| BACKGROUND:It is reported that about 100 million people suffered from chronic kidney disease with a high prevalence with 10%in China.And the prevalence rate is still increasing in recent years.Renal transplantation is one of the main method of treatment of end-stage renal failure,but is the most effective and most mature way for the treatment of patients with end-stage renal failure to improve life quality.However,the complications,acute or chronic rejection and immune inhibitor side effects after renal transplantation have been regarded as the main reasons to impact the long curative effect and recovery in postoperative patients.Since the invention and application of immunosuppressant Cyclosporine was used in organ transplantation at the 1970s,survival rate of renal transplantation has been increased by 15%?30%,and 1 year survival rate of renal transplantation has been increased from 50%to 85%.Immunosuppressant promotes graft survival by inhibition of rejection,however,played a "double-edged sword" role.On the one hand,immunosuppressant can inhibit rejection,on the other hand,can also lead to toxic injury in recipients and graft.Tacrolimus(FK506)belongs to calcineurin inhibitor with the characteristics of insoluble in water and high fat,which plays higher(1?100 times)role in cellular immunity and humoral immunity than Cyclosporine.Meanwhile,compared with Cyclosporine,Tacrolimus is more less liver toxicity,which greatly improves the survival rate of the organ transplantation and now has replaced Cyclosporine as the first immune inhibitors after organ transplantation.However,compared with Cyclosporine,Tacrolimus is lower incidence of adverse reactions,but still induce some serious adverse reactions,such as,renal toxicity,nervous system toxicity,blood toxicity,high blood pressure,diabetes,hyperlipidemia,hyperkalemia and other adverse reactions.SCys C is a kind of cysteine protease inhibitors,is constantly transcripted and expressed in all nuclear organization,is widely expressed in the nucleated cells and body fluids.Kidney is the only organ for the metabolism of SCys C.SCys C can be almost completely absorbed by the proximal convoluted tubules after glomerular filtration,and cann't be secreted by renal,also can't be recycled back to the blood,and cann't be affected by gender,age,race,inflammatory response,muscle mass and protein intake.Thus,SCys C is well regarded as a marker to assess glomerular filtration rate,and also can be used as markers for early renal damage.The purpose of this paper is to explore the correlation between FK506 blood drug concentration and Cys C,also to explore the effect of FK506 on glucolipid metabolism in transplant patients.Our study may get more accurate and reasonable application about FK506 and provide helpful treatment basis for clinicalin renal transplant patients.Research purpose:1.To investigate the plasma concentration of FK506 in different time periods after renal transplantation;2.To investigate the correlation between FK506 plasma concentration and age,sex and serum cystatin C after renal transplantation.3.To investigate the relationship between FK506 plasma concentration and glucose and lipid metabolism after renal transplantation.Research methods:1.The relationship between the plasma concentration of tacrolimus and serum cystatin C after renal transplantationA total of 325 follow-up patients were enrolled in this study.From January 2014 to September 2015,325 patients with FK506 were monitored for renal transplantation.There were 210 males and 115 females with an age range of 12 to 85 years(mean age 41.6 ± 11.7 years).Inclusion criteria:primary renal transplantation;regular use of FK506 more than 6 months and regular detection of renal function and FK506 plasma concentration;normal blood lipids;preoperative history of no diabetes and renal function stability(creatinine clearance>40ml/min).Elimination criteria:transplanted renal dysfunction(Scr>300?mol/L);multiple organ transplant patients;severe infection,cancer and other major diseases affected liver or kidney function.Blood samples were collected and placed with ethylenediamine tetraacetic acid(EDTA)before and after operation.Anticoagulant kit homogeneous enzyme immunoassay was used to monitor the blood FK506 concentration.At the same time,the expression level of serum cystatin C was measured by particle-enhanced transmission immunoturbidimetry(PETIA).2.The effect of plasma concentration of tacrolimus on glucose and lipid metabolism after renal transplantationA total of 325 follow-up patients were enrolled in this study.From January 2014 to September 2015,325 patients with FK506 were monitored for renal transplantation.Inclusion and elimination criteria as described above.Blood samples were collected and placed with ethylenediamine tetraacetic acid(EDTA)before and after operation.Anticoagulant kit homogeneous enzyme immunoassay was used to monitor the blood FK506 concentration.At the same time,the blood glucose level was measured by enzyme end point method.Glucose oxidase method was used to measure the blood glucose level before and after treatment.3.Statistical analysisSPSS 13.0 software was used for statistical analysis.The comparison between the two samples was based on an independent sample t test.The comparison between multiple samples was based on one-way ANOVA.If the variance was similar,LSD was used for multiple comparisons.If the variance was different,the multiple comparisons between groups were analyzed by Dunnett's T3.Correlation analysis was analyzed by using Spearman rank correlation.P<0.05 was regarded as a statistically significant difference.Results1.The relationship between the plasma concentration of tacrolimus and serum cystatin C after renal transplantationFirstly,we investigated the plasma concentration of FK506 after 1 year of renal transplantation.The results showed that the plasma concentrations of FK506 in<1 month,1-3 months,4-6 months and 7-12 months were(7.89±3.27)?g/L,(7.53±2.22)?g/L,(7.51 ±2.49)?g/L,(7.33±2.42)?g/L,which were gradually decreased with the prolongation of time trend.Among them,the plasma concentration of FK506 in<1 month was greater than that in 7-12 months,the difference was statistically significant(P<0.05).The plasma concentration of FK506 in 1-3 and 4-6 was significantly greater than that in 7-12 months,the difference was statistically significant(P<0.05).Secondly,we analyzed the relationship between FK506 plasma concentration and patients' age and sex.The results showed that the plasma concentration of FK506 in the age group<20 years old group was significantly different from that in the age group>60 years old group(P<0.05).The serum concentrations of FK506 in<1,1-3,4-6 and 7-12 were significantly different from those in the>60 years group(P<0.05).The plasma concentration of FK506 in<1,4-6 and 7-12 was significantly different from that in group>60 years(P<0.05).In addition,the plasma concentrations of FK506 in male in<1,1-3,4-6,7-12 months were(7.94±3.39)?/L,(7.43±2.4)?g/L,(7.21 ±2.98)?g/L and(7.28±2.82)?g/L,respectively(P<0.05).The plasma concentration of FK506 in female in<1,1-3,4-6,7-12 months were(7.84±3.15)?g/L,(8.05±2.96)jig/L,(7.81±2.0)?g/L and(7.38±2.02).The statistical analysis showed that the plasma concentration of FK506 in female patients was significantly higher than those in male patients,and the difference were statistically significant(P<0.05).Finally,we analyzed the correlation between FK506 plasma concentration and Cys C and Scr.The results showed that Cys C levels were decreased gradually(P<0.05).FK506 plasma concentration was significantly correlated with Cys C(P<0.05,r=0.985).The The levels of Scr in<1,1-3,4-6 and 12 months were:(93.6±33.5)pmol/L,(94.9±34.1)pmol/L,(92.4±30.9)?mol/L,(93.5±32.9)?mol/L.Statistical analysis showed that FK506 had no significant correlation with Scr(P>0.05).2.The effect of plasma concentration of tacrolimus on glucose and lipid metabolism after renal transplantationThe results showed that the levels of blood glucose in<1,1-3 and 4-6 month were(5.53± 1.55)mmol/L,(5.53± 1.59)mmol/L,(5.59± 1.62)mmol/L,compared with preoperative blood glucose(5.53± 1.55 mmol/L),the difference was not statistically significant(P>0.05).However,the incidence of hyperglycemia was 38.2%,when FK506 plasma concentration was>15?g/L,which was significantly lower than that of FK506 plasma concentration ?15?g/L(13.3%)with a significant difference(P=0.000).The incidence of hyperglycemia was 25%,when FK506 plasma concentration was>10?g/L,which was significantly higher than that of FK506 plasma concentration<10?g/L(0.0%),and the difference was statistically significant(P=0.000).Subsequently,we also analyzed the levels of serum lipids in 6 months after FK506 treatment in patients after renal transplantation.The results showed that the levels of total cholesterol before operation,<1,1-3 and 4-6 month were:(1.47±0.75)mmol/L,(1.49±0.84)mmol/L,(1.51±0.88)mmol/L,(1.55±0.92)mmol/L.The total cholesterol levels were increased gradually,but statistical analysis showed that the difference wasn't significant statistical(P>0.05).Similarly,no significant difference was found in triglyceride,low density lipoprotein and very low density lipoprotein(P>0.05).Moreover,we also evaluated the correlation between FK506 plasma concentration and toxic response and rejection.The results showed that the incidence of poisoning in patients with FK506 plasma concentration>10?g/L was significantly higher than that in patients with blood concentration?10?g/L(P=0.000).The incidence of poisoning in patients with FK506 plasma concentration>10?g/L was 16.7%,which was significantly higher than that in patients with blood concentration ?10?g/L.In addition,we also analyzed the relationship between rejection and FK506 plasma concentration.The results showed that the incidence of rejection was about 3.7%when the concentration of FK506 was>15?g/L,which was significantly lower than that of blood concentration?15?g/L(24.7%),and the difference was significant(P=0.000).At the same time,the incidence of rejection was about 8.6%,when the concentration of FK506 was>10p,g/L within 4-6 months after operation,which was significantly higher than that of blood concentration:?10?g/L(0.0%),and the difference was significant.Conclusions1.After treatment with FK506,the plasma concentration of FK506 showed a decreasing trend with the prolongation of time.The plasma concentration of FK506 was significantly correlated with age,sex and Cys C,but not with Scr.2.After FK506 treatment in renal transplantation patients,the level of blood sugar will be not significantly affected.But after transplantation in<1 and 6 month,high FK506 plasma concentration can increase the incidence of hyperglycemia.3.FK506 treatment in renal transplantation patients after surger will not significantly affect the total cholesterol,triglycerides,low density lipoprotein and very low density lipoprotein levels.4.In early time,FK506 plasma concentration can effectively reduce the rejection,but will not increase the incidence of toxic reactions,however,high FK506 plasma concentration can increase the rejection and poisoning reaction at late stage. |
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