Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

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.