Early Graft Dysfunction Research Articles

Early Allograft Dysfunction Is Associated with Higher Complication Rate after Liver Transplantation

Introduction: Liver transplantation is considered as the standard of care for patients with end-stage liver diseases. However, an early graft dysfunction (EAD) is still one of the many challenges that clinicians have to overcome. EAD has a varying incidence between 10.8% to 36.3% and the association between EAD and worse graft or patient survival rate has been repeatedly reported; however, little has been conducted about the postoperative complications after occurrence of EAD which lead subsequently to higher mortality among EAD patients. Method: We performed a retrospective analysis on patients who underwent liver transplantation from January 2007 to July 2012. For definition of EAD we adopted the Olthoff criteria. All complications were classified in accordance to the time-dependent occurrence as “early”, “intermediate” or “late”. Results: From a total of 555 patients, 214 (38.6%) developed EAD. Both 12 month graft and patient survival rate were significantly worse in EAD patients. Analysis of complications rate showed that EAD patients had higher rate of sepsis (p=0.001), acute renal failure (p<0.001) and bleeding postoperatively (p=0.012). EAD development was associated with higher likelihood for reoperation and retransplantation (p=0.04 and p<0.001). Within first week after transplantation, EAD patients had higher rate of sepsis and postoperative bleeding (p<0.001, p=0.015); however incidences of intermediate and late complications did not differ. Conclusions: Patients who develop EAD have significantly higher rate of early sepsis, postoperative bleeding and acute kidney injury, which constitute worse outcomes. Patients with EAD are more likely to have a reoperation and/or retransplantation.

Liver transplant biopsy interpretation: Diagnostic considerations and conundrums.

Liver transplantation is now a well-established therapeutic strategy for irreversible acute and chronic liver diseases. There is a broad spectrum of complications encountered in early and late period after transplantation and these contribute to significant morbidity and mortality. Distinguishing among these complications often requires interpretation of allograft biopsies. Histology is the gold standard for the diagnosis of rejection. However, interpretation of these biopsies is quite challenging due to the atypical and complex histomorphology. Multiple simultaneous insults, effects of immunosuppression (IMS), de novo complications, and presentations distinct from non-transplant setting are a few cardinal concerns. Awareness of the time period of occurrence of various complications, the most characteristic histological features or patterns, and distinguishing features between various complications are crucial. The management can be completely divergent; hence, recognition of dominant problem and interpretation in appropriate clinical context is much needed. This review focuses on histopathology of major complications accountable for early and late graft dysfunction. Tabulation of clinico-pathological features to distinguish various complications helps to solve the conundrums and arrive at the correct diagnosis.

Comments on "Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society".

To the Editor: We read with great interest the article by Hessheimer et al titled “Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.”1 The authors summarize relevant literature and provide guidelines for donation after circulatory death (DCD) liver transplant procurement on behalf of the International Liver Transplantation Society (ILTS). Our research group recently emphasized the variations in DCD organ procurement policies in the United States with a national organ procurement organization (OPO) survey.2 We discovered tremendous disparities across regions that frequently diverged from American Society for Transplant Surgeons (ASTS) recommendations for DCD procurement and the latest consensus in the literature. It is paramount to optimize graft utilization and outcomes to meet the high demand for transplantable organs and growing waitlist. We commend the authors for their important contributions. We highlight the role of asystolic wait time in DCD liver procurement that was not addressed in the work and provide observations on DCD liver transplant (LT) and machine perfusion (MP) from the United States. Our OPO survey underscored the variations in the mandatory asystolic observation period. Despite current ASTS recommendation of a 2-min waiting time, there is little standardization across institutions that vary between 2 and 5 min. Similarly, other publications have demonstrated the lack of standardization in the declaration of circulatory death.3 Additional guidance by the ILTS on these topics would optimize DCD liver procurement process to further reduce warm ischemic times and ultimately improve patient outcomes. Currently, 11 high-volume transplant centers perform nearly half (46.3%) of all DCD LT in the United States.4 However, recent changes to the allocation policies will result in wider sharing of DCD organs and increase distribution to lower volume centers. This will undoubtedly place greater emphasis on procedures to maintain outcomes, such as broader use of hypothermic machine perfusion and normothermic machine perfusion in LT. Machine perfusion with LT has shown promising results in the United States. One investigation discovered no difference in patient survival in ex vivo MP despite substantially longer CIT.5 MP has the potential to significantly improve DCD liver procurement and reduce discard rates. In 2019 alone, 1945 potential DCD livers were not transplanted including 306 grafts, which were discarded after recovery. The trend of increasing DCD LT in the United States has been accompanied with 30% discard rate compared with 7.1% for DBD LT.5 Furthermore, one center reported that only 47.9% of DCD liver offers resulted in a successful procurement, compared with 92.3% for DBD.6 Nasralla et al demonstrated 50% reduction in graft injury, discard, and postreperfusion injury rates in an normothermic machine perfusion clinical trial.7 A publication by the Groningen group on dual hypothermic oxygenated MP highlighted lower rates of nonanastomotic biliary strictures, postreperfusion syndrome, and early graft dysfunction compared with static cold storage in DCD LT.8 MP could remarkably impact the American LT waitlist by increasing potential DCD livers that are transplanted. We congratulate Hessheimer et al on their valuable contributions. We are pleased to see the growing support for procurement procedures such as withdrawal of life support treatment in the operating room and premortem heparin administration. Despite strong surgeon preference for both of these, our survey revealed that 26 OPO did not have specific regulations on the location of withdrawal of life support treatment and 3 OPO prohibited heparin use.2,3 We hope that the ILTS recommendations lead to updates in DCD procurement protocol and regulations to comply with the latest evidence in the literature. We hope to see more analyses of liver perfusion solutions and the various additives. We anticipate similar best practice guidance by the ASTS for normothermic and hypothermic regional perfusion in liver transplantation in the near future. Reduction in variable DCD liver recovery will be tremendously impactful in increasing the utilization of DCD livers and reducing graft discard rates.

Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality.

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.

Treatment with sodium (S)-2-hydroxyglutarate prevents liver injury in an ischemia-reperfusion model in female Wistar rats

BackgroundIschemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors (HIF), which are downregulated by the EGLN family of prolyl-4-hydroxylases, a potential biological target for the development of strategies based on pharmacological preconditioning. For that reason, this study aims to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] on liver IR injury in Wistar rats.MethodsTwenty-eight female Wistar rats were divided into the following groups: sham (SH, n = 7), non-toxicity (HGTox, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days), IR (n = 7, total liver ischemia: 20 minutes, reperfusion: 60 minutes), and (S)-2HG+IR (HGIR, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days, total liver ischemia as the IR group). Serum ALT, AST, LDH, ALP, glucose, and total bilirubin were assessed. The concentrations of IL-1β, IL-6, TNF, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured in liver tissue, as well as the expression of Hmox1, Vegfa, and Pdk1, determined by RT-qPCR. Sections of liver tissue were evaluated histologically, assessing the severity of necrosis, sinusoidal congestion, and cytoplasmatic vacuolization.ResultsThe administration of (S)-2HG did not cause any alteration in the assessed biochemical markers compared to SH. Preconditioning with (S)-2HG significantly ameliorated IR injury in the HGIR group, decreasing the serum activities of ALT, AST, and LDH, and the tissue concentrations of IL-1β and IL-6 compared to the IR group. IR injury decreased serum glucose compared to SH. There were no differences in the other biomarkers assessed. The treatment with (S)-2HG tended to decrease the severity of hepatocyte necrosis and sinusoidal congestion compared to the IR group. The administration of (S)-2HG did not affect the expression of Hmox1 but decreased the expression of both Vegfa and Pdk1 compared to the SH group, suggesting that the HIF-1 pathway is not involved in its mechanism of hepatoprotection. In conclusion, (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers, without evidence of the involvement of the HIF-1 pathway. No hepatotoxic effect was observed at the tested dose.

Value of Plasmatic Villin-1 in the prediction of early graft dysfunction in kidney transplant recipients among Egyptian population

Abstract Background One of the main complications of kidney transplantation is delayed graft function (DGF). There has been enormous growing research interest in the potential for the rapidly expanding fields of medical technology to generate new biomarkers with the aim of early prediction of DGF and modifying its therapy accordingly. Villin-1 has been detected in urine of patients with AKI. Additionally, it is redistributed during AKI from the brush borders of the proximal tubular cells toward the basolateral membrane which positions villin-1 closer to the renal vasculature and suggests that it could be released in the blood as well, so can be as a novel biomarker for DGF. Methods Of 70 patients with end-stage renal disease with one or more risk factor for developing delayed graft function attending renal transplantation preparation clinics in ASUSH, IMC and NILE Badrawi hospital in Egypt from May 2016 to July 2019, 41 patients were eligible and assigned into two groups according to the correlation with the serum creatinine levels in the first two days post-transplantation after signed informed consent for participation in our study into group 1 (DGF group) and group 2 (NGF group). We measured the presence of villin-1 by ELISA technique (quantitative) in comparison to serum creatinine levels in plasma at the time of declamping (zero level), 1st, 3rd, 5th, 7th, 12th, 24th, 48th, 72th 96th, 120th hour post declamping, also samples from normal population and chronic kidney disease stage V patients have been collected to establish reference range guide for plasmatic villin-1 in both groups. Results Statistically significant differences were noted in the comparison between both groups as regard the plasmatic villin-1 levels at the same measurement points in both groups, also plasmatic villin-1 started to rise above its reference range in the ESRD patients at the 5th hour post declamping while its peak was at the 7th hour in the DGF group’s recipients then started to decrease after that but didn’t settle down between the reference range guide during the regular follow up of its level till the 120th hour post declamping. the reference range guide was from 0.08 and 0.35 ng\ml in males and from 0.055 to 0.35 ng\ml in females in normal population while from 0.38 and 1.4 ng\ml in males and from 0.28 to 1.1 ng\ml in females in the ESRD patients. Conclusions Plasmatic villin-1 is a promising novel biomarker for detection of early graft dysfunction in kidney transplant. Due to restrictions of the study design these observations need further confirmation by prospective studies.

Prognostic role of levels of extracellular histones H3 for diagnosis of early dysfunction of transplant after hepatic transplantation

Objective. The aim of this study was to determine the prognostic role of extracellular histones in the diagnosis of early graft dysfunction after liver transplantation..&#x0D; Materials and methods. The 93 recipients undergoing LDLT were enrolled in this prospective study. Blood samples of patients were collected on postoperative day 1 and histone levels in the plasma samples were measured with Total Histone H3 sandwich ELISA kits. 19 (20.4%) subjects had early graft dysfunction (EAD) which was diagnosed on postoperative day 7 according to Ol-thoff’s criteria, based on liver function tests and coagulation profiles. Other 74 (79.6%) recipients did not have EGD.&#x0D; Results. Levels of circulating histones were depressed in patients with EGD (0,808±0.026, 95% (CI) 0.752-0.864) than in patients without EGD (0.820±0.017, 95% (CI) 0.786-0.854) (P=0.727). These differences were not significant. The sources of histones in the circulation are not etiologies specific and levels of total histone H 3 after 24 h of operation had not stronger predictive value with AUC 0.477 (95 % CI 0.329 to 0.625) for liver dysfunction. The AUC value of the total bilirubin (AUC 0.685, 95 % CI 0.546 to 0.825) in predicting early graft dysfunction outperformed other LFTs and was less than CRP (AUC 0.705, CI 0.573 to 0.838).&#x0D; The optimal cutoff value of total bilirubin obtained from the analysis of ROC curves was 4,5 and surpassed all other parameters with a sensitivity of 94.4% and a specificity of 40.7% respectively for prognoses of EGD (P=0.012). The univariate analysis determined that postoperative neutrophils level and CRP were identified as independent risk factors for early graft dysfunction. Neutrophils had a higher predictive value for liver dysfunction than any other parameter within 24 h (Odds ratio (OR) 16.3; 95% CI: 1.7-156.3, P = 0.016). &#x0D; Conclusion. Collectively, extracellular histone H3 levels were depressed, total bilirubin and CRP levels were elevated in patients with EGD, which can be used as early predictors for liver tissue damage and early allograft dysfunction in patients after liver transplantation.

Impact of human leukocyte antigen compatibility on outcomes of living donor liver transplantation: Experience from a tertiary care center.

The role of HLA compatibility in kidney, heart, and stem cell transplantation is well known, but with regard to living donor liver transplantation (LDLT), there is a different scenario. In the present study, we aim to examine the effects of donor-recipient HLA mismatches at A, B, and DR loci on various outcomes of LDLT-like graft survival, early allograft dysfunction (EAD), acute rejection, length of hospital (LOH) stay, sepsis, and cytomegalovirus (CMV) reactivation. This is a retrospective single center study of a cohort of adult patients who underwent first time ABO-compatible (ABOc) LDLT between January 2010 and December 2018. Transplants with incomplete records or without HLA typing data were excluded. Donor-recipient HLA-A, B, and DR mismatches were assessed in the host versus graft (HVG) direction and were correlated with various post-transplant outcomes. Among 140 transplants being evaluated, approximately two third had total HLA mismatches between 2 and 3. HLA mismatches at each locus as well as cumulative HLA mismatches did not show any association with overall graft survival, EAD, acute rejection episodes, and LOH stay. However, the presence of minimum one mismatch at HLA-A and DR loci was associated with the development of CMV reactivation (P=.03) and sepsis (P=.02) post-LDLT respectively. HLA mismatch is not associated with acute rejection, early graft dysfunction, and overall survival in LDLT. Its impact on CMV reactivation and sepsis needs further evaluation.

Characteristics of B-lymphocyte subpopulations in renal transplant recipients

Introduction. The presence of multiple subsets of B-cells with specific regulatory functions capable of modulating inflammatory responses havebeen detected. Most of the studies of Bregs function were carried out in the context of autoimmune and infectious diseases, whereas the objective of this research was to study the characteristics of the main, activated and tolerogenic subpopulations of B lymphocytes in patients who underwent kidney transplantation. Objective. To study the indices of B-lymphocyte subpopulations and determine their role in the development of immunological tolerance after kidney transplantation.Material and methods. We have examined 197 recipients who underwent kidney transplantation. We determined B lymphocyte subpopulation levels (CD19+IgD+CD27+ and CD19+IgD-CD27+) before transplantation, on the 1st, 3rd, 7th and 30th days after the transplantation. Allograft function was assessed on day 7 with the division of patients into two groups: with primary graft function and graft dysfunction.Results and discussion. Significant differences were revealed between the groups of recipients over three months in the following cell subpopulation levels CD19+IgD+CD27+ and CD19+IgD-CD27+. During the first 7 days, lower levels of these subpopulations were associated with satisfactory allograft function. However, by the 90th day after surgery, an increase in CD19+IgD+CD27+ B lymphocytes was noted in the group of patients with graft dysfunction.Conclusions. Low levels of not-switched (CD19+IgD+CD27+) and switched (CD19+IgD-CD27+) memory В lymphocytes in the peripheral blood of kidney transplant recipients are associated with a favorable postoperative course. We have found that on the 3rd post-transplant day, the relative level of non-switched memory B lymphocytes (CD19+IgD+CD27+) exceeding or equal to 11.47%, and the level of switched memory B lymphocytes (CD19+IgD-CD27+) exceeding or equal to 20.74% might predict the development of early renal graft dysfunction with a sensitivity and specificity of 88.40% and 84.30% for the former parameter and of 88.70% and 82.40% for the latter one, respectively.

Case report of transplant renal artery stenosis secondary to mechanical renal artery kinking: Balloon angioplasty as a supportive diagnostic tool?

Introduction and importanceRenal vascular complications are a significant cause of morbidity in living donor renal transplantation. Among renal vascular complications, transplant renal artery stenosis (TRAS) secondary to mechanical kinking is a rare but important cause of early graft dysfunction. Identifying this phenomenon and correcting the underlying cause is critical to graft viability in the post-operative period. This case illustrates the importance of balloon angioplasty in identifying this complication and prompting surgical correction.Case presentationWe describe the case of a 67-year-old male who received a right-sided living donor kidney graft for Stage IV Chronic Kidney Disease secondary to biopsy proven Ig-A nephropathy. In the post-operative course, serum creatinine remained elevated and Doppler showed low-normal vascular flow velocities. Renal angiogram indicated transplant renal artery stenosis secondary to the rare phenomenon of mechanical kinking. Findings noted during unsuccessful angioplasty supported the diagnosis and surgical repositioning of the graft provided definitive repair. Post-operative serum creatine trended down and urine output improved within 24 h. Patient was stable at two month follow up.Clinical discussionTransplant renal artery stenosis secondary to mechanical kinking can cause significant graft dysfunction in the post operative period. Previous case reports and literature review has found balloon angioplasty to be ineffective in correcting this underlying cause of TRAS. In line with previous reports, balloon angioplasty failed to correct the stenosis; however, this provided additional diagnostic information by identifying the kink and prompting surgical repair.ConclusionTransplant renal artery stenosis secondary to mechanical kinking can be difficult to identify by renal angiogram alone. Attempted balloon angioplasty can confirm the diagnosis and prompt definitive surgical repair.

Heart transplantation from donors with left ventricular ejection fraction under forty percent.

Heart transplantation (HTx) remains the treatment of choice for patients with end-stage advanced heart failure. In 2016, the Shumakov National Medical Research Center commenced performing HTx from donors with abnormal left ventricular systolic function (LVEF<40%). The aim of this study was to evaluate early and late outcomes of recipients after HTx from donors with abnormal LV systolic function. Four hundred eighty seven patients underwent HTx in our institution from January 2016 to December 2018. 27 (5.5%) patients were transplanted using cardiac allografts from donors with LVEF <40%. A total of 47 donors with LVEF <40% were evaluated for potential donation. Most heart donors revealed a left ventricular ejection fraction ranging between 30% and 40%. Twenty-five recipients required urgent HTx. Four recipients presented with early allograft dysfunction. All surviving recipients demonstrated early (85.2%) or delayed (14.8%) recovery of systolic function (LVEF>60%). The use of dysfunctional donor hearts with impaired LV systolic function may be a realistic approach for expanding the donor pool. However, organs from such donors should be used for recipient cohorts requiring an urgent HTx, particularly for those with pretransplant mechanical circulatory support allowing for hemodynamic support in cases of early graft dysfunction in the post-transplant period.

"Graft Recipient Weight Ratio" or "Graft Volume Standard Liver Volume Ratio" in clinical practice in living donor liver transplantation.

We enjoyed the recently published article by Toshima et al,1 demonstrating the importance of recipient BMI for choosing graft in living donor liver transplantation (LDLT) to prevent small-for-size graft syndrome (SFSS). They retrospectively analyzed the incidence of SFSS in 694 recipients who underwent LDLT according to required graft volume based on graft-to-recipient body weight ratio (GRWR) or graft weight to standard liver weight (GW/SLW) in strata of recipient body mass index (BMI). They concluded that GRWR was useful, but GW/SLW was not useful in obese recipients (BMI > 30 kg/m2). Small-for-size graft syndrome has high mortality and morbidity after LDLT because of early graft dysfunction. The importance of accurate estimation for required liver volume in LDLT has been growing with increased number of LDLT worldwide due to the shortage of donor organs. GW/SLW was proposed in 1995 by calculating standard liver volume using the formula, which includes body surface area.2 However, the formula might have less generalizability because they calculated standard liver volume in 96 patients in one prefecture in Japan. In addition, the average of height and body weight were 164.8 cm and 56.5 kg, respectively. Therefore, it may be difficult to estimate standard liver volume and graft weight in obese donors and recipients. In fact, Toshima et al showed GW/SLW was not associated with SFSS in obese patients. GRWR has been another way to estimate required liver volume. Since GRWR could take the body weight of a recipient into account, it may give us a better estimation in obese patients. The estimation of graft weight has been performed using volumetric analysis by three-dimensional computed tomography (CT). However, the discrepancy between estimated graft volume and actual graft weight are often observed, and can potentially cause SFSS. A study showed that estimated liver volume was the largest using the venous phase of enhanced CT, while the smallest using unenhanced CT.3 In addition, estimated liver volume by volumetry is provided as “volume” (i.e. mL), while actual graft size is measured by “weight” (i.e. g). To address this difference, another study suggested using conversion factor (1.20 mL/g) in estimation of graft weight.4 Furthermore, the actual graft weight measured on the back table could decrease from preoperatively estimated liver volume due to several factors including dehydration caused by University of Wisconsin solution, and the difference between the virtual and actual resection line of the liver. The coefficient factor of 0.85 in non-cirrhotic liver for graft weight estimation from preoperative CT volumetry has been proposed to address these factors.5 Although Toshima et al described the utility of GRWR in obese patients, they used actual procured graft weight for the analysis. Since graft weight could not be changed once it has been taken out from the donor, it is important to predict actual graft weight more accurately in the setting of preoperative volumetric analysis. We believe that this article by Toshima et al would provide a compelling rationale for further investigations into comprehensive ways to estimate liver volume more accurately, potentially avoiding SFSS and improving donor shortage. Conflict of Interest: The authors declare no conflicts of interest. Author Contribution: Study concept and design: Koichiro Haruki and Toru Ikegami. Drafting of the manuscript: Koichiro Haruki and Kenei Furukawa. Critical revision of the manuscript for important intellectual content: all authors. Study supervision: Toru Ikegami. Final approval of manuscript: all authors.

Evaluation of Early Renal Allograft Dysfunction from Living Donors among Egyptian Patients (Histopathological and Immunohistochemical Study)

BACKGROUND: Early renal graft dysfunction is a major problem in the early post-transplantation period and is considered a major cause of graft loss. Clinical diagnosis based on the clinical criteria alone is unreliable; therefore, biopsy remains the gold standard to differentiate between rejection and non-rejection causes. AIM: This study was designed to identify and differentiate between causes of early graft dysfunction during the first post-transplantation month and to correlate between histological lesions and immunohistochemistry (IHC) for accurate diagnosis and a better outcome. MATERIALS AND METHODS: A total of 163 renal allograft biopsies, performed in the first post-transplantation month over 6 years, were included in the study. New sections were prepared from the paraffin blocks and stained with conventional stains. Additional sections were prepared and treated by complement fragment 4d (C4d) and cluster differentiation 3 (CD3) antibodies for IHC evaluation. RESULTS: All the studied cases were from living donors. The mean patient age was 39 years with predominant males. The clinical indication for most biopsies (94.5%) was impaired graft function. Acute rejection (AR) was the main diagnostic category observed in (98/163, 60.1%); out of which, T cell-mediated rejection (TCMR) was observed in (62/98, 63.2%). Drug toxicity was suspected in (53/163, 32.5%), acute tubular injury (ATI) not otherwise specified (nos) in (21/163, 12.9%), and other lesions including thrombotic microangiopathy were observed in the remaining biopsies. The most common cause of graft dysfunction in the 1st and 2nd weeks was AR representing. A significant correlation was seen between mild glomerulitis (g1) and mild peritubular capillaritis (PTC) 1, on the one side, and negative C4d staining, on the other side. No significant correlation was seen between moderate glomerulitis (g2) and moderate ptc2 at one side and positive C4d staining at the other side reflecting the poor association between the microvascular inflammation (“g” and “ptc” scores) and C4d positivity (r = 0.2). Missed mild tubulitis (t1) was found in a single case and missed moderate tubulitis (t2) was found in a single case detected by CD3 IHC. CONCLUSION: AR and drug toxicity account for the majority of early graft dysfunction, however, other pathological lesions, per se or coincide with them may be the cause. The significance of g2 per se as a marker for diagnosis of antibody-mediated rejection requires further study. Considering C4d score 1 (by IHC) positive; also requires further study with follow-up.

Early Graft Dysfunction Following Kidney Transplantation: Can Thermographic Imaging Play a Predictive Role?

The shortage of organs and the growing need for them over recent years have led to the adoption of less stringent donor acceptance criteria, resulting in the approval of marginal organs for transplant, especially from elderly donors. This implies a higher risk of graft dysfunction, a higher frequency of immunological and vascular complications, and shorter graft survival. Several strategies have been implemented in clinical practice to assess graft quality and suitability for transplantation. We have started to test the prospective intraoperative use of thermo-vision cameras during graft reperfusion. Images were acquired using the FLIR One Pro thermo-vision camera for android devices. We hypothesized that thermal images would give a better perspective about the quality of arterial perfusion and graft revascularization of the renal cortex. Thermo-vision cameras provide an easy-to-use, noninvasive, cost-effective tool for the global assessment of kidney graft cortical microcirculation in the immediate post-reperfusion period, providing additional data on the immediate viability and function of a graft.

Role of MicroRNA in Heart Transplant.

The need for noninvasive biomarkers for diagnostic, prognostic, and therapeutic purposes is increasingly being recognized in the field of heart transplantation. MicroRNAs are a class of novel biomarkers that control gene expression and influence cellular functions, including differentiation, proliferation, and functional regulation of the immune system. They can be detected in the serum, plasma, and urine and may serve as early noninvasive biomarkers for various disease processes. Despite significant advances in heart transplantation, challenges remain in the short and long term with early graft injury and dysfunction, both cellular and antibody-mediated rejection, infections of varying types and severity, and cardiac allograft vasculopathy, which require an interventional approach for diagnosis and management. In this article, we review the current knowledge on the role of microRNAs in heart transplantation and its related complications and discuss their potential impact in future strategies to manage heart transplantation.

Extracorporeal Membrane Oxygenation for Early Graft Dysfunction Following Heart Transplantation: A Systematic Review and Meta-Analysis

<h3>Purpose</h3> Early graft dysfunction (EGD) is a major cause of morbidity and mortality following heart transplantation (HT). Severe EGD often includes the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Studies evaluating its effectiveness are mostly single centre observations with variable outcomes. This systematic review and meta-analysis appraises the available evidence and evaluates prognosis in HT patients with EGD requiring VA-ECMO. <h3>Methods</h3> We conducted a systematic search of Ovid Medline, Embase and the Cochrane databases to 05/15/2020. Studies of adults who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint were included. We included observational studies published after 2009, in any language, as abstracts or full texts. Outcomes of interest were short-term mortality, 1-year mortality and VA-ECMO complications. We used QUIPS to assess risk of bias and GRADE to assess the quality of the evidence. Data was pooled using random-effects models. <h3>Results</h3> We included 50 studies of 1472 patients with 504 short-term mortality events. Most studies were retrospective (94%), single centre (88%), and at low/acceptable risk of bias overall (76%). Pooled short-term mortality was 33% (95%CI: 27-38%, I² =76%) and 1-year mortality was 46% (95%CI: 37-54%, I² =81%). Risk of bias, publication type, recruitment timeframe, and use of VA-ECMO for only primary graft dysfunction as per the ISHLT definition did not explain heterogeneity in subgroup analyses. Reported VA-ECMO complications were 38% (95%CI: 27-49%) for dialysis, 36% (95%CI: 26-47%) for bleeding, 22% (95%CI: 14-31%) for infection and 5% (95%CI: 1-10%) for limb ischemia. <h3>Conclusion</h3> One-third of HT patients with EGD supported with VA-ECMO are at risk of short-term death. An individual patient data meta-analysis is warranted to further understand the mortality risk and gain insight into risk factors associated with outcomes in this population.

Implementation of a Chatbot Mobile Health Intervention with Home Spirometry to Monitor Lung Transplant Recipients Remotely

<h3>Purpose</h3> The COVID-19 pandemic accelerated the need to develop remote monitoring of graft function in lung transplant (LT) recipients. While home spirometry has been used previously in LT, long-term engagement has been poor. We aimed to improve engagement and allow efficient data and symptom collection using Bluetooth enabled home spirometers coupled with a digital chatbot. <h3>Methods</h3> We implemented an automated, chat-based mobile health intervention via text message or email paired with Bluetooth-enabled hand-held spirometers. The chatbot engaged LT recipients weekly in a personalized, automated chat with symptom assessment, education modules, and spirometer data collection. Clinical team members received automatic notification of concerning symptoms or FEV1 declines of >10%. The correlation between home spirometry FEV1 values and lab-based values were assessed with Pearson's coefficient. <h3>Results</h3> We mailed home spirometers to 424 patients. Between 5/4/2020 and 10/21/2020, 311 patients enrolled in the automated chat and, of these, 273 patients submitted ≥1 FEV1 measure, (median 13; IQR 6-23) over 24 weeks. The largest drop in FEV1 engagement came after the first week in each patient's chat experience; 65% of those that submitted an FEV1 at baseline entered a value at week one and 72% at week two. However, after this initial decline, engagement remained stable through 24 weeks (57-72%, Figure 1.A). Home spirometry FEV1 correlated closely with in-lab spirometry (rho = 0.94) (Figure 1.B) <h3>Conclusion</h3> LT recipients engaged at high rates with a chatbot mobile health intervention and home spirometers to report their FEV1, allowing reliable home-based monitoring of LT recipients. Further investigation will be needed to improve engagement further. Given the projected need for social distancing, and increasing role of telemedicine for long-term management, a chatbot-linked home spirometer may be a powerful tool to detect early graft dysfunction.

The Relationship Between Pre-Transplant Serum Phosphorus Before Kidney Transplantation with Early Graft Dysfunction.

Introduction. Pre-transplant serum phosphorus level is shown to be associated with some transplant outcomes in patients with chronic kidney disease. However, its association with Delayed graft function (DGF) has an aura of ambiguity. DGF means either the patient needs dialysis during the first week after transplantation or the creatinine level is ≥ 3. This study was aimed to assess the relationship between pre-transplant serum phosphorus levels with DGF. Methods. A total of 306 patients, who had undergone kidney transplantation in the Montaserieh organ transplantation hospital in Mashhad, Iran, during 2016 to 2019; were enrolled in this study. Demographic data and clinical characteristics of patients including dialysis type and duration, donor type, medications, pre-transplant serum levels of calcium, phosphorus and DGF development were measured. Then, all patients were divided into five groups according to their serum phosphorus: P < 3.5, 3.5 ≤ P < 5.5, 5.5 ≤ P < 7.5, 7.5 ≤ P < 9.5, and P ≥ 9.5 mg/dL. The association with DGF was evaluated by statistical analysis. Results. Patients age ranged from 18.00 to 64.00 years old, with an average of 37.08 ± 10.9. About 55.6% of them were men, and 26.1% came up with DGF. Among patients with DGF, 36.25% were recipients with pre-transplant phosphorus level of 3.5 ≤ P < 5.5 and 50% of 5.5 ≤ P < 7.5. Conclusion. Our study suggested that pre-transplant serum phosphorus might be associated with an increased risk of delayed graft function. Further studies are needed to assess, whether adjusting serum phosphorus level before kidney transplantation could reduce delayed graft function or not.

Current status of left lobe adult to adult living donor liver transplantation.

This review describes the history and current state of left lobe living donor liver transplantation (LDLT). The transplant community continues to face an organ shortage on a global scale, and the expansion of LDLT is attractive because it allows us to provide life-saving liver transplants to individuals without drawing from, or depending on, the limited deceased donor pool. Donor safety is paramount in LDLT, and for this reason, left lobe LDLT is particularly attractive because the donor is left with a larger remnant. This article reviews the donor and recipient evaluations for left lobe LDLT, discusses small for size syndrome and the importance of portal inflow modification, and reviews recipient outcomes in right lobe versus left lobe LDLT. Left lobe LDLT was the first adult-to-adult LDLT ever to be performed in Japan in 1993. Since that time, the use of both right and left lobe LDLT has expanded immensely. Recent work in left lobe LDLT has emphasized the need for inflow modification to reduce portal hyperperfusion and early graft dysfunction following transplant. Accumulating evidence suggests, however, that even though early graft dysfunction following LDLT may prolong hospitalization, it does not predict graft or patient survival.

Value of Plasmatic Villin-1 in the Prediction of Early Graft Dysfunction in Kidney Transplant Recipients: Diagnostic Accuracy Test.

One of the complications of kidney transplant is delayed graft function. Villin-1 has been detected in urine of patients with acute kidney injury. In addition, it is redistributed during acute kidney injury from the brush borders of the proximal tubular cells toward the basolateral membrane, which positions villin-1 closer to the renal vasculature, suggesting that it could be also released in the blood and thus can be a novel biomarker for delayed graft function. In this diagnostic accuracy test multicenter study, 41 patients undergoing kidney transplant and attending renal transplant clinics were assigned into 2 groups according to serum creatinine levels during the first 2 days posttransplant: delayed graft function group and normal graft function group. We measured plasmatic villin-1 in comparison to serum creatinine levels at the time of declamping (time 0) and at 1, 3, 5, 7, 12, 24, 48, 72, 96, and 120 hours after declamping. Statistically significant differences were noted in comparisons between groups at same time points with regard to plasmatic villin-1 levels; also, plasmatic villin-1 started to increase above reference range in patients with end-stage renal disease at 5 hours after declamping; a peak was shown at hour 7 in the delayed graft function group, which decreased but did not reach the reference range until 120 hours after declamping. Plasmatic villin-1 is a promising novel biomarker for detection of early graft dysfunction in kidney transplant recipients.