Immunosuppressive Medications Research Articles

Survival in dogs with meningoencephalomyelitis of unknown etiology with and without lesions detected by magnetic resonance imaging.

The prognosis of individual dogs with meningoencephalomyelitis of unknown etiology (MUE) remains difficult to predict. MUE cases with no lesions detected by magnetic resonance imaging (MRI) occur, but it is unknown whether this finding is associated with prognosis. MUE cases without detectable lesions on MRI have a better outcome than cases with detectable lesions. Study included 73 client-owned dogs with MUE presenting to Purdue University Veterinary Hospital from 2010 to 2020. Retrospective study. Dogs with a clinical diagnosis of MUE were identified by medical record search. MRI reports were reviewed for presence or absence of lesions consistent with MUE. Clinical findings at presentation, treatment, disease-specific survival, and outcomes including rates of remission and relapse were compared between cases with normal MRI or abnormal MRI. Overall, 54 dogs (74%) were classified as abnormal MRI, and 19 dogs (26%) were classified as normal MRI cases. Death caused by MUE occurred in 1/19 (5%) normal MRI dogs and 18/54 (33%) abnormal MRI dogs (P = .016). Median survival was >107 months in both groups, but survival was significantly longer in the normal MRI group (P = .019). On multivariate analysis, abnormal MRI was significantly related to death (hazard ratio, 7.71; 95% confidence interval 1.03-58.00, P = .0470), whereas significant relationships with death were not identified for either the use of secondary immunosuppressive medications or cerebrospinal fluid nucleated cell count. MUE dogs with no detectable lesions on MRI have reduced disease-related death compared with dogs with abnormal MRI. The presence or absence of MRI lesions in MUE dogs is prognostically relevant.

Clinical Characteristics and Outcomes of Disseminated Strongyloidiasis in the United States-A Multicenter Network Analysis.

Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.

Herpes Zoster Infection in A Case of Nephrotic Syndrome (On Alternate Day Prednisolone Therapy) - A Case Report

Herpes Zoster infection is caused by Varicella Zoster virus. Its characteristic feature is the appearance of unilateral clustered vesicles on an erythematous base. The vesicles heals within two weeks from appearance of vesicles. The symptoms of Nephrotic Syndrome include severe proteinuria, edema, hypoalbuminemia and hyperlipidemia. Minimal Change Nephrotic Syndrome is the most prevalent type of nephrotic syndrome in children, for which prednisolone is the preferred medication. Administration of prolonged corticosteroid causes decreased cell mediated immunity which causes immunosuppression and therefore chance of infection increases. Herpes zoster infection is usually a self-limiting disease. It is usually diagnosed clinically on the basis of characteristic appearance of the rash. Treatment is mainly by administration of oral acyclovir for 7 days. Severe illness may require hospitalization for intravenous acyclovir. In individuals with nephrotic syndrome on corticosteroids or other immunosuppressive medications, complication arising from varicella infections can be life-threatening. Keywords: Herpes zoster, Nephrotic syndrome, Minimal Change Nephrotic Syndrome, Prednisolone, Acyclovir, Cell mediated immunity

#1039 Characteristics and outcome of IgA nephropathy in Switzerland – a single center perspective

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide leading to end-stage kidney disease (ESKD) in roughly 40% of affected patients by ten years. Geographic differences in clinical course and response to treatment may partly result from different disease entities. The purpose of this retrospective cohort analysis was to study all cases of IgAN from a single tertiary center with respect to clinical and histological characteristics, treatment practices and outcome. Method This retrospective cohort analysis identified 158 cases of adult biopsy-proven IgAN by chart review diagnosed between 1980 and 2017. Detailed phenotypisation including clinical, paraclinical, histological, treatment and outcome parameters was performed. Remission status was defined as described previously (Reich 2007). Statistical analysis was performed using Excel and SPSS software and included standard descriptive methods and included standard descriptive methods and student's t-test on a significance level of 0.05. Results Subjects were majorly male and of Caucasian descent. Mean estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration formula at diagnosis was 55.3 ml/min/1.73 m2, mean proteinuria was 3.2 g/d. 70.3% of patients were hypertensive at presentation. Clinical presentation varied according to age. Thus, younger patients (18-39 years) presented more frequently with macrohematuria, asymptomatic urine abnormalities and by trend acute kidney injury whereas nephrotic syndrome and extrarenal symptoms were recorded in similar proportions of patients (Fig. 1). 28.5% of initial biopsies showed moderate to severe tubular atrophy and interstitial fibrosis (IFTA), 38% included crescents, 1.9% > 50% crescents. 86.1% of the patients were treated by renin-angiotensin-aldosterone-system inhibitors, 46.8% received immunosuppressive therapy including steroids in 46.2% and other immunosuppressive medications in 19.6% the most common being azathioprine (Fig. 2). There were 33.5% complete and 13.3% partial remissions. Progression to ESKD was noted in 42.1%. 51.4% of patients treated with immunosuppressive therapy experienced remission. Recurrence rate after transplantation was 18.4%. Patients treated by immunosuppressants had higher levels of baseline proteinuria (3.2 ± 2.3 vs. 1.6 ± 1.6 g/d, p < 0.00001), lower baseline eGFR (50 ± 31 vs. 61 ± 30 ml/min/1.73 m2, p = 0.04), higher number of crescents (9.4 ± 15.0 vs 2.3 ± 8.5%, p = 0.001), higher IFTA scores (1.7 ± 0.8 vs. 1.3 ± 0.6, p = 0.007) and higher fluorescence intensity scores for C3 (2.0 ± 0.9 vs. 1.6 ± 0.9, p = 0.02) on initial biopsy as compared to patients treated conservatively. Patients progressing to ESKD presented with higher blood pressure (146 ± 26 vs. 135 ± 18 mmHg systolic, p = 0.005; 89 ± 14 vs. 82 ± 14 mmHg diastolic, p = 0.006), lower eGFR (41 ± 29 vs. 64 ± 28 ml/min/1.73 m2, p = 0.00001), higher levels of proteinuria (3.4 ± 2.0 vs. 1.8 ± 1.9 g/d, p = 0.0001), higher number of crescents (9 ± 17 vs. 4 ± 9%, p = 0.03) and higher IFTA scores (1.8 ± 0.8 vs. 1.3 ± 0.6, p = 0.00001) as compared to patients without ESKD at last follow up. Baseline blood pressure (134 ± 18 vs. 147 ± 26 mmHg systolic, p = 0.004; 82 ± 14 vs. 89 ± 15 mmHg diastolic, p = 0.01), eGFR (60 ± 29 vs. 41 ± 27 mmHg, p = 0.0007), proteinuria (2.3 ± 1.9 vs. 3.2 ± 2.3 g/d, p = 0.03) and severity of IFTA (1.4 ± 0.6 vs. 1.8 ± 0.9, p = 0.003) differed significantly between patients who experienced any remission vs. those who did not achieve remission respectively. Conclusion This analysis gives insight into the characteristics and treatment practices of a Swiss single center cohort of IgAN patients from 1980-2017.

#567 Early application of treatment to patients with IgA nephropathy who were supposed to have steroid regimen predicts good renal outcome

Abstract Background and Aims Progressive deterioration of proteinuria and glomerular filtration rate (GFR) is notified in 20-30% of patients with IgA nephropathy during 20-30 years follow-up period. Popular traditional approach for patients with rapid deterioration of renal function is the immunosuppressive treatment with steroid, which efficacy is still remained in debate. We searched the factors related to renal outcomes among patients presumed to need steroid treatment. Method Among 472 adult patients with IgA nephropathy diagnosed by renal biopsy during 2003-2017 in a tertiary hospital, we selected 86 patients with initiation of steroid treatment for more than 1 months and with dose of more than 1000 mg of prednisolone after renal biopsy. We excluded patients with steroid treatment started one month or more before renal biopsy. The renal outcome was defined as decrease of GFR more than 50% from GFR at renal biopsy, decrease of GFR to less than 15 ml/min/1.73 m2, or a status to need renal replacement therapy during follow-up period after renal biopsy. Results At admission for renal biopsy, estimated GFR by CKD-EPI 2009 equation was 68.5 ± 33.3 ml/min/1.73 m2 and urine protein to creatinine ratio (UPCR) was 2.81 ± 2.23 g/g creatinine (no missing data). The renin-angiotensin-aldosterone inhibitor was used in 80 patients (93.0 %) after renal biopsy. Steroid was started at 8.4 ± 23.1 months after renal biopsy. Majority of patients (63 patients) had been prescribed steroid medication within 2 months after renal biopsy. Total dose of steroid was 13.5 ± 13.1 g. The results of eGFR and UPCR before starting steroid medication were 63.7 ± 31.2 ml/min/1.73 m2 and 2.82 ± 2.01 g/g creatinine, respectively. During 63.6 ± 48.8 months of follow-up period after renal biopsy, there were 39 patients (45.3 %) developed the renal outcome. Factors related to development of the renal outcome searched by correlation coefficient were eGFR and UPCR at renal biopsy, medications of anti-diabetic agent, anti-hypertensive agent, immunosuppressive agent other than steroid, dose of steroid, or vitamin D3 agent after renal biopsy, pathologic findings of segmental sclerosis, interstitial inflammation, and tubular atrophy on light microscopic examination, deposition of C3 and IgA on immunofluorescent staining, and Oxford classification of T, period of starting steroid treatment after renal biopsy, and eGFR before starting steroid medication. With Cox's hazard proportional model, the independent factors to predict the renal outcome were eGFR before steroid treatment or eGFR at renal biopsy, immunosuppressive medication other than steroid, pathologic finding of C3 deposition, and period of starting steroid treatment. Hazard ratio to estimate the renal outcome (HR) was 1.025 (95% CI: 1.010-1.039, p = 0.001) for one-month delay of starting steroid medication after renal biopsy. The HR for the renal outcome in patients started steroid medication at 2 months after renal biopsy was 2.353 (95% CI: 1.140-4.856, P = 0.021) compared to patients started steroid within 2 months after renal biopsy. Conclusion For the patients supposed to have indications for steroid treatment at renal biopsy, early initiation of steroid treatment would indicate better renal outcome.

#2861 Real-life efficacy of tolvaptan for polycystic kidney disease (PKD) and association with patient adherence in London North-West specialist clinic

Abstract Background and Aims Tolvaptan is approved by NICE in the treatment of PKD afterrandomised controlled trials demonstrated a reduction in decline in eGFR. Aquaresis occurs as an effect, and this may limit tolerability as the second dose in a day causes nocturia and disturbed sleep. Thirty-three patients in our specialist PKD clinic were treated based on criteria of bipolar renal length >=15cm and decline in eGFR by > −5 ml/min/yr. We evaluated their real-life outcome regarding measures of adherence including an adapted Basel Assessment of Adherence to Immunosuppressive Medication Scale © (by permissions.nursing.unibas.ch/) originally validated for immunosuppression medications in transplant patients. A further 24 patients had finished treatment at our centre and were excluded as BAASIS could not be applied in hindsight. However, they illustrated a notably high level of intolerance leading to cessation in 16/24 (9 with nocturia, 4 transaminitis, 1 angioedema, 1 rash, 1 fatigue) emphasizing the importance of this work on adherence and response. Method BAASIS addresses recall of treatment adherence in the preceding 4 weeks, all 33 patients currently treated as of 16/1/24 were screened on telephone by two independent auditors with a standard non-judgemental introductory script designed to result in candid engagement. Investigators were blinded to renal outcomes. A decline in eGFR of less than 5 ml/min/yr was defined as treatment response. Results Of the 33 patients included, 14 males and 19 females, median age 49yrs (range 32-72), were on treatment for a mean of 2.7yr (SD 2.2, range 0.3-7.5). Mean eGFR (CKD-EPI) was 58 ml/min (SD 19, range 28-110) at start and 48 ml/mi (SD 23, range 17-102) at end of treatment. Median total daily dose was 120 mg/d (range 60-120). Attendance at clinic for monitoring was 100%. 18/33 patients had responded to treatment, with delta eGFR –0.1 ml/min/year (SD 3.4) versus non-responders’' delta eGFR –13 ml/min/year (SD 8.7) There was a total of 35 instances of non-implementation in 23/33 patients with missed (20 instances), delayed (13 instances) or self-alteration in doses (2 instances). Only 10/33 patient made no failure to implement Tolvaptan at any time. There were 9 patients with non-persistence of Tolvaptan treatment. Associative analysis of renal outcome with adherence was made for all 31 patients who had more than 6 months treatment, 2 patients being excluded because treatment had been too short-term. 25/31 had non-adherence defined by non-implementation or non-persistence or both, but this did not statistically associate with treatment failure ChiSq 1.951 p = 0.16. The element of non-implementation alone was however associated with treatment failure ChiSq 4.949 p = 0.03, this term includes patient behaviour of not taking and mistiming drug taking, and patient-initiated dose reduction and drug holidays. Conclusion Just over half (55%) of currently treated patients had made a clinical response to Tolvaptan. 23/33 patients had non-implementation within the 4 weeks preceding the validated adherence survey, and this was significantly associated with treatment failure. This study is limited to a small single-centre patient cohort but could easily be applied more widely. This study informs shared-decision making and we should encourage our patients to take this high-cost drug in the right amount and at the right times, and notably not to miss doses, thereby to achieve higher clinical response rates.

#1844 Pregnancy outcome among kidney transplant recipients

Abstract Background and Aims Background The possibility of a term pregnancy is one of the benefits of solid organ transplantation for women. The gonadal dysfunction, caused by the failure of the kidney or another organ, is reverted within a few months after normal graft function. Unplanned pregnancies in transplant recipients, however, may compromise graft function and survival, and may also risk unnecessary fetal exposure to immunosuppressive medications. Aims To study the prevalence of pregnancy and pregnancy related complication after kidney transplantation (KT). Method Retrospective cohort study conducted on 236 patients out of 3000 kidney transplant recipient who underwent renal transplantation (RT) at Mansoura Urology and Nephrology Centre between March 1976 and December 2019. divided into group I; 118 kidney transplant female's recipient experienced pregnancy at any time after kidney transplant and group II; 118 kidney transplant female's recipients who didn`t experience pregnancy after renal transplantation, they were matched according to age and duration of renal transplantation and comparable in primary immunosuppressant drugs. all kidney recipients were reviewed for preoperative & operative and post-operative details also we record maternal and fetal complication. Results Prevalence of pregnancy in our center is 191 pregnancies in 118 women who had underwent kidney transplantation between 1976 and 2019. We have found that the mean age of pregnancy between (26.27 ± 4.37-29.89 ± 4.6), the mean gestational age between (33.69 ± 6.4 – 33 ± 7.5) weeks, the live birth rate is 126 (66%). Preterm delivery rate in our study is 85 (44.5%), neonatal death 8 (4.1%), miscarriage 59 (30.9%), intrauterine fetal death 6 (3.1%) and birth defect 4 (2%). The prevalence rates of gestational hypertension is 87 (45.5%), pre-eclampsia 48 (25.1%), gestational diabetes 19 (9.9%), urinary tract infection 36 (18.8%), and graft rejection 8 (4.1%) during pregnancy. caesarean section is the most common method of delivery in our study 133 (69.6%). Kidney transplant recipients who aged more than or equal to 30 years at time of pregnancy are at higher risk for having non live-birth outcome (OR: 3.2, p value: 0.05). Proteinuria more than or equal to 0.5 g/day before pregnancy is a significant risk factor for having non live-birth outcome (OR: 4.7, p value: 0.009). Also, proteinuria ≥0.5 g/day during pregnancy is associated with increases risk for non-live-birth (OR: 10.2, p value: 0.013). Gesatational hypertension is associated with increases risk for non-live-birth (OR: 8.3, p value: 0.010).Preeclampsia is associated with increases risk for non-live-birth (OR: 4.6, p value: 0.005). Conclusion Although the outcome of live births is favourable, the risks of maternal and fetal complications are high in kidney transplant recipients including pregnancy-induced hypertension, increased rates of preeclampsia, gestational diabetes, and caesarean section rates. The risk of miscarriage, prematurity, and low birth rate is also high.

#1985 Tocilizumab in chronic active antibody-mediated rejection: a randomized controlled open-label multi-center trial (INTERCEPT study)

Abstract Background and Aims Chronic active antibody mediated graft rejection (caAMR) caused by immune-mediated injury is the leading cause of long-term graft loss in kidney transplant recipients. Nevertheless, no effective treatment exists for caAMR to date, highlighting a great unmet need for evaluation of novel treatment options. Recently, tocilizumab (TCZ), a monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, by antagonizing IL-6-triggered inflammation and B cell/plasma cell-driven immune activation, has shown promise in the treatment of caAMR. However, TCZ has not been assessed systematically in a randomized study. The INTERCEPT study aims to evaluate the efficacy of addition of TCZ to standard of treatment (SOC) as compared to SOC alone in reducing the decline of graft function from baseline at 24 months after start of treatment as assessed by estimated glomerular filtration rate (eGFR) in kidney transplant recipients with caAMR. Method This ongoing randomized controlled open-label multi-center investigator-initiated trial plans to include a total of 50 adult kidney transplant recipients with biopsy-proven caAMR using Banff 2019 criteria at least 12 months after transplantation and eGFR ≥20 ml/min/1.73 m2. Any subject who underwent kidney transplantation in Sweden or is currently living in Sweden and being followed up at any of the Swedish transplant centers or their affiliated regional centers can be considered for participation. Participants are randomized to receive either TCZ (n=25) added to our standard of care (SOC) maintenance treatment or SOC alone (n=25) for a period of 24 months and followed for additional 12 months after cessation of the study medication. After the inclusion transplant biopsy at baseline, protocol biopsies are performed at 12 and 24 months. The study design flow-chart is shown in the Figure. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The eGFR is assessed using Modification of Diet in Renal Disease (MDRD) formula. The secondary endpoints include assessment of the following at 12, 24 and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection. Results We expect that addition of TCZ to SOC will slow down the decline of graft function in kidney transplant recipients with caAMR. Conclusion Currently there is no effective treatment for caAMR. Based on the hypothesis that inhibition of IL-6 by TCZ will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR. If TCZ is found to be effective, our study has the potential to improve long-term graft survival and quality of life, reduce morbidity and mortality in kidney transplant patients as well as lower the health care costs.

#717 Recipient/donor characteristics and immunosuppression impact eGFR creatinine and creatinine-cystatin c equations in kidney transplant recipients

Abstract Background and Aims Previous studies have shown substantial heterogeneity in the performance of estimated glomerular filtration rate (eGFR) equations when applied to kidney transplant recipients (KTRs). The impact of transplantation-related characteristics on eGFR equations based on creatinine (eGFRcr) compared with creatinine and cystatin C (eGFRcr-cys), however, remains insufficiently studied. Method We analyzed 596 KTRs transplanted at the University Hospital Zurich. The accuracies of four eGFRcr equations (CKD-EPI 2009 and 2021, EKFC 2021, KRS-GFR 2023) were compared with three eGFRcr-cys (CKD-EPI 2012 and 2021, EKFC 2023), and evaluated across a detailed range of transplantation-related variables. Performances were assessed using bias, P30, P20 and correct classification (CC). Multivariate analysis identified transplantation-related characteristics independently associated with a smaller or greater difference between eGFRcr and eGFRcr-cys equations. Results Based on eGFRcr-cys CKD-EPI 2012 as the reference, CKD-EPI 2021 (P30: 77.0%, P20: 56.4%, CC: 56.4%) and KRS-GFR 2023 (P30: 80.2%, P20: 64.9%, CC: 60.1%) had lower performance, while EKFC 2021 (P30: 88.6%, P20: 75.8%, CC: 66.8%), and CKD-EPI 2009 (P30: 87.1%, P20: 70.3%, CC: 64.6%) showed higher performance. Belatacept use was associated with a smaller difference between eGFRcr CKD-EPI 2009 and eGFRcr-cys CKD-EPI 2012 (OR 3.295, 1.605-6.764, p = 0.001), while a higher donor BMI was associated with a greater difference between eGFRcr KRS-GFR 2023 and eGFRcr-cys CKD-EPI 2012 (OR 1.077, 1.001-1.158, p = 0.046). Conclusion More recent eGFRcr equations do not overcome the limitations of non-GFR determinants of creatinine in KTRs, however European equations seem to be equally feasible in transplanted patients. Transplantation-related characteristics of the recipient, donor, and immunosuppressive medication affect the differences between eGFRcr and eGFRcr-cys, which needs attention in clinical practice.

#2252 Outcome of pregnancy after kidney transplantation

Abstract Background and Aims Background The possibility of a term pregnancy is one of the benefits of solid organ transplantation for women. The gonadal dysfunction, caused by the failure of the kidney or another organ, is reverted within a few months after normal graft function. Unplanned pregnancies in transplant recipients, however, may compromise graft function and survival, and may also risk unnecessary fetal exposure to immunosuppressive medications. Aims To study the prevalence of pregnancy and pregnancy related complication after kidney transplantation (KT). Method Retrospective cohort study conducted on 236 patients out of 3000 kidney transplant recipient who underwent renal transplantation (RT) at Mansoura Urology and Nephrology Centre between March 1976 and December 2019. divided into group I; 118 kidney transplant female's recipient experienced pregnancy at any time after kidney transplant and group II; 118 kidney transplant female's recipients who didn't experience pregnancy after renal transplantation, they were matched according to age and duration of renal transplantation and comparable in primary immunosuppressant drugs. all kidney recipients were reviewed for preoperative & operative and post-operative details also we record maternal and fetal complication. Results Prevalence of pregnancy in our center is 191 pregnancies in 118 women who had underwent kidney transplantation between 1976 and 2019. We have found that the mean age of pregnancy between (26.27 ± 4.37 - 29.89 ± 4.6), the mean gestational age between (33.69 ± 6.4 - 33 ± 7.5) weeks, the live birth rate is 126 (66%). Preterm delivery rate in our study is 85 (44.5%), neonatal death 8 (4.1%), miscarriage 59 (30.9%), intrauterine fetal death 6 (3.1%) and birth defect 4 (2%). The prevalence rates of gestational hypertension is 87 (45.5%), pre-eclampsia 48 (25.1%), gestational diabetes 19 (9.9%), urinary tract infection 36 (18.8%), and graft rejection 8 (4.1%) during pregnancy. caesarean section is the most common method of delivery in our study 133 (69.6%). Kidney transplant recipients who aged more than or equal to 30 years at time of pregnancy are at higher risk for having non live-birth outcome (OR: 3.2, p value: 0.05). Proteinuria more than or equal to 0.5 g/day before pregnancy is a significant risk factor for having non live-birth outcome (OR: 4.7, p value: 0.009). Also, proteinuria ≥0.5 g/day during pregnancy is associated with increases risk for non-live-birth (OR: 10.2, p value: 0.013). Gestational hypertension is associated with increases risk for non-live-birth (OR: 8.3, p value: 0.010).Preeclampsia is associated with increases risk for non-live-birth ( OR: 4.6, p value: 0.005). Conclusion Although the outcome of live births is favourable, the risks of maternal and fetal complications are high in kidney transplant recipients including pregnancy-induced hypertension, increased rates of preeclampsia, gestational diabetes, and caesarean section rates. The risk of miscarriage, prematurity, and low birth rate is also high.

Ectopic cervical thymoma in myasthenia gravis: a case report

BackgroundEctopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG).Case presentationWe report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies.ConclusionsDiagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside

Acquired hemophilia A (AHA) is a bleeding disorder characterized by the immunological inhibition of factor VIII (FVIII) of the hemostatic pathway leading to hemorrhagic events. Different domains of FVIII are the target of autoantibodies (mainly immunoglobulin (Ig) G) leading to the deficiency of FVIII. Several factors have been associated with the activation of the auto-immunity towards FVIII. Emerging evidence implicates CD4+ T cell activation in mediating this autoimmune response, with their involvement like that observed in congenital hemophilia A. Several genes such as HLA II DRB*16, DQB1*0502, and CTLA-4 + 49 are responsible for the pathogenesis of AHA. Epigenetic modifications and mainly long-coding RNAS (lncRNAs) are potentially contributing to the pathogenesis of AHA. The treatment approach of AHA includes the management of acute bleeding events and the administration of immunosuppressive medications. This review aimed to summarize the published data on the genetics and epigenetics of AHA. The severity and the mortality of this disease are creating an emerging need for further research in the field of the genetics and epigenetics of acquired hemorrhagic disorder.

#1849 Returning to dialysis after kidney transplant failure: preliminary findings of a multi-centre database

Abstract Background and Aims Kidney transplant failure contributes to a considerable proportion of new dialysis starters. In some centres there are dedicated clinics for patients with failing kidney transplants, however, the specific needs of patients with dialysis after graft loss (DAGL) may be lost in the non-specific clinical review practiced in the general dialysis community. This study examines the mortality and morbidity risk in patients returning with DAGL and compares it to transplant-naïve (T-N) dialysis starters, to determine if the former warrant a more specialised approach. Method This is a retrospective observational study of mortality in all adult patients who started dialysis treatments in Fresenius Medical Care (North America, Latin America, Europe, Middle East, Africa, and Asia Pacific) from 1st January 2018 to 31st March 2021, were identified in the Apollo Dial DB dataset. DAGL was identified from the ICD-10 codes ‘Kidney transplant failure’, ‘Unspecified complication of kidney transplant’ and ‘Other complication of kidney transplant’ at dialysis start. The T-N control group had not previously received a kidney transplant and had not received immunosuppressive medication during the first six months of dialysis start. The first six months on dialysis were defined as baseline, months 7 to the end of year 5 were defined as the follow-up period. All-cause mortality was recorded during follow-up. Cox proportional hazards models were applied to explore the association between DAGL and all-cause mortality. Results A total of 360 469 dialysis starter patients from 41 countries were included in the analysis. 10 010 patients had DAGL and were compared with 350 459 in the T-N control group. In univariate analysis, DAGL patients were significantly younger in all age categories and had a higher proportion of male sex. Serum creatinine, ferritin, phosphate and neutrophil-to-lymphocyte ratio were higher in the DAGL group. Haemoglobin was lower in the DAGL group (Table 1). In the Cox proportional model adjusted for age, gender, and other laboratory and clinical markers, patients with DAGL had an equivalent survival probability compared with T-N dialysis starters (HR: 0.93, 95% CI: 0.86, 1.02) (Table 2). Conclusion DAGL patients appeared to have an increased mortality compared to T-N dialysis starters historically in the literature. Our large and recent study is in line with other recent publications suggesting a more equivalent survival in the two groups. Our results are compatible with younger patients receiving kidney transplantation early in their renal replacement therapy journey, thus constituting a significant proportion of DAGL patients. We posit that DAGL patients may start dialysis at a lower level of renal function, with higher levels of inflammation. Our analysis is preliminary and limited, not fully accounting for confounding factors. Future analysis of this large and well recorded dataset will allow us to examine these interesting associations and design a more specialised management approach to DAGL more closely.

#1731 Clinico-epidemiological characteristics of early versus late onset cytomegalovirus disease among renal transplant recipients: two decade experience

Abstract Background and Aims The epidemiology of the Cytomegalo virus (CMV) disease among renal transplant recipients has changed with the advent of effective antiviral prophylaxis usually occurs in the later part of the post transplant period. To study the difference between CMV infections occurring in early versus late post renal transplant period with respect to nature of immunosuppressive medications (induction agents, maintenance agents and heightening of immunosuppression), type of CMV infection and occurrence of biopsy proven rejection post CMV infection. Method A single centre retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between 1st January, 2002 and 31st December, 2021. CMV disease was classified as early or late depending on detection before or after 90 days post transplant. The differences in clinical presentation between early and late onset CMV disease, use of immunosuppression, and the impact on graft outcomes were studied. Results Total number of recipients with CMV disease was 156 (7.2%) out of total 2164 renal transplant recipients. Twenty-five (16%) patients had early CMV while one hundred and thirty one (84%) had late CMV. The two groups did not differ with respect to induction or use of maintenance immunosuppressive agents. Proportion of CMV syndrome was more among early CMV group (56.0% vs 26.7%, p = 0.01) while tissue invasive disease was more frequent among late CMV group (44.0% vs. 73.3%, p = 0.01). Diarrhoea was more frequent in late (63.4%) versus early CMV (36%) (p = 0.01). Graft loss occurred in 4.0% of early and 25.2% of late CMV cases (p = 0.03). However, both groups did not differ with respect to occurrence of biopsy proven rejection post infection. Conclusion Early CMV presents more frequently as CMV syndrome while late CMV usually manifests as tissue invasive disease. Graft loss is more common in patients with late onset disease.

Coronavirus infection and neutralizing antibody responses among liver transplant recipients: single-center study

BackgroundLiver transplant (LT) recipients are classified as a high-risk group and should receive regular surveillance for COVID-19 and are expected to have higher viral load and prolonged viral shedding. Virus-specific neutralizing antibodies (NAb), induced by infection, can prevent viral infection by deactivating viral access to host receptors.AimTo estimate the incidence of SARS-CoV-2 infections and ascertain the levels of NAb among LT recipients.MethodThis cross-sectional study included LT recipients. The survey included 14 parameters about demography, date since operation, and immunosuppressant medications and 11 parameters about COVID-19 infection. NAb was done by electrochemiluminescence immunoassay.ResultsOnly 39 LT recipients responded to this survey. Their median age was 57, and 74.4% of them were men. Comorbidities were present in 64% of cases, and DM was the most common comorbidity. Immunosuppressants used were Tacrolimus in 56.4% and Tacrolimus with mycophenolate mofetil in 15.4%. Fifteen cases (38.5%) had suspected infection, and 2 (5.1%) had confirmed infection. Three patients (17.6%) were hospitalized with no mortality. NAb was done in 34 cases, and it was positive in 5 cases (14.7%) with a median level (range) of 0.075 (0.04–27). Three out of 5 cases with a positive NAb test did not give a history of either suspected or confirmed COVID-19 infection.ConclusionCOVID-19 surveillance in LT recipients is important and suggests a relatively favorable clinical course despite the presumed challenges of immunosuppression. COVID-19 was associated with low hospitalization in LT recipients. NAb indicates a potential immune response even in asymptomatic LT recipients.Trial registrationClinical Trial.gov NCT04565782. September 15 2022.

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM To improve overall understanding of this disease’s diagnosis and prognosis. METHODS We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin’s lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Prevalence of Intestinal Parasites among Diabetes Mellitus Patients in Tertiary Care Hospital

Intestinal parasitosis constitutes a serious problem of public health, especially in developing countries. Even though the population of immunocompromised individuals is growing, this is a primary cause of illness and mortality. Numerous studies have demonstrated that immunosuppressive medications, such as those used after transplantation, as well as immune suppression as a primary immunodeficiency in HIV infection, increase the possibility of infection and persistent states of carriage. People whose immune systems were weakened, like in the case of chronic internal disorders or abnormal metabolism, were thought to be more susceptible to infection. A group of metabolic non-communicable diseases known as diabetes mellitus (DM) are characterized by hyperglycemia or elevated blood sugar, which can be brought on by either inadequate secretion of insulin, insulin-resistant cells, or both. Parasitic infections in immunocompromised people are becoming more well-known as major opportunistic microorganisms that cause clinical illnesses. The goal of this research is to see how common intestinal parasite infections are in people with diabetes. The research was carried out at the Chandulal Chandrakar Memorial Medical College, Bhilai, Durg district of Chhattisgarh, India. From March to August 2020, diabetic patients who visited hospitals were studied in this cross-sectional study. This study comprised 188 diabetic individuals with type I or type II diabetes who were taking anti-diabetic medication. With a little spoon and a sterile, dry, leak-proof plastic container with a tight-fitting cover that had the patient’s name and identification number on it, the feces samples were taken. The container was then quickly sent to the parasitology lab of the microbiology department for processing. Stool samples were examined under three headings: macroscopic examination, microscopic examination, and formal ether concentration procedure. A total of 188 DM patients was included with data on socio-demographic characteristics, and from each patient stool sample were collected and processed. Out of which, 27 stool samples were positive for intestinal parasites; showed a prevalence of 14.36%. Female 16 (16.49%) revealed a greater frequency than that of men 11 (12.09%). The age range of 51 to 60 years old exhibited the highest incidence 8 (29.63 %). Stool samples were positive for intestinal parasites with one suffering from a dual infection. Various parasites were detected in which Entamoeba histolytica 10 (5.32%) was most common parasite to isolate followed by Ascaris lumbricoides 9 (4.79%) and Giardia lamblia 6 (3.19%) was least isolated parasite. The most prevalent isolated parasite was Entamoeba histolytica, which was followed by Cryptosporidium parvum. Diabetic patients have an increased risk of parasitic infections, particularly when they have the opportunistic infection Entamoeba histolytica. Patients with diabetes who have been diagnosed with Cryptosporidium parvum have a weaker immune system. Therefore, for the sake of societal welfare, people with diabetes mellitus should have routine stool examination screening for parasite infection.

Review of drug-drug interactions in patients with prostate cancer.

The objective of this review is to provide an overview of common drug-drug interactions (DDIs) associated with prostate cancer treatments and outline recommendations for managing polypharmacy. A literature search of PubMed, Embase, and CINAHL was carried out to identify pharmacokinetic and pharmacodynamic changes caused by DDIs that are relevant for prostate cancer patients, DDIs between prostate cancer therapies and co-administered medications (both prescription and over-the-counter), and measures to prevent DDIs. Medication package inserts were used to identify the impact of DDI on the prostate cancer therapy and suggested interventions. No DDIs are expected for the LHRH agonists leuprolide acetate, histrelin, goserelin, or leuprolide mesylate. However, DDIs have been reported for GnRH antagonists, anti-androgens, PARP inhibitors, and taxanes. Although there are no confirmed DDIs for sipuleucel-T to date, it is not generally recommended to use sipuleucel-T concurrently with immunosuppressive medications. Interventions to prevent DDIs include the use of software that can detect clinically significant DDIs, up-to-date medication reconciliation, the inclusion of dedicated clinical pharmacists in cancer treatment teams, and patient/caregiver education. Prostate cancer patients have a high risk of potential DDIs due to numerous new anti-cancer therapies, the increased use of treatment combinations, and the likelihood of comorbid conditions also requiring drug therapy. Drug-drug interaction screening software, up-to-date medication reconciliation, inclusion of oncology pharmacists on healthcare teams, and patient/caregiver education will aid the development of treatment plans that focus on achieving an optimal risk-benefit profile whilst reducing the risk of DDIs.

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

BackgroundTacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms.Methods and resultsThirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-β1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations.ConclusionLina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.

Herpes Simplex Virus Encephalitis in Patients With Autoimmune Conditions or Exposure to Immunomodulatory Medications.

Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is most common, accounting for ∼15%-40% of adult encephalitis diagnoses. We aim to investigate the association between immune status and HSV encephalitis (HSVE). Using a US Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. We used the US Medicaid Analytic eXtract data between 2007 and 2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age and sex-matched adult cases of HSVE with a sufficient enrollment period (12 months before HSVE diagnosis) to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson Comorbidity Index, and non-autoimmune comorbidities. Incidence of HSVE was ∼3.01 per 105 person-years among adults. A total of 951 HSVE cases and 95,100 age and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong (adjusted odds ratio (OR) 2.6; 95% CI 2.2-3.2). The association of HSVE and immunomodulating medications had an OR of 2.2 (CI 1.9-2.6), also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: OR 2.3 (CI 1.9-2.7) for autoimmune disease and 2.0 (CI 1.7-2.3) for immunosuppressive and immunomodulatory medications. In a large, national population, HSVE is strongly associated with preexisting autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date.