| Objective:As a common chronic complication of diabetes,Diabetic nephropathy?DN?has become the leading cause of end-stage renal disease and has been the focus of clinical attention.The reason why diabetic nephropathy has received widespread clinical attention is not only because of its high prevalence,but also because of the lack of effective treatment.Microalbuminuria?MAU?is the main clinical basis for early diagnosis of DN.However,from the perspective of clinical prognosis,most patients with MAU have lost their chances of healing even after active treatment.In 10 years,only 20-25%of urine protein returned to normal,30-35%remained in the MAU stage for a long time,and 30-40%gradually.Progress to massive albuminuria.Therefore,it is necessary to diagnose diabetes kidney damage earlier.Prof.Pan Changyu et al.[1]found that13.1%of patients with prediabetes have had MAU.A survey of 5,000 Maori and European populations found that 16%of patients with impaired glucose tolerance?IGT?had MAU[2].Therefore,it is necessary to observe the occurrence of renal damage in the earlier stage of IGT.In our previous animal experiments,we found that when there is no apparent elevation of UMA in the IGT stage,different levels of tubular structure and function have been impaired,and urinary indexes reflecting renal tubular damage:urinary retinol-binding protein?RBP?The excretion of N-acetyl-?-glucosaminidase?NAG?and neutrophil gelatinase-associated apolipoprotein?NGAL?increased.Compared to DN,we refer to kidney injury that occurs during IGT as"IGT nephropathy"[3,4].The concept of"IGT nephropathy"has provided new ideas for the early prevention and treatment of DN.So,is there also"IGT nephropathy"in clinical practice?The new biomarkers for the early diagnosis of diabetic nephropathy are also hot spots in clinical research.Studies have found that some biomarkers in urine have risen before urinary microalbumin rises,mainly including transferrin,type IV collagen,laminin,mucopolysaccharides?GAGs?,and immunoglobulin G?IgG?and lipocalin prostaglandin D2 synthase?L-PGDS?.Among them,transferrin,IgG,and L-PGDS can even predict the occurrence of microalbuminuria[5].So,what happens to these biomarkers during the period of“IGT nephropathy”?In recent years,proteomic analysis has provided a new perspective for the early assessment of diabetic nephropathy.The development of diabetic nephropathy involves a variety of pathophysiological processes,and there is no single biomarker that can represent the risk of nephropathy with albuminuria.In contrast,the use of a set of multiple protein markers to capture different pathophysiological pathways of diabetic nephropathy may be more reliable and more accurate in predicting the progression of renal disease or ESRD.By comparing and analyzing proteomes between normal individuals and pathological individuals,we can find certain “disease-specific protein molecules”that may provide molecular markers for early diagnosis of diseases.So,can we find a variety of differentially expressed proteins in the period of“IGT nephropathy”through proteomics.Can they reveal how early kidney damage occurs?Therefore,we want to observe whether“IGT nephropathy”also exists in the clinic,that is,when there is no apparent increase in blood glucose during the IGT stage,tubular structural and functional damage has already occurred;and in the clinical observation of the literature Changes of early markers of diabeticnephropathy in"IGT nephropathy"and DN;meanwhile,the differential expression of IGT nephropathy,IGT nephropathy,DM and DN in normal controls,IGT,IGT nephropathy,IG nephropathy Proteins provide more basis for the early prevention and treatment of DN.Method:1.This study will use normal controls,IGT,IGT nephropathy,DM and early DN patients as the study object to clinically verify the existence of"IGT nephropathy"and compare urine biomarkers?transferrin,type IV collagen Differences in laminin,L-FABP,MCP-1,and L-PGDS?;2.Using urine proteomics to study the changes of protein expression in the above groups of populations,to explore new biomarkers reflecting renal damage in IGT patients,and to evaluate their sensitivity,specificity and diagnostic value for early nephropathy as"IGT nephropathy""The early screening and diagnosis provide a theoretical reference.Results:1.Validation of"IGT nephropathy"clinically;compared with normal controls,urinary laminin?LN?,high molecular weight adiponectin?HMW-ADP?,liver type fatty acid binding protein?L-FABP?in patients with IGT nephropathy Collagen type IV collagen was significantly elevated?P<0.05?,among which LN,L-FABP,and type IV collagen showed a trend of increasing gradually in healthy control group,IGT group and DN group?P<0.05?.2.Through ITRAQ,128 differentially expressed proteins in the urine of the normal control group,IGT group,"IGT nephropathy"group,DM group,and DN group were found,and the differentially expressed protein was performed after the increase of the sample size.In the validation,the protein with the same verification result and the most obvious difference was the cyclic nucleotide cation pathway?3?CNGA3?.The expression of CNGA3 in the normal control group,the“IGT nephropathy group”and the DN group decreased in turn.The results of ELSA were consistent with the results of ITRAQ.Immunohistochemistry and Western-blot showed the kidneys of IGT and DM diabetic rats.The expression of CNGA3 was significantly increased in the tissues?P<0.05?.Conclusions1."IGT nephropathy"has been further validated from a clinical perspective.2.Patients with"IGT nephropathy"have different degrees of glomerular and tubular damage.Glomerular injury mainly showed increased UMA,TF,and IgG excretion in urine;renal tubular injury was mainly manifested in increased NAG,RBP,GAL,?2-MG,NGAL,and CysC in urine.3.Insulin resistance and hyperinsulinemia are closely related to the pathogenesis of"IGT nephropathy".4.In the"IGT nephropathy"period,there were many proteins with different expressions.Compared with the healthy control group,the CNGA3"IGT nephropathy group"and DN group in urine were significantly lower.5.The level of CNGA3 in urine was significantly lower in IGT nephropathy group and DN group,which may be a biomarker in early stage of IGT nephropathy. |
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