Analysis Of Urinary MIF Excretion Level In Diabetic Kidney Disease And Intervention Of Metformin

Objective:To observe the dynamic changes of the excretion of urinary macrophage migration inhibitory,podocalyxin and albumin in type 2 diabetic model rats and investigate its clinical significance.Methods:Type 2 diabetic models were established by high fat diet combined with a single injection of streptozotocin(STZ 30 mg·kg-1).Diabetic model was successfully established and stabled for 7 days,we set the time to 0 week.Meanwhile,eight rats were enrolled in the normal control group.The peripheral blood glucose and urinary excretions of macrophage migration inhibitory,podocalyxin and albumin were dynamically monitored weekly.To eliminate the impact of urine volume,the parameters in urine aforementioned were expressed as UMCR,UPCR and UACR,respectively.The study period lasted 8 weeks.Results:(1)Compared with normal control group,the levels of blood glucose throughout the study in diabetic rats were significantly higher at the same period(P<0.01).(2)After the onset of diabetes,the level of UMCR,UPCR and UACR were progressively increased until the end of the experiment.(3)At the 3rd week,UMCR in diabetic group were significantly higher than those in normal control group(P<0.05).However,there were no apparent differences between the two groups in terms of UPCR and UACR(P>0.05).At the 4th week,UPCR in diabetic group were significantly higher than those in normal control group(P<0.05).At the 6th week,UACR in diabetic group were significantly higher than those in normal control group(P<0.05).(4)UMCR was positively related with UPCR and UACR,respectively(r=0.68,r=0.73,P<0.01).Conclusions:Inflammation may be implicated in the development of diabetic kideny.disease.The utilization of UMCR as a novel biomarker for the early diagnosis of DKD and indicate the significance of increased UMCR as another risk factor for podocyte injury,earlier than the onset of microalbuminuria.UMCR was associated with podocyte injury and increased urinary albumin excretion.Aims:To observe the progression of renal injury in patients with different levels of urinary MIF excretion after five years,and to evaluate the predictive efficacy of urinary MIF excretion on the progression of diabetic kidney disease.Methods:A total of 420 non-obese and non-smoking type 2 diabetes patients with normal albuminuria or microalbuminuri were enrolled in the cohort study.General information was collected at the time of enrollment,including duration of diabetes,gender,age,height,weight,blood pressure,and urinary albumin creatinine ratio(UACR),urine MIF to creatinine ratio(UMCR).A five-year longitudinal study was conducted to investigate the association between UMCR and progression of nephropathy and determine the clinical index differences between progressors and those without significant progression after five years.In addition,binary logistic regression was performed to determine the independent risk factors that influence the progression of nephropathy.Results:1)After adjusting for the index of duration of diabetes,fasting blood glucose postprandial 2-hour blood glucose,glycosylated haemoglobin Alc,systolic blood pressure,diastolic blood pressure were higher in the progression group in comparison with those in the non-progression group.The progression group had significantly higher urinary MIF excretion contents than the non-progression group.2)There was a remarkable progression of nephropathy in the patients with higher content of urinary MIF excretion in comparison with the patients with moderate or lower excretion of MIF.3)Longer duration of diabetes,higher levels of UMCR and HbAlc,diastolic blood pressure and systolic blood pressure were independently associated with the development of nephropathy.Conclusions:MIF in urine could display a prognostic biomarker in the development of diabetic kidney diseases.A local activation of inflammation in diabetic kidney might explain the possible linkage between the increased urinary MIF excretion and the development of nephropathy.Objectives:To observe the effects of metformin on urinary excretion of MIF,CD74,IL-6,TNF-? and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.Methods:202 type 2 diabetics,who were previously prescribed sulfonylurea monotherapy(n=100)or sulfonylurea in combination with metformin(n=102)were enrolled in the study.Another 100 healthy volunteers were chosen as normal control group.The amount of macrophage migration inhibitory factor(MIF)and CD74 in serum,urinary MIF to creatine ratio(UMCR),urinary CD74 to creatine ratio(UCCR),urinary albumin to creatine ratio(UACR),urinary IL-6 to creatinine ratio,urinary TNF-a to creatinine ratio and urinary podocalyxin to creatine ratio(UPCR)were determined.Results:l)Compared with normal control group,the levels of FBG,P2hBG,HbAlc,serum MIF and CD74,UACR,UMCR,UCCR and UPCR were significantly higher in diabetic patients.2)Anthropologic and laboratory characteristics including age,gender,duration of diabetes,fasting blood glucose,postprandial 2 hours blood glucose,hemoglobin Ale,MIF and CD74 in serum were comparable between the two groups.3)Moreover,metformin add-on therapy showed significantly better efficacy in..reducing UMCR,UCCR,UICR,UTCR,UPCR and UACR in comparison with those in sulfonylurea monotherapy group,respectively.4)UMCR had positive correlation with UACR(r=0.70),UPCR(r=0.69),UICR(r = 0.66)and UTCR(r = 0.73),respectively.Conclusions:Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response.