The Relationship Between Retinoic Acid Receptor Responder Protein 1 And Pathological Presentation In Diabetic Kidney Disease

BackgroundDiabetic kidney disease(DKD)is the leading cause of end stage renal disease(ESRD)and one of the main reasons for the increased need for renal replacement therapy and kidney transplantation.In recent years,studies have found that renal damage caused by diabetes is not limited to glomeruli,and renal tubules play a key role in the pathophysiological process of early and advanced DKD.Basic studies have shown that retinoic acid receptor responder protein 1(RARRES1)is likely to be one of the risk factors for renal disease,which can not only mediate podocyte injury and damage the function of glomerular basement membrane,but also closely related to renal interstitial fibrosis and renal tubular injury through inflammatory factors.Renal pathological changes which are closely related to the prognosis,are the gold standard for reflecting the degree of diabetic renal injury.However,there is no comprehensive report on the relationship between RARRES1 and DKD pathological changes in renal tissue of patients with DKD.Based on this,this study aims at investigating the expression of RARRES1 in renal tissues of patients with DKD,as well as the comparison of RARRES1 expression in different pathological grades and different renal tubulointerstitial and vascular scores,in order to provide theoretical basis for the role of RARRES1 in DKD.ObjectiveTo observe the expression of RARRES1 in DKD by immunohistochemical staining,and explore the characteristics of RARRES1 expression in different pathological grades and different renal tubulointerstitial and vascular scores.Methods1.Twenty-four renal tissue samples were collected from September,2021 to January,2023.There are 20 renal tissue samples diagnosed as DKD by renal biopsy(1 case of grade Ⅰ,4 cases of grade Ⅱa,4 cases of grade Ⅱb,5 cases of grade Ⅲ,and 5 cases of grade Ⅳ),and other 4 cases of normal renal tissue.HE staining,PAS staining,PASM staining and Masson staining were performed on paraffin section of renal tissue diagnosed as DKD in order to observe glomerular pathological changes under light microscopy and assess the degree of renal tubulointerstitial and vascular damage.According to the criterion of renal tubulointerstitial and vascular scores,a total score of 1～3,4～6 and 7～9 was divided into mild,moderate and severe damage group,respectively.Immunohistochemical staining was also performed on paraffin sections of renal tissues to detect RARRES1 expression semi-quantitatively.2.Statistical methods:SPSS26.0 statistical software was used to analyze the data.Normality test was applied to the measurement data by explore test.The data conformed to the normal distribution were expressed in the form of mean ± standard deviation(x±s),while the data conformed to non-normal distribution were expressed as median(interquartile spacing).When the measurement data showed normal distribution,independent sample t-test was used for comparison between two groups.When the measurement data showed normal distribution and conformed to the test of homogeneity of variance,One-way ANOVA test was used for comparison among groups.LSD method was used for multiple comparisons after ANOVA.When the data was in line with the non-normal distribution or the variance was not homogeneous,nonparametric tests were used.p<0.05 was considered as the standard for statistically significant difference.Results1.According to immunohistochemistry,the expression of RARRES1 was significantly higher in DKD than that of the normal control(p<0.05).2.By comparing the pathological grade and renal tubulointerstitial and vascular scores at the same time,it was found that the renal tissue diagnosed with DKD gradeⅣ showed higher pathological scores of renal tubulointerstitial and vascular damage.But in the group of DKD grade Ⅰ～Ⅲ,the scores did not seem to increase synchronously with the pathological grade.3.When the samples were grouped by the pathological grade of DKD,the expression of RARRES1 were statistically different among the four groups of DKD grade Ⅰ+Ⅱa,grade Ⅱb,grade Ⅲ and grade Ⅳ(the values of mean optical density were 128.238±19.037、173.998±18.599、225.559±25.397、88.682±21.497,respectively;F=68.329,p<0.001).Further multiple comparisons revealed that there were significant differences in the expression of RARRES1 between DKD grade Ⅰ+Ⅱa and grade Ⅱb,grade Ⅱb and grade Ⅲ,grade Ⅲ and grade Ⅳ,grade Ⅰ+Ⅱa and grade Ⅳ groups(p<0.05).4.When using the criterion of renal tubulointerstitial and vascular scores,the expression of RARRES1 were statistically different among the three groups with mild,moderate and severe degree of renal injury(the values of mean optical density were 152.131±20.789、189.640±53.984、123.208±49.429,respectively;F=3.869,p=0.040).Further multiple comparisons revealed that the expression of RARRES1 in the moderate renal tubulointerstitial and vascular injury group was significantly higher than that in the severe injury group(p=0.013).Besides,renal tissue samples with tubulointerstitial score ≤3points was significantly higher in those with the score>3points(the values of mean optical density were 175.002±47.181 and 105.394±45.227;p=0.007).But there was no significant difference in the expression of RARRES1 among different renal vascular scores(p>0.05).Conclusion1.The expression of RARRES1 was higher in biopsy-proven DKD than that of the normal control.2.There was a certain degree of inconsistency between glomerular pathological grade and renal tubulointerstitial and vascular scores.3.There were significant differences in RARRES1 expression in different DKD glomerular pathological grades.Moreover,the expression of RARRES1 increased accordingly as the DKD pathological grade increased within a certain range.4.There were also significant differences in RARRES1 expression in different degrees of renal tubulointerstitial and vascular injury.And the different expression of RARRES1 was more closely related to tubulointerstitial injury rather than vascular injury.