Association Of Urinary DcR2/Cr Levels And Poor Prognosis Of Diabetic Tubulopathy

Objective To observe the pathological features of diabetic tubulopathy,analyze the relationship between renal tubular score and poor prognosis of DT and explore whether urinary DcR2/Cr can be used as a biomarker to predict poor prognosis of DT.Methods A total of 121 patients diagnosed with diabetic tubulopathy by pathological biopsy in our department from 2018-2021,of which 65 patients had urine specimens retained,were collected for retrospective analysis of pathological types,basic data,and laboratory examination-related indexes,and patients were followed up.Follow-up endpoints were defined as doubling of serum creatinine level,entry into ESRD,or initiation of renal replacement therapy.The follow-up cut-off date was December 31,2021,and follow-up time was recorded for endpoint events that occurred during the follow-up period;the follow-up period was monthly.The patients were divided into 3 groups according to the different IFTA scores: group 1(n=20),group 2(n=55),and group 3(n=46);the patients were divided into three groups according to the urinary DcR2/Cr level,group 1: DcR2/Cr <321ng/mmol,group2: 321 ≤DcR2/Cr≤505ng/mmol,group 3: DcR2/Cr>505ng/mmol;adverse prognosis was based on the occurrence of endpoint events.Statistical analysis was performed using SPSS26.0 statistical software,and measures were expressed as mean ± standard deviation or median(P25,P75),and categorical variables were expressed as percentages.Two-by-two comparisons in normally distributed data were performed using the independent samples t test(systolic blood pressure,diastolic blood pressure,body mass index,hemoglobin,e GFR,serum albumin,etc.),and one-way ANOVA was used for comparison between groups;Kruskal-Wallis test was used for differences between groups in skewed data(ACR,blood creatinine,cystatin C,triglycerides,etc.);χ2 test was used for comparison of rates(incidence of proteinuria,lower limb edema,hypertension,etc.).Correlation analysis was performed using Pearson for correlation of measurement data(NAG,SCr,CYC,e GFR);Spearman for correlation of count data(e.g.,each pathological impairment score);COX regression analysis was used to assess the relationship between IFTA score and urinary DcR2/Cr levels and poor prognosis of DT.p < 0.05 indicates a statistically significant difference,and P < 0.01 indicates a statistically significant difference.Results There were 121 patients with diabetic nephropathy with a mean age of(53±10.2)years,of whom 84(69.4%)were male and 99(81.8%)suffered from hypertension.A comparative analysis by different IFTA groupings revealed that the incidence of nocturia,lower limb edema,proteinuria,and diabetic retinopathy increased with higher IFTA scores in patients with diabetic tubulopathy(P<0.01),but there was no statistically significant difference in the development of comorbidities such as coronary heart disease,cerebrovascular disease,and chronic liver disease with higher IFTA scores(P>0.05).The incidence of nocturia,lower limb edema,proteinuria,and diabetic retinopathy increased with increasing IFTA scores in patients with diabetic tubulopathy with different pathology scores(P<0.01),but there was no statistically significant difference(P>0.05)in the development of comorbidities such as coronary heart disease,cerebrovascular disease,and chronic liver disease with respect to the IFTA scores.As IFTA score increased,urine microalbumin,urine protein quantification,ACR,corrected NAG,CYC,and blood creatinine levels tended to increase,while urine creatinine and e GFR gradually decreased(P<0.01).Among the pathological changes,glomerular injury,renal artery vitreous degeneration(hyaline degeneration)were closely associated with tubular injury.There was a correlation between IFTA score and poor prognosis of patients(model-corrected P=0.021,HR=2.740,95% CI1.167-6.410),where the risk of poor prognosis was 2.74 times higher in patients with IFTA score 3 than in patients with IFTA score 1.In 65 patients with retained urine specimens,urine protein quantification,ACR,NAG,CYC,and blood creatinine levels tended to increase with increasing urinary DcR2/Cr levels,while urinary creatinine and e GFR gradually decreased(P<0.05).Hemoglobin and serum albumin levels decreased with increasing DcR2/Cr levels(P<0.05),and triglyceride and LDL levels increased with increasing DcR2/Cr levels(P<0.05).Correlation analysis revealed that DcR2/Cr levels were positively correlated with ACR(P<0.01),cystatin C(P<0.01),NAG(P<0.01)and negatively correlated with e GFR(P<0.05);DcR2/Cr levels were positively correlated with IFTA score(P<0.01),renal artery hyalinosis score(P<0.05),renal atherosclerosis score(P<0.05).COX regression analysis revealed a significant correlation between DcR2/Cr levels and the occurrence of adverse prognosis in patients(model-corrected P=0.002,HR=9.903,95% CI 2.349-41.752),with the risk of adverse prognosis in patients in the DcR2/Cr3 group being 9.903 times higher than that in patients in the DcR2/Cr1 group.Kaplan-Meier survival curves showed that patients with higher DcR2/Cr levels had a worse prognosis.ROC curve analysis showed the largest area under the urinary DcR2 curve(AUC=0.811),which was higher than ACR,CYC and SCr,demonstrating that urinary DcR2/Cr levels were better predictors of poor prognosis in DT than other clinical indicators.Its optimal intercept value was 389.0 ng/mmol,which means that a urinary DcR2/Cr level greater than 389.0 ng/mmol in DT patients indicates a poor prognosis.Conclusion IFTA scores are strongly associated with poor prognosis in DT patients,and urinary DcR2/Cr is a noninvasive biomarker for predicting poor prognosis in DT.