Detection and clinical significance of urinary monocyte chemoattractant protein-1 and interleukin-18 in children with primary nephrotic syndrome

Objective To investigate the concentration of monocyte chemoattractant protein-1 (MCP-1) and interleukin-18 (IL-18) in the urinary of children with primary nephrotic syndrome(PNS) at different time points,and to explore their correlation with occurrence,development,progression,and prognosis of PNS.Methods A total of 65 pediatric cases from our hospital was enrolled in this study,and was divided into three groups based on the retrospective the follow-up results including steroid-sensitive NS (SSNS) (n =35),steroid-resistant NS (SRNS) (n =15),and frequent-relapse NS (FRNS) (n =15) groups.Another 20 healthy children served as normal controls.Peripheral blood samples and urine specimen were collected at three time points (without glucocorticoids,treatment after 8 weeks,and treatment after 16 weeks or recurrence).The levels of MCP-1 and IL-18 in the urine were assayed by enzyme-linked immunosorbent assay (ELISA).The levels of blood urea nitrogen,creatinine,and 24-hour urinary protein excretion were assayed by full-automatic biochemical study appliance.Results (1)In SSNS group,the levels of urinary IL-18 before treatment and treated for 8 weeks were higher than the normal control group [before treatment:(160.30 ±27.29) pg/ml; treated for 8 weeks:(157.62 ±26.85) pg/ml; normal control group:(70.88 ± 14.43) pg/ul].However,after treated for 16 weeks,the levels of urinary MCP-1 and IL-18 were markedly decreased compared with that of control group and those before treatment and treated for 8 weeks [treated for 16 weeks:(20.98 ±4.53) pg/ml,and (79.09 ±7.23) pg/ml,P ＜0.05].(2)In SRNS group,the levels of urinary MCP-1 and IL-18 before treatment were remarkably higher than that of control group and that of SSNS group before treatment[SSNS group before treatment:(76.84 ± 5.58) pg/ml,and (252.37 ± 25.34)pg/ml,P ＜0.05],but no significant difference was found when it was compared with that treated for 8 weeks [treated for 8 weeks:(72.32 ±4.30) pg/ml,and (243.70 ±35.43) pg/ml,P ＞0.05] ; However,its level was markedly decreased after treated with immunosuppressants of CTX for 16 weeks when it was compared with those before treatment and treated for 8 weeks[treated for 16 weeks:(34.03 ± 2.56) pg/ ml,and (114.42 ± 21.33)pg/ml,P ＜ 0.05].(3)In FRNS group,the levels of urinary MCP-1 and IL-18 were no remarkable difference between control and SSNS groups [before treatment:(30.43 ± 4.61) pg/ml,and (156.65 ± 34.39)pg/ml; treated for 8 weeks:(29.41 ± 4.76) pg/ml,and (152.21 ± 34.73) pg/ml,P ＞ 0.05],but its level was markedly lower than SRNS group (P ＜ 0.05).When it was recurred,the levels of urinary MCP-1 and IL-18 were significantly increased compared with before treatment and treated for 8 weeks[recurred:(72.92 ±3.01)pg/ml,and (224.33 ±26.07)pg/ml,P ＜0.05].(4)No correlation was found between the levels of MCP-1 and IL-18 and the levels of blood urea nitrogen and creatinine (P ＞0.05).Positive correlation was found between the levels of MCP-1 and IL-18 and the 24-hour urinary protein excretion (r =0.706,0.556,P ＜0.01).There's a correlation between urinary MCP-1 and IL-18 (r =0.811,P ＜ 0.01).Conclusions For children with PNS,the detection of urinary MCP-1 and IL-1 8 contributed to the early prediction of children'sensitivity on glucocorticoid.The elevated levels of urinary MCP-1 and IL-18 in combination with clinical symptoms and proteinuria can be used as an important noninvasive marker to monitor PNS recurrence. Key words: Nephrotic syndrome/urine; Child; Chemokine CCL2/urine; Interleukin-18/urine