他克莫司对小儿原发性肾病综合征高凝状态及hs-CRP的影响

Effects of Tacrolimus on hypercoagulability and hs-CRP in children with primary nephrotic syndrome

目的探讨他克莫司(FK506)对小儿原发性肾病综合征(PNS)高凝状态及超敏C-反应蛋白(hs-CRP)的影响。方法将2014年12月至2016年12月十堰市妇幼保健院收治的78例难治性PNS患儿随机分为两组,各39例。观察组在口服泼尼松治疗的基础上,应用FK506;对照组在口服泼尼松治疗的基础上,应用环磷酰胺(CTX)。所有患儿随访至少6个月,测评治疗前、治疗6个月后患儿肾功能、凝血功能指标及hs-CRP变化情况。结果两组患儿治疗前肾功能、凝血功能指标及hs-CRP水平接近,组间差异均无统计学意义(均P>0.05)。治疗后两组患儿肾功能均较治疗前明显改善(t值分别为63.692、15.439、21.861、15.008、16.144、22.197、54.150、14.425、15.475、13.674、20.702、23.454,均P<0.05),且观察组治疗后24h尿蛋白定量明显低于对照组(t=13.166,P<0.05)。治疗后观察组纤维蛋白原(FIB)、D-二聚体(D-D)水平均较治疗前明显下降(t值分别为10.524、9.688,均P<0.05),对照组无明显变化(P>0.05)。治疗后两组患儿hs-CRP较治疗前均明显下降(t值分别为14.568、14.583,均P<0.05),且治疗后组间无明显差异(P>0.05)。观察组FIB、D-D的变化量与肾功能指标的变化量均无明显相关性(均P>0.05);hs-CRP的变化量与肾功能指标的变化量存在明显的正相关性(r值分别为0.324、0.537、0.637、0.607、0.495、0.571,均P<0.05)。结论 FK506能够有效改善难治性PNS患儿高凝状态与hs-CRP水平,且对高凝状态的改善机制可能与对肾功能的改善无直接相关性,对hs-CRP的改善机制则与对肾功能的改善有直接相关性。

Objective To investigate the effects of Tacrolimus（FK506）on hypercoagulable state and high sensitivity C reactive protein（hs-CRP）in children with primary nephrotic syndrome（PNS）.Methods Seventy-eight children with refractory PNS treated in Shiyan Maternal and Child Health Care Hospital from December 2014 to December 2016 were randomly divided into 2 groups with 39 cases in each group.Based on oral prednisone,patients in observation group were treated with FK506 and those in control group were treated with Cyclophosphamide（CTX）.All cases were followed up for at least 6 months.Renal function,coagulation function indexes and hs-CRP changes were evaluated before treatment and at 6 months after treatment.Results Renal function,coagulation function indexes and hs-CRP level before treatment were similar in two groups,and there were no significant differences between them（all P〉0.05）.Renal function in two groups after treatment were significantly improved than that before treatment（t value was 63.692,15.439,21.861,15.008,16.144,22.197,54.150,14.425,15.475,13.674,20.702 and 23.454,respectively,all P〈0.05）,and quantitative test of 24 hurinary protein（24 h-Ur）after treatment in observation group was significantly lower than that in control group（t=13.166,P〈0.05）.Fibrinogen（FIB）and D-dimer（D-D）in observation group after treatment decreased obviously when compared to those before treatment（t value was 10.524 and 9.688,respectively,both P〈0.05）,but there was no obvious change in control group（P〉0.05）.Hs-CRP after treatment decreased significantly in both groups（t value was 14.568 and 14.583,respectively,both P〈0.05）,and there was no significant difference between two groups after treatment（P〉0.05）.There were no significant correlations between changes of FIB and D-D and changes of renal function indexes in observation group（all P〉0.05）,and there were positive correlations between change of hs-CRP and changes of renal function indexes（r value was 0.324,0.537,0.637,0.607,0.495 and 0.571,respectively,all P〈0.05）.Conclusion FK506 can effectively relieve hypercoagulable state and hs-CRP level in children with refractory PNS,and mechanism of relieving hypercoagulable state may have no direct correlation with improvement of renal function,but the inhibition mechanism of hs-CRP maybe directly correlate with improvement of renal function.