Serum Cystatin C As A Marker To Detect Chemotherapy-induced Early Renal Disfunction In Patients With Malignant Tumors

Objective:To evaluate the applicability and the feasibility of serum cystatin C(Cys C)as a endogenous marker for detection of chemotherapy -induced early renal disfunction in patients with malignant tumors.Methods:Serum samples were obtained from 35 cases with malignant tumors,who were hospitalized patients,and 14 healthy controls taking health examination in the outpatient department in the 2nd XiangYa hospital and the affiliated HePing hospital of ChangZhi medical college from September,2007 to March,2008.The studied objects were divided into two groups(Group A--Patients,Group B--Contols).Serum cystatin C(Cys C)concentration was determined by enzyme linked immune sorbent assay(ELISA),β₂-microglobulin(β₂-MG)by radioimmunoassay method,Serum creatinine(Scr)by alkaline trinitrophenal method and Creatinine clearance rate(Ccr)were calculated using Cockroft-Gault formula for every patient.The correlation between Ccr and the above three parameters(Cys C,β₂-MG,Scr)were compared, the area under the Receiver Operating Characteristic curve(AUC^ROC) were used for evaluating the reliability of cystatin C.Results:1.There was no significant difference in ages,gender,heights, weights and body surface areas(BSA)between Group A(Before Chemotherapy)and Group B.Compared with Group B,there were normal levels of Cys C(P=0.558),β₂-MG(P=0.086),Scr(P=0.74)and Ccr(P=0.791)in Group A;2.The level of Ccr after chemotherapy was significantly lower than before chemotherapy[89.7(78.4-109.7)vs 93.9(81.3-119.4)mL/min/1.73 m²,P=0.004],and the level of Cys C[2.15(1.21-2.62)vs 1.57(1.17-1.89) mg/L,P＜0.001],β₂- MG[2.15(2.0-3.19)vs 1.60(1.47-2.20)mg/L,P= 0.01]after chemotherapy was significantly higher than before chemotherapy. However,there was no significant difference in level of Scr [66.5(51.6-76.7)vs 70.0(59.4-80.7)μmol/L,P=0.245]before and after chemotherapy;3.Ccr negatively correlated significantly with both Cys C andβ₂-MG levels(r=-0.819,P＜0.001;r=-0.572,P＜0.001,respectively)before chemotherapy and also 1/2 month after chemotherapy(r=-0.883,P＜0.001; r=-0.335,P=0.049,respectively).However,no significant correlation was found between Ccr and Scr before chemotherapy(P=0.718),nor did it after chemotherapy(P= 0.087);4.When the levels of Cys C,β₂-MG and Scr before chemotherapy were used to predict patients who developed a reduction in Ccr of more than 20%after chemotherapy,only the cystatin C level was statistically significant(P=0.01)—a cutoff point of 0.80 mg/L with sensitivity of 90.5%,specificity of 43%,and Youden's index of 0.335.The AUC^ROC for Cys C was 0.84,which was the best among the above three parameters.Conclusion:1.The early renal damage induced by chemotherapy can not be detected effectively by the routine clinical measurements of renal function(such as Scr).2.Current study has found that Cys C was more closely correlated to Ccr thanβ₂-MG and Scr were,indicating that Cys C is an sensitive parameter in assessing chemotherapy induced renal damage.3.Serum Cys C could accurately reflect the GFR changes,thus Cys C is more effective in predicting the early renal damage induced by chemotherapy thanβ₂-MG and Scr.