Urinary KIM-1 in children undergoing nephrotoxic antineoplastic treatment: a prospective cohort study

Abstract

Background Acute kidney injury (AKI) is a significant complication in patients with cancer, and nephrotoxic drugs are among the most common causes of AKI. To date, there is no study evaluating the potential role of renal biomarkers in children receiving nephrotoxic chemotherapy. Methods A prospective study was conducted in children receiving methotrexate (MTX) or platinum-based treatment. Urinary kidney injury molecule-1 (KIM-1) was measured 24 h after the initiation of the chemotherapy infusion, and serum creatinine (sCr) was measured prior to drug infusion and at 24, 48, 72, and 96 h, 1 and 2 weeks, and 3 months postinitiation of treatment. Results A total of 64 children were evaluated, of whom 21 (32.8 %) developed AKI. The majority had AKI stage 1 (n= 12, 57.1 %) and only one developed AKI stage 3. Median values of urinary KIM-1 were higher in patients with AKI than in those without AKI [10.7, interquartile range (IQR) 1.6-17.9 vs. 4.3 (IQR 1.3-6.1) ng/mg creatinine; p<0.01]. Urinary KIM-1 showed good discrimination for AKI in patients receiving nephrotoxic chemotherapy, with an area under the receiver operator characteristic curve for AKI up to 1 week later of 0.82 (95% confidence interval 0.66-0.95). Even when measured only 24 h after drug infusion, urinary KIM-1 still showed good discrimination to predict persistent renal impairment three months later. Conclusion Urinary KIM-1 measured 24 h after the start of drug infusion has the potential to detect early AKI in pediatric patients treated with MTX or platinum-class drugs.

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

“…They reported the increase of KIM‐1 in renal tissue and an augmented urinary NAG and Cys C . On the other hand, Carvalho Pedrosa et al showed a direct correlation between MTX serum levels and urinary KIM‐1 levels 24 hours after MTX infusion in paediatric patients. In the same way, plasma Cys C was useful to evaluate the renal performance before and after the infusion of HDMTX in paediatric patients with acute lymphoblastic leukaemia .…”

“…After different MTX treatments in rats, some studies employed novel biomarkers to assess renal damage, besides measuring the traditional ones (such as blood urea nitrogen and plasma creatinine). They reported the increase of KIM-1 in renal tissue 30,31 and an augmented urinary NAG 32 and Cys C. 33 On the other hand, Carvalho Pedrosa et al 34 showed a direct correlation between MTX serum levels and urinary KIM-1 levels 24 hours after MTX infusion in paediatric patients. In the same way, plasma Cys C was useful to evaluate the renal performance before and after the infusion of HDMTX in paediatric patients with acute lymphoblastic leukaemia.…”

Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy

“…Few studies (almost only in adults) evaluated AKI biomarkers in chemotherapy AKI . In Cis‐treated adults, AKI biomarker concentrations were elevated before treatment .…”

Markers of acute kidney injury in children undergoing hematopoietic stem cell transplantation

“…34 Kidney injury molecule 1 is also a useful marker of kidney function in children undergoing chemotherapy with MTX or cisplatin derivatives. 35 Although the value of KIM-1 as a marker for AKI has been demonstrated in a recent meta-analysis, 36 none of the data concerned the detection of AKI following HSCT.…”