Evaluation Of Risk Factors Of Postoperative Acute Kidney Injury In Patients With Kidney Cancer And The Predictive Value Of Dickkopf-3 In Acute Kidney Injury After Nephrectomy

【Objective】Acute Kidney Injury(AKI)is a common postoperative adverse event in patients with kidney cancer,which is closely related to the development of chronic renal disease(CKD).The purpose of this study is to identify the independent risk factors of postoperative AKI in patients with Kidney cancer and to establish a predictive model of AKI.To explore the value of serum dickkopf-3(DKK3)in early prediction of AKI after nephrectomy by detecting the content of serum DKK3 at different time points in patients with nephrectomy.【Methods】1Clinical features of Kidney Cancer patients receiving nephrectomy.We collected 684 RCC patients who underwent radical or partial nephrectomy in the department of urology in our hospital from January 2015 to April 2020.A total of631 patients were enrolled in the study through inclusion exclusion criteria.The subjects were randomly divided into a training set(n=443)and a validation set(n=188)at a ratio of 7:3.Recorded variables included demographic data,hospitalization information,preoperative data,intraoperative data,surgical information.Demographic data include:age of operation;sex;body mass index(BMI).Hospitalization information:length of stay and postoperative hospitalization days.Preoperative data included:diabetes mellitus,hypertension and cardiovascular diseases,blood routine,blood coagulation markers,blood biochemical examination,preoperative blood pressure and so on.Intraoperative data include:intraoperative blood pressure;intraoperative urine volume;intraoperative blood loss.Surgical information includes:operative time;surgical approach(Laparoscopic or Open);the type of operation(RN and PN).The continuous data between two groups were compared by independent sample t-test or Wilcoxon rank-sum test.Categorical variables were expressed as frequencies and proportions,and comparisons between two groups were made by the independent sample t-test or Fisher’s exact test.The classification of each indicator is based on the CUT-OFF value calculated by ROC.Logistic regression analysis was performed to estimate the associations of independent risk factors and AKI.Significant variables were selected using the“Backwald:Wald”method,and used to built a nomogram.The ROC curve,calibration curve,C-index(1000 bootstrap resamples)and decision curve(DCA)were used to evaluate the prediction accuracy of the nomogram.The R packages used for nomogram establishment and validation included rms,rmda,p ROC and Hmisc.2 To evaluate the predictive value of serum DKK3 in preoperative,4 hours and 1day after operation on AKI after nephrectomy.A prospective study was conducted to collect 70 patients who met the inclusion exclusion criteria in urology from May 2020 to January 2021.According to postoperative AKI as the main event,they were divided into AKI group and non-AKI group.The contents of DKK3、CREA and other markers in serum samples before operation,4 hours after operation and the first day after operation were detected and compared between the two groups.The demographic data,clinical data and laboratory indexes of 70 patients were analyzed by independent sample t test,Mann-Whitney U test,χ~2test and Fisher exact probability method.The serum samples of the two groups were analyzed by Repeated ANOVA,independent sample t-test,Pearson correlation analysis and ROC analysis to explore the value of serum DKK3 in early prediction of AKI after nephrectomy.【Results】1 Clinical features of Kidney Cancer patients receiving nephrectomy.A total of 631 RCC patients receiving radical or partial nephrectomy were enrolled,and divided into the training set(n=443)and the validation set(n=188).There was no statistical difference from demographics,laboratory parameters,surgery and operation information,hospitalization data between the analysis of training set and validation set(all P>0.05),except for RBC(P=0.038)and total proteins(p=0.039).Among the complications,only CKD was different,but the sample size was very small(P=0.047).postoperative AKI occurred in 123 patients(27.7%)in the training set.Kidney cancer patients underwent RN are more likely to develop AKI than p N(P<0.001).However,there was no significant difference in surgical approach between the two groups(P=0.436).AKI patients’surgical age,hypertension,the type of operation,preoperative fibrinogen(FIB),Ca,red blood cell(RBC),blood urea nitrogen(BUN),percentage of eosinophil(EOS%),albumin-to-alkaline phosphatase ratio(AAPR),lactic dehydrogenase(LDH),preoperative systolic blood pressure(SBP),duration of surgery,Length of hospital stay,postoperative hospitalization day and intraoperative minimum diastolic blood pressure(DBP)were statistically significant(all P<0.05).Multivariate analysis showed that the RN,EOS%,BUN,low AAPR,and LDH were independent risk factors.A nomogram based on these five variables showed a good predictive performance,with an area under ROC of 0.803[95%confidence interval(CI)0.758-0.848]in the training set and 0.780(95%CI0.709-0.852)in the validation set.The calibration curve confirmed that the predicted values were consistent with the actual observations.Decision curve indicated clinical net benefits of the prediction model,ranging from 3%to 66%.2 To evaluate the predictive value of serum DKK3 in preoperative,4 hours and 1day after operation on AKI after nephrectomy.The analysis of clinical data showed that there were significant differences in age and mode of operation between AKI group and non-AKI group(P<0.05).The expression of serum DKK3 in AKI group was significantly higher than that in non-AKI group(P<0.01).DKK3 predicted that the area under the ROC curve of AKI after nephrectomy was 0.787(95%CI 0.673-0.876).When the truncation value was1400.44 pg/m L,the sensitivity was 100%and the specificity was 57.14%.As AKI is a risk factor for chronic kidney disease and missed diagnosis of patients may bring serious consequences,a more sensitive method should be adopted to find as many suspicious patients as possible.Preoperative multivariate logistic regression analysis showed that DKK3 and RN were independent predictors of postoperative AKI.When RN and DKK3 combined to predict the area under the ROC curve of postoperative AKI was 0.864(95%CI 0.760-0.934),the sensitivity was 78.57%,and the specificity was 83.93%.There was no significant difference in the distribution of serum creatinine(s Cr)between the two groups before operation.In one day after operation,the area under the ROC curve of AKI was 0.782(95%CI 0.667-0.872),the sensitivity was 64.29%,and the specificity was 91.07%.It is suggested that DKK3 alone has a good efficiency in predicting AKI,and the prediction efficiency is greatly improved when combined with RN.Can more clearly identify the risks of AKI.【Conclusions】1.Radical nephrectomy is an important independent risk factor for patients with RCC.2.Based on the type of operation,AAPR,BUN,LDH and the lowest DBP during operation,the area under the ROC curve of the training set is 0.796,and the area under the ROC curve of the validation set is 0.773,which has a good prediction performance.The calibration diagram and DCA showed that the preoperative prediction model had better prediction performance and clinical net benefit rate.3.Preoperative serum DKK3 can early predict the occurrence of AKI after nephrectomy.