Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival

BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains controversial.AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease.METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without(kidney transplant alone(KTA)group)and 77 with associated ipsilateral nephrectomy(KTIN group),were retrospectively reviewed.Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival.RESULTS Creation of space for future graft positioning was the main reason(n=74,96.1%)for associated ipsilateral nephrectomy.No significant difference in surgical comorbidity(lymphocele,wound infection,incisional hernia,wound hematoma,urinary infection,need for blood transfusion,hospitalization stay,Dindo Clavien classification and readmission rate)was observed between the two study groups.The incidence of primary nonfunction and delayed graft function was comparable in both groups[0%and 2.6%(P=0.497)and 9.1%and 16.9%(P=0.230),respectively,in the KTA and KTIN group].The 1-and 5-year graft survival were 94.8%and 90.3%,and 100%and 93.8%,respectively,in the KTA and KTIN group(P=0.774).The 1-and 5-year patient survival were 96.1%and 92.9%,and 100%and 100%,respectively,in the KTA and KTIN group(P=0.168).CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short-and long-term graft survival.

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.

Predicting outcomes after kidney transplantation: Can Pareto’s rules help us to do so?

Kidney transplantation is the best option for kidney replacement therapy,even considering that most of the times the grafts do not survive as long as their recipients.In the Khalil et al's experience,published in this issue of the Journal,they analyze their second kidney graft survival and describe those significant predictors of early loss.This editorial comments on the results and put in perspective that most of the times,long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason,and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Gut microbiota is often modified after kidney transplantation.This principally happens in the first period after transplantation.Antibiotics and,most of all,immunosuppressive drugs are the main responsible.The relationship between immunosuppressive drugs and the gut microbiota is bilateral.From one side immunosuppressive drugs modify the gut microbiota,often generating dysbiosis;from the other side microbiota may interfere with the immunosuppressant pharmacokinetics,producing products more or less active with respect to the original drug.These phenomena have influence over the graft outcomes and clinical consequences as rejections,infections,diarrhea may be caused by the dysbiotic condition.Corticosteroids,calcineurin inhibitors such as tacrolimus and cyclosporine,mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known.In contrast is well known how the gut microbiota may interfere with glucocorticoids,which may be transformed into androgens.Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus.The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase,may be transformed into the inactive product.

Supportive care in transplantation: A patient-centered care model to better support kidney transplant candidates and recipients

Kidney transplantation(KT),although the best treatment option for eligible patients,entails maintaining and adhering to a life-long treatment regimen of medications,lifestyle changes,self-care,and appointments.Many patients experience uncertain outcome trajectories increasing their vulnerability and symptom burden and generating complex care needs.Even when transplants are successful,for some patients the adjustment to life post-transplant can be challenging and psychological difficulties,economic challenges and social isola-tion have been reported.About 50%of patients lose their transplant within 10 years and must return to dialysis or pursue another transplant or conservative care.This paper documents the complicated journey patients undertake before and after KT and outlines some initiatives aimed at improving patient-centered care in transplantation.A more cohesive approach to care that borrows its philosophical approach from the established field of supportive oncology may improve patient experiences and outcomes.We propose the"supportive care in transplantation"care model to operationalize a patient-centered approach in transplantation.This model can build on other ongoing initiatives of other scholars and researchers and can help advance patient-centered care through the entire care continuum of kidney transplant recipients and candidates.Multi-dimensionality,multi-disciplinarity and evidence-based approaches are proposed as other key tenets of this care model.We conclude by proposing the potential advantages of this approach to patients and healthcare systems.Core Tip:Kidney transplant recipients and candidates face several uncertainties in their care journey and have several expressed unmet healthcare needs.We recommend a structured and comprehensive approach to transplant care across the entire continuum of a transplant patient’s journey similar to what has been developed in the field of oncology.The supportive care in transplantation model can operationalize patient-centered care and build on the efforts of other researchers in the field.We postulate that such a model would significantly improve care delivery and patients’experiences and outcomes and potentially decrease healthcare utilization and cost.INTRODUCTION Patients with kidney failure benefit from(KT)[1,2],and experience improved survival rates when compared with dialysis[3-6].KT studies,using validated instruments,have also consistently demonstrated that kidney transplant recipients(KTRs)experience better health-related quality of life and several improvements in other disease-specific domains when compared with dialysis[7].In countries where dialysis is out of reach for many,the diagnosis of kidney failure would be futile without KT[8].Thus,increasing KT has been a priority for the nephrology and transplant communities.This priority has been reflected in recent global trends:Of the 79 countries where data were available,the International Society of Nephrology’s Global Kidney Atlas reported that the prevalence of KTRs in 2023 was 279 per million population which represented an increase of 9.4%from the data published four years prior[8].Despite this growth,KT can be a challenging journey for many patients and it is sometimes regarded as a‘cure’,which does not conform with the reality that many patients experience[9-13].KTRs must maintain a life-long treatment regimen of medications,lifestyle changes,self-care and medical appointments[14-17].As poignantly stated by a young female transplant recipient,“I thought everything would change once I got my kidney.I thought I would be healthy again”but after experiencing multiple side effects of immunosuppressive medications and graft loss,she stated,“I am just a different kind of patient now”[18].Indeed,a significant proportion of patients experience graft failure and return to dialysis;it is estimated that over 50%return to dialysis within 10 years of KT[19-23].Patients are often not prepared for this outcome and report several psychosocial and physical ramifications of graft failure[24,25].Overall,high symptom burden,adverse effects of immunosuppressants,risk of graft rejection or failure and mortality,contribute to complex needs,vulnerability and uncertainties for patients,increasing their care needs and treatment burden[26-30].In this paper,we highlight the complex journey that KTRs and candidates undertake that can generate varied outcome trajectories and complex healthcare needs.We highlight the need for a comprehensive patient-centered approach to care and conclude with a proposal for a“supportive care in transplantation”care model.

Impact of small-for-size liver grafts on medium-term and long-term graft survival in living donor liver transplantation: A meta-analysis

BACKGROUND Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking. AIM To evaluate the impact of small-for-size liver grafts on medium-term and longterm graft survival in adult to adult LDLT. METHODS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted. RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies. CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation.

Effect of donor age on graft function and longterm survival of recipients undergoing living donor liver transplantation

BACKGROUND： Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation（LDLT） has been considered as a valuable approach to shortening waiting time. The objectives of this study were to investigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient survival.METHODS： All LDLT cases（n=159） were divided into the older（donor age ≥50 years, n=10） and younger（donor age 〈50 years,n=149） donor groups. Donor graft and recipient condition pre-,intra- and post-operation were compared between the two groups.In particular, graft functions and recipient survivals were analyzed.RESULTS： The median donor age was 58.5（52.5-60.0） years in the older donor group and 25.0（23.0-32.0） in the younger donor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups（P〉0.05）. However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group（1900 vs 1200 m L, P=0.023）. The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87% and 87% for the younger donor group, respectively（P=0.459）.The 1-, 3- and 5-year survival rates were 100%, 90% and 90% for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively（P=0.811）.CONCLUSION： It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients’ survival.

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.

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.

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.

Relationship of Transforming Growth Factor-β1 and Arginase-1 Levels with Long-term Survival after Kidney Transplantation

In this study, we compared the serum levels of transforming growth factor-β1 （TGF-β1）, interleukin-10 （IL-10）, and arginase-1 in long-term survival kidney transplant recipients （LTSKTRs） with those in short-term survival kidney transplant recipients （STSKTRs）. We then evaluated the relationship between these levels and graft function. Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs （graft survival approximately 1-3 years post-transplantation）. All patients had stable kidney function. The samples were collected at our institution during the patients＇ follow-up examinations between March 2017 and September 2017. The plasma levels of TGF-β1, IL- 10, and arginase- 1 were analyzed using enzyme-linked immunosorbent assays （ELISA）. The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs. The time elapsed since transplantation was positively correlated with the levels of TGF-β1 and arginase-1 in the LTSKTRs. The estimated glomerular filtration rate was positively correlated with the TGF-β1 level, and the serum creatinine level was negatively correlated with the TGF-β1 level. Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs, and we found that TGF-β1 was positively correlated with long-term graft survival and function. Additionally, TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation. On the basis of these findings, TGF-β1 and arginase- 1 may play important roles in determining long-term graft survival. Thus, we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.

Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study

BACKGROUND Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation.AIM To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients,mainly early allograft dysfunction.METHODS This multicenter retrospective study included brain-dead donors and adult liver graft recipients.Donor-recipient matching was obtained through a crossover list.Clinical and laboratory data were recorded for both donors and recipients.Donor hepatectomy,cold ischemia,and warm ischemia times were recorded.Primary outcome was early allograft dysfunction.Secondary outcomes included need for retransplantation,length of intensive care unit and hospital stay,and patient and graft survival at 12 months.RESULTS From January 2019 to December 2021,a total of 243 patients underwent a liver transplant from a brain-dead donor.Of these,57(25%)developed early allograft dysfunction.The median donor hepatectomy time was 29(23–40)min.Patients with early allograft dysfunction had a median hepatectomy time of 25(22–38)min,whereas those without it had a median time of 30(24–40)min(P=0.126).CONCLUSION Donor hepatectomy time was not associated with early allograft dysfunction,graft survival,or patient survival following liver transplantation.

Middle hepatic vein reconstruction in adult right lobe living donor liver transplantation improves recipient survival

Background: The efficacy and necessity of middle hepatic vein(MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation(LDLT) remain controversial. The present study aimed to evaluate the survival beneficiary of MHV reconstructions in LDLT. Methods: We compared the clinical outcomes of liver recipients with MHV reconstruction( n = 101) and without MHV reconstruction( n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. Results: The overall survival(OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation( P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments(segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment(segment 5 or segment 8) hepatic vein reconstruction( P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction( P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS(hazard ratio = 0.519, 95% CI: 0.282–0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction(28.7% vs 11.6%, P = 0.027). Conclusions: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries(segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.

New-onset diabetes mellitus after kidney transplantation:Current status and future directions

A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short-and long-term implications of type 2 diabetes seen in the general population.NODAT usually occurs early after transplantation,and is usually diagnosed according to general population guidelines.Non-modifiable risk factors for NODAT include advancing age,African American,Hispanic,or South Asian ethnicity,genetic background,a positive family history for diabetes mellitus,polycystic kidney disease,and previously diagnosed glucose intolerance.Modifiable risk factors for NODAT include obesity and the metabolic syndrome,hepatitis C virus and cytomegalovirus infection,corticosteroids,calcineurin inhibitor drugs(especially tacrolimus),and sirolimus.NODAT affects graft and patient survival,and increases the incidence of post-transplant cardiovascular disease.The incidence and impact of NODAT can be minimized through pre-and post-transplant screening to identify patients at higher risk,including by oral glucose tolerance tests,as well as multi-disciplinary care,lifestyle modification,and the use of modified immunosuppressive regimens coupled with glucose-lowering therapies including oral hypoglycemic agents and insulin.Since NODAT is a major cause of post-transplant morbidity and mortality,measures to reduce its incidence and impact have the potential to greatly improve overall transplant success.

Early acute kidney injury after liver transplantation: Predisposing factors and clinical implications

To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI) following liver transplantation. METHODSThis was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation (OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT (> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration (CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase (AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor (< 1000 IU/L), moderate (1000-5000 IU/L) or severe (> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications (AKI and HIRI) alone and then as a combined outcome. RESULTSOut of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustained moderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation (P < 0.001) and intensive care length of stay (P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication (P = 0.049). CONCLUSIONHIRI has an important role in the development of AKI post-OLT and has a negative impact on patient outcomes, especially when occurring alongside AKI.

Pre-and intraoperative predictors of acute kidney injury after liver transplantation

BACKGROUND Acute kidney injury(AKI)after liver transplantation(LT)is a frequent and multifactorial event related to increased morbidity and mortality.Risk factors for AKI after LT still need to be clarified.AIM To identify the predictors of acute kidney injury after liver transplantation.METHODS The frequency and pre-and intraoperative predictors of AKI within the first 7 d after LT were evaluated in adult liver transplant candidates in a single LT center in Croatia.AKI was defined according to the Kidney Disease:Improving Global Outcomes criteria.RESULTS Out of 205 patients(mean age 57±10 years;73.7%males,52.7%with alcoholrelated liver disease)93(45.36%)developed AKI,and the majority of them(58.06%)had stage 1.Only 5.38%of patients required renal replacement therapy after LT.The majority of patients(82.8%)developed AKI within the first two days after the procedure.Multivariate logistic regression identified pre-LT body mass index(OR=1.1,95%CI:1.05-1.24)and red blood cell transfusion(OR=1.66,95%CI:1.09-2.53)as independent predictors of early post-LT AKI occurrence.30-d survival after LT was significantly better for patients without AKI(P=0.01).CONCLUSION Early AKI after LT is a frequent event that negatively impacts short-term survival.The pathogenesis of AKI is multifactorial,but pre-LT BMI and intraoperative volume shifts are major contributors.

Low platelet count: Predictor of death and graft loss after liver transplantation

BACKGROUND The impact of platelets on liver transplantation(LT) is well recognized, but not completely understood. Platelets exert dichotomous effects on the graft and on the patient. On the one hand, they are essential for primary hemostasis and tissue repair and regeneration. On the other hand, they support ischemia/reperfusion injury and inflammatory processes. Recent evidence has shown a new role for platelet count(PC) in predicting outcomes after LT.AIM To evaluate if low PC is a predictor of short-and long-term outcomes after LT.METHODS Four hundred and eighty consecutive LT patients were retrospectively assessed.PC from the preoperative to the seventh postoperative day(POD) were considered. C-statistic analysis defined the ideal cutoff point for PC. Cox regression was performed to check whether low PC was a predictor of death,retransplantation or primary changes in graft function within one year after LT.RESULTS The highest median PC was 86 × 109/L [interquartile range(IQR) = 65–100 ×109/L] on seventh POD, and the lowest was 51 × 109/L(IQR = 38–71 × 109/L) on third POD. The C-statistic defined a PC < 70 × 109/L on fifth POD as the ideal cutoff point for predicting death and retransplantation. In the multivariate analysis, platelets < 70 × 109/L on 5 POD was an independent risk factor for death at 12 mo after LT [hazard ratio(HR) = 2.01; 95% confidence interval(CI) 1.06-3.79;P = 0.031]. In the Cox regression, patients with PC < 70 × 109/L on 5 POD had worse graft survival rates up to one year after LT(HR = 2.76; 95%CI 1.52-4.99; P =0.001).CONCLUSION PC < 70 × 109/L on 5 POD is an independent predictor of death in the first year after LT. These results are in agreement with other studies that indicate that low PC after LT is associated with negative outcomes.

INFLUENCE OF HEPATITIS B AND HEPATITIS C VIRUS INFECTION ON THE OUTCOME OF KIDNEY TRANSPLANTATION

Objective To investigate the impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the long-term survival of renal transplantation recipients. Methods A total of 443 patients who received renal allografts from 1992 to 2002 were analyzed. Outcome and survival were compared among four groups retrospectively. Results Twelve patients were positive for both hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) (group 1), 18 were HBsAg-positive and anti-HCV-negative (group 2), 26 were HBsAg-negative and anti-HCV-positive (group 3) and 387 were negative for both markers (group 4). The mean follow-up period was 6.1 ± 2.8 years (range, 0.5-10 years) for all patients. Group 2 had significantly higher liver-related complications (38.9%) and liver-related death (16.7%) than did group 4 (0%, P < 0.01). Among all patients, 4 HBsAg-positive patients had fulminant hepatitis and died within two years of transplantation. Three patients (group 2) who died were seropositive for HBeAg and/or HBV DNA and none had a history of or positive serologic marker to indicate hepatitis of other etiologies. One (group 1), two (group 2), and one patient (group 3) developed liver cirrhosis respectively, and hepatocellular carcinoma occurred in two patients (group 2) and one patient (group 3). Despite high liver-related mortality in HBV-infected patients, no significant differences among the four groups in the long-term graft and patient survivals were demonstrated. The presence of HBsAg or anti-HCV was not associated with poor prognosis as determined by Cox regression analysis. Conclusion HBV or HCV infection is not a contraindiction to kidney transplantation in Chinese patients. However, it should be noted that serious liver-related complications may occur and limit survival in patients infected with HBV and/or HCV after kidney transplantation.

Kidney transplantation from donors with hepatitis C infection

The increasing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led to most transplant centers developing protocols that allow safe utilization from donors with special clinical situations which previously were regarded as contraindications. Deceased donors with previous hepatitis C infection may represent a safe resource to expand the donor pool. When allocated to serology-matched recipients, kidney transplantation from donors with hepatitis C may result in an excellent short-term outcome and a significant reduction of time on the waiting list. Special care must be dedicated to the pre-transplant evaluation of potential candidates, particularly with regard to liver functionality and evidence of liver histological damage, such as cirrhosis, that could be a contraindication to transplantation. Pre-transplant antiviral therapy could be useful to reduce the viral load and to improve the long-term results, which may be affected by the progression of liver disease in the recipients. An accurate selection of both donor and recipient is mandatory to achieve a satisfactory long-term outcome.

Role of novel biomarkers in kidney transplantation

Clinical application of biomarkers is an integral component of transplant care.Clinicians and scientists alike are in search of better biomarkers than the current serologic(serum creatinine,donor-specific antibodies),urine-derived(urinalysis,urine protein),and histologic ones we now use.The science behind recent biomarker discovery spans across multiple molecular biologic disciplines,including transcriptomics,proteomics,and metabolomics.Innovative methodology and integration of basic and clinical approaches have allowed researchers to unearth molecular phenomena preceding clinical disease.Biomarkers can be classified in several ways.In this review,we have classified them via their origin and outcome:Primarily immunologic,i.e.,representative of immune regulation and dysfunction and non-immunologic,pertaining to delayed graft function,cardiovascular events/mortality,infection,malignancy,posttransplant diabetes,graft,and patient survival.Novel biomarker uses to guide the diagnosis and management of transplant-related outcomes is a promising area of research.However,the use of biomarkers to predict outcomes after kidney transplantation is not well studied.In this review,we summarize the recent studies illustrating biomarker use and transplant outcomes.