Impact Of Cold Ischemia Time And Massive Fluid Replacement In The Polyuria Stage On Recovery Of Renal Allograft Function After Renal Transplantation

Background:Perioperative management has great influence on renal function recovery of renal transplant recipients.Cold ischemia time（CIT）is a factor that is thought to affect outcomes in renal transplantation.Surgeons are often reluctant to transplant kidneys with prolonged CIT for fear of an additional deleterious effect.Although studies have provided evidences that prolonged CIT has limited bearing on long-term outcomes,several investigators reported that prolonged CIT is a risk factor for delayed graft function during the early post-transplant period,which may increase duration of hospitalization and medical costs post renal transplantation.In clinic,there is still a paucity of an ideal biomarker in renal graft monitoring.Otherwise,previous studies have mainly focused on nephrectomy,preservation,improvement of transplantation techniques,and monitoring and treatment of anti-rejection reaction after renal transplantation.However,fluid treatment and management after renal transplantation have been in a non-standardized state,and even different hospitals have different postoperative liquid treatment plans.Theoretically,since the donor kidney inevitably experienced ischemic and hypoxic damage in the early stage after renal transplantation,Na+pump was temporarily inactivated,and the renal tubular reuptake function was weakened,and a large amount of Na+,C1-,K+and water were discharged out of the body.However,excessive infusion or inappropriate liquid treatment will not correct the disorder of water and electrolyte balance,but will aggravate the condition,and even more seriously,may lead to heart failure.Patients with end-stage renal disease inevitably have a series of pathological and physiological changes such as hyponatremia,hyperkalemia,atherosclerosis,hypertension,congestive heart failure,etc.,and the necessity of massive fluid infusion for the polyuria period after renal transplantation remains to be discussed.The purpose of this study was to investigate the relationship between the duration of cold ischemia after renal transplantation and the duration of cold ischemia with various circulating biomarkers in serum and the effect of massive fluid infusion on the early renal function recovery after renal transplantation.Objective:The purpose of this study was to investigate the effects of cold ischemic time on renal function by using four low molecular proteins and their ratio to creatinine,and the effects of high-dose fluid supplementation on renal function recovery after renal transplantation.Methods:1.Forty-severn renal recipients were identified into two groups（CIT<10h and CIT≥10h）.LMWPs,such as retinol-binding protein（RBP）,alpha-1 microglobulin（α1-M）,beta-2 microglobulin（β2-M）and cystatin-C（Cyst-C）,and their ratios to creatinine were retrospectively analyzed according to CIT.The four LMWPs were measured using the immunonephelometric method.Resistive indices（RI）were measured in the main,upper arcuate,lower arcuate and interlobar arteries of each transplanted kidney using the Mindray M9 portable color Doppler ultrasound machine（Mindray Medical International Ltd,Shenzhen,China）on post-transplant days 1,10 and 30,respectively.Data were summarized as mean±SD for normal continuous data and median（Q₁,Q₃）for skewed data and percentages for categorical data.Differences in frequency distribution of categorical variables were evaluated by Chi-square test.Comparisons between groups for continuous data were performed using either t-test or the Wilcoxon rank sun test（non-parametric data）,as appropriate.Correlation analysis were performed by using the spearman’s rank correlation.Multivariable regression was used to determine the influence of cold ischemia time on low molecular weight protein/creatinine ratios after controlling for potential confounders.2.A retrospective cohort study was conducted on forty renal transplant recipients:the high fluid replacement group（n=24）and the low fluid replacement group（n=16）.We evaluated the recovery of renal allograft function in the first 3 days after grafting.The correlation between the index of renal function above and the total urine volume was analyzed.Indicators for evaluating renal function include estimation of glomerular filtration rate,creatinine,cystatin C,urea nitrogen and retinol-binding protein levels.We conducted a statistical analysis of the levels and changes of the above indicators within 3days after renal transplant recipients.We also analyzed the electrolyte level and plasma osmotic pressure after operation.Statistical software SPSS 20.0 was used for statistical analysis.The measurement data that conform to normal distribution are represented by x±s,and t test is used for comparison.If not,median（M）and quartile（IQR）are used for description,and non-parametric test is applied.The classified data were compared using the x² test or Fisher exact probability method.Spearman correlation analysis was adopted for correlation analysis.Results:1.On post-transplant day 5,10 and 15,all four kinds of serum LMWPs showed a significant or borderline significant difference between groups.We found the pre-and post-renal transplant changes of serum RBP were all significantly inversely associated with CIT on post-transplant day 5,10 and 15,which is similar to the relationship between CIT and creatinine changes.Serum RBP/Creatinine ratios were higher in the CIT<10h group than CIT≥10h group on post-transplant day 5,10 and 15.In a multivariate linear regression model controlling for potential confounders,the relationships of CIT and serum RBP/Creatinine ratios were all significant on post-transplant day 5,10 and 15.Serumα1-M/Creatinine ratios and Cyst-C/Creatinine ratios were higher in the CIT<10h group than CIT≥10h group on post-transplant day 5 and 15,but no correlation betweenβ2-M/Creatinine ratios and CIT were observed.2.There was no significant difference in eGFR,creatinine,Cystatin C,urea nitrogen and retinol binding protein level and their change rates between the two groups of renal transplant recipients within 3 days after grafting（p>0.05）.No correlation between index above and total urine output was observed within 3 days after grafting（p>0.05）.Besides,there was no significant physiological and statistical difference in electrolyte level and plasma osmotic pressure between groups within 3 days after grafting（p>0.05）.Conclusion:1.Delayed reduction of LMWPs and slower increases of LMWP/Creatinine ratios in the longer CIT group,especially for RBP and RBP/Creatinine ratio,may be due to the temporal damage of the proximal renal tubule related with longer CIT.2.Massive fluid replacement in the polyuria stage after renal transplantation has no significant benefits on the recovery of renal function.At the same time,massive rehydration to increase the amount of urine can’t promote the recovery of renal function.