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Background: Acute rejection occurs at any time following renal transplantation. The study aims to find the incidence, risk factors, and outcome of acute rejection in kidney transplantation. Materials and Methods: Retrospective cohort study conducted from January 2015 to April 2023, included patients with biopsy-proven acute graft rejection. Data were collected from electronic medical records. Rejection and no rejection groups were compared for the variables. Results: Out of 371 patients, acute rejection occurred in 36 (9.7%) patients at 1 year of transplantation. Thirty (8%) were early acute rejections (EARs) and 22 (6%) were late acute rejections (LARs). Higher human leukocyte antigen (HLA) mismatches, historical positive crossmatch, and history of blood transfusions were risk factors for acute rejection (P < 0.05). Incidence of LAR beyond 1 year was 11/23 (48%) in those who had received induction therapy at transplantation versus 5/29 (17.2%) in those who did not (P = 0.045). One out of five patients (3.4%) who received antithymocyte globulin (ATG) experienced EAR, in contrast to 8/18 (5.2%) patients who received basiliximab (P = 0.037). A complete response to treatment was observed in 22/30 (73.3%) patients with EAR and 2/22 (9.09%) with LAR (P < 0.001). At 23.77 ± 24.6 months of follow-up, graft survival was 12/12 (100%) in those with early T-cell-mediated rejection (TCMR) compared to 5/9 (55.6%) with late acute TCMR (P = 0.01). Conclusion: The incidence of acute rejection was highest within the first posttransplant year. Higher HLA mismatches, historical positive crossmatch, and history of blood transfusion were risk factors for acute rejection. ATG was effective in preventing EAR. LAR occurring beyond the first posttransplant year was independent of induction therapy at time of transplantation. Treatment response was better with EAR compared to LAR. Graft survival was better with early acute TCMR compared to late acute TCMR. [ABSTRACT FROM AUTHOR]

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 ( 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.

Introduction: Late acute rejection (LAR) is different from early acute rejection with respect to risk factors, management, and prognosis. The long-term graft survival has been shown to be adverse after LAR. Materials and Methods: This was a prospective study including 15 biopsies reported as LAR in 12 patients. The clinical details, transplant duration, risk factors, biopsy findings, antirejection treatment, and outcome are studied. Results: The risk factors for developing LAR in our study included delayed graft function, associated infections, and noncompliance. Majority were combined cellular and antibody mediated. Antibody-mediated rejection (ABMR) component was identified in 13 biopsies. Plasma cell-rich form was seen in four biopsies. Most of the patients had persistent graft dysfunction with five of them going into graft loss. Conclusion: It is important to identify LAR, especially late ABMRs. They are different from chronic rejections. The graft outcome was found to be poor.

Object: Rejections observed in live donor liver transplants (LDLT) after the 6th month are defined as "late acute rejection" (LAR). Liver biopsy is still the gold standard for diagnosis of these cases. However, considering the morbidity and complications caused by this biopsy, can the non-invasive elevated serum eosinophil count be used as a predictive biomarker for LAR? Materials and Methods: Our research included patients with LDLT performed from June 2000 to June 2017 at Dokuz Eylül University Faculty of Medicine General Surgery Liver Transplant Unit, aged over 18 years and surviving at least 6 months. Patients developing late acute rejection were investigated in terms of demographic data, necessary graft weight/graft weight present ratio, cold ischemia duration, Child and MELD scores, doses of immunosuppressive agents before rejection, serum therapeutic levels and comorbidities. Our study retrospectively screened blood laboratory samples before biopsy and pathologic results of liver biopsies performed on patients with suspected LAR. Elevated serum eosinophil values were investigated and their effective role in diagnosis of LAR was researched. Results: Of 240 liver transplant cases included in the study, 65 (26.9%) had liver biopsy performed due to consideration of rejection linked to elevated liver function tests during follow-up. Of the biopsy transplant cases, 28 (43%) had LAR identified, while 37 (57%) had no finding of rejection encountered. The distribution of rejection in cases with rejection diagnosis was 10 (35.7%) mild, 13 (46.4%) moderate and 5 (17.9%) severe according to Banff pathology scoring. Of patients 21 (75%) were male and 7 (25%) were female. The mean follow-up duration was 3056 days (184-4877). The mean time of liver biopsy was the postoperative 660th day (180- 4354). There was a statistically significant correlation identified between elevated eosinophil count found in blood laboratory values before biopsy with LAR (p<0.001). Discussion and Conclusion: For diagnosis of LAR which may occur during follow-up of LDLT, the non-invasive method compared to liver biopsy of elevated serum eosinophil values may be used as a predictive marker. [ABSTRACT FROM AUTHOR]

Introduction: Late acute rejection (LAR) is different from early acute rejection with respect to risk factors, management, and prognosis. The long-term graft survival has been shown to be adverse after LAR. Materials and Methods: This was a prospective study including 15 biopsies reported as LAR in 12 patients. The clinical details, transplant duration, risk factors, biopsy findings, antirejection treatment, and outcome are studied. Results: The risk factors for developing LAR in our study included delayed graft function, associated infections, and noncompliance. Majority were combined cellular and antibody mediated. Antibody-mediated rejection (ABMR) component was identified in 13 biopsies. Plasma cell-rich form was seen in four biopsies. Most of the patients had persistent graft dysfunction with five of them going into graft loss. Conclusion: It is important to identify LAR, especially late ABMRs. They are different from chronic rejections. The graft outcome was found to be poor. [ABSTRACT FROM AUTHOR]

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., Competing Interests: None

Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non-immune-related post-transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long-term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival. [ABSTRACT FROM AUTHOR]

Background: In the early post-transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post-transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post-transplant, has any impact on graft survival and function. Methods: We selected cases, both cadaveric as well as living donor renal transplant recipients, in whom acute rejection with PTC C4d deposition was first detected after the first year post-transplant. Recipients with multiple acute rejection episodes during the first year post-transplant were excluded from the study. The first biopsy diagnosed with LAR was considered the index biopsy (n = 40). We formed two groups: group 1, C4d-positive LAR (n = 20), and group 2, C4d-negative LAR (n = 20). Groups were matched for maintenance and post-rejection immunosuppressive therapy, baseline serum creatinine levels before the time of the index biopsy, time from transplant to index biopsy, as well as chronic allograft damage index (CADI) score in the index biopsies. We compared the rate of graft loss, and the graft function of the surviving grafts at the end of the study period, as well as histologic parameters in the index biopsy specimens between the two groups. The mean follow-up period was 20 months. Results: No significant differences in the rate of graft loss or graft function were found between groups 1 and 2 at the end of the follow-up period. Histologically, PTC margination and transplant glomerulopathy were more common in the C4d-positive group, and this difference was statistically significant. There was no statistically significant difference in the degree of plasma cell infiltrates. Conclusions: Unlike in the acute setting, the presence or absence of PTC C4d staining in renal allografts with LAR may not have a predictive value regarding graft outcome. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the clinical and pathologic features of C4d-positive steroid-resistant acute rejection (AR) at different phases after renal transplantation. Fifty-six kidney allograft recipients with C4d-positive AR were divided into three groups, very early rejection (VER, occurring 14 days following transplantation, n=28), early rejection (ER, occurring 15–180 days following transplantation, n=5), and late rejection (LR, occurring >180 days following transplantation, n=23). Clinical and pathological features were evaluated. Significantly more patients in the ER and LR groups were associated with a reduction or withdrawal of immunosuppressants. More patients in the ER and LR groups experienced a significant (>3 g/l) decrease in serum albumin (80% ER, 91.3% LR, 7.1% VER, P<0.001) and a decrease in hemoglobin (>1 g/dl) (80, 100 vs 17.9%, P<0.001). Most VER patients reported a fever and had very rapid graft dysfunction requiring dialysis. Significantly more patients (87%) had interstitial fibrosis and tubular atrophy in the LR group compared with the other groups and 13% had transplant glomerulopathy. Most cases of VER were reversed with tacrolimus and mycophenolate mofetil treatment, with or without immunoadsorption, with a 1-year survival rate of 96.4%, compared with only 60 and 52.2% in the ER and LR groups. In conclusion, C4d-positive steroid-resistant AR at different time points is associated with unique clinico-histopathological manifestations requiring distinct treatment strategies. Late episodes are usually associated with significantly reduced serum albumin and hemoglobin levels and a poorer outcome. A more specialized treatment protocol should be established for these patients.Kidney International (2006) 70, 377–383. doi:10.1038/sj.ki.5001552; published online 7 June 2006 [ABSTRACT FROM AUTHOR]

Introduction: We examined the relationship between late acute rejection (LAR) after cadaveric kidney transplantation and medical compliance utilizing a modified version of the Long-term Medication Behaviour Self-efficacy Scale (LTMBS-scale), a validated patient self-report questionnaire. The original LTMBS-scale uses a five-point scale, however, our pilot study showed that patients found it difficult to discriminate between the five options. We therefore modified this to a three-point scale. Patientsand methods: We carried out a retrospective analysis of all patients who received a kidney transplant in our unit in the cyclosporin (CyA) era. We divided rejections into early and late rejection based on the time interval after transplantation. Graft rejection was confirmed by biopsy; LAR was defined as acute rejection occurring after 90 d. We retrospectively administered the modified LTMBS-scale to determine individual patient confidence and self-efficacy in taking their medications in a variety of situations (home, work, leisure, psychological and physical). Individual patient confidence and self-efficacy was analysed in relationship to compliance behaviour. Results: Twenty-four questionnaires were distributed, 22 (92%) were returned fully completed. The overall results suggested that our patients surveyed were not particularly confident (mean score 2.17 out of maximum possible 3) in taking their medications in a variety of contexts. They demonstrated significantly less confidence (mean score 1.0) when experiencing physical (brittle bones, feeling `ill') and psychological (`sadness') side-effects of medication and emotional reactions to the experience of chronic illness. Conclusion: Negative physical and psychological states were related to low self-efficacy with the taking of immunosuppressive medication, non-compliance and subsequent LAR in our cohort of patients. [ABSTRACT FROM AUTHOR]

Background: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term graft and patient outcome of AR occurring late in the post-transplant period. Aim: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR). Materials and methods: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival. Analysis: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared. Results: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy-eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5-yr graft survival for those who had LAR was 45% and 10-yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA-DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency... [ABSTRACT FROM AUTHOR]