Abstract
The deterioration of renal function after childhood solid tumors treatment is the result of using the intensive multimodal therapy. In recent years, urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL) have been introduced as potential promising biomarkers of early kidney damage. The aim of the present study was to determine whether anticancer treatment has any effect on the concentration of KIM-1 and NGAL and its association with renal impairment in survivors of childhood solid tumors. Sixty patients previously treated for solid tumors were involved in this study. The median time after end of treatment was 8.35 years. Urine KIM-1 and NGAL levels were measured using immunoenzymatic ELISA commercial kits. Higher levels of urine NGAL, KIM-1/cr. (creatinine), and NGAL/cr. ratios were found in comparison with healthy controls (p < 0.0001). Among all subjects, 23% were found to have decreased estimated glomerular filtration rate (eGFR). A strong correlation between KIM-1/cr. and a cumulative dose of ifosfamide was observed (r = 0.865, p < 0.05). In addition, a moderate correlation between NGAL/cr. and a cumulative dose of cisplatin was identified (r = 0.534, p < 0.05). The AUC for KIM-1/cr. was 0.52, whereas NGAL/cr. showed a diagnostic profile describing the AUC of 0.67. Univariable regression showed significant associations between NGAL/cr. ratio and subjects after unilateral nephrectomy (coeff. 63.8, p = 0.007), cumulative dose of cisplatin (coeff. 0.111, p = 0.033), and age at diagnosis (coeff. 3.75, p = 0.023). The multivariable model demonstrated only cumulative dose of cisplatin as an independent factor influence on NGAL/cr. ratio. The results of our study showed increased levels of urine KIM-1 and NGAL many years after completion of the childhood solid tumors treatment, which correlated positively with a cumulative dose of ifosfamide and cisplatin. This study also suggests that unilateral nephrectomy could affect the concentration of the studied biomarkers.
Highlights
In recent decades, the number of childhood cancer survivors (CCS) has increased significantly with the improvement of diagnostic and treatment methods with the cure rate of over 80% for all types of cancers
The aim of the present study was to determine whether anticancer treatment used in childhood has any effect on the concentration of urinary kidney injury molecule-1 (KIM-1)
On the basis of the fact that there is an urgent need for improved diagnostic tools to predict nephrotoxicity in CCS in this study, we focused on the best promising urinary proteins (KIM-1 and neutrophil gelatinase-associated lipocalin (NGAL)) based on previous studies
Summary
The number of childhood cancer survivors (CCS) has increased significantly with the improvement of diagnostic and treatment methods with the cure rate of over 80% for all types of cancers. These patients experience many health problems after the end of the treatment. Kidney injury may have many distinct clinical pictures, including reduced estimated glomerular filtration rate (eGFR), loss of tubular function, and hypertension [5,6,7]. There are no suitable, widely used markers of tubular damage Due to all these limitations, new biomarkers to assess tubular function of the kidney are recently being sought. Urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL) have been introduced as potential promising biomarkers with high prognostic profile [10]
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