| Background and ObjectiveAcute lymphoblastic leukemia(acute lymphoblastic leukemia, ALL) was one of the most common hematologic malignancy in childhood and was caused by hematopoietic stem cell proliferation and differentiation of abnormalities.With the rapid development of science and technology and other aspects of molecular genetics, ALL's treatments had developed from a single chemotherapy to advanced molecular targeted therapy and immunotherapy and genetic biological therapy and through these means, the long-term free survival of ALL's patients and cure rate had more improved. For this moment, conventional chemotherapy was still one of the effective treatment of ALL. In the chemotherapy of ALL, the application of high-dose methotrexate(High-dose Methotrexate, HD-MTX) combined with chemotherapy drugs was the most usually clinical treatment. However, as one of the nephrotoxic drugs,MTX not only could kill tumor cells,but also could reduce some kidney injury and it meaned that MTX will result in acute renal function impairment.In the treatment program of acute lymphoblastic leukemia in children,after application of high-dose methotrexate of 36 hours,the doctor must give rescue with leucovorin, while emphasizing the given of adequate hydration and alkalization applications, at the same time,giving examination of renogram or srume creatinine before the using chemotherapy and during the chemotherapy. Nevertheless,the classical detection index in the diagnosis and measure of acute renal function,for example the renogram not only was invasive,but also was less sensitive,moreover,the index of serum creatinine and urine volume was later and unstable.So that the children having renal function impairment could not be discovered in time or diagnosed in mistake. The incidence of acute kidney injury in children not only increased the time of staying the hospital, but also increased mortality in children, and therefore timely for children with acute kidney injury to make an accurate diagnosis, giving the relevant intervention for children with ALL was particularly important.Many studies had showen that neutrophil gelatinase-associated lipocalin(NGAL) was a member of lipocalin superfamily, when renal epithelial cells were damaged, NGAL was a state of high expression. Kidney injury molecule-1( KIM-1) was a member of immunoglobulin gene superfamily, a large of experiments had found that it highly expressed in proximal tubular epithelial cells of ischemic and nephrotoxic injury. In recent years, both of biological indicators were induced as more sensitive and specific indicators in the aspect of research evaluation of acute kidney injury. However, the studies of two biomarkers were focused in cardiac surgery, critical care patients, and contrast-induced nephropathy, etc., and high-dose methotrexate chemotherapy for ALL with acute kidney injury was not almostly studyed. This study measures the levels of urinary NGAL and KIM-1 to discuss the correlation of urinary NGAL and KIM-1 determination in ALL children with acute renal function impairment by HD-MTX chemotherapy before and after application of high dose methotrexate,to discover and evaluate the incidence and development inducing acute kidney injury, in addition that providing a reference for clinical laboratory parameters. MethodsA total 30 children diagnosing ALL with use of 51 times' treatments of High-dose Methotrexate(HD-MTX)5g/m2 treated from October 2014 to October 2015 were selected as the chemotherapy group;another 24 healthy children were selected as the control group.The chemotherapy group were collected random urine specimens before the 24 hours using HD-MTX chemotherapy and after the 2 hours using chemotherapy. The levels of blood routine,serum creatinine and urine routine were within the reference range in the chemotherapy group. 30 children were collected a total of 48 urine samples before using chemotherapy and 48 parts match the total urine specimens after chemotherapy. All of the subjects were measured the levels of urine NGAL, KIM-1, N- acetyl-?-D-glucosaminidase(NAG) and creatinine(Cr), result corrected with urine Cr(UCr).SPSS 21.0 statistical software was used for data analysis.Normally distribution of measurement data using mean ± standard deviation,t test was used to compare between the two groups; Urine NAGL, KIM-1, NAG measuring results UCr correction, namely calculate the the ratio of items with UCr. Upon examination of each group ratio data were skewed distribution, with a median(M) [percentile(25%-75%)] that the groups were compared using Mann-Whitney U test for two independent samples. Between abnormal rate test of the two groups were compared using ?2 test. P <0.05 was considered statistically significant. Results1.Chemotherapy group of 30 cases, a total line HD-MTX51 cases, including 20 males and 10 females, aged 6.20 ± 2.88 years. The control group 24 cases, including 16 males and 8 females.The difference of age, gender in two groups was not statistically significant(P> 0.05).2. The levels of NGAL/UCr, KIM-1/UCr, NAG/UCr in the chemotherapy group before using HD-MTX compared with the control group, the difference was not statistically significant((Z=-0.442?-1.409?-0.961,P> 0.05).3.The levels of NGAL/UCr, KIM-1/UCr, NAG/UCr in the chemotherapy group after using HD-MTX were significantly increasing compared with before using chemotherapy,the difference was statistically significant(Z=-3.619?-3.373?-1.827,P <0.05).4.Comparing NGAL/UCr,KIM-1/UCr abnormality with NAG /UCr and the combined result abnormalities of the 3 indicators,the differences of their abnormalities in children before chemotherapy were not statistically significant( P>0.05).The NGAL/UCr,KIM-1/UCr abnormality and the combined result abnormalities of the 3 indicators were higher than those of NAG/UCr in children after chemotherapy(P<0.05). Conclusions Urine NGAL, KIM-1 have clinical application significance in children of ALL with acute kidney injury by HD-MTX. For drug-induced renal toxicity injury, urinary NGAL, KIM-1 may be used as an ideal biological marker. |
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