Presence Of Rejection Research Articles

Comparison of BK virus nephropathy risk between double-J-stent with anti-reflux mechanism and standart double-J-stent: single-center experience

Aim: Ureteral stend use is a risk factor for BK nephropathy (BKVN). In 2015, we compared the patients with anti-reflux mechanism DJS (ARD-DJS) and those used standard DJS (st-DJS) in terms of BKV and BKVN frequency in 90 kidney transplant patients in two centers. With the increase in the number of our patients over time and lengthening of the follow-up duration, we needed to re-evaluate the data in one center. Material and Method: We retrospectively evaluated 211 patients who underwent kidney transplantation at Gazi Yaşargil Training and Research Hospital between September 2012 and September 2019. The following parameters were recorded, demographic data, immunosuppression protocols, presence of rejection, graft loss, plasma BKV levels, and presence of BKVN. Median and IQR follow-up time for ARD-DJS and St-DJS patients was 72 months (62,5-80,3 months) and 27,8 months (17,4-39,6 months) respectively. Results: Thirteen patients (6,1%) had BKV viremia. BKVN was revealed by kidney biopsy in 3 of 13 patients. However, graft loss due to BKVN was observed in only one patient. ARD-DJS was used in 4 of these cases and standard DJS was used in 9 of these cases. Patients in whom BKV revealed in the first 3 months were compared in the aspect of DJS technique, BKV was significantly less observed in the ARD-DJS group (ARD-DJS: 2 patients; St-DJS:9 patients), (p=0,046). Conclusion: In our study, BKV was observed less in patients with ARD-DJS that were clinically significant but not statistically significant. Therefore, prospective randomized studies with high patient numbers are needed to determine the effectiveness of ARD-DJS.

332.12: Association Between CYP3A5*1 and CYP3A5*3 Polymorphisms, With the Formation of ADES and the Presence of Rejection in Renal Transplant Recipients

332.12: Association Between CYP3A5*1 and CYP3A5*3 Polymorphisms, With the Formation of ADES and the Presence of Rejection in Renal Transplant Recipients

MO974: Post-Transplant Glomerulonephritis: A Comparative Cohort Study

Abstract BACKGROUND AND AIMS Post-transplant glomerulonephritis (GMNPTR) is considered the third cause of graft loss. This entity is associated with worse outcomes when compared with the rest of the transplanted population; however, it is little explored whether this risk is maintained despite comparing it with a similar immunological risk. METHOD Retrospective cohort study of 12-year kidney transplant recipients (KT) with active follow-up and biopsy-proven diagnosis of GMNPTR. The objectives were to describe the incidence of GMNPTR, describe the frequency of histological diagnoses, and perform a comparative analysis of outcomes with 1: 1 matched controls by: gender, age ± 3 years, shared haplotypes, and year of RT ± 3 years. Kaplan–Meier was used for the analysis of time-dependent variables and Mann–Whitney U was used for comparison of graft function. RESULTS In the study period, 632 TR were performed, 54 cases of GMNPTR were found for an incidence of 8.5%. Of these 44 (81.5%) correspond to primary nephropathies, the most frequent being the mesangioproliferative pattern (n = 14, 25.9%), IgA nephropathy (n = 10, 18.5%), focal and segmental glomerulosclerosis (n = 7,12.9%); 10 cases of secondary GMNPTR were reported, of which the most frequent were: diabetic nephropathy and lupus nephritis, in 9.3% and 7.4% respectively. Of the total cases, 4 (7.4%) correspond to true recurrence, 4 (7.4%) to de novo disease and 46 (85%) to graft glomerulonephritis with unknown primary disease. The median time for the diagnosis of GMNPTR was 10 months (IQR: 3–14), the eGFR by CKD-EPI was 67.4 (± 21.2) mL/min/1.73 m2 and proteinuria 231 mg/24 h (IQR: 100–600 mg/day). Fifty-four controls were selected with the previously described matching criteria: age at the time of RT was 38.6 (± 12) years, female gender was 57.4% and the median time on dialysis was 45 months (IQR: 35–61), similar between both groups. The haplotypes shared with the donor were: 0 (n = 33, 61%), 1 (n = 13, 24%), 2 (n = 8, 15%) and 0 (n = 32, 59%), 1 (n = 14, 26%), 2 (n = 8, 15%) for cases and controls, respectively, P = NS. Renal transplantation from a deceased donor was 41% for both groups; the median follow-up for the cases was 43 months (IQR: 24–90) and for the controls 53.5 (IQR: 33–85), P = 0.5. An overall incidence of rejection of 31.8% was observed at a median of 140 months (95% CI: 28–252), log-rank P = 0.27, it was striking that the median time for the appearance of cellular rejection showed a tendency to be higher in the cases of GMNPTR (168 versus 123 months), log-rank P = 0.08; the overall incidence of graft loss was 7.5% at a median follow-up of 149 months (95% CI: 130.5–168.3) log-rank P = 0.91. Finally, when comparing eGFR by CKD-EPI in the last follow-up, no difference was observed (eGFR 64.6 ± 26 versus 60.9 ± 27 mL/min/1.73 m2 P = 0.4). CONCLUSION In this study the incidence of GMNPTR is similar to that reported in other cohorts, the most frequent were the primary ones and those with a mesangioproliferative pattern; After adjusting for immune risk factors, GMNPTR did not affect survival compared to a homogeneous immune risk population. On the contrary, and as is well known, the presence of rejection was associated with lower graft function. Maintenance with triple therapy could modulate the severity of GMNPTR, and therefore we see histological diagnoses of little clinical impact.

The Impact of Nutritional Status and Sarcopenia on the Outcomes of Lung Transplantation

<h3>Purpose</h3> Malnutrition and sarcopenia have been widely reported to negatively influence patients' outcomes in different clinical settings, but information is lacking about their impact on short and long-term outcomes after lung transplantation (LT). The aim of this study was to investigate which nutritional and sarcopenia indices independently predict prolonged post-operative invasive mechanical ventilation (IMV), intensive care unit (ICU) and hospital length of stay (LOS), re-intubation and rejection after LT. <h3>Methods</h3> Observational, retrospective study on patients undergoing LT in a single University Hospital was conducted between February 2016 and November 2020. Within 6 months before LT, the following data were collected: a) nutritional indices (Body Mass Index (BMI), serum albumin concentration, Prognostic Nutritional Index (PNI), Mini Nutritional Assessment Short-Form (MNA-SF)); b) sarcopenia indices (Creatinine Height Index (CHI), Skeletal Muscle Index (SMI) and densitometry of paravertebral muscles at chest CT-scan); c) postoperative clinical data related to the outcomes of interest. Univariable logistic regression models were used for binary outcomes and univariable gamma models for continuous outcomes. <h3>Results</h3> 108 of 114 patients were enrolled after excluding 6 patients for incomplete records. Seventy-two patients (67%) were male, median age was 52 [43-60] years. The main indications for BLT were interstitial (46%), septic (22%) and obstructive (19%) diseases. The IMV duration was non-linearly associated with pre-operative serum albumin (range 30-35 g/L: effect -1.67 [-2.45 - -0.89] hours, p<0.01). The ICU LOS was non-linearly correlated to albumin (range 30-35 g/L: effect -0.84 [-1.23 - -0.45] days, p<0.01) and PNI (range 25-40: effect -1.79 [-3.09 - -0.50] days, p=0.01), but linearly associated to BMI (range 20.7-27.4 kg/m²: effect +0.34 [0.03 - 0.68] days, p=0.04). No nutritional or muscle parameters predicted the need for re-intubation, the presence of rejection at 30 days and hospital LOS. <h3>Conclusion</h3> Pre-operative low serum albumin independently predicts prolonged IMV after LT, while pre-transplant low albumin, low PNI and high BMI values are associated with prolonged postoperative ICU LOS. Further studies are needed to identify the most appropriate nutritional and muscular assessment tools in BLT recipients.

The Safety of a Non-Invasive Monitoring Protocol in Heart Transplant Recipients

<h3>Purpose</h3> Heart transplant (HT) recipients require monitoring for allograft rejection with frequent endomyocardial biopsies (EMB). The aim of this study was to evaluate the safety of transitioning heart transplant recipients to a non-invasive monitoring protocol utilizing HeartCare (combination of gene expression profiling [Allomap] and donor derived cell free DNA [Allosure]). <h3>Methods</h3> This is a prospective single-center cohort study evaluating the utilization of HeartCare from as early as one month post-HT. Positive Allomap test was defined as ≥32 in patients ≤6 months and ≥34 in patients > 6 months post-HT. Positive Allosure test was defined as ≥0.12%. Positive biopsy included ISHLT Grades ≥1B. <h3>Results</h3> 320 heart transplant recipients enrolled to this study. Mean age was 57.5±14.0, 231 were males (72.0%). There was a total of 523 HeartCare blood tests drawn and 148 biopsies were performed (Figure). Of 82 patients with elevated Allomap and Allosure, only 7 (8.5%) of them had a confirmed rejection episode. Among 71 patients with elevated Allosure with normal Allomap, only 2 (2.8%) patients had confirmed rejection. 2 patients (4.3%) with negative Allomap and Allosure had rejection. During the study period 55 patients (17.2%) were admitted to the hospital for a total of 67 admissions. 17 patients were admitted for rejection (5.3%). None of the patients died during the study period. <h3>Conclusion</h3> Transitioning from invasive endomyocardial biopsy monitoring to a non-invasive HeartCare protocol in HT recipients seems feasible based on the high negative value of the combined Allomap and Allosure tests. However, further study is needed to follow the long-term outcomes and presence of rejection in patients post-transplant with this protocol.

Release the Pressure! Does Jugular Venous Pressure Predict Rejection in Cardiac Biopsy?

<h3>Purpose</h3> Rejection in heart transplant recipients is often diagnosed by surveillance biopsies as most patients are asymptomatic. Nevertheless, rejection, if left untreated, can produce progressive diastolic dysfunction followed by systolic heart failure. This in turn will cause an increase in central venous pressure due to decreased ventricular compliance. With this in mind we sought out to determine if elevated central venous pressures measured invasively at the time of the biopsy correlated with the presence of rejection. <h3>Methods</h3> Patients undergoing an endomyocardial biopsy between June and October 2020 were included. The invasive JVP was measured before and after the procedure by measuring the height of the blood column in the side port of the sheath open to the atmospheric pressure. The biopsy results were reported according to the 2004 ISHLT revision. Differences in median JVP for each biopsy result group (0, 1R, 2R, 3R) were compared using a Mann-Whitney test. The histogram density for each biopsy group was graphed using a Kernel density plot. <h3>Results</h3> Eighty-four patients underwent one or more endomyocardial biopsies, with a total of 374 biopsies performed. Of all procedures, 187 were grade 0 for rejection, 168 were grade 1R and 18 were grade 2R. One patient had Grade 3R rejection (not shown in illustration) The median JVP was not statistically different between the three groups and the numerical difference was not clinically meaningful (figure 1 A). The Kernel density plot (figure 1 B) demonstrates the similarities between the groups. The lack of correlation between invasive JVP and rejection persists if data from the first 2 weeks post heart transplant are excluded. <h3>Conclusion</h3> In our dataset, there was no clinical or statistical difference in median invasive JVP and rejection grade between the biopsy result groups. One limitation is that we only had one patient with severe rejection (3R). Overall, our findings reinforce the need for surveillance biopsies.

Lower soluble Klotho levels in the pretransplant period are associated with an increased risk of renal function decline in renal transplant patients.

Serum soluble Klotho levels are associated with renal function in predialysis patients with chronic kidney disease. However, few reports exist regarding the association between soluble Klotho levels and renal function in kidney transplant (KTx) recipients. This was a retrospective observational study of 41 living KTx recipients. The serum soluble Klotho levels were classed as "high" (>456 pg/mL [i.e., high-Klotho group]) or "low" (≤456 pg/mL [i.e., low-Klotho group]). Renal function decline was defined as a decrease in the estimated glomerular filtration rate (eGFR) of 30% or more from the baseline value within 3 months after KTx. A multivariable time-to-event analysis between the groups was conducted. Among the KTx recipients, the incidence of a 30% decrease in the eGFR was significantly higher in the low-Klotho group than in the high-Klotho group (P = .036). After adjusting for donor age, donor sex, the presence of rejection, and the number of cytomegalovirus infections, multivariable Cox models revealed that low soluble Klotho levels remained associated with a higher risk of a 30% decrease in the eGFR (hazard ratio, 2.38; 95% confidence interval, 1.02-6.41). These findings suggested that lower soluble Klotho levels in the pre-KTx period are associated with an increased risk of renal function decline in KTx recipients.

Profilaxis combinada con inmunoglobulina intravenosa y plasmaféresis en pacientes altamente sensibilizados, receptores de trasplante renal o combinado hígado-riñón: experiencia en un centro médico colombiano

&#x0D; &#x0D; &#x0D; &#x0D; Introducción. El trasplante renal constituye la mejor opción de tratamiento para los pacientes con enfermedad renal crónica terminal. La supervivencia del injerto es de gran importancia y puede ser afectada por factores inmunológicos o no inmunológicos; esto unido al número de pacientes en las listas de espera, hace necesario definir estrategias de manejo que permitan tener mejores resultados a largo plazo. Objetivo. Determinar las características clínicas y humorales, y los de- senlaces en receptores de trasplante renal o combinado hígado-riñón, altamente sensibilizados, que recibieron profilaxis combinada con inmunoglobulina intravenosa y plasmaféresis en el Hospital San Vicente Fundación, en Colombia. Materiales y métodos. Se realizó un estudio retrospectivo, observacional, descriptivo, que incluyó los pacientes trasplantados entre el 4 de julio de 2010 y el 19 de abril de 2017. Como variables se incluyeron, entre otras, la etiología de la enfermedad renal crónica, el tipo de terapia recibida, y el tiempo en lista de espera en días. Como desenlace se evaluó la presencia de rechazo, el tipo de rechazo, la pérdida del injerto, las complicaciones y la muerte. Resultados. Del total de 25 pacientes, el 100% recibió inmunoglobulina intravenosa y el 84% plasmaféresis. El 12% presen-tó rechazo del injerto, todos de tipo humoral, y el 20% perdió el injerto. Discusión. A pesar de la gran variedad de protocolos propuestos en la literatura, en esta población especial no se ha establecido un protocolo óptimo de inmunosupresión. El protocolo en nuestra pequeña cohorte no tuvo un impacto negativo en el porcentaje de infecciones postrasplante ni en la pérdida del injerto renal, pero sí redujo el tiempo en las listas de espera; por lo tanto, se requieren estudios adicionales para confirmar los hallazgos encontrados en este estudio.&#x0D; &#x0D; &#x0D; &#x0D;

Temporal changes in left ventricular strain with the development of rejection in paediatric heart transplant recipients

Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients. All paediatric heart transplant recipients (2004-2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable. A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (-18.2 versus -14.1), global circumferential strain (-24.1 versus -19.6), longitudinal strain rate (-1 versus -0.8), circumferential strain rate (-1.3 versus -1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction. Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

Long-term Clinical Outcomes of First and Second Kidney Transplantation in Patients With Biopsy-Proven IgA Nephropathy

IntroductionThe recurrence of IgA nephropathy (IgAN) after kidney transplantation (KT) has an effect on graft survival, but there are few reports about long-term clinical outcomes of KT with recurrent IgAN. This study shows the long-term clinical outcomes of KT in patients with IgAN. MethodsAll recipients who had biopsy-proven IgAN were followed from February 1990 to February 2016. We analyzed overall graft and patient survival rates, incidence of recurrent IgAN, factors affecting graft survival, and IgAN recurrence. ResultsThere were 88 patients with first KT. The mean follow-up duration was 82.5 months. Twenty patients went through graft loss and 1 patient died due to sepsis. IgAN recurred in 15 patients, and 11 patients experienced graft failure. Among the patients who had failed graft after first KT, 7 patients underwent retransplantation. The graft survival period, presence of rejection, and proteinuria were the relevant risk factors for recurrence of IgAN. In the first KT patients, presence of rejection and 1-year serum creatinine were the significant risk factors for graft loss. But recurrence of IgAN was not a relevant risk factor. Overall graft survival rates at 5 and 10 years were 93.8% and 73.1% in the first transplantation group and 100% and 100% in the retransplantation group, respectively. ConclusionAlthough IgAN recurrence was a significant risk factor for graft failure, the patient who underwent retransplantation showed favorable results. Retransplantation should be considered in patients who lost their first graft after recurrence of IgAN.

Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection.

To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients. The USPIO ferumoxytol has a long blood half-life and is phagocytosed by macrophages. In an IRB-approved single-center prospective clinical trial, 26 pediatric patients and adolescents (age 10-26years) with acute allograft rejection (n=5), non-rejecting allografts (n=13), and normal native kidneys (n=8) underwent multi-echo T2* fast spoiled gradient-echo (FSPGR) MRI after intravenous injection (p.i.) of 5mg Fe/kg ferumoxytol. T2* relaxation times at 4h p.i. (perfusion phase) and more than 20h p.i. (macrophage phase) were compared with biopsy results. The presence of rejection was assessed using the Banff criteria, and the prevalence of macrophages on CD163 immunostains was determined based on a semi-quantitative scoring system. MRI and histology data were compared among patient groups using t tests, analysis of variance, and regression analyses with a significance threshold of p<0.05. At 4h p.i., mean T2* values were 6.6±1.5ms for native kidneys and 3.9ms for one allograft undergoing acute immune rejection. Surprisingly, at 20-24h p.i., one rejecting allograft showed significantly prolonged T2* relaxation times (37.0ms) compared to native kidneys (6.3±1.7ms) and non-rejecting allografts (7.6±0.1ms). Likewise, three additional rejecting allografts showed significantly prolonged T2* relaxation times compared to non-rejecting allografts at later post-contrast time points, 25-97h p.i. (p=0.008). Histological analysis revealed edema and compressed microvessels in biopsies of rejecting allografts. Allografts with and without rejection showed insignificant differences in macrophage content on histopathology (p=0.44). After ferumoxytol administration, renal allografts undergoing acute rejection show prolonged T2* values compared to non-rejecting allografts. Since histology revealed no significant differences in macrophage content, the increasing T2* value is likely due to the combined effect of reduced perfusion and increased edema in rejecting allografts.

Upregulation of PIM2 by Underexpression of MicroRNA-135-5p Improves Survival Rates of Skin Allografts by Suppressing Apoptosis of Fibroblast Cells.

BackgroundIt has been reported that miR-135-5p is involved with many diseases. In this study, we aimed at define the relationship between miR-135-5p level and burn patient survival after skin transplantation.Material/MethodsExpression of miR-135-5p and PIM2 was measured using real-time PCR and Western blot analysis in the skin samples collected from burn patients who received skin graft or in the fibroblast cells transfected with miR-135-5p mimics or inhibitors. The regulatory association between miR-135-5p and PIM2 was verified using bioinformatics analysis and luciferase assay.ResultsThe expression level of miR-135-5p was determined in 60 tissue samples divided into 2 groups based on the presence of rejection (long survival n=30, and short survival n=30). We found that miR-135-5p was substantially downregulated in the long survival group. We then searched the miRNA database online with the “seed sequence” located within the 3′-UTR of the target gene, and then validated PIM2 to be the direct gene via luciferase reporter assay system. We also established the negative regulatory relationship between miR-135-5p and PIM2 via studying the relative luciferase activity. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of PIM2 among different groups (long survival n=30, short survival n=30) or cells treated with scramble control, miR-135-5p mimics, PIM2 siRNA, and miR-135-5p inhibitors, indicating the negative regulatory relationship between MiR-135-5p and PIM2. We also conducted experiments to investigate the influence of miR-135-5p and PIM2 on viability and apoptosis of cells. The results showed miR-135-5p reduced the viability of cells, while PIM2 negatively interfered with the viability of cells, and miR-135-5p inhibited apoptosis and PIM2 suppressed apoptosis.ConclusionsMiR-135-5p is involved with the prognosis of burn patients after skin transplantation. PIM2 is a virtual target of miR-135-5p, and there is a negative regulatory relationship between miR-135-5p and PIM2. MiR-135-5p and PIM2 interfered with the viability and apoptosis in cells.

Lack of Association Between Elevated Urinary Levels of Interleukin-10 and Interferon Gamma With the Presence of Inflammation in Kidney Transplant Recipients

IntroductionA lot of evidence has demonstrated the importance of different cytokines in acute renal rejection. Previous studies have examined the presence or absence of interleukin (IL)-10 in related immunopathologic rejection grafts as well as other interleukins. Studies in human transplantation show elevated levels of IL-10 and gamma interferon (INF-γ) in inflammation and rejection. ObjectiveThe objective of this study was to demonstrate the lack of association of elevated urinary levels of IL-10 and IFN in the presence of active inflammation. MethodsAn observational, descriptive, cross-sectional study conducted in transplant recipients at 12 months of follow-up after renal transplantation. In those who were held biopsy after renal transplantation at one year follow-up, or allograft dysfunction, we also measured IL-10 and INF-γ in the urine. The following were considered as variables: age, body mass index (BMI), gender, transplant type, creatinine, chronic kidney disease epidemiology collaboration equation, (CKD-EPI), modification of diet in renal disease study equation (MDRD), Banff classification, and levels of IL-10 and INF-γ. Statistical analysis was performed calculating a sample size of 25 patients, with an alpha bias of 0.05%, yielding measures of central tendency and determining no association between levels of IL-10 and INF-γ with the presence of rejection using SPSS 21.0 program. ResultsA total of 50 patients, 34 (68%) males, 16 (32%) females, with an average 31.7 ± 9.9 years, weight of 64.91 ± 13.84 kg, size 1.60 ± 0.10 m and 24.97 ± 4.07 BMI were included,39 (78%) living donor and 11 (22%) cadaveric. Twenty-six (52%) showed inflammation in the biopsy and 24 (48%) showed none. Mean creatinine was 1.81 ± 1.5, and the estimated glomerular filtration rate (eGFR) was 55.27 ± 22.46, 65.76 ± 26.7. (MDRD and CKD-EPI, respectively). No statistical difference was found in the levels of IL-10 and IFN-γ using analysis of variance. (ANOVA; P = .467 and P = .063, respectively) Based on Banff, the inflammation on biopsy score was 2.78 ± 2.84. There was statistical significance (P < .05) with respect to the Cr and eGFR by different equations. There were no significant interactions between cytokine levels and more than 1 factor. (as indicated by P < .2). Discussion and ConclusionsNo significant differences were observed in the level of interleukins in patients with and without inflammation, denoting an adequate immunosuppression in most of these patients. Determination of inflammatory cytokines in urine could be used as a determinant of a good immunosuppression status, rather than as an early marker of rejection.

Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

BackgroundIt remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.Methods and FindingsIn this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412) that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without). We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient’s net state of immunosuppression (correlation with tacrolimus level, r = −0.867, 95% CI −0.968 to −0.523, p = 0.0014), as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9%) and a specificity of 82.0% (95% CI 72.1% to 89.1%) (cell-free donor-derived DNA as noninvasive gold standard). To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the availability of a large number of samples and the absence or presence of rejection events.ConclusionsIf confirmed in larger, prospective studies, the method described here has potential applications in the tailored management of post-transplant immunosuppression and, more broadly, as a method for assessing the overall activity of the immune system.

(367) - Hypogammaglobulinemia After Lung Transplantation Increases Risk of Recurrent Pneumonia

Immunosuppressive therapies have led to vast improvements in survival in lung transplant (LT) recipients but these therapies can lead to hypogammaglobulinemia (HGG). To assess the impact of HGG on transplant outcomes, we reviewed one year findings from a prospective observational study examining the relationship of HGG to incidence of pneumonia, antibiotic use, presence of rejection, and steroid use. This is a single center study of LT recipients at the University of Pittsburgh Medical Center. IgG levels were measured pre-transplant, at time of transplant and at 3, 6, and 12 months post-transplant and related to incidence of pneumonia, antibiotic use, presence of rejection, and steroid use. Analysis was performed using non-parametric tests. 133 LT recipients were evaluated. Post-transplant subjects receiving Basiliximab had lower IgG levels at 3 and 6 months than those induced with Alemtuzamab, but those differences were absent at one year after transplant (p=0.2). In subjects who had one or more incidence of pneumonia, there was a negative correlation between IgG level and the number of pneumonias (Spearman’s rho= -0.31, p=0.05). In addition, one-year mortality was associated with lower IgG levels at 3 months post-transplant (p=0.04). There was no relationship between IgG levels and the number of courses of antibiotics, CMV status, steroid use, or presence of rejection. Our results suggest that LT recipients with HGG are at risk for developing recurrent pneumonias and increased mortality at 1 year. Additional analyses to better characterize these patients and to evaluate the efficacy of IgG replacement therapy for prevention of pneumonia and improvement in survival will be needed to further define the clinical importance and treatment of HGG in lung transplant recipients.

An analysis of tacrolimus-related complications in the first 30 days after liver transplantation

OBJECTIVES:Orthotopic liver transplantation has improved survival in patients with end-stage liver disease; however, therapeutic strategies that achieve ideal immunosuppression and avoid early complications are lacking. To correlate the dose and level of Tacrolimus with early complications, e.g., rejection, infection and renal impairment, after liver transplantation. From November 2011 to May 2013, 44 adult liver transplant recipients were studied in this retrospective comparative study.RESULTS:The most frequent indication for liver transplantation was hepatitis C cirrhosis (47.7%), with a higher prevalence observed in male patients (68.18%). The ages of the subjects ranged from 19-71 and the median age was 55.5 years. The mean length of the hospital stay was 16.1±9.32 days and the mean Model for End-stage Liver Disease score was 26.18±4.28. There were five cases of acute cellular rejection (11.37%) and 16 cases of infection (36.37%). The blood samples that were collected and analyzed over time showed a significant correlation between the Tacrolimus blood level and the deterioration of glomerular filtration rate and serum creatinine (p<0.05). Patients with infections had a higher serum level of Tacrolimus (p = 0.012). The dose and presence of rejection were significantly different (p = 0.048) and the mean glomerular filtration rate was impaired in patients who underwent rejection compared with patients who did not undergo rejection (p = 0.0084).CONCLUSION:Blood Tacrolimus levels greater than 10 ng/ml were correlated with impaired renal function. Doses greater than 0.15 mg/kg/day were associated with the prevention of acute cellular rejection but predisposed patients to infectious disease.

Deep anterior lamellar keratoplasty versus penetrating keratoplasty for treating keratoconus.

Deep anterior lamellar keratoplasty versus penetrating keratoplasty for treating keratoconus.

Impact of Pre-Transplant PRA Level On Renal Graft Survival in Patients With Negative Cross-Match and No Donor Specific Antibody.

Purpose: The aim of this study was to investigate the impact of pre-transplant PRA level on rejection and graft survival after kidney transplantation in patients with negative cross-match(CXM(-)) and no donor specific antibody(DSA(-)). Method: We analyzed retrospectively 513 kidney recipients transplanted at our center. And among them, those who identified positive test on cross-match, those who had donor specific antibodies, ABO incompatible, and those who had no information of PRA were excluded(n=130). The factors included peak PRA, age, gender, HLA mismatch number, transplant number, donor source, rejection were reviewed. Peak PRA was stratified into 3 groups according to their PRA levels group I, PRA=0; group II, PRA 0< ≤50%, and group III, PRA 50%<. Graft failure was defined as return to dialysis, transplant nephrectomy, or death with functioning kidney. Results: The mean follow up duration was 29.4±14.6month(0-59). The rejection rate was 20.1%(group I 18.5%(n=58) vs. group II 23.8%(n=10) vs. group III 33.3%(n=9) (p=0.053)). The graft failure rate was 21.7%(group I 6.4%(n=20) vs. group II 7.1%(n=3) vs. group III 7.4%(n=7)(p=.792))Table: No Caption available.Univariate analysis by log-rank test, donor source and rejection were significantly associated with graft survival(p=.000 and .000, respectively), however subcatergories of PRA were not(p=.851). On multivariate Cox regression analysis, donor source and rejection were also significantly associated with graft survival(p=0.002 and 0.000, respectively), however including subcatergories of PRA(p=.552), other variables were not significant. Conclusion: The rejection rate was higher as PRA group increasing, however it was not statistically significant(p=.053). Pre-transplant PRA value was not significantly associated with graft survival, in patients with CXM(-) and DSA(-). However, donor source and presence of rejection were significantly associated with graft failure.

The use of transient elastography and non‐invasive serum markers of fibrosis in pediatric liver transplant recipients

The use of non-invasive markers to diagnose liver allograft fibrosis is not well established in children after LTx. TE, FT, and ELF score were performed in 117 liver-transplanted children (60M, 8.9 [0.5-18.5]yr) and 336 healthy controls. Liver biopsy was available in 36 children. Results of histology and non-invasive markers were compared using correlation coefficient or Mann-Whitney U-test as appropriate. TE correlated best with histological degree of fibrosis (r=0.85 vs. r=0.04 [FT] or r=-0.38 [ELF]). Liver stiffness values for transplanted children without fibrosis were significantly higher than those of healthy controls (7.55 [5.4-20.4]kPa vs. 4.5 [2.5-8.9]kPa). Presence of rejection was a potent confounder for the performance of TE. Both TE and FT reflected clinical changes (acute rejection, cholestasis, increasing fibrosis) in a total of 16 patients who underwent serial measurements. TE correlates better with histological degree of fibrosis in liver-transplanted children than FT or ELF, but an individual baseline value needs to be determined for each patient. Normal or cutoff values for pathological degrees of fibrosis cannot be transferred from non-transplanted children. Follow-up studies, preferably with protocol biopsies, might help to improve the diagnostic quality of TE.