisplatin/carboplatin (P = 0.006). Differences in KIM-1 concentrations in particular subgroups were nearly significant (P = 0.11). Patients after nephrectomy had significantly higher concentrations of IL-18 (P = 0.0007) and lower concentrations of KIM-1 than patients with both kidneys (P = 0.03). Data is shown in Figures 1(a) and 1(c).


Interleukin 18 as a marker of chronic nephropathy in children after anticancer treatment.

Zubowska M, Wyka K, Fendler W, Młynarski W, Zalewska-Szewczyk B - Dis. Markers (2013)

(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.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3860090&req=5

fig1: (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.
Mentions: Assessments of beta-2 microglobulin, IL-18, and KIM-1 concentrations in urine showed significant differences between particular subgroups of patients. We found statistically significant connections between previously used treatments (without nephrotoxic drugs, with moderately nephrotoxic drugs, with highly nephrotoxic drugs, and nephrectomy) and concentrations of IL-18 (P = 0.0004) and beta-2 microglobulin (P = 0.004). Concentrations of IL-18 were lower in children treated with cyclophosphamide compared to children treated with ifosfamide/cisplatin/carboplatin (P = 0.006). Differences in KIM-1 concentrations in particular subgroups were nearly significant (P = 0.11). Patients after nephrectomy had significantly higher concentrations of IL-18 (P = 0.0007) and lower concentrations of KIM-1 than patients with both kidneys (P = 0.03). Data is shown in Figures 1(a) and 1(c).

Bottom Line: 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).Beta-2 microglobulin and IL-18 seem to be promising markers of chronic renal injury in children after chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Łódź, Poland.

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.

Show MeSH
Related in: MedlinePlus