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ABSTRACT Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients discontinued steroid therapy from among 678 RT patients transplanted from living donors between 1999-2020 were included. The mean age of the study group was 45.8±8.8 years. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications, laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure (BP), body mass index, delayed acute rejection (DAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between DAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. Conclusion: Per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.
RESUMEN Introducción: Con frecuencia se registran niveles elevados de ácido úrico en receptores de trasplantes renales que pueden estar asociados a disfunción de aloinjerto. El presente estudio tiene por objeto examinar la relación entre los niveles de AU y la función del injerto en pacientes que interrumpieron la terapia con esteroides. Métodos: En este estudio retrospectivo en un solo centro participaron 56 pacientes con interrupción de la terapia con esteroides de un total de 678 pacientes con TR receptores de trasplante de donantes vivos en el período 1999-2020. La edad promedio de la población de estudio fue de 45,8 ± 8,8 años. En el estudio se registraron causas de la interrupción de la terapia con esteroides, niveles de creatinina concurrentes con niveles de ácido úrico antes y después de la interrupción de la terapia con esteroides (promedio de 3,9 ± 2,1 años), números de rechazo agudo, datos demográficos, duraciones del período de diálisis y trasplante, medicación (uso de inmunosupresores, antihipertensivos), datos de laboratorio, números de desajuste del antígeno leucocitario humano (HLA), presión arterial (PA), índice de masa corporal, números de rechazo agudo retardado (DAR) (3 meses después del trasplante). Resultados: Se observó que los niveles de creatinina y ácido úrico aumentaron tras interrumpir la administración de esteroides, con una relación significativa entre ambos (p<0,001). Se identificó una correlación estadísticamente significativa entre el aumento en los niveles de creatinina tras la interrupción de la terapia de esteroides y la supervivencia del injerto con un mayor desajuste de HLA: 39 pacientes (el 69,6%) con desajuste ≥2 y 17 (el 30,4%) pacientes con desajuste <2 (p=0,049). No se encontró una relación significativa entre el número de DAR antes y después de la interrupción del tratamiento con esteroides, así como en los niveles de creatinina tras la interrupción de la terapia con esteroides. Conclusión: De acuerdo con el modelo obtenido como resultado del análisis lineal multivariable, la hiperuricemia y los números de desajuste de HLA (p=0,048 y p=0,044, respectivamente) constituyen factores predictivos independientes para la disfunción del injerto en pacientes que interrumpen la terapia con esteroides. En consecuencia, se deben tener en cuenta los efectos negativos del modelado para la supervivencia del injerto a largo plazo en pacientes que planean proseguir con regímenes con reducción de la administración esteroides.
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Prevention and treatment of complications after liver transplantation play a significant role in maintaining liver graft function and improving clinical prognosis of the recipients. Neutrophil extracellular trap (NET) are fibrous net-like structures composed of DNA as the skeleton and histones and granular proteins released by activated neutrophils. Studies have shown that the activation of neutrophils and the release of NET in donor liver after liver transplantation are involved in the incidence of multiple liver transplantation-related complications including ischemia-reperfusion injury, acute rejection, acute liver failure and recurrence of hepatocellular carcinoma, etc. In this article, the effect of NET on the complications after liver transplantation was mainly assessed, and research progress on NET as a potential target for the prevention and treatment of complications after liver transplantation was reviewed, aiming to provide reference for the prevention and treatment of complications after liver transplantation, enhance clinical efficacy of liver transplantation and improve clinical prognosis of the recipients.
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Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m2) vs. (60±15) mL/(min·1.73 m2), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.
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Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.
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Early diagnosis of acute rejection is of significance for the protection of renal allograft function. Pathological puncture biopsy is the gold standard for the diagnosis of acute rejection of renal allografts. Nevertheless, it may provoke multiple complications, such as bleeding, infection and renal parenchymal injury, which limit its widespread application. In recent years, the sensitivity of contrast-enhanced ultrasound in the diagnosis of acute rejection has been constantly improved. Ultrasound-targeted microbubble technique has further enhanced the diagnostic specificity of contrast-enhanced ultrasound, making it possible to replace pathological puncture biopsy. Besides, in the field of acute rejection treatment, microbubble ultrasonic cavitation may promote local delivery of immunosuppressants by inducing sonoporation and exhibit anti-rejection effect. In this article, the application of contrast-enhanced ultrasound in the diagnosis and treatment of acute rejection after kidney transplantation was reviewed, aiming to provide reference for widespread application of contrast-enhanced ultrasound in kidney transplantation.
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Objective To investigate the changes of macrophage polarization during acute rejection (AR) after intestinal transplantation. Methods Six Brown Norway (BN) rats and 24 Lewis rats were divided into the sham operation group (6 Lewis rats), syngeneic transplantation group (Lewis→Lewis, 6 donors and 6 recipients) and allogeneic transplantation group (BN→Lewis, 6 donors and 6 recipients). At postoperative 7 d, the intestinal graft tissues in all groups were collected for hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Pathological manifestations and cell apoptosis were observed. The expression levels of serum cytokines related to M1 and M2 macrophage polarization were determined by enzyme-linked immunosorbent assay (ELISA). Surface markers of M1 and M2 macrophages of intestinal graft tissues in each group were co-localized and counted by immunofluorescence staining. Results HE staining and TUNEL assay showed that the intestinal epithelial morphology and structure were normal and no evident apoptotic bodies were found in the sham operation and syngeneic transplantation groups. At 7 d after transplantation, the epithelial villi structure of intestinal graft tissues was severely damaged, the number of crypts was decreased, the number of apoptotic bodies was increased, and inflammatory cells infiltrated into the whole intestinal wall, manifested with moderate to severe AR in the allogeneic transplantation group. ELISA revealed that the expression levels of serum cytokines related to M1 macrophage polarization, such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-12, of the recipient rats in the allogeneic transplantation group were higher than those in the sham operation and syngeneic transplantation groups. The expression levels of serum cytokines related to M2 macrophage polarization, such as IL-10 and transforming growth factor (TGF)-β, in the syngeneic transplantation group were higher compared with those in the sham operation and allogeneic transplantation group, and the differences were statistically significant (all P<0.05). Immunofluorescence staining showed that the number of M1 macrophages in the allogeneic transplantation group was higher than those in the sham operation and syngeneic transplantation groups, and the number of M2 macrophages in the syngeneic transplantation group was higher than those in the sham operation and allogeneic transplantation groups, and the differences were statistically significant (all P<0.05). Conclusions Among the allografts with AR after intestinal transplantation, a large number of macrophages, mainly M1 macrophages secreting a large number of pro-inflammatory cytokines, infiltrate into the whole intestinal wall. Regulating the direction of macrophage polarization is a potential treatment for AR after intestinal transplantation.
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Objective:To explore the influencing factors of acute rejection (AR) within one year after pediatric kidney transplantation (KT) and the effect of AR onset time on prognosis.Methods:From January 2011 to October 2021, a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection, 106 cases were examined.There were 63 males and 43 females with the age of 15(12, 16) years.The donors were living related (n=26) and deceased (n=80).According to the presence/absence and onset time of AR, they were assigned into three groups of AR within one year, AR after one year and non-AR.The relevant clinical data of donor/recipient, influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up, the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results:The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups, 19 episodes of AR occurred in 17(16.0%) patients and 89 recipients exhibited no AR episode by the end of follow-up (non-AR group).As for initial AR, 9 episodes of AR occurred within one year (AR within one year group) and 8 episodes of AR after one year (AR after one year group).After anti-rejection treatment, 8 patients (47.1%) achieved full recovery and 6 patients (35.3%) failed to completely normalize and 3 patients (17.6%) developed graft failure.Univariate analysis indicated that, as compared with non-AR group, female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year ( P=0.032, P=0.039, P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55) and 30.0%(3/10) respectively.They were significantly higher than 2.0%(1/51) and 6.3%(6/96) of patients with donors aged above 8 years and those without parvoviral infection ( P=0.012, P=0.004).With graft-function loss as an end-point event of follow-up, Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9% and 65.6%.Both were significantly lower than that in non-AR group (98.9%).And the inter-group differences were statistically significant ( χ2=4.286, P=0.038; χ2=7.787, P=0.005).However, no significant difference existed in survival rate between AR within one year and AR after one year groups ( P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were (76.8±51.6), (80.6±56.6) and (85.6±40.2) ml·min -1·1.73 m -2.The values of 3/6 months were lower than (125.3±39.2) and (124.7±38.2) ml·min -1·1.73 m -2 in AR after one year group.And the inter-group differences were statistically significant ( P=0.021, P=0.039).The values of 3/6/12 months were lower than (112.2±34.2), (115.3±33.2) and (117.4±30.2) ml·min -1·1.73 m -2 in non-AR group.And the inter-group differences were also statistically significant ( P=0.019, P=0.020, P=0.020). Conclusions:Female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.
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Objective:To explore the risk factors related to acute rejection (AR) after pediatric kidney transplantation (KT).Methods:Retrospective analysis was performed for 189 pediatric KT recipients from September 2011 to August 2022.They were divided into two groups of AR (n=33) and non-AR (n=156).Univariate and multivariate Logistic regression analyses were performed for identifying potential risk factors of AR.And the effects of AR on graft function and survival were also examined.Results:During follow-ups, a total of 33(17.5%) patients developed AR with a 1-year cumulative incidence of AR of 16.9%(32/189).Univariate analysis revealed that median time on dialysis was longer in AR group than that in non-AR group (19 vs. 11 months, P=0.034).Median age of donors (12 vs. 24 months, P=0.033), median weight of donors (9.5 vs. 12 kg, P=0.025) and median donor/recipient body weight ratio (0.36 vs. 0.50, P=0.005) were lower in AR group than those in non-AR group.And the proportion of subtherapeutic tacrolimus (TAC) trough level was higher in AR group than that in non-AR group (45.5% vs. 21.2%, P=0.004).Multivariate regression analysis indicated that subtherapeutic TAC trough level was an independent risk factor for AR ( OR=2.977, 95% CI: 1.314-6.743, P=0.009).At the last follow-up, serum creatinine and eGFR were (78.4±24.3) vs. (74.6±24.7) μmol/L and (85.3±26.3) vs. (89.5±24.2) ml·min -1·1.73 m -2 in AR and non-AR groups respectively.There were no significant differences.1/5-year patient survival rate was both 97% in AR group and both 99.4% in non-AR group; 1/5-year graft survival rate both 90.9% in AR group and was 98.1% and 97.4% in non-AR group.No significant inter-group differences existed in patient and graft survival. Conclusions:Although an occurrence of early AR does not negatively impact graft outcomes, the incidence of AR remains high after pediatric KT.Therefore prompt diagnosis and treatment of AR should be strengthened.
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Objective:To explore the efficacy and safety of low-dose rabbit anti-human thymocyte globulin (rATG) for induction therapy of kidney transplantation (KT) in children.Methods:From October 2018 to May 2021, clinical data were reviewed retrospectively for 77 pediatric KT recipients on a low-dose rATG induction protocol.Recipient/graft survival rate, renal function recovery, acute rejection (AR) and adverse reactions were observed at 1 year post-operation.The postoperative changes of renal function were examined by Friedman’s test; According to the preoperative baseline data, Pearson’s Chi-square or Fisher's exact test was utilized for examining the influencing factors of postoperative AR.Results:A total of 16(20.78%) recipients had AR within the first 6 months post-operation.The incidence of delayed graft function (DGF) was 14.29%(11/77); The incidence of severe infection post-transplantation 18.18%(14/77), the infection rate of BK virus 25.97%(20/77) and the incidence of neutropenia 32.47%(25/77).The recipient/graft survival rate at 1 year post-operation was 97.40%(75/77) and 94.81%(73/77) respectively.Chi-square test indicated that the incidence of postoperative infection in children with body weight ≤30 kg and height ≤138 cm was 28.95%(11/38) and 27.50%(11/40) respectively, Both were higher than 7.69%(3/39) and 8.11%(3/37) of children with body weight >30 kg and height>138 cm.The difference between groups was statistically significant ( P=0.016 and 0.028). Conclusions:Low-dose rATG is generally excellent in preventing AR in pediatric KT recipients.And the risk of related AR may be lower.The infection rate of recipients with decent preoperative development is low.
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Objective:To summarize the incidence of acute rejection (AR) after pediatric kidney transplantation (KT) at a single center and examine its impact on graft/patient survival and risk factors for AR.Methods:This is a retrospective cohort study including pediatric recipients who underwent kidney transplantation in past 8 years.After excluding recipients of graft thrombosis within a week post-transplant and lost to follow-ups, a total of 143 cases were ultimately recruited and assigned into two groups of AR (n=29) and non-AR (n=114).Basic profiles of both donors and recipients and graft/patient survival rate were compared between two groups.Relative risk factors for AR episodes were also examined by Logistic regression.Results:Renal grafts for 130/143 cases (90.9%) were harvested from deceased donors and 120(83.9%) cases from children.Twenty-seven transplants (18.9%) were performed in infants and young recipients aged < 3 years.During a median follow-up of 33 months, 34 AR episodes occurred in 29(20.3%) patients.Rate of re-transplantation (27.6% vs. 7.9%), pediatric donor (96.5% vs. 80.7%) and rabbit anti-human thymocyte globulin (rATG) induction (79.3% vs. 36%) were significantly higher in AR group than non-AR group ( P=0.007, P=0.046, P<0.001).Multivariate regression analysis indicated that basiliximab induction caused a significant reduction in the risk of AR incidence as compared with rATG induction (odds ratio 0.13, 95% confidence interval 0.04-0.43, P<0.001).The median time of AR incidence was 1.3 months post-transplantation and 23 episodes (67.6%) were confirmed by biopsy.After anti-rejection treatment, 52.9%(n=18) of the cases achieved a full recovery and 38.3% (n=13) had improved graft function.However, 3 cases (8.8%) developed irreversible graft failure.The 1/3-year graft survival rates were significantly lower in AR group than those in non-AR group (75.3% vs. 95.2%, 68.4% vs. 90.4%, P=0.01), and there was no significant difference in 1-and 3-year patient survival rates between two groups. Conclusions:The incidence of AR is relatively high in pediatric renal transplantation, which has an impact on graft survival.Basiliximab induction can effectively reduce the risk of AR.
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Because of the current national organ allocation policy of "pediatric donor kidneys are given priority to pediatric recipients", Chinese pediatric kidney transplantation has achieved rapid development, but the outcomes of pediatric kidney transplantation need to be further systematically summarized.In this paper, by summarizing the characteristics of children's immune system and related research progress, the incidence and influencing factors of acute rejection after pediatric kidney transplantation, the prevention effects of rabbit anti-human thymocyte immunoglobulin (rATG) and anti-CD25 monoclonal antibody induction therapy on acute rejection after pediatric kidney transplantation were compared, and suggestions were put forward for their future application.
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Background: Liver biopsy plays a crucial role in evaluating allograft dysfunction. Comprehensive analysis of the histological spectrum of complications, particularly rejection, in different time zones is lacking. Aim: To evaluate the histological spectrum of rejection, in four time zones, in a large Living donor liver transplant series. Patients and Methods: Retrospective analysis of 313 biopsies for the last 10 years of living donor liver transplantation (LDLT) recipients. 123 of which had rejection as diagnosis, were redistributed in four time zones [1-early (<3), 2-intermediate (3–6), 3 and 4-late (6–12 and > 12) months] and were assessed for sixteen histological parameters. Results: Biopsies in time zone 1 (26.5%), 2 (20.7%), 3 (24.6%), and 4 (28.1%)] were nearly equal. Multiple coexistent complications existed in 12% of the cases. Rejection diagnosed in time zone groups: 1 = 22 (17.9%), 2 = 27 (22%), 3 = 36 (29.3%), and 4 = 38 (30.9%). Portal inflammation mixed type (P < 0.000), portal vein (P = 0.001) and hepatic vein endothelialitis (P < 0.000), portal eosinophils (P = 0.001), and lymphocytic bile duct damage (P = 0.01) were most pronounced in group 1. Perivenulitis without hepatic vein endothelialitis was observed (P = 0.03) in groups 3, whereas bile duct atypia (P = 0.01) and duct loss (P < 0.000) were observed in group 4. Multiple episodes of rejection displayed significant association with central perivenulitis (P = 0.002) and bile duct loss (P < 0.001). Conclusions: Histological analysis in large series of LDLT recipients highlights the spectrum of complications in different time zones. Late acute and chronic rejection occurred as early as 3 months posttransplant. Central perivenulitis and bile duct atrophy were associated with repeated episodes of rejection and deterioration.
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Objective To evaluate the changes and significance of lymphocyte subsets in the recipients with acute rejection after liver transplantation. Methods The recipients presenting with acute rejection after liver transplantation were assigned into the rejection group (n=17), and their counterparts with stable liver function were allocated into the control group (n=17) according to the ratio of 1∶1 by propensity score matching method. The incidence of acute rejection after liver transplantation was analyzed, and the concentration of tacrolimus in the recipients was compared between two groups. The absolute value and proportion of lymphocyte subsets in peripheral blood were compared between two groups. The diagnostic value of lymphocyte subsets for acute rejection after liver transplantation was assessed by the receiver operating characteristic (ROC) curve. The absolute value and proportion of lymphocyte subsets in the rejection group were compared before and after treatment. Results Among 17 recipients in the rejection group, 4 cases developed acute rejection within postoperative 28 d, and 13 cases had acute rejection within postoperative 29-180 d. No significant difference was noted in the tacrolimus concentration between two groups (P=0.295). Compared with the control group, the proportions of peripheral blood T cells, CD4+T cells, B cells and natural killer (NK) T cells were significantly increased in the rejection group (all P < 0.05). The elevated proportion of NKT cells in the early stage after liver transplantation was an independent risk factor for acute rejection following liver transplantation[odds ratio (OR) 1.774, 95% confidence interval (CI) 1.059-2.971, P=0.029]. ROC curve analysis showed that the area under curve (AUC) of CD4+T cells, B cells and NKT cells was 0.76, 0.73 and 0.77, respectively. The AUC of combined use of CD4+T cells, B cells and NKT cells was 0.89, with a cut-off value of 0.69, sensitivity of 0.706 and specificity of 0.941. After corresponding treatment, all recipients were gradually recovered, and liver functions were eventually restored to normal in the rejection group. After treatment, the proportion of T cells, CD4+T cells, CD8+T cells and NK cells was significantly decreased (all P < 0.05). Conclusions The elevated proportion of NKT cells indicates an increased risk of acute rejection after liver transplantation. Combined use of CD4+T cells, B cells and NKT cells may deliver early detection and diagnosis of acute rejection after liver transplantation.
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Objective:To investigate the effect of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) on the intestinal barrier function in rats with acute rejection of liver transplantation.Methods:Specific pathogen free 2 male Brown Norway (BN) rats (4-5 weeks, 40-60 g) were used to isolat BMMSCs, and HO-1 was infected by adenovirus. Of 24 male Lewis rats (7-8 weeks old, 200-220g) were used as donors, 30 male BN rats (8-9 weeks old, 220-240 g) were used as recipients. Acute rejection models of orthotopic liver transplantation were established in rats using two cuff technique. BN recipient rats were randomly divided into five groups: sham group, abdomen of the mice was open and closed within 30 min; NMP livers were simply mechanically perfused for 4 h; the BMP group were perfused with BMMSCs through the portal vein; the HBP group were perfused with HO-1/BMMSCs through the portal vein; the FK506 livers were mechanically perfused for 4 h and administered intragastrically of tacrolimus daily following surgery, 6 per group, on days 14 after surgery, the relevant indicators were taken and the rejection activity index (RAI) changes were investigated. The changes of intestinal pathological were analyzed by HE staining and transmission electron microscope, the expression levels of zonula occludens-1 (ZO-1) and occludin protein in intestinal tissue were detected by Western blotting, the concentrations of lipopolysaccharide, D-lactic acid and diamine oxidase (DAO) in serum were detected by ELISA.Results:The RAI of HBP group (2.80±0.84) and FK506 group (2.20±0.84) were significantly lower than that of NMP group (7.60±1.14) and BMP group (6.00±1.58), the differences were statistically significant (all P<0.05). The intestinal villi in NMP group were significantly sparse, wrinkled and disorderly arranged while the degree of intestinal injury in BMP group, HBP group and FK506 group were more mitigated. Electron microscope observation showed that the microvilli of intestinal epithelial cells in HBP group were rich and orderly, and the tight junction structure between cells was complete. The protein expression levels of ZO-1 and Occludin in the intestinal tissues of HBP group [(0.87±0.06) (1.28±0.26)] were higher than those of NMP group [(0.41±0.12) (0.27±0.18)] and FK506 group [(0.52±0.15) (0.63±0.22)], the differences were statistically significant (all P<0.05). The concentration of lipopolysaccharide, D-lactic acid and DAO in serum of HBP group was lower than those of NMP group and FK506 group, the differences were statistically significant (all P<0.05). Conclusion:HO-1/BMMSCs combined with NMP protects the intestinal mucosal barrier function of BN rats with acute rejection after liver transplantation.
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Objective To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation. Methods Liver transplantation rat models of spontaneous tolerance [Brown Norway (BN)→Lewis, tolerance group, n=6] and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay. Results Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11+mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11+mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05). Conclusions As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.
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Objective:To establish risk stratifying criteria for acute rejection(AR)after kidney transplantation(KT)through analyzing the preoperative risk factors of KT recipients from deceased donor(DD).Methods:A retrospective study is conducted for 1 382 KT recipients of DD kidney at First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2020.According to the presence or absence of AR within 1 year post-KT, they are divided into two groups of acute rejection(group AR, 115 cases)and non-rejection(group non-AR, 1 267 cases). Clinical data of two groups are examined by univariate and multivariate analyses for determining the risk factors of AR and a scoring standard is established on the basis of regression coefficients.They are divided into three groups of low-risk(907 cases), middle-risk(450 cases)and high-risk(25 cases)according to the scoring results and the incidence of AR is compared among different scoring groups.Results:Univariate analysis indicates that donor age(AR, 793 cases; non-AR, 474 cases, P=0.033), age difference between recipients and donors≥25 years(AR, 63 cases; non-AR; 315 cases; P<0.001), recipient panel-reactive antibodies(PRA)plus donor-specific antibody(DSA)(+ )(AR, 96 cases; non-AR, 1 169 cases, P=0.002), donor kidney cold ischemic time≥12h(AR, 81 cases; non-AR, 1 064 cases, P<0.001), donor/recipient HLA mismatch≥3(AR, 70 cases; non-AR, 984 cases, P<0.001)and expanded criteria donor(ECD)(AR, 50 cases; non-AR, 790 cases, P<0.001)are high risk factors for AR(all P<0.05). Variables with statistical significance during univariate analysis are included for multivariate analysis.Five variables are finally determined, including age difference between recipients and donors≥25 years(β=0.61, P=0.006), PRA+ DSA(+ )(β=0.74, P=0.008), donor kidney cold ischemic time≥12 h(β=0.74, P<0.001), HLA mismatch(≥3)(β=0.81, P<0.001)and ECD(β=0.82, P<0.001). Score for each risk factor is calculated according to the relevant regression coefficient and scoring standard formulate on the basis of the above five risk factors with a total score of 36.With an overall incidence of AR at 8.32%(115/1 382), the incidence of AR is 4.3%, 14.7% and 40.0% in low/middle/high-risk group and the difference is statistically significant.It hints that immune risk stratification can effectively determine the risk of postoperative AR for KT recipients.The incidence of AR is significantly higher in middle/high-risk group than that in low-risk group ( P<0.001). Conclusions:For recipients with middle/high immune risk, intensity and dose of immunosuppressants should be appropriately boosted during preoperative induction and maintenance period.And the occurrences of AR and infection should be dynamically monitored.
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Objective:To evaluate the diagnostic value of multiparametric cardiac magnetic resonance(CMR)or detecting the occurrence of acute rejection(AR)after heart transplantation(HT).Methods:From 2019 to 2021, 44 HT recipients are prospectively recruited from Guangdong Provincial People's Hospital.Another 51 healthy volunteers are recruited from a local community as healthy controls.CMR studies are performed for obtaining baseline parameters.According to the clinicopathological diagnostic criteria of AR by the consensus of International Society for Heart and Lung Transplantation, 81 CMR studies of 44 HT recipients are further divided into two groups of AR (18 cases)and non-AR(71 cases). CMR parameters includ global ventricular structure/function, T2, T1, extracellular volume(ECV)and late gadolinium enhancement(LGE). A combined model is established by binary Logistic regression and receiver operator characteristic curve(ROC)constructed.Results:The age range is(41.8±16.8)years in 44 HT recipients and(41.8±9.7)years in 51 healthy controls.T1 mapping indicated that myocardial global ECV of left ventricle is significantly higher in AR patients than non-AR controls(32.4%±6.0% vs 28.5%±2.4%; P<0.001 9). Global native T1 is higher in AR group than that in non-AR group(49.8±3.1 vs 47.5±2.8 ms, P=0.009)and the difference is statistically significant.The cutoff value of global ECV is 30.62% with a sensitivity of 61% and a specificity of 86% for detecting AR.And T2 mapping reveale that T2 value of global left ventricle is significantly higher in AR group than that in non-AR group(49.8±3.1 vs 47.5±2.8 ms, P=0.009). LGE extent is significantly higher in AR group than those in non-AR group( P=0.004). Through including global native T1 and ECV into a logistic regression model, multiparametric CMR can yield an area under curve(AUC)of 0.794.It hints at the potential of CMR for detecting AR. Conclusions:Multiparametric cardiac magnetic resonance offers an excellent predictive capacity for a noninvasive detection of AR.
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Objective:To explore the clinical data of acute rejection in kidney transplant recipients of different ages with elderly donor kidneys.Methods:During January 2012 and June 2020, a retrospective review was conducted for clinical data of 298 recipients undergoing kidney transplantation from elderly donors aged ≥60 years after citizen's death.According to the age, recipients were divided into group A(age<30 yr, 59 cases), group B(30~39 yr, 125 cases), group C(40~49 yr, 83 cases)and group D(age≥50 yr, 31 cases). The incidence of acute rejection(AR)was analyzed.Also based upon age difference between donors and recipients, they were divided into two groups of(30~39 yr)and (40~49 yr)and the occurrence of AR was recorded.Results:The incidence of AR within 1 year post-transplantation in groups A, B, C, and D were 15.3%(9/59), 8.8%(11/125), 7.2%(6/83) and 3.2%(1/31)respectively.The incidence of AR in age difference≥25 yr group(12.5%)and age difference <25 yr group(5.3%) had significant difference( P<0.05). The proportion and absolute value of peripheral blood lymphocytes in each group at 1 week/month post-transplantation had significant difference( P<0.05). No significant difference was observed in serum level of creatinine(SCr), the incidence of pulmonary infection and urinary tract infection or the survival rate of recipients and transplanted kidneys in each group within 1 year post-transplantation among four groups( P>0.05). Conclusions:Elderly donor kidneys can obtain better transplant outcomes in kidney transplant recipients of different ages.As the age of recipients decreases, AR shows an upward trend.Clinicians should pay more attention to the prevention and treatment of AR in recipients with large age difference between donors and recipients.
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BACKGROUND: The expression of long chain non-coding RNA PGM5-AS1 (lnc RNA PGM5-AS1) is reduced in peripheral blood of patients with acute immune rejection after renal transplantation. The effect of its expression on human glomerular endothelial cell (HRGEC) survival and macrophage chemotaxis remains to be studied. OBJECTIVE: To investigate the expression of lnc RNA PGM5-AS1 in serum of patients with acute rejection of renal transplantation and non-acute rejection patients and its effect on proliferation, cell cycle, apoptosis and macrophages chemotropism of HRGECs. METHODS: Forty-six patients with renal transplantation were divided into acute rejection group (n=17) and non-acute rejection group (n=29) according to whether or not acute rejection occurred within 1 month after operation. Peripheral blood sample was drawn from each patient at 1 day before operation, 1, 2, 3, and 4 weeks after operation. qRT-PCR was used to detect the expression of PGM5-AS1 in serum of patients with or without acute rejection. si-control and si-PGM5-AS1 were transfected into glomerular endothelial cells, and the expression of PGM5-AS1 in the transfected cells was detected by qPCR. MTT was used to detect cell proliferation, flow cytometry was applied to detect apoptosis and cell cycle, ELISA was adopted to detect cellular inflammatory factor secretion, and Transwell was used to detect chemotaxis of macrophages. Approval for this study was obtained from the Ethics Committee of Zhengzhou People’s Hospital, and all patients signed informed consent prior to the participation in the trial. RESULTS AND CONCLUSION: Compared with non-acute rejection patients, patients with acute rejection to renal transplantation had significantly lower PGM5-AS1 expression in serum at 1, 2, 3, and 4 weeks after transplantation (P <0.05). After PGM5-AS1 silencing, the expression of GM5-AS1 in HRGEC cells was significantly lower than that in the si-control group and normal control group (F=379.658, P < 0.05). MTT results showed that PGM5-AS1 silencing significantly inhibited HRGEC cell proliferation (P < 0.05). Flow cytometry results showed that PGM5-AS1 silencing induced HRGEC cell arrest in G0/G1 phase and increased apoptosis (P < 0.05). ELISA results showed that PGM5-AS1 silencing inhibited interleukin-13 expression and increased interleukin-6, interferon-γ and tumor necrosis factor-α expression (P < 0.05). Transwell results indicated that HRGEC cells silenced by PGM5-AS1 significantly increased the chemotaxis of macrophages (P < 0.05). All these findings indicate that PGM5-AS1 is lowly expressed in serum of patients with acute rejection of renal transplantation, and inhibition of PGM5-AS1 can promote HRGEC cell damage, which can be used as a peripheral blood diagnostic marker for early acute rejection, and may be a molecular target for the treatment of acute rejection.
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Lung transplantation is the only effective therapeutic option for end-stage lung diseases, and postoperative rejection is the main factor affecting clinical prognosis of the recipients. Imaging examination can be utilized as a noninvasive tool to assist other examinations in monitoring rejection after lung transplantation. At present, multiple imaging examination methods have been reported. The advantages and disadvantages of various imaging examinations have been clarified, which may promote early diagnosis of rejection, deliver timely treatment for lung transplant recipients and improve the quality of life and clinical prognosis. In this article, the advantages, disadvantages and research progress upon different imaging examinations for rejection after lung transplantation were reviewed, aiming to provide reference for identifying the optimal noninvasive examination approach for rejection after lung transplantation and enhance the long-term survival of the recipients.