Time-zero Biopsies Research Articles

Histologic Findings of Sinusoidal Dilatation and Congestion in Liver Grafts Do Not Correlate with Hepatic Venous Anastomotic Gradients.

Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting. This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed. No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02). There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting.

First experiences with machine learning predictions of accelerated declining eGFR slope of living kidney donors 3years after donation.

Living kidney donors are screened pre-donation to estimate the risk of end-stage kidney disease (ESKD). We evaluate Machine Learning (ML) to predict the progression of kidney function deterioration over time using the estimated GFR (eGFR) slope as the target variable. We included 238 living kidney donors who underwent donor nephrectomy. We divided the dataset based on the eGFR slope in the third follow-up year, resulting in 185 donors with an average eGFR slope and 53 donors with an accelerated declining eGFR-slope. We trained three Machine Learning-models (Random Forest [RF], Extreme GradientBoosting [XG], Support Vector Machine [SVM]) and Logistic Regression (LR) for predictions. Predefined data subsets served for training to explore whether parameters of an ESKD risk score alone suffice or additional clinical and time-zero biopsy parameters enhance predictions. Machine learning-driven feature selection identified the best predictive parameters. None of the four models classified the eGFR slope with an AUC greater than 0.6 or an F1 score surpassing 0.41 despite training on different data subsets. Following machine learning-driven feature selection and subsequent retraining on these selected features, random forest and extreme gradient boosting outperformed other models, achieving an AUC of 0.66 and an F1 score of 0.44. After feature selection, two predictive donor attributes consistently appeared in all models: smoking-related features and glomerulitis of the Banff Lesion Score. Training machine learning-models with distinct predefined data subsets yielded unsatisfactory results. However, the efficacy of random forest and extreme gradient boosting improved when trained exclusively with machine learning-driven selected features, suggesting that the quality, rather than the quantity, of features is crucial for machine learning-model performance. This study offers insights into the application of emerging machine learning-techniques for the screening of living kidney donors.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH>1× and>2× the URL 1 year after transplantation. We included 325 KTRs (56% female, age 38±13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of>25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53%vs. 62%, P=.16, HR.94 [95% CI:.67-1.32]) and KDOQI (60%vs. 60%, P=1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs>88 pg/mL (58%vs. 64%, P=.33) and>176 pg/mL (55%vs. 62%, P=.19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Cumulative smoking dose is associated with subclinical renal injury: a pathological study in individuals without chronic kidney disease.

Epidemiological studies have identified smoking as an independent risk factor for development of chronic kidney disease. However, the early renal pathological lesions have not been clearly elucidated. We investigated time-zero biopsy specimens from 547 living kidney donors and evaluated the relationships between smoking and renal histological changes, including arteriolar hyalinization, intimal thickening of small-medium arteries, global glomerulosclerosis, and interstitial fibrosis and tubular atrophy (IF/TA). A total of 199 subjects (36.4%) had smoking history; 92 (16.8%) and 107 (19.6%) subjects had <20 pack-years and ≥20 pack-years of smoking, respectively. Cumulative smoking dose was significantly associated with prevalence of arteriolar hyalinization: the multivariable-adjusted odds ratio (OR) per 20 pack-year increase was 1.50 (95% confidence interval 1.15-1.97). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.76 (1.01-3.09) and 2.56 (1.48-4.44), respectively. Smoking was also associated with prevalence of >10% global glomerulosclerosis: the OR per 20 pack-year increase was 1.24 (0.96-1.59). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.50 (0.98-2.78) and 2.11 (1.18-3.79), respectively. The ORs for these pathological changes increased significantly depending on cumulative smoking dose. Intimal thickening of small-medium arteries and IF/TA were not associated with smoking status. The prevalence of arteriolar hyalinization remained higher in patients with ≥10 years since smoking cessation than in never-smokers [OR 2.23 (1.03-4.83)]. Subclinical pathological injury caused by smoking is potentially associated with renal arteriolar hyalinization and glomerular ischaemia.

Predicting Early Graft Dysfunction and Mortality After Liver Transplant Using the De Ritis Ratio

Predicting complications after liver transplantation (LT) remains challenging. We propose incorporating the De Ritis ratio (DRR), a widely known parameter of liver dysfunction, into current or future scoring models to predict early allograft dysfunction (EAD) and mortality after LT. A retrospective chart review was conducted on 132 adults receiving a deceased donor LT from April 2015 to March 2020 and their matching donors. Donor variables, postoperative liver function, and DRR were correlated with the occurrence of EAD, post-transplant complications expressed by the Clavien-Dindo score, and 30-day mortality as outcome variables. Early allograft dysfunction was observed in 26.5% of patients and 7.6% of patients who died within 30 days after transplant. Recipients were more likely to experience EAD when receiving grafts from donation after circulatory death (P=.04), donor risk index (DRI) >2 (P=.006), ischemic injury at time-zero biopsy (P=.02), longer secondary warm ischemia time (P < .05), or higher Clavien-Dindo scores (IIIb-V; P < .001). The DRI, total bilirubin, and DRR on postoperative day 5 yielded significant associations with the primary outcomes and were used to develop the Gala-Lopez score using a weighted scoring model. This accurately predicted EAD, high Clavien-Dindo, and 30-day mortality in 75%, 81%, and 64% of patients. Including recipient and donor variables in predictive models, and for the first time DRR, as a constituent, should be regarded to predict EAD, severe complications, and 30-day mortality post-LT. Further studies will be required to validate the present findings and their applicability when using normothermic regional and machine perfusion technologies.

Histopathological Features of Time-Zero Kidney Biopsy Are Predictive Factors for Posttransplant Anemia

Introduction: Posttransplant anemia (PTA) is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of PTA with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. Methods: We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our center. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis (AH), vascular fibrous intimal thickening (CV), interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. Results: The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and PTA in both time points, independently from estimated glomerular filtration rate. AH and interstitial fibrosis were identified as independent risk factors for anemia 6 months after transplantation. Conclusion: Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20–50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA.

Predictors of hepatic steatosis in living liver donors

Fatty liver disease (steatosis) is considered a risk factor in donor liver transplantation (LT). Macrosteatosis (&gt;50%) is associated with primary graft dysfunction and may reduce long-term recipient survival.Objective: to identify predictors of macrovesicular steatosis (&gt;50%) by analyzing donor characteristics.Materials and methods. The retrospective study included 525 potential liver donors between January 1, 2019 and December 31, 2020. Clinical and morphological characteristics of donors were studied using logistic regression and receiver operating characteristic (ROC) analysis. Threshold values of parameters demonstrating statistical significance in multivariate analysis as predictors of &gt;50% hepatic steatosis were obtained by ROC analysis based on calculation of the optimal cutoff point.Results. Diabetes mellitus (DM), cause of donor’s death (traumatic brain injury), alanine transaminase (ALT) &gt;90 units/L and aspartate transaminase (AST) &gt;110 units/L were predictors of &gt;50% steatosis, revealed by time-zero biopsy in the donor. Almost identical sensitivity and specificity indicators were determined in ROC analysis for liver enzymes – ALT and AST – which were 69.1 and 80.6; 72.2 and 81.1, respectively. Given the obtained values, we can say that with elevated levels of liver enzymes in the donor’s blood, there is a high degree of probability of liver parenchymal damage, but low sensitivity indicates possible multifactoriality of liver damage, and fatty liver disease may be one of the factors, but there may also be no damage to the liver parenchyma. At the same time, the rather high specificity revealed in ROC analysis for liver enzymes is a reliable sign of the absence of fatty liver disease at enzyme values less than the threshold.Conclusion. The thresholds established for ALT and AST and their corresponding levels of sensitivity and specificity indicate that these parameters have a relatively low predictive level in the context of the presence of severe fatty liver disease in a donor. This allows, nevertheless, to use models built on their basis as screening models in the primary evaluation of liver donors.

242.3: Is Kidney Time-Zero Biopsy Useful to Predict Graft Function at 1-Year?

Introduction: Clinical and histological characteristics of donors are known to influence graft outcome after kidney transplantation. One of the most common reasons for donor kidney discard is unfavorable histology on procurement biopsies. Many centers perform time-zero biopsies (Bx0), although there is no consensus about the histological findings significance or its association with post-transplant biopsies results. We aim to determine if findings in Bx0 could predict the allograft function at 1-year after transplantation. Methods: Adult kidney-transplant patients from October 2014 to December 2020 with Bx0, post-transplant biopsy performed and at least 1-year follow-up were included. Recipient’s gender and age, clinical donor characteristics, histological findings in Bx0 and post-transplant biopsies and 1-year creatinine levels were analyzed using SPSS® V.25. Results: During the analyzed period 138 kidney transplants were performed. Bx0 was performed in 68 (49%) patients, and of those, 60 patients (88%) had at least one post-transplant biopsy. Mean age was 46 ± 14-year-old and 37 (54%) were male. Fifty-three patients (78%) received a kidney from deceased donor and 15 (22%) from living donor. Donor mean age was 43 ± 13-year-old. Fourteen (20%) had hypertension and the mean body mass index (BMI) was 27.3 ± 5.1 kg/m2. Donor’s mean serum creatinine before procurement surgery was 1.14 ± 0.53 mg/dL and the mean cold ischemia time (CIT) was 17:21 ± 9:40hs. Bx0 histological findings were: acute tubular necrosis (ATN) in 62 biopsies (19%), glomerulosclerosis (GS) in 40 (59%) and interstitial fibrosis and tubular atrophy (IFTA) in 41 (60%), with a mean of 6 ± 9% and 5 ± 7% respectively; 15 (22%) had arteriolar hyaline thickening. A risk factor for allograft GS was donor’s age >43-year-old (OR 4.4 95%IC 1.7 – 11.7 p= 0.000). In addition, we found that donor’s age >43-year-old and history of hypertension were risk factors for IFTA (OR 3.7 95%CI 1.6 – 8.8 p= 0.000 and OR 2.57 95%CI 1.4 – 4.4 p= 0.004 respectively). The mean of 1-year serum creatinine was 1.8 ± 1.6 mg/dL. Clinical and pathological parameter effects on 1-year serum creatinine are shown in table 1. The risk factors for worse outcomes in terms of 1-year serum creatinine are shown in table 2. We also found that GS and IFTA persist in post-transplant biopsies in 85% and 100% of patients respectively. Conclusion: We have found that not only donor age and hypertension are risk factors for pathological findings in Bx0 but also those findings impact negatively on 1-year serum creatinine.

Clinicopathological analysis of ischemia/reperfusion time-zero injury biopsies and its role in early allograft dysfunction in hepatic transplantation (retrospective cross-sectional study)

Background and objectives Orthotropic liver transplantation is the only choice for treatment of end-stage liver diseases. B cell lymphoma 2 (BCL2) is a protein that regulates apoptosis. We aim to pinpoint the role of time-zero biopsies in predicting early graft dysfunction following liver transplantation by evaluation of BCL2 expression in hepatocyte. Patients and methods Thirty seven liver biopsies were evaluated histopathologically for ischemia–reperfusion injury and immunohistochemically by expression of BCL2. Results Out of 37 cases studied, 33 (89.2%) males and four (10.8%) females with a mean±SD age of 46.48 ± 12.05 years old. Their alanine aminotransferase average was 137.56 ± 76.46 U/l, the aspartate aminotransferase average was 62.84 ± 58.26 U/l, while international normalized ratio average was 1.79 ± 0.59. Histopathology shown, ballooning degeneration in 28 (75.7%), apoptosis was negative in 12 (32.4%), few in 13 (35.1%), and many in 12 (32.4%). Immunostaining with anti-BCL2 antibodies for apoptotic hepatocytes was negative in 12 (32.4%) and positive in 25 (67.6%). BCL2 expression was significantly higher with ballooning degeneration (P=0.019). BCL2 expression was significantly higher with apoptosis (P&lt;0.001). Alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were significantly higher with positive BCL2 expression (P=0.002, 0.025, and 0.002, respectively) and with positive ischemia/reperfusion injury (moderate or severe changes) (P=0.005, 0.032, and 0.008, respectively). Conclusion Liver pathology biopsy remains the ‘gold standard’ for the diagnosis of allograft dysfunction as when the clinical picture, liver enzymes, and imaging parameters are unclear.

Abnormal time-zero histology is predictive of kidney transplant outcomes.

Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System. We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes. We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR. In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

Impact of Time-Zero Biopsy on the Outcome of Transplanted Kidneys

A low supply of donated organs led to the expansion of criteria for kidney transplantation (KT), and the impact on late glomerular function rates (eGFR) is still uncertain. This study aimed to correlate the histologic findings at time-zero biopsy (TzB) with the final eGFR, to identify criteria that could help achieve a more thorough preimplantation evaluation of the organ. Records from 395 adult deceased KTs were reviewed. TzBs were analyzed considering histologic criteria by compartment (vascular, interstitial, tubular, and inflammatory) and correlated with the eGFR after 1 year. Among donors, 56.9% were men (mean age 39 years), with the main causes of death being brain trauma (44.2%) and stroke (46.0%). Histologic analysis of TzB revealed 6.0% of glomerulosclerosis; 18.8% presenting vascular alterations; interstitial fibrosis in 54.6%; tubular changes in 76.9%, and nonspecific inflammatory infiltrate in 2.3%. Linear regression analysis showed that the main histologic findings that had impact in the eGFR were interstitial fibrosis (P=.000), followed by tubular alterations (P=.036) and glomerulosclerosis (P=.008). Histologic variables like interstitial fibrosis and tubular alterations show the most significant negative correlation with final eGFR. The effect of glomerulosclerosis may not be as important as formerly suggested in the literature.

Endogenous Interleukin-33 Acts as an Alarmin in Liver Ischemia-Reperfusion and Is Associated With Injury After Human Liver Transplantation.

Ischemia and reperfusion injury is an early inflammatory process during liver transplantation that impacts on graft function and clinical outcomes. Interleukin (IL)-33 is a danger-associated molecular pattern involved in kidney ischemia/reperfusion injury and several liver diseases. The aims were to assess whether IL-33 was released as an alarmin responsible for ischemia/reperfusion injury in a mouse model of warm hepatic ischemia, and whether this hypothesis could also apply in the setting of human liver transplantation. First, a model of warm hepatic ischemia/reperfusion was used in wild-type and IL-33–deficient mice. Severity of ischemia/reperfusion injury was assessed with ALT and histological analysis. Then, serum IL-33 was measured in a pilot cohort of 40 liver transplant patients. Hemodynamic postreperfusion syndrome, graft dysfunction (assessed by model for early allograft scoring >6), renal failure, and tissue lesions on time-zero biopsies were assessed. In the mouse model, IL-33 was constitutively expressed in the nucleus of endothelial cells, immediately released in response to hepatic pedicle clamping without neosynthesis, and participated in the recruitment of neutrophils and tissue injury on site. The kinetics of IL-33 in liver transplant patients strikingly matched the ones in the animal model, as attested by serum levels reaching a peak immediately after reperfusion, which correlated to clinical outcomes including postreperfusion syndrome, posttransplant renal failure, graft dysfunction, and histological lesions of ischemia/reperfusion injury. IL-33 was an independent factor of graft dysfunction with a cutoff of IL-33 at 73 pg/ml after reperfusion (73% sensitivity, area under the curve of 0.76). Taken together, these findings establish the immediate implication of IL-33 acting as an alarmin in liver I/R injury and provide evidence of its close association with cardinal features of early liver injury-associated disorders in LT patients.

The clinical significance of receiving a kidney allograft from deceased donor with chronic histologic changes.

Allograft survival of deceased donor kidneys with suboptimal histology (DRTx/suboptimal histology: >10% glomerulosclerosis, >10% tubulointerstitial scarring, or >mild vascular sclerosis) is inferior to both DRTx with optimal histology (DRTx/optimal histology) and living donor kidneys irrespective of histologic changes (LRTx). In this report, we explored the reasons behind this guarded outcome with a special focus on the role of alloimmunity. We initially assessed gene expression in 39 time-zero allograft biopsies using the Nanostring 770 genes PanCancer Immune Profiling Panel. Subsequently, we studied 696 consecutive adult kidney allograft recipients that were grouped according to allograft type and histology at time-zero biopsy [DRTx/suboptimal histology (n = 194), DRTx/optimal histology (n = 166), and LRTx (n = 336)]. Part-1: Several immune pathways were upregulated in time-zero biopsies from DRTx/suboptimal histology (n = 11) compared to LRTx (n = 17) but not to DRTx/optimal histology (n = 11). Part-2: Amongst the three groups of recipients, DRTx/suboptimal histology had the highest incidence of acute rejection episodes, most of which occurred during the first year after transplantation (early rejection). This increase was mainly attributed to T cell mediated rejection, while the incidence of antibody-mediated rejection was similar amongst the three groups. Importantly, early acute T cell mediated rejection was a strong independent predictor for allograft failure in DRTx/suboptimal histology (adjusted HR: 2.13, P = 0.005) but not in DRTx/optimal histology nor in LRTx. Our data highlight an increased baseline immunogenicity in DRTx/suboptimal histology compared to LRTx but not to DRTx/optimal histology. However, our results suggest that donor chronic histologic changes in DRTx may help transfer such increased baseline immunogenicity into clinically relevant acute rejection episodes that have detrimental effects on allograft survival. These findings may provide a rationale for enhanced immunosuppression in recipients of DRTx with baseline chronic histologic changes to minimize subsequent acute rejection and to prolong allograft survival.

Intrahepatic Microdialysis for Monitoring of Metabolic Markers to Detect Rejection Early After Liver Transplantation

ObjectivesThe clinical and biochemical manifestations of acute rejection after liver transplantation are nonspecific, and a liver biopsy is often needed to verify the diagnosis. This may delay treatment. The aim of this study was to evaluate whether monitoring of intrahepatic glucose, lactate, pyruvate, and glycerol by microdialysis can be used to predict rejection early after liver transplantation. MethodsSeventy-one patients undergoing liver transplantation were included in the study. The patients were monitored using microdialysis for up to 6 days postoperatively. Patients who developed acute rejection within 1 month were identified according to standard protocol. Area under the curve (AUC) was calculated for 12-hour intervals for glucose, lactate, pyruvate, glycerol, and lactate/pyruvate ratio. Patients with and without rejection were compared with respect to these parameters, as well as standard liver blood investigations and time-zero biopsies. ResultsThe lactate/pyruvate ratio was higher at 0 to 12 hours in the group with rejection as compared to the group without rejection. Glucose was lower in the group with rejection at 24 to 48 hours. Also, the intrahepatic lactate levels at 48 to 72 hours and pyruvate levels at 60 to 72 hours after liver transplantation, were higher in the rejection group. The lactate/pyruvate ratio at 0 to 12 hours and lactate at 60 to 72 hours were two independent risk factors for rejection within the first month after liver transplantation. No significant differences in glycerol levels could be detected between the two patient groups. ConclusionsMicrodialysis monitoring following liver transplantation may be useful in the detection of the metabolic events that precede rejection. The metabolic patterns detected by microdialysis early after transplantation indicate a possible relation between primary ischemia-reperfusion injury and the development of rejection. Identifying these patterns may help to identify patients at risk for the development of acute rejection and may help select those who may benefit from higher dose of immunosuppression early after liver transplantation.

Morphofunctional evaluation of liver grafts obtained from standard donors and expanded criteria donors

Donor organ shortage stimulated an active use of donors with expanded evaluation criteria. The main evaluation method was a histological examination of liver graft biopsy specimens before (time-zero biopsy) and after reperfusion (time-1 biopsy). Severe ischemic and reperfusion injuries among recipients who received a liver graft made 20.4% and 16.6% respectively. The study showed no impact of small droplet, medium droplet, or even large droplet steatosis (less than 50%) on graft reperfusion injury.

Dilemma of Hepatic Ischemia Reperfusion Injury after Liver Transplantation

Liver transplantation, whether from a deceased or living donor (LDLT), is still a definite line of treatment for decompensated cirrhosis, early stage of hepatocellular carcinoma, and acute liver failure. Organs from living donors offer many potential advantages over organs from deceased donors; the most important is the optimization of the timing of transplantation. Also preservation time is minimal, so there is significantly less ischemic damage. Time-zero biopsies sampled after graft revascularization predicts adverse clinical outcomes after liver transplantation. It is well known that severe Ischemia/reperfusion injury (IRI) signals the likely need for early retransplantation. This fact emphasizes the value of the time –zero biopsy sampled immediately after graft reperfusion. Hepatic Ischemia-Reperfusion Injury after Liver Transplantation is a common and major complication after liver surgery and transplantation. It impairs liver function, increases postoperative morbidity and mortality, interferes with recovery and thus has a major impact on clinical outcomes.

Effect of Hypothermic Machine Perfusion on the Preservation of Kidneys Donated After Cardiac Death: A Single-Center, Randomized, Controlled Trial.

To assess the application of a hypothermic machine perfusion device (LifePort) in kidney transplantation from donation after cardiac death (DCD) donors, 24 pairs of DCD kidneys were randomly divided into two groups: one of the paired kidneys from the same donor was perfused with the LifePort machine (hypothermic machine perfusion [HMP]), and the contralateral kidney was prepared using common static cold preservation (CCP). The two groups were compared with respect to the incidence of delayed graft function (DGF), level of graft function, and pathological changes in time-zero biopsy specimens. The incidence of DGF was 16.7 and 37.5% in the HMP and CCP groups, respectively; the difference between the two groups was statistically significant (P < 0.05). The incidence of acute rejection was 4.1 (1/24) and 8.3% (2/24) in the HMP and CCP groups, respectively; this difference was not statistically significant (P > 0.05). Forty-eight kidney patients were followed up for 6 months, and the two groups of recipients all survived, yielding a survival rate of 100%. The mean 6-month serum creatinine levels were 98.7 ± 23.6 µmol/L in the HMP group and 105.3 ± 35.1 µmol/L in the CCP group; there was no significant difference between the two groups. HMP can reduce the incidence of DGF in DCD kidneys, and this effect is greater for expanded criteria donors kidneys. HMP can also improve early renal function.

Factors influencing renal graft survival: 7-Year experience of a single center

Background and objectiveThe demand for kidney transplants exceeds the existing supply. This leads to a recently growing interest of research in the area of factors that could prolong graft long-term outcomes and survival. In Lithuania, approximately 90% of kidney transplantations are from deceased donors. Donor organs are received and shared only inside the country territory in Lithuania; therefore, donor data is accurate and precise. This study was performed to present particularities of kidney transplantation data in Lithuania and to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. The aim of this study was to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. Materials and methodsWe analyzed the influence of deceased donor and recipient factors and histological findings on the graft function in 186 renal transplant patients. Graft survival was estimated within the first year after transplantation. ResultsThe donors and recipients were older in worse eGFR group 1 year after transplantation. Dissimilarity of degree of glomerulosclerosis (GS), interstitial fibrosis (IF) and arteriolar hyalinosis (AH) were significant in inferior and superior renal function groups (GS >20% 11.4 vs. 0%, P=0.017; IF 9.3 vs. 0%, P=0.034; AH 69 vs. 26.2%, P<0.001). Nine independent variables were significantly associated with a worse renal transplant function 1 year posttransplantation: AH (OR=6.287, P<0.001), an episode of urinary tract infection (OR=2.769, P=0.020), acute graft rejection (OR=3.605, P=0.037), expanded criteria (OR=4.987, P=0.001), female gender donors (OR=3.00, P=0.014), cerebrovascular disease caused donor brain death (OR=5.00, P=0.001), donor's age (OR=1.07, P<0.001), and recipient's age (OR=1.047, P=0.022). Worse renal graft survival 1 year posttransplantation was associated with a delayed graft function and a higher level of glomerulosclerosis in time-zero biopsy. ConclusionsDonor factors, such as age, female gender, brain death of cerebrovascular cause and expanded criteria donor status had a significant negative impact on the renal graft function 1 year after transplantation. Recipients’ age, urinary tract infection and acute graft rejection episodes after transplantation were associated with a worse kidney function 1 year after transplantation. Lower 1-year graft survival was related to a delayed graft function (DGF) and a higher degree of glomerulosclerosis.

Simple Cysts in Donor Kidney Contribute to Reduced Allograft Function

Background: Simple renal cysts may be an early marker of renal disease. We investigated whether simple cysts in donor kidney are associated with the decline of allograft function in living donor kidney transplantation. Methods: We retrospectively reviewed records of donors and recipients from 716 living donor kidney transplants performed between April 2007 and April 2015 in our hospital. Ninety-one donors with renal cysts and 64 recipients with cysts in donor kidney were noted. We compared these 64 cases to 128 no cyst-bearing controls matched for the donor gender, recipient gender, donor baseline serum creatinine (sCr), donor/recipient body surface area ratio, donor age, recipient age and the date of kidney transplantation in turn. Results: The presence of cysts was interrelated with age, gender and renal function independently in donors. Pathological findings of time-zero biopsy revealed that donor kidney harboring cysts existed more glomerular sclerosis compared with no cyst-bearing controls (p = 0.040). The estimating glomerular filtration rate levels of recipients were 80.82 ± 26.61 vs. 88.21 ± 23.12, 66.95 ± 17.42 vs. 72.15 ± 16.42 and 60.92 ± 22.17 vs. 68.72 ± 14.43 ml/min· 1.73 m² in cyst-bearing and no cyst-bearing group on day 7, month 6 and year 5, respectively, after surgery (p < 0.05). The mean sCr were 112.14 ± 48.32 vs. 98.75 ± 29.71 and 126.28 ± 42.32 vs. 115.05 ± 26.35 μmol/l on the 7th day and a half year after transplant, respectively (p < 0.05). The 2 groups did not significantly differ in terms of the other characteristics. Conclusion: Simple cysts in donor kidney can influence the early and long-term allograft function. In living donor transplantation, kidney presenting cysts should be considered carefully at the time of donor selection.

Significance of Time-Zero Biopsy for Graft Renal Function After Deceased Donor Kidney Transplantation.

Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.