Abstract
The objectives of this study were to evaluate urinary beta-2-microglobulin (β2M) levels in long-term childhood cancer survivors and to establish its association with anticancer drug-induced nephrotoxicity. The study consisted of 165 childhood cancer survivors (CCS) who were in continuous complete remission. We reported that CCS had a significantly higher level of β2M (p < 0.001) and β2M/Cr. ratio (p < 0.05) than healthy peers. Among all participants, 24 (14.5%) had decreased eGFR (<90 mL/min/1.73 m2). A significant positive correlation between β2M/Cr. ratio and body mass index (coef. 14.48, p = 0.046) was found. Furthermore, higher levels of urinary β2M were detected among CCS with a longer follow-up time (over 5 years) after treatment. Subjects with decreased eGFR showed statistically higher urinary β2M levels (20.06 ± 21.56 ng/mL vs. 8.55 ± 3.65 ng/mL, p = 0.007) compared with the healthy peers. Twelve survivors (7.2%) presented hyperfiltration and they had higher urinary β2M levels than CCS with normal glomerular filtration (46.33 ± 93.11 vs. 8.55 ± 3.65 ng/mL, p = 0.029). This study did not reveal an association between potential treatment-related risk factors such as chemotherapy, surgery, radiotherapy, and the urinary β2M level. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). We demonstrated that urinary beta-2-microglobulin may play a role in the subtle kidney injury in childhood cancer survivors; however, the treatment-related factors affecting the β2M level remain unknown. Further prospective studies with a longer follow-up time are needed to confirm the utility of urinary β2M and its role as a non-invasive biomarker of renal dysfunction.
Highlights
Improvements in the diagnosis and treatment of pediatric cancers have resulted in significantly higher survival rates
There are many known causes of renal damage among cancer survivors (CCS). These may result from the multimodal therapy, supportive treatment used, and the cancer itself— by tumor infiltration, disruption of glomerular and tubular development, acute tumor lysis syndrome, or urinary tract obstruction
All the children were treated according to the international protocols in line with the diagnosis, approved by the Polish Pediatric Leukemia and Lymphoma Group, and Polish Pediatric Solid Tumors Group
Summary
Improvements in the diagnosis and treatment of pediatric cancers have resulted in significantly higher survival rates. Childhood cancer survivors (CCS) are at greater risk of experiencing many treatment-related adverse effects that substantially affect later quality of life [1,2]. Nephrotoxicity is one of the most common late sequelae with prevalence ranging up to 80% based on the population studied [3]. There are many known causes of renal damage among CCS. These may result from the multimodal therapy (chemotherapy, radiotherapy, immunotherapy, and surgery), supportive treatment used (aminoglycoside antibiotics, diuretics, or antifungal agents), and the cancer itself— by tumor infiltration, disruption of glomerular and tubular development, acute tumor lysis syndrome, or urinary tract obstruction. CCS have a nine-fold increased risk of developing chronic nephrotoxicity compared to their siblings, according to one of the largest studies available [4]
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