Future of non-invasive graft evaluation:A systematic review of proteomics in kidney transplantation

BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.

Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study

BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation:A Retrospective Study

Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.

Complement activation and long-term graft function in ABO-incompatible kidney transplantation

BACKGROUND ABO-incompatible and ABO-compatible kidney transplantation are equivalent in terms of short-term graft and patient survival. This is thought to be the result of ABO-incompatible graft accommodation, which occurs when anti-blood group antibodies re-occur after transplantation but somehow do not yield their detrimental effect. The underlying mechanism is unclear, but one of the hypotheses is that this is the result of complement inhibition. Since virtually all ABO-incompatible graft biopsies are C4d positive, this complement inhibition must occur somewhere in the complement cascade after the formation of C4d has already taken place, but where exactly is unclear. It is also unclear whether complement inhibition is complete. Incomplete accommodation could explain why recent studies have shown that long-term graft function in ABOincompatible transplantation is somewhat inferior to ABO-compatible kidney transplantation.AIM To unravel the relationship between pre-transplant anti-ABO antibodies,complement activation, and long-term graft function.METHODS We included all 27 ABO-incompatible transplantations that were performed between 2008 and 2013 at the Academic Medical Center Amsterdam and the University Medical Center Groningen. For each ABO-incompatible transplantation, we included four ABO-compatible controls matched by age, sex,and transplantation date.RESULTS Graft and patient survival were not significantly different. The slope of kidney function during five-year follow-up was also not significantly different, but ABOincompatible recipients did have a lower kidney function at three months(creatinine clearance 58 vs 69 mL/min, P = 0.02, Modification of Diet in Renal Disease 46 vs 52 mL/min/1.73 m^2, P = 0.08), due to a high rate of early rejection(33% vs 15%, P = 0.03), mostly T-cell mediated. Pre-transplant anti-ABO Ig G titers were positively correlated with C5b-9 staining, which itself was positively correlated with the occurrence of T-cell mediated rejection. This may be the result of concurrent C5a formation, which could function as a costimulatory signal for T-cell activation.CONCLUSION Co-stimulation of T-cell activation by ongoing complement activation by antiABO antibodies may be responsible for an impaired long-term graft function in ABO-incompatible kidney transplantation.

Predictors of graft function and survival in second kidney transplantation: A single center experience

BACKGROUND The increasing kidney retransplantation rate has created a parallel field of research,including the risk factors and outcomes of this advanced form of renal replacement therapy.The presentation of experiences from different kidney transplantation centers may help enrich the literature on kidney retransplantation,as a specific topic in the field of kidney transplantation.AIM To identify the risk factors affecting primary graft function and graft survival rates after second kidney transplantation(SKT).METHODS The records of SKT cases performed between January 1977 and December 2014 at a European tertiary-level kidney transplantation center were retrospectively reviewed and analyzed.Beside the descriptive characteristics,the survivals of patients and both the first and second grafts were described using Kaplan-Meier curves.In addition,Kaplan-Meier analyses were also used to estimate the survival probabilities at 1,3,5,and 10 post-operative years,as well as at the longest followup duration available.Moreover,bivariate associations between various predictors and the categorical outcomes were assessed,using the suitable biostatistical tests,according to the predictor type.RESULTS Out of 1861 cases of kidney transplantation,only 48 cases with SKT were eligible for studying,including 33 men and 15 women with a mean age of 42.1±13 years.The primary non-function(PNF)graft occurred in five patients(10.4%).In bivariate analyses,a high body mass index(P=0.009)and first graft loss due to acute rejection(P=0.025)were the only significant predictors of PNF graft.The second graft survival was reduced by delayed graft function in the first(P=0.008)and second(P<0.001)grafts.However,the effect of acute rejection within the first year after the first transplant did not reach the threshold of significance(P=0.053).The mean follow-up period was 59.8±48.6 mo.Censored graft/patient survival rates at 1,3,5 and 10 years were 90.5%/97.9%,79.9%/95.6%,73.7%/91.9%,and 51.6%/83.0%,respectively.CONCLUSION Non-immediate recovery modes of the first and second graft functions were significantly associated with unfavorable second graft survival rates.Patient and graft survival rates of SKT were similar to those of the first kidney transplantation.

Prediction of delayed graft function using different scoring algorithms: A single-center experience

AIM To compare the performance of 3 published delayed graftfunction(DGF) calculators that compute the theoretical risk of DGF for each patient.METHODS This single-center,retrospective study included 247 consecutive kidney transplants from a deceased donor.These kidney transplantations were performed at our institution between January 2003 and December 2012.We compared the occurrence of observed DGF in our cohort with the predicted DGF according to three different published calculators. The accuracy of the calculators was evaluated by means of the c-index(receiver operating characteristic curve).RESULTS DGF occurred in 15.3% of the transplants under study.The c index of the Irish calculator provided an area under the curve(AUC) of 0.69 indicating an acceptable level of prediction,in contrast to the poor performance of the Jeldres nomogram(AUC = 0.54) and the Chapal nomogram(AUC = 0.51). With the Irish algorithm the predicted DGF risk and the observed DGF probabilities were close. The mean calculated DGF risk was significantly different between DGF-positive and DGF-negative subjects(P < 0.0001). However,at the level of the individual patient the calculated risk of DGF overlapped very widely with ranges from 10% to 51% for recipients with DGF and from 4% to 56% for those without DGF.The sensitivity,specificity and positive predictive value of a calculated DGF risk ≥ 30% with the Irish nomogram were 32%,91% and 38%. CONCLUSION Predictive models for DGF after kidney transplantation are performant in the population in which they were derived,but less so in external validations.

Blessing and a curse of outpatient management of delayed graft function

Delayed graft function (DGF) is a common complication occurring most often after deceased donor kidney transplant with several donor characteristics as well as immunologic factors that lead to its development post-transplant.These patients require dialysis and close kidney function monitoring until sufficient allograft function is achieved.This has resulted in limited options for DGF management,either prolonged hospitalization until graft function improves to the point where dialysis is no longer needed or discharge back to their home dialysis unit with periodic follow up in the transplant clinic.DGF is associated with a higher risk for acute rejection,premature graft failure,and 30-d readmission;therefore,these patients need close monitoring,immunosuppression management,and prompt allograft biopsy if prolonged DGF is observed.This may not occur if these patients are discharged back to their home dialysis unit.To address this issue,the University of Wisconsin-Madison created a clinic in 2011 specialized in outpatient DGF management.This clinic was able to successfully reduce hospital length of stay without an increase in 30-d readmission,graft loss,and patient death.

The Effect of Non-Invasive Goal Directed Fluid Administration on Graft Function in Deceased Donor Renal Transplantation: A Pilot Study

Background: Non-invasive goal directed fluid therapy during deceased donor renal transplant (CRT) may reduce the incidence of delayed graft function. Plethysmograph Variability Index (PVI) has been shown to predict fluid responsiveness during surgery. This pilot study evaluated the feasibility of goal directed fluid administration protocol based upon PVI studying the incidence of delayed graft function (DGF) in renal transplant recipients. Methods: Twenty patients underwent primary CRT. The Control group received intravenous fluid (IVF) at a calculated constant rate. The Treatment group received a baseline IVF infusion throughout the surgery. PVI values greater than 13% were treated with 250 ml boluses of IVF. Primary end point was DGF;total IVF administration and urinary biomarker NGAL levels were secondary endpoints. Results: Treatment group at every time point received significantly less IVF. There was no significant difference in incidence of DGF between the groups. 2 patients in the Control group and 6 in the Treatment group developed DGF. NGAL was not associated with the group assignment or total IVF given (p < 0.2). Conclusions: The effectiveness of goal directed fluid therapy with non-invasive dynamic parameters has not been validated in renal transplant surgery and larger prospective studies are needed to determine its utility in renal transplantation.

Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment

Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.

Successful kidney transplantation from an expanded criteria donor with long-term extracorporeal membrane oxygenation treatment: A case report

BACKGROUND Due to a shortage of donor kidneys, many centers have utilized graft kidneys from brain-dead donors with expanded criteria. Kidney transplantation(KT)from donors on extracorporeal membrane oxygenation(ECMO) has been identified as a successful way of expanding donor pools. However, there are currently no guidelines or recommendations that guarantee successful KT from donors undergoing ECMO treatment. Therefore, acceptance of appropriate allografts from those donors is solely based on clinician decision.CASE SUMMARY We report a case of successful KT from a brain-dead donor supported by ECMO for the longest duration to date. A 69-year-old male received a KT from a 63-yearold brain-dead donor who had been on therapeutic ECMO treatment for the previous three weeks. The recipient experienced slow recovery of graft function after surgery but was discharged home on post-operative day 17 free from hemodialysis. Allograft function gradually improved thereafter and was comparatively acceptable up to the 12 mo follow-up, with serum creatinine level of 1.67 mg/d L.CONCLUSION This case suggests that donation even after long-term ECMO treatment could provide successful KT to suitable candidates.

Innovative immunosuppression in kidney transplantation:A challenge for unmet needs

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries,new innovative drugs in kidney transplantation are difficult to be encountered.The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market.These unmet needs are the prevention of delayed graft function(DGF),the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection.These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts.The first are particularly exposed to DGF,the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur.Particular caution is needed in treating these drugs.First,they are described in very recent studies and the follow-up of their effect is of course rather short.Second,some of these drugs are still in an early phase of study,even if in well-conducted randomized controlled trials.Particular caution and a careful check need to be used in trials launched 2 or 3 years ago.Indeed,is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.

Predictive Score Model for Delayed Graft Function Based on Hypothermic Machine Perfusion Variables in Kidney Transplantation

Background: Hypothermic machine perfusion(HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function(DGF) by HMP parameters is still controversial. Therefore,we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios(ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.Results: HMP duration(OR = 1.165, 95% confidence interval [CI ]: 1.008–1.360, P = 0.043), resistance(OR = 2.190, 95%CI: 1.032–10.20, P < 0.001), and flow rate(OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories(scores 0–3, 4–7, 8–11, and 12–14)according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c?statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow(P = 0.012) and resistance(P = 0.006).Conclusion: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.

Role for contrast-enhanced ultrasound in assessing complications after kidney transplant

Kidney transplantation(KT)is an effective treatment for end-stage renal disease.Despite their rate has reduced over time,post-transplant complications still represent a major clinical problem because of the associated risk of graft failure and loss.Thus,post-KT complications should be diagnosed and treated promptly.Imaging plays a pivotal role in this setting.Grayscale ultrasound(US)with color Doppler analysis is the first-line imaging modality for assessing complications,although many findings lack specificity.When performed by experienced operators,contrast-enhanced US(CEUS)has been advocated as a safe and fast tool to improve the accuracy of US.Also,when performing CEUS there is potentially no need for further imaging,such as contrast-enhanced computed tomography or magnetic resonance imaging,which are often contraindicated in recipients with impaired renal function.This technique is also portable to patients’bedside,thus having the potential of maximizing the cost-effectiveness of the whole diagnostic process.Finally,the use of blood-pool contrast agents allows translating information on graft microvasculature into time-intensity curves,and in turn quantitative perfusion indexes.Quantitative analysis is under evaluation as a tool to diagnose rejection or other causes of graft dysfunction.In this paper,we review and illustrate the indications to CEUS in the post-KT setting,as well as the main CEUS findings that can help establishing the diagnosis and planning the most adequate treatment.

Calcineurin inhibitor sparing strategies in renal transplantation, part one: Late sparing strategies

Kidney transplantation improves quality of life and reduces the risk of mortality. A majority of the success of kidney transplantation is attributable to the calcineurin inhibitors(CNIs), cyclosporine and tacrolimus, and their ability to reduce acute rejection rates. However, longterm graft survival rates have not improved over time, and although controversial, evidence does suggest a role of chronic CNI toxicity in this failure to improve outcomes. Consequently, there is interest in reducing or removing CNIs from immunosuppressive regimens in an attempt to improve outcomes. Several strategies exist to spare calcineurin inhibitors, including use of agents such as mycophenolate mofetil(MMF), mycophenolate sodium(MPS), sirolimus, everolimus or belatacept to facilitate late calcineurin inhibitor withdrawal, beyond 6 mo post-transplant; or using these agents to plan early withdrawal within 6 mo; or to avoid the CNIs all together using CNI-free regimens. Although numerous reviews have been written on this topic, practice varies significantly between centers. This review organizes thedata based on patient characteristics(i.e., the baseline immunosuppressive regimen) as a means to aid the practicing clinician in caring for their patients, by matching up their situation with the relevant literature. The current review, the first in a series of two, examines the potential of immunosuppressive agents to facilitate late CNI withdrawal beyond 6 mo post-transplant, and has demonstrated that the strongest evidence resides with MMF/MPS. MMF or MPS can be successfully introduced/maintained to facilitate late CNI withdrawal and improve renal function in the setting of graft deterioration, albeit with an increased risk of acute rejection and infection. Additional benefits may include improved blood pressure, lipid profile and serum glucose.Sirolimus has less data directly comparing CNI withdrawal to an active CNI-containing regimen, but modest improvement in short-term renal function is possible, with an increased risk of proteinuria, especially in the setting of baseline renal dysfunction and/or proteinuria. Renal outcomes may be improved when sirolimus is used in combination with MMF. Although data with everolimus is less robust, results appear similar to those observed with sirolimus.

Correlation of Surgical Times with Laparoscopic Live Donor Kidney Transplant Outcomes

Most studies revealed that ischemic time has substantial role in occurrence of delayed graft function (DGF) after deceased donor kidney transplantation. However, less is known about the potential impact of surgical times on early outcomes following live donor kidney transplantation. A retrospective cohort of 189 consecutive laparoscopic live donor kidney transplant (LDKT) recipients from January 2006 to August 2012 was analyzed to reveal the impact of pneumoperitoneum time (PT) and anastomosis time (AT) on donor and recipient length of hospital stay and early graft function (EGF). DGF was observed in 13 (6.8%) patients while slow graft function (SGF) was seen in 27 (14%) of the recipients. The median AT was 28 minutes (interquartile range 23, 35 minutes). AT was associated with DGF (Odds Ratio [OR] 1.044, per minute, 95% CI 1.007, 1.082, p = 0.018). Median recipient length of hospital stay was 8 (interquartile range 7, 11) days. Every 13.5 minutes of longer AT was associated with 1 extra day in hospital. The median PT was 180 minutes (interquartile range 144, 234 minutes). PT was associated with both DGF (OR 1.013 per minute, 95% CI 1.005, 1.021, p = 0.001) and SGF (OR 1.009 per minute, 95% CI 1.002, 1.016, p = 0.016). Every extra hour of PT was associated with 0.42 more days in hospital for the donor. Surgical times may be underestimated variables in dictating use of hospital resources. The effect of surgical times on long term hard outcomes entails further study.

Delayed graft function is correlated with graft loss in recipients of expanded-criteria rather than standard-criteria donor kidneys:a retrospective,multicenter,observation cohort study

Background:Although the use of expanded-criteria donors(ECDs)alleviates the problem of organ shortage,it significantly increases the incidence of delayed graft function(DGF).DGF is a common complication after kidney transplantation;however,the effect of DGF on graft loss is uncertain based on the published literature.Hence,the aim of this study was to determine the relationship between DGF and allograft survival.Methods:We conducted a retrospective,multicenter,observation cohort study.A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included.We used logistic regression analysis to verify the association between clinical parameters and DGF,and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss.Results:Among the 284 deceased donors,65(22.8%)donors were ECD.Of the 541 recipients,107(19.8%)recipients developed DGF,and this rate was higher with ECD kidneys than with standard-criteria donor(SCD)kidneys(29.2%vs.17.1%;P=0.003).The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF(95.8%vs.95.4%;P=0.580).However,there was a significant difference between ECD kidney recipients with and without DGF(71.4%vs.97.6%;P=0.001),and the adjusted hazard ratio(HR)for graft loss for recipients with DGF was 1.885(95%confidence interval[CI]=1.305–7.630;P=0.024).Results showed that induction therapy with anti-thymocyte globulin was protective against DGF(odds ratio=0.359;95%CI=0.197–0.652;P=0.001)with all donor kidneys and a protective factor for graft survival(HR=0.308;95%CI=0.130–0.728;P=0.007)with ECD kidneys.Conclusion:DGF is an independent risk factor for graft survival in recipients with ECD kidneys,but not SCD kidneys.

Predictive Score Model for Delayed Graft Function Based on Easily Available Variables before Kidney Donation after Cardiac Death

Background： How to evaluate the quality of donation after cardiac transplantation in China. Hence, the aim of this study was to develop kidneys before DCD. death （DCD） kidneys has become a critical problem in kidney a simple donor risk score model to evaluate the quality of DCD Methods： A total of 543 qualified kidneys were randomized in a 2：1 manner to create the development and validation cohorts. The donor variables in the development cohort were considered as candidate univariate predictors of delayed graft function （DGF）. Multivariate logistic regression was then used to identify independent predictors of DGF with P 〈 0.05. Date from validation cohort were used to validate the donor scoring model. Results： Based on the odds ratios, eight identified variables were assigned a weighted integer; the sum of the integer was the total risk score for each kidney. The donor risk score, ranging from 0 to 28, demonstrated good discriminative power with a C-statistic of 0.790. Similar results were obtained from validation cohort with C-statistic of 0.783. Based on the obtained frequencies of DGF in relation to different risk scores, we formed tour risk categories of increasing severity （scores 04, 5 9, 10-14, and 15 28）. Conclusions： The scoring model might be a good noninvasive tool for assessing the quality of DCD kidneys before donation and potentially useful for physicians to make optimal decisions about donor organ offers.

Kidney donation after cardiac death

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death （DCD） and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to con-trolled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function （DGF） and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that signifcantly infuences the outcome of allografts, for example, limiting it to 〈 12 h markedly reduces DGF. DCD kidneys from donors 〈 50 function like stan-dard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled dona-tion, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kid-neys from DCD include： implementing organ recovery from emergency department setting; improving family consent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

Changes in biochemical parameters on the first day after kidney transplantation： risk factors for nosocomial infection？

Background Nosocomial infection in early post-transplantation period is a tough problem for kidney transplantation. Few reports have explored the relations between biochemical parameters and nosocomial infection in kidney transplantation. This retrospective study was carried out to describe the characteristics of nosocomial infection in the very early period of kidney transplantation and to determine the risk factors in biochemical parameters and their alterations. Methods Patients who underwent their first kidney transplantation from January 2001 to March 2009 in Beijing Chao-Yang Hospital were recruited and the nosocomial infectious episodes were collected for this study. Gender, age, donor type, delayed graft function （DGF） and biochemical parameters such as serum uric acid, lipids files and albumin on day 0 （before transplantation） and day 1 （24 hours after transplantation） and their changes were analyzed with Logistic regression models for nosocomial infection. Results A total of 405 patients （315 men and 90 women） were involved in this study. There were 80 patients experiencing 113 infection episodes and 105 strains of microorganism were indentified. In univariate analysis, there were significant differences in DGF, albumin on day 0, lipoprotein （a） （Lp（a）） on day 1, change in low density lipoprotein-cholesterol （LDL-C, day 1-day 0） and change in uric acid （day 1-day 0） between nosocomial infection patients and noninfectious patients （P 〈0.05）. In multivariate analysis, change in uric acid （day 1-day 0） （OR 5.139, 95% CI 1.176-22.465, P 〈0.05）, change in LDL-C （day 1-day 0） （OR4.179, 95% CI 1.375-12.703, P 〈0.05） and DGF （OR 14.409, 95% CI 1.603-129.522, P 〈0.05） were identified as independent risk factors for nosocomial infection in kidney transplantation. Conclusions Most nosocomial infections in early postoperative period of kidney transplantation are bacterial, especially with Gram-negative bacteria. The most common infection sites are respiratory tract, urinary tract and surgical site. DGF, decrease of LDL-C and increase of uric acid could increase the risk for nosocomial infections.

Predictive value of hypothermic machine perfusion parameters combined perfusate biomarkers in deceased donor kidney transplantation

Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor(DD)kidney transplantation.Methods:HMP parameters,perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1,2019 to August 31,2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.Results:In this study,the DGF incidence was 17.7%(20/113);The multivariate logistic regression results showed that terminal resistance(OR:1.879,95%CI 1.145-3.56)and glutathione S-transferase(GST)(OR=1.62,95%CI 1.23-2.46)were risk factors for DGF;The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time(HR=0.823,95%CI 0.735-0.981).The model combining terminal resistance and GST(AUC=0.888,95%CI:0.842-0.933)significantly improved the DGF predictability compared with the use of terminal resistance(AUC=0.756,95%CI 0.693-0.818)or GST alone(AUC=0.729,95%CI 0.591-0.806).Conclusion:According to the factors analyzed in this study,the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.