History Of Acute Rejection Research Articles

Very Low Frequency of Pathological Findings in One-year Protocol Biopsies of Uneventful Standard Risk Kidney Transplant Recipients: Results From the Nordic Protocol Biopsy Study.

The clinical significance of kidney transplant protocol biopsies has been debated. We studied the frequency of borderline changes and T cell-mediated rejection (TCMR) in 1-y protocol biopsies in standard risk kidney transplant recipients. Consecutive non-HLA-sensitized recipients of kidney transplants between 2006 and 2017, who underwent a protocol biopsy at 1 y in 2 national transplant centers were studied retrospectively (N = 1546). Donor-specific HLA antibodies (DSAs), graft function (plasma creatinine), and proteinuria were measured at the time of 1-y protocol biopsy. The occurrence of subclinical acute TCMR (i2t2v0 or higher) or borderline changes suspicious of TCMR (i1t1v0 or higher) in the protocol biopsy was studied, together with frequency of findings causing changes in the composite score iBox. Subclinical acute TCMR was detected in 30 of 1546 (1.9%) of the protocol biopsies, and borderline or TCMR in 179 of 1546 (12%). Among patients with no history of acute rejection, and no proteinuria or DSA, TCMR was detected in only 1 of 974 (0.1%) and borderline or TCMR in only 48 of 974 (4.9%) patients at 1 y. In the absence of proteinuria (<30 mg/g, or equivalent as measured with a negative dipstick proteinuria) or DSA, or history of acute rejection, only 50 of 974 (5.1%) biopsies showed any lesions significant for the iBox score. The likelihood of pathological findings in 1-y protocol biopsies in non-HLA-sensitized patients without previous immunological events is low. Clinical usefulness of protocol biopsies seems limited in these patients.

The Relationship between Acute Rejection, Hemoglobin Level, and BK Virus Infection Among Renal Transplant Recipients.

This study aimed to explore the risk factors for BK virus (BKV) infection in renal transplant recipients (RTRs) routinely treated with tacrolimus. Forty-two cases with BKV infections and 51 patients without BKV infections were enrolled in the study. Eighty-seven healthy individuals and 77 patients undergoing dialysis were randomly included as controls. A logistic regression model was used to analyze potential variables in order to evaluate factors related to BKV infection in the renal transplant recipients. The number of individuals with acute rejection in BKV positive RTRs is significantly higher than that in BKV negative RTRs. Hemoglobin levels in BKV positive RTRs were significantly lower than those in BKV negative RTRs (109.61 ± 20.11 vs. 130.16 ± 26.297, p < 0.001). There was a positive correlation between tacrolimus levels and hemoglobin concentration in RTRs (r = 0.329, p = 0.023). The results of a multivariate regression analysis indicated that a history of acute rejection (OR = 4.157, p = 0.031) and low hemoglobin (OR = 0.963, p < 0.001) were risk factors for BKV infection. Acute rejection and low hemoglobin were risk factors for BKV infection after renal transplantation.

Prevalence of frailty and associated factors among kidney transplant recipients

Objective: To investigate the prevalence of frailty among kidney transplant recipients and to analyze the influential factors of frailty after kidney transplantation. Methods: We retrospectively included 201 kidney transplant recipients who were followed up in the Department of Urology, Beijing Chao-yang Hospital, Capital Medical University from November 2020 to May 2022. We investigated the prevalence of frailty based on the Fried Frailty Scale (including unexpected shrinking, slow walking speed, poor grip strength, low physical activity, and exhaustion). Then the logistic regression model and CART decision tree model were established separately to explore the influential factors of frailty after kidney transplantation. Results: Frail kidney transplant recipients accounted for 25.9% (n=52) of all participants. The age [M (Q1, Q3)] of the frailty group was higher than that of the non-frailty group, and the median ages of the two groups were 57(49, 62) and 46(38, 56) (P<0.001); the males accounted for 51.9% (n=27) and 62.4% (n=93), respectively. There was no significant difference in gender composition (P=0.244). Among the five components of Fried Frailty Scale, the incidence of unexpected shrinking was the lowest (19.4%, 39/201). In the frailty group, the frailty combination with the highest incidence was slow walking speed+low physical activity+exhaustion, which was 19.2% (10/52). The logistic regression model showed that advanced age (OR=1.062, 95%CI: 1.005-1.123), history of acute rejection (OR=16.776, 95%CI: 2.288-123.028), increased neutrophil/lymphocyte ratio (NLR) (OR=2.096, 95%CI: 1.158-3.792), and comorbidity (OR=10.600, 95%CI: 1.828-61.482) were risk factors for frailty among kidney transplant recipients, and high serum albumin level (OR=0.623, 95%CI: 0.488-0.795) was a protective factor. The CART decision tree grew in three layers with four terminal nodes, and three explanatory variables were screened out: serum albumin, NLR, and age. The accuracy, sensitivity, and specificity of the logistic regression model were 87.1% (95%CI: 82.5%-91.7%), 69.2% (95%CI: 54.7%-80.9%), and 93.3% (95%CI: 87.7%-96.6%), respectively. The area under the ROC curve (AUC) of the logistic regression model was 0.951 (95%CI: 0.923-0.978). The accuracy, sensitivity, and specificity of the CART decision tree model were 91.0% (95%CI: 87.0%-95.0%), 82.7% (95%CI: 69.2%-91.3%), and 94.0% (95%CI: 88.5%-97.0%), respectively. The AUC of the CART decision tree model was 0.883 (95%CI: 0.819-0.948). Conclusions: The prevalence of frailty among kidney transplant recipients in this study is 25.9%. Advanced age, history of acute rejection, low serum albumin level, increased NLR, and comorbidity are likely to be associated with the long-term frailty among kidney transplant recipients.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020.Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients

PurposeOne of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation.Materials and methodsThis is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression.ResultsAmong the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01–1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86–0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05–40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29–53.20; p = 0.026).ConclusionPatients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Pediatric kidney retransplantation focused on surgical outcomes

Despite survival rates after pediatric kidney transplantation (KT) are on the rise it is still likely that most pediatric recipients will require more than one retransplant in their lifetime. The earlier the age at the first KT the higher is the risk of repeat pediatric kidney transplantation (RPKT). The current study aims to analyze the outcomes of repeat pediatric kidney transplantation (RPKT) among pediatric kidney transplant recipients focusing on surgical complications and compare the outcomes of second and subsequent grafts with those of the first kidney graft. Retrospective study of RPKT (<18 years) undertaken between January 2000-2020. We analyzed primary etiology of renal disease, time to graft loss (GL), etiology of initial graft failure, history of acute rejection, previous delayed graft function, HLA-mismatches at the initial transplant, surgical complications and outcomes. Additionally, we compared the characteristics and outcomes of patients who underwent RPKT (group 1) with those who received a first kidney graft (group 2). Out of 229kT, 59 patients underwent RPKT (26 females/33 males). At the time of RPKT median age was 11.37 years (SD:5.7). The most frequent primary renal disease was congenital nephrotic syndrome in 11 (18.6%). Fifty-four (91.5%) were on renal replacement therapy at the time of transplant. Fourty-one patients received their second KT (69.5%), 14 (23.7%) the third, 3 (5.1%) the fourth and 1 (1.7%) the fifth. Transplant graft nephrectomy (GN) was performed in 26 patients (44.1%) prior to retransplantation. Fifty-four (91.5%) received a cadaveric graft and 5 (8.5%) a living-related graft. An extraperitoneal approach was achieved in 53 patients (89.8%), whereas in the remaining 6 (10.2%) the graft was placed intraperitoneally. We observed 10 surgical complications (16.9%): 9 major which required reintervention and 1 minor (perirenal hematoma). No vascular complications were observed and none of the surgical complications were involved in graft loss. Graft survival at 1,3 and 5 years was 91%, 84% and 73% respectively. The most frequent cause of GL was chronic graft nephropathy in 15 (25.4%). After a mean follow-up of 9.40 years (SD: 4.7) only 2 patients died (3.4%), both with functioning grafts. Pediatric recipients of second and subsequent kidney grafts constitute a remarkable high-risk population but are becoming more frequent at reference pediatric transplant centers. RPKT is technically challenging but can yield good results. In our series overall the incidence of surgical complications and particularly vascular complications was low.

MO986: Incidence And Predictors of Post-Transplant De-Novo Malignancy: A Single-Centre Retrospective Cohort Study

Abstract BACKGROUND AND AIMS Improvement in short to medium term kidney transplant outcomes and increasingly successful transplantation older patients have led to increasing occurrence of long-term complications of transplantation. Amongst these complications, cancer has become an important cause of mortality following kidney transplantation necessitating the need to better understand the risk factors for the development of de novo malignancy. This study aimed to evaluate the prevalence and the risk factors of de-novo malignancy in a single UK tertiary nephrology centre. METHOD This retrospective cohort study included all kidney transplant recipients (KTR) at our centre, that underwent kidney transplantation between 2000 and 2020 and followed up at our centre. The incidence and types of malignancies excluding non-melanoma skin cancer (NMSC) were analysed. The characteristics of KTR with post-transplant malignancy (excluding NMSC) were compared to those without post-transplant malignancy. Univariate and multivariate logistic regression analyses were conducted to identify the risk predictors of post-transplant cancers. Graft survival and dialysis free survival and death with functioning graft were assessed using Kaplan-Mayer analysis and Cox-regression. RESULTS We analysed the records of 962 KTR (mean age = 47 ± 15 years), followed-up over a median period of 16 years. About 365 (38%) were women, and 783(81%) were Caucasian. 268(32%) had a pre-emptive transplant and 277(29%) had a live donor transplant. Post-transplant malignancy was diagnosed in 84(9%) KTR. KTR with post-transplant cancers were likely to be older (53 ± 14 versus 47 ± 15 years; P = 0.004), on long-term steroid maintenance therapy (64% versus 47%; P = 0.004) and have a history of post-transplant DNA virus infection (40% versus 29%; P = 0.029). Conversely, those with cancers are less likely to be on mycophenolic acid (MPA) therapy (65% versus 78%; P = 0.023). The most common cancers diagnosed were genitourinary cancers (27%) followed by gastrointestinal (24%) and haematological cancers (24%). Respiratory, neurological and others accounted for 10%, 2.4% and 11% of the diagnosed cancers. In multivariate logistic regression analysis, increasing risk of post-transplant cancer was associated with older age at transplantation [OR: 1.81 (1.3–2.5; P &amp;lt; 0.001)], male gender [OR 2.3 (1.3–8.3; P = 0.01)], corticosteroid maintenance [OR 2.3 (1.1–5.2: P = 0.03)], Tobacco smoking [OR: 3.33 (1.2–8.9: P = 0.01)], higher Baseline estimated glomerular filtration rate (eGFR), [OR: 1.2 (1.0–1.4; P = 0.02)], and post-transplant DNA-virus infection [OR: 2.3 (1.0–5.1; P = 0.02)] (Figure 1). There was no difference in the death censored graft survival between the cancer group and the no-cancer group (log-rank, P = 0.51). However, those with cancers had a significantly worse dialysis free survival (log-rank; P = 0.04) and significantly higher death with functioning graft (log-rank; P = 0.02). In the multivariate Cox regression, adjusted for several confounders, dialysis free survival did not differ significantly between the cancer and non-cancer groups (adjusted hazard ratio; aHR: 1.6; P = 0.10). However, age (aHR: 1.16; P = 0.01), male gender (aHR: 1.6; P = 0.01), cardiovascular disease (CVD) (HR: 1.6; P = 0.01) and acute rejection (aHR: 1.7; P = 0.02) were predictors of lower dialysis free survival. CONCLUSION Post-transplant cancers occurred in 9% of our cohort during a median follow-up of 16years. Genitourinary cancers were the most commonly occurring cancers. Older age, male gender, corticosteroid maintenance, smoking and DNA virus infections were the risk factors of malignancy. There was no significant difference in dialysis free survival between the cancer group and the no cancer groups. Lower dialysis free survival was predicted by age, gender, CVD and a history of acute rejection.

Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach

Background: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. Aim: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C0/D) over 6–12 months on reduced estimated glomerular filtration rate (eGFR) values in the late period after kidney transplantation (Tx), applying Monte Carlo (MC) simulation. Methods: The previously published linear regression was the basis for MC simulation, performed to determine how variations in significant predictors affect the distribution of eGFR from 13 to 36 months post-transplantation. The input C0/D values were derived from CYP3A5 genotype subgroups. Results: Patients characterized by high Tac IPV and low mean C0/D over 6–12 months could have been at greater risk of lower eGFR values in a three-year period following Tx compared to the other patient groups. This effect was more pronounced in patients with a lower eGFR at the 6th month and a history of acute rejection. The proven contribution of CYP3A5 expresser genotype to low C0/D values may suggest its indirect effect on long-term graft function. Conclusion: The findings indicate that simultaneous assessment of Tac IPV, C0/D, and CYP3A5 genotype may identify patients at risk of deterioration of graft function in the long-term post-transplantation period.

Acute T cell-mediated rejection after administration of the BNT162b2 mRNA COVID-19 vaccine in a kidney transplant recipient without a history of acute rejection for 13 years: a case report

Acute T cell-mediated rejection after administration of the BNT162b2 mRNA COVID-19 vaccine in a kidney transplant recipient without a history of acute rejection for 13 years: a case report

Underlying Causes and Risk Factors of Chronic Renal Allograft Dysfunction Among Renal Transplant Recipients

Objective: Dialysis or renal transplantation are the two treatment options for end-stage renal disease patients. Renal transplantation from an appropriate donor increases survival and quality of life compared to treatment with dialysis. Recent advances in immunosuppressive therapy have significantly improved the success in 1-year graft survival. However, the long-term graft survival remains the same. Therefore, we aimed to determine the underlying causes and risk factors of chronic allograft dysfunction in renal transplant recipients.&#x0D; Materials and Methods: From 2000 to 2012, all consecutive renal transplant recipients followed in our tertiary referral center who underwent renal biopsy due to an increase in serum creatinine level were enrolled. Etiologies of chronic allograft dysfunction were assessed according to pathologic results of renal biopsy specimens and laboratory findings. The immunological and non-immunological risk factors of chronic allograft dysfunction were screened and recorded retrospectively.&#x0D; Results: Eighty (80) renal transplant recipients with a mean age of 38±10 years were included in the study. Delayed graft function (p=0.007), history of acute rejection (p&lt;0.001), positive panel reactive antibody (p=0.033) (Class I (p=0.013), Class II (p=0.006)), positive donor specific antibodies (p=0.001), number of recurrent acute rejections (p&lt;0.001), number of human leukocyte antigens mismatches (p=0.051), cold ischemia time (p=0.001) were found to be risk factors for chronic allograft dysfunction. The donor specific antibodies positivity (p&lt;0.001) and the panel reactive antibody positivity (Class I (p=0.003), Class II (p=0.001)) were significantly higher in patients with antibody mediated rejection than patients without antibody mediated rejection (p=0.002).&#x0D; Conclusion: Delayed graft function, presence and the number of acute rejections, increased cold ischemia time, panel reactive antibody positivity, donor specific antibodies positivity, and the number of human leukocyte antigens mismatches were risk factors for chronic allograft dysfunction.

The retrospective analysis of urinary tract infection in renal transplant recipients

Infection is the most common reason for admission to the emergency department in the early period after transplantation. Urinary tract infections (UTIs) in adult kidney transplant patients are common. Their incidence is significantly higher than in the general population.1 The majority of sepsis cases in this period are composed of UTIs.2 While mild UTIs generally do not affect graft function, acute pyelonephritis observed in the post-transplant period causes a decrease in graft function and an increase in mortality.3 In the literature, a small amount of data has been published regarding the incidence, epidemiological features, and risk factors of UTIs in kidney transplant recipients. In this retrospective study, we evaluated the data of 550 patients who underwent kidney transplantation between January 2006 and May 2019 at our center and analyzed UTIs' characteristics.&#x0D; Among 550 recipients, 633 episodes were detected in 200 patients (36.4%). Recurrent infection was encountered in 74 (37%) of 200 patients. We determined 1 episode in 63 (31.5%), 2 episodes in 39 (19.5%), 3 episodes in 31 (15.5%), 4 episodes in 14 (7%), 5 episodes in 10 (5%), 6 episodes in 8 (4%), and 7 or more episodes in 35 (17.5%). While 48.3% (n=306) of 633 episodes were asymptomatic bacteriuria, 51.6% (n=327) was symptomatic. The risk factors for UTI were female gender, the advanced age of transplant and advanced donor age, long-term dialysis period before transplant, prolonged urinary catheterization and hospitalization time after transplant, cytomegalovirus infection, vesicoureteral reflux, and neurogenic bladder history. At the survival analysis, a transplant from living donor, female gender, use of tacrolimus, mycophenolate mofetil and corticosteroid combination as maintenance immunosuppressive therapy, preemptive transplant compared to patients receiving peritoneal dialysis was found to be associated with longer survival; advanced age of transplant, obesity, delayed graft function, acute rejection, diabetes mellitus and a history of cytomegalovirus infection was also associated with a shorter life span. Escherichia coli (64.9%) and Klebsiella pneumonia (51.6%) were the most common causative microorganisms, and ESBL (Expanded Spectrum Beta-Lactamase) was positive in 19.9% and 67.5% of them, respectively. &#x0D; Similarly, female gender, the advanced age of transplant, prolonged catheterization time, history of vesicoureteral reflux, neurogenic bladder, acute rejection, and deceased donor were dependent risk factors for developing of UTI in transplant recipients in other studies,4-6 but not body mass index, history of diabetes mellitus, dialysis type and duration, primary kidney disease, donor type, delayed graft function, and history of acute rejection in another study.7 UTI frequency in the female gender increases due to anatomical differences such as the shorter urethra compared to men and its relative proximity to the perianal region and vulva, as in the general population. Age-related changes in the urinary tract and existing additional diseases are important factors that predispose to bacterial colonization. Prolonged urinary catheterization and hospitalization durations facilitate pathogen entry into sterile body parts in the post-operative period. Immunosuppression, frequent hospitalizations, and surgical interventions increase the risk of nosocomial infections in dialysis patients. A history of vesicoureteral reflux facilitating bacterial invasion and a neurogenic bladder causing urinary stasis poses a UTI risk. &#x0D; Hospitalizations for septicemia are most commonly associated with UTI.8 In our cohort, antibiotics in the carbapenem group, started in more than half of the episodes. There is an increase in trimethoprim/sulfamethoxazole, ciprofloxacin and ceftazidime resistance in Klebsiella species.9 Although the microorganism spectrum in the studies is similar all world, ESBL positivity is noticeably higher than the average in UTI episodes is an observation in parallel with the increasing antibiotic resistance both in our country and in the world in recent years. This observation was considered as a cautionary finding for the review of antibiotic selection preferences in our clinic. Finally, UTIs being a threat to graft and patient survival in the post-transplant period should be treated effectively by carefully evaluating risk factors.

Low rate of COVID-19 pneumonia in kidney transplant recipients-A battle between infection and immune response?

BackgroundWith COVID‐19 pandemic, concerns about kidney transplant recipients are rising. However, the incidence, clinical course, outcome, and predictive factors of disease severity are obscured.MethodsWe describe clinical and laboratory manifestations, radiologic findings, clinical course, and finally outcome of kidney transplant recipients with COVID‐19 pneumonia.ResultsOf 2493 kidney transplant recipients under follow‐up in our clinic, 19 cases (4 cases diagnosed based on radiologic findings) were admitted. The mean age of patients was 47.6 ± 12.4 years, and the mean time from transplantation was 115.6 ± 70.3 months. Lymphopenia and eosinopenia were 84.2% and 78.9%, respectively. Nine patients did not survive the hospital course. History of acute rejection during the past 12 months, diabetes, higher N/L ratio, lower platelet count, elevated N/L x CRP, higher levels of LDH, positive D‐dimer, higher troponin, and prolonged PT were associated with mortality. Among patients with positive COVID‐19 test, history of acute rejection, low platelet count, and positive D‐dimer were associated with poor outcome. Treatment with cyclosporine was associated with better clinical outcome.ConclusionsLow rate of admission in transplant recipients specially in the very first years of transplantation might be due to protective effects of immunosuppressive agents against cytokine storm or modification of immunity function. We suggest evaluation of T‐cell number, function, and cytokine profile as a guide to manage COVID‐19 mainly in patients with higher risk of mortality.

MON-164 CLINICAL AND PATHOLOGICAL ANALYSES IN CASES OF TRANSPLANT GLOMERULOPATHY AFTER KIDNEY TRANSPLANTATION IN MONGOLIA

Transplant glomerulopathy (TG) is included as one of the criteria of chronic active antibody-mediated rejection (c-AMR) in Banff 09 classification. TG is a morphologic lesion of renal allografts that is characterized histologically by duplication and/or multilayering of the glomerular basement membrane (GBM). TG is well documented to be associated with the presence of donor-specific antibodies (DSAs), most notably against HLA class II antigens, and in the majority of cases is felt to represent a morphologic manifestation of chronic antibody-mediated rejection (ABMR). The First Central Hospital of Mongolia is the only hospital that perform Kidney transplantation (KT) in Mongolia. We perform 20 KT per year and currently we performed total of 164 KT in end stage kidney disease patients in our hospital. In addition, we follow-up nearly 400 kidney transplanted patients in our clinic (including patients had transplantation in overseas). In this report, we discuss the clinical and pathological analyses of cases of TG after renal transplantation. TG was diagnosed in 10 renal allograft biopsy specimens (BS) obtained from transplant patients who was under follow up at our clinic between 2017 and 2018. We checked DSA and stained the specimens with H&E, masson's trichrome, PAS, silver staining and used Banff 09 classification. Immunofluorescence and C4d stainings were also done. Among the 10 patients,20% had a history of acute rejection (AR); of these,10% had acute antibody-mediated rejection (a-AMR).Among the 86 BS of TG,the TG was mild in 35 cases (cg1),moderate in 28 cases (cg2) and severe in 23 cases (cg3).Peritubular capillaritis was present in 74 bs (86%), transplant glomerulitis in 65 (76%),interstitial fibrosis and tubular atrophy (if/ta) in 71 (83%),thickening of the peritubular capillary (ptc) basement membrane in 72 (84%), and interstitial inflammation in 40 (47%).C4d deposition in the ptc was present in 49 bs (57%); 39 of these 49 bs showed diffuse c4d deposits in the ptc (c4d3),while the remaining 10 bs showed focal deposits (c4d2).Diffuse c4d deposition in the glomerular capillaries (GC) was seen in 70 bs (81%), while focal c4d deposition in the GC was seen in 9 (11%). In the assay using plastic beads coated with HLA antigen performed in 67 serum samples obtained in the peri-biopsy period, circulating ant-HLA alloantibody was detected in 55 (82%); in 33 of the 55 (49%) samples, donor-specific antibodies (DSA) were detected. Among our study, the findings in 22 bs (26%) fully met the criteria for c-AMR in banff '09 classification, including TG, c4d deposition in the ptc and presence of DSA, while those in 27 BS were suspicious of c-AMR. Deterioration of the renal allograft function after the biopsies was seen in 31 patients (62%). We suggest that histopathological changes of transplant glomerulopathy might be accompanied by inflammation of the microvasculature, such as transplant glomerulitis and peritubular capillaritis, thickening of the peritubular capillary basement membrane, and circulating anti-HLA antibodies. C4d deposition in the ptc is not always present in biopsy specimens of TG. Anti-HLA antibody class II, particularly when the antibody was DSA class II, appeared to be associated with the development of TG. The prognosis of grafts exhibiting TG was poor even under the currently used standard triple immunosuppressive regimen.

Factors Associated with Post-Transplant Anemia among Renal Transplant Recipients with Functioning Grafts in Sana’a City, Yemen

Objective: To assess the factors associated with anemia in renal transplant recipients with functioning grafts in Sana’a city, Yemen.&#x0D; Methods: One hundred and thirteen adult renal transplant recipients with functioning grafts were enrolled in this study in the period from Janury to December 2014. Biodata and clinical data were collected using a pre-designeddata collection sheet. Hemoglobin (Hb) concentration was measured, and anemia was defined as Hb concentration less than13.0 g/dLin males and less than 12.0 g/dL in females. The factors associated with anemia were analyzed, and independent predictors of post-transplant anemia (PTA) among renal transplant recipients were identified using a multivariable logistic regression model.&#x0D; Results: PTA was detected in 23.0% of renal transplant recipients with functioning grafts. Bivariate analysis showed a significant association of PTA with age of 50 years or older (Odds ratio (OR) = 2.7; 95% CI: 1.10–6.72; P = 0.03), history of acute rejection (OR = 3.6; 95% CI: 1.17–11.28; P = 0.019) and delayed graft function (OR = 6.2; 95% CI:1.60–24.16; P = 0.004). Multivariable analysis using a logistic regression model identified history of acute rejection (adjusted OR = 3.9; 95% CI: 1.11–12.94; P = 0.034) and delayed graft function (adjusted OR = 4.6; 95% CI: 1.07–19.81; P = 0.04) as independent risk factors for PTA among recipients. However, no association was found between PTA and recipient’s gender, graft source, immunosuppressive protocols, erythropoietin treatment or use of antihypertensive drugs.&#x0D; Conclusions: The prevalence of PTA among Yemeni renal transplant recipients is high, with history of acute rejection and delayed graft function being the independent risk factors. Therefore, it is recommended that physicians involved in renal transplantation consider the investigation and follow-up of transplant recipients for PTA and adopt appropriate preventive and therapeutic measures.

Factors Associated with Post-Transplant Anemia among Renal Transplant Recipients with Functioning Grafts in Sana’a City, Yemen

Objective: To assess the factors associated with anemia in renal transplant recipients with functioning grafts in Sana’a city, Yemen.&#x0D; Methods: One hundred and thirteen adult renal transplant recipients with functioning grafts were enrolled in this study in the period from Janury to December 2014. Biodata and clinical data were collected using a pre-designeddata collection sheet. Hemoglobin (Hb) concentration was measured, and anemia was defined as Hb concentration less than13.0 g/dLin males and less than 12.0 g/dL in females. The factors associated with anemia were analyzed, and independent predictors of post-transplant anemia (PTA) among renal transplant recipients were identified using a multivariable logistic regression model.&#x0D; Results: PTA was detected in 23.0% of renal transplant recipients with functioning grafts. Bivariate analysis showed a significant association of PTA with age of 50 years or older (Odds ratio (OR) = 2.7; 95% CI: 1.10–6.72; P = 0.03), history of acute rejection (OR = 3.6; 95% CI: 1.17–11.28; P = 0.019) and delayed graft function (OR = 6.2; 95% CI:1.60–24.16; P = 0.004). Multivariable analysis using a logistic regression model identified history of acute rejection (adjusted OR = 3.9; 95% CI: 1.11–12.94; P = 0.034) and delayed graft function (adjusted OR = 4.6; 95% CI: 1.07–19.81; P = 0.04) as independent risk factors for PTA among recipients. However, no association was found between PTA and recipient’s gender, graft source, immunosuppressive protocols, erythropoietin treatment or use of antihypertensive drugs.&#x0D; Conclusions: The prevalence of PTA among Yemeni renal transplant recipients is high, with history of acute rejection and delayed graft function being the independent risk factors. Therefore, it is recommended that physicians involved in renal transplantation consider the investigation and follow-up of transplant recipients for PTA and adopt appropriate preventive and therapeutic measures.

Clinical and pathological analyses of interstitial fibrosis and tubular atrophy cases after kidney transplantation.

We carried out a clinicopathological analysis of cases presenting with interstitial fibrosis and tubular atrophy (IF/TA) after renal transplantation in an attempt to clarify the mechanisms underlying the development and prognostic significance of IF/TA. IF/TA was diagnosed in 35 renal allograft biopsy specimens (BS) obtained from 35 renal transplant recipients under follow up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital, between January 2014 and March 2015. IF/TA was diagnosed at a median of 39.9 months after the transplantation. Among the 35 patients with IF/TA, 19 (54%) had a history of acute rejection. Among the 35 BS showing evidence of IF/TA, the IF/TA was grade I in 25, grade II in 9, and grade III in 1. Arteriosclerosis of the middle-sized arteries was observed in 30 BS (86%). We then classified the 35 BS showing evidence of IF/TA according to their overall histopathological features, as follows; IF/TA alone (6 BS; 17%), IF/TA + medullary ray injury (12 BS; 34%), and IF/TA + rejection (12 BS; 34%). Loss of the renal allograft occurred during the observation period in one of the patients (3%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 15 patients (43%). The results of our study suggests that rejection contributes to IF/TA in 30-40% of cases, medullary ray injury in 30-40% of cases, and nonspecific injury in 20% of cases. IF/TA contributes significantly to deterioration of renal allograft function.

Increased phosphorylation of the renal Na+-Cl- cotransporter in male kidney transplant recipient patients with hypertension: a prospective cohort.

Evidence in rodents suggests that tacrolimus-induced posttransplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl- cotransporter NCC. Here, we analyzed whether a similar mechanism is involved in posttransplant hypertension in humans. From January 2013 to June 2014, all adult kidney transplant recipients receiving a kidney allograft were enrolled in a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery, we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-h blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At 6 mo after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 of 17 women. The hypertensive patients were significantly older than the normotensive group; however, there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus trough levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7±0.19) than normotensive (1±0.13) (P=0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57±0.16 vs. 1±0.07; P=0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes and the development of hypertension in posttransplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension.

Clinical and pathological analyses of chronic vascular rejection after kidney transplantation.

We discuss the clinicopathological analysis of cases of chronic vascular rejection (CVR) cases after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of CVR. CVR was diagnosed in 46 renal allograft biopsy specimens (BS) obtained from 34 renal transplant patients being followed up at the Department of Urology, Tokyo Women's Medical University, between January 2009 and December 2013. CVR was diagnosed at a median of 47.4 months post-transplant. Among the 36 patients, 23 had a history of acute rejection. Among the 46 BS showing evidence of CVR, the CVR was mild (cv1 in Banff's classification) in 23, moderate (cv2) in 17, and severe (cv3) in 6. Of the 40 samples obtained at the time of the biopsy and assayed with plastic beads coated with HLA antigen, 31 (78%) showed circulating ant-HLA alloantibody, and 15 (38%) showed donor-specific antibodies. We then classified the 46 BS showing evidence of CVR by their overall histopathological features, as follows; cv alone was seen in 16 (35%) BS, cv + antibody-mediated rejection (AMR) in 26 (56%), and cv + T-cell-mediated rejection in 9 (19%). Loss of the renal allograft occurred during the observation period in nine of the patients (26%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 11 patients (32%). The results of our study suggest that AMR may underlie CVR in many cases, while T cell-mediated rejection may play an important role in some cases.

De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection.

Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4 ± 6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1 ± 3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P = 0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P < 0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores. Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.

Klebsiella spp Urinary Tract Infections During First Year After Renal Transplantation

BackgroundUrinary tract infections (UTIs) are the most common infections in renal transplant recipients (RTR). Klebsiella spp is a well-recognized source of nosocomial infections in immunocompromised patients and is also the most common pathogen capable of producing extended-spectrum β-lactamases (ESBLs). MethodsWe performed a retrospective cohort study reviewing medical records of patients followed-up at Gdańsk Transplantation Centre. We analyzed urine cultures performed within the first 12 months after renal transplantation (RT) with reference to clinical data. We recorded all Klebsiella spp UTIs. ResultsWe studied urine cultures and clinical data from 335 RTRs. We observed 59 Klebsiella spp episodes in 24 RT patients, including 10 cases of acute graft pyelonephritis and 8 of urosepsis. More than half were caused by ESBL+, whereas there were no carbapenemase-producing strains. Almost 80% of episodes were diagnosed beginning from the second month post-transplantation. More than 60% of upper Klebsiella spp UTIs were due to ESBL+ strains, although we did not identify any host risk factors including vesico-ureteral reflux, strictures at the uretero-vesical junction, history of recurrent UTIs before RT, comorbidity measured by Charlson Comorbidity Index, history of acute rejection, use of induction, and type of immunosuppression used. Upper Klebsiella spp UTIs were slightly more prevalent in males with urinary flow impairment due to various reasons. ConclusionsKlebsiella spp virulence factors, not the host factors, seem to be mostly responsible for developing upper UTIs in RT patients.