Induction Immunosuppressive Therapy Research Articles

Reversibility of pulmonary hypertension in systemic lupus erythematosus after induction immunosuppressive therapy: An inflammatory manifestation?

To evaluate the possible reversibility of PAH to a normopressoric state in SLE after induction immunosuppressive (IS) and predictors of response. We retrospectively evaluated all SLE-PAH patients who underwent IS therapy at our center. PAH reversion was defined as the normalization of pulmonary arterial pressure (PAP), either by the presence of systolic PAP <40mmHg on echocardiogram or mean PAP <20mmHg on right heart catheterization (RHC). SLE patients were divided in Reversion and No-Reversion of SLE-PAH groups for comparative analysis at baseline and after IS. Among 2,074 SLE patients, 28 SLE-PAH received IS therapy (1.3%). Ten patients (35.7%) achieved SLE-PAH reversion. Demographic data, disease duration, SLEDAI-2K, and SDI Damage scores were similar between Reversion and No-Reversion of SLE-PAH groups (p > 0.05). At baseline, Reversion of SLE-PAH had lower sPAP (p = 0.032), lower right ventricle dilatation (p = 0.003) and hypokinesia (p = 0.017) frequencies on echocardiogram, and also lower BNP levels (p = 0.041) and risk stratification score (p = 0.014). Hemodynamic parameters were similar among groups (p > 0.05). After IS, a significant decrease in CRP levels was identified only in Reversion of SLE-PAH (p = 0.013), although both groups had a significant reduction in SLEDAI-2K (p < 0.05). Both groups had significant improvement in risk stratification score (p = 0.009 and p < 0.001) with a better survival rate in Reversion of SLE-PAH (p = 0.047). This is the first study that identified that more than one third of SLE-PAH had a complete reversion of PAH after IS therapy with a significant impact on their survival. These findings strongly support the notion of an underlying inflammatory etiology of this condition, which reinforces the use of immunosuppressive treatment for all SLE patients at PAH onset.

Prospective study on immune function in renal transplant patients during perioperative period: A prospective cohort study.

Delayed graft function (DGF) is a type of acute renal failure that is closely linked to the immune system. The objective of this study is to investigate immune trends during the perioperative period of renal transplantation and compare the variations between patients with DGF and immediate graft function (IGF). A total of 48 kidney transplant patients were enrolled. Parameters including stimulated adenosine triphosphatase concentrations (sATP), nonstimulated ATP concentrations, white blood cells, and lymphocyte count were assessed. Patients were categorized into the DGF or IGF group. Clinical information and changes in immune markers were compared. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity in predicting DGF. Additionally, separate immune function analyses were conducted for the 3 infection cases. Following induction immunosuppressive therapy, white blood cells, and neutrophil count showed a significant initial increase followed by a gradual decline. Lymphocyte count, nonstimulated ATP concentrations, and sATP exhibited an initial significant decrease followed by a slow recovery. Immune markers between the DGF and IGF groups were significantly different at day 4 after renal transplantation. Only sATP levels at day 4 after renal transplantation (area under the curve = 0.731, sensitivity = 0.864, specificity = 0.684) demonstrated predictive value for DGF occurrence. Among the 3 infection cases, 2 cases exhibited persistently decreased sATP levels and died within the first month and 6 months, while the remaining case showed a recovery of sATP levels at D9 and survived. These findings indicate that sATP level can potentially serve as a biomarker reflecting the impact of immunosuppressants. Poor recovery of sATP may be associated with DGF, infection, or even mortality.

Role of interferon-gamma release assay for screening and monitoring of latent tuberculosis infection in kidney transplant recipients

BackgroundThe reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored.MethodsBetween September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant.ResultsNinety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study.ConclusionsIn a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.

#2207 CD3(+) T cell depletion does not predict short term outcomes in kidney transplant patients

Abstract Background and Aims Anti-thymocyte globulin (ATG) is the most frequently agent used for immunosuppression induction therapy after kidney transplantation. The efficacy of the ATG treatment is monitored by peripheral blood CD3(+) T cell counts. ATG dosing can be tailored to reach and keep the target commonly accepted as below 50/μL within the week of transplant. In this study, we investigated the significance of reaching CD3(+) T cell target regarding short term adverse outcomes of biopsy-proved rejection, BK viremia and infection related hospitalization in living donor kidney transplant recipients. Method This retrospective observational study was conducted on adult patients who received living donor kidney transplants from January 1, 2015 to October 1, 2022. Demographic, clinical and laboratory information were collected using electronical medical records. The average CD3(+) T cell counts of postoperative first 3 days were calculated. Patients with CD3(+) T cell counts ≤ 50/μL were classified as “Optimally Treated”, while the patients with CD3(+) T cell counts &amp;gt;50/μL were classified as “Suboptimally Treated”. The incidence of biopsy-proven rejection, BK viremia and infection related hospitalization in 6 months following the transplant surgery were compared in these two groups. Results Sixty one patients were included in the study. Twenty eight were women and the average age was 39 ± 12.7 years. Average HLA mismatch count was 3.6 ± 1.7. Ten patients were desensitized before kidney transplant. Average ATG dose was 6.8 ± 2.3 mg/kg. Mean average CD3(+) T cell count of postoperative first 3 days were 93.9 ± 87.8/μL. During 6 months of follow up, 34.4% (n = 21) had at least one biopsy proved rejection episode, 21.3% (n = 13) had at least one infection related hospitalization and 11.4% (n = 7) had BK viremia. According to average CD3(+) T cell counts of postoperative first 3 days, 16 patients were in “Optimally Treated” group, whereas 45 patients were in “Suboptimally Treated” group. The patients in both groups had similar mean age, gender distribution, HLA mismatch, pretransplant desensitization status and total ATG doses. In 6 months of follow-up, the patients in “Optimally Treated” and “Suboptimally Treated” groups had no statistically difference in incidence of biopsy-proved rejection, BK viremia and infection related hospitalization. Conclusion In our study, we could not find any evidence to confirm the significance of reaching CD3(+) T cell target of 50/μL in first 3 days after transplant surgery regarding short term adverse outcomes of biopsy-proved rejection, BK viremia and infection related hospitalization. The value of CD3(+) T cell monitoring to adjust ATG therapy after kidney transplant surgery is questionable. Thus, in the light of our findings, we do not support the use of CD3(+) T cell counts in optimization of induction therapy with ATG after renal transplantation.

Intravenous Human Immunoglobulin in the Treatment of BK Virus Nephropathy in Kidney Transplant: A Case Report

The BK virus infection is common in the immunocompetent population and is asymptomatic in the majority of cases. However, in renal transplant patients, reactivation and replication can occur, leading to the development of BK virus-associated nephropathy (BKVN), which is associated with renal injury and graft loss. The objective of this case report was to demonstrate a case of BKVN that showed a good response to the use of human immunoglobulin. A 37-year-old man who underwent a second transplant received rabbit-derived anti-thymocyte human immunoglobulin at a dose of 6mg/kg intravenously as induction immunosuppressive therapy, and maintenance therapy with tacrolimus, prednisone, and mycophenolate sodium (MFS). At 3 months post-transplant, he presented sustained BK virus viremia (70,000-100,000 copies/mL), leading to a reduction in the dose of MFS and tacrolimus. A biopsy diagnosed BKVN class 2/B2, and viremia increased to over 1 million copies/mL at 22 months, prompting the discontinuation of tacrolimus without response. Intravenous human immunoglobulin (IVIG) was administered at 2g/kg at 22 months and again at 33 months, with viremia peaking at 2 million copies three months later. However, it steadily declined to 5,500 copies/mL at 52 months post-transplant. Currently, the only proven therapy for BKVN is the reduction of immunosuppression. However, in patients who do not respond, IVIG is considered as an option, with good results demonstrated in case reports, as shown here. Nevertheless, the data are based on case reports or case series, and the development of controlled clinical trials is necessary for confirmation of the efficacy.

Influence of induction therapy and antiretroviral regimen on outcomes in kidney transplant recipients living with human immunodeficiency.

Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.

Comparison of induction immunosuppressive therapies in adult liver transplant recipients

Comparison of induction immunosuppressive therapies in adult liver transplant recipients

Comparison of induction immunosuppressive therapies in adult liver transplant recipients

Comparison of induction immunosuppressive therapies in adult liver transplant recipients

Impact of Induction Immunosuppressants on T Lymphocyte Subsets after Kidney Transplantation: A Prospective Observational Study with Focus on Anti-Thymocyte Globulin and Basiliximab Induction Therapies.

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4+ T cell expression decreased significantly compared with that in the BXM group. However, CD4+CD161+ and CD4+CD25+CD127low T cell expression levels increased significantly. In the CD8+ T cell subset, a decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4+CD161+ and CD4+CD25+CD127low T cells and an early decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cells, some of which are associated with acute rejection.

Early occurrence of acute myelomonocytic leukemia (M4/M5) after liver transplantation: a case report

IntroductionAcute myeloid leukemia is a rare event in post-liver-transplantation recipients. In the present report, we described a case of extramedullary acute myeloid leukemia, M4/M5 subtype, following orthotopic liver transplant.Case presentationThe patient was a 50-year-old Iranian woman who underwent orthotopic liver transplant due to hepatitis B-related cirrhosis (Child C, MELD (model for end-stage liver disease score) = 22). Orthotopic liver transplant was performed using the piggy back technique in January 2022. Induction immunosuppressive therapy was 1 gm methylprednisolone for 3 days followed by a triple maintenance immunosuppressive regimen including mycophenolate mofetil, prednisolone, and tacrolimus. About 5 months after orthotopic liver transplant in June 2022, the patient presented with leukocytosis, with white blood cell count of 99.4 × 103/µl, and physical examination revealed only cervical lymphadenopathy. Biopsy of cervical lymph nodes showed a myeloid tumor. She was immediately hospitalized. Eight hours after hospitalization, the patient gradually developed lethargy and decreased O2 saturation to approximately 89%. Flow cytometry demonstrated the markers of a myelomonocytic acute myeloid leukemia (M4/M5). Cytoreduction was immediately started by intensive leukopheresis followed by induction therapy. Because of a septic complication during the induction therapy, further chemotherapy was discontinued and broad-spectrum antibiotics and antifungal treatments started. Unfortunately, our patient died of severe septic shock 42 days after hospitalization.ConclusionAcute myeloid leukemia is a rare phenomenon after liver transplantation, and it can follow a rapidly fatal clinical course.

Clinical and immunological characteristics for BK polyomavirus-associated nephropathy after kidney transplantation.

BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) can cause a significant risk of allograft impairment after kidney transplantation (KT). Intact BKPyV-specific immunity is associated with viral containment. This study investigated BKPyV-specific immunological factors among KT recipients. This prospective study in a single transplant center from January 2019 to August 2019 assessed associations between clinical and immunological characteristics, with a focus on BKPyV-cell-specific immunity and BKPyVAN, among KT recipients aged ≥15 years. The numbers of interferon-gamma (IFN-γ)-producing CD4+ T, CD8+ T, natural killer (NK), and natural killerT (NKT) cells were measured after stimulation with large T antigen and viral capsid protein 1 (VP1). In total, 100 KT recipients were included (mean age ± SD, 42 ± 11 years); 35% of the recipients were female patients, and 70% had received induction immunosuppressive therapy. The 1-year cumulative incidence of high-level BKPyV DNAuria (possible BKPyVAN) and (presumptive BKPyVAN) was 18%. Among 40 patients with immunological factor data, pre-KT %NK cells (hazard ratio [HR], 1.258; 95% confidence interval [CI], 1.077-1.469; p = .004) and %VP1-specific NK cells (HR, 1.209; 95% CI, 1.055-1.386; p = .006) were factors independently associated with possible and presumptive BKPyVAN. KT recipients with possible and presumptive BKPyVAN were more likely to exhibit significant mean coefficients of %NK, %VP1-specific NK, and %NKT cells at 1 month after KT than before KT (all p < .05). Individuals with nonspecific and VP1-specific NK cells before KT and increasing numbers of these cells after KT may be at risk for high-level BKPyV DNAuria and presumptive BKPyVAN. Further studies are needed to determine the utility of BKPyV-specific innate immune surveillance in predicting the occurrence of BKPyVAN.

Rabbit Anti-thymocyte Globulin (rATG) as Induction Immunosuppression Therapy in Patients Undergoing Renal Transplantation: Clinical Experience from RISE Registry

Rabbit Anti-thymocyte Globulin (rATG) as Induction Immunosuppression Therapy in Patients Undergoing Renal Transplantation: Clinical Experience from RISE Registry

#2649 INFECTIOUS COMPLICATIONS AFTER KIDNEY TRANSPLANTATION IN RELATION TO INDUCTION IMMUNOSUPPRESSIVE THERAPY

Abstract Background and Aims Infections are the most common non-cardiac cause of death after kidney transplantation (KT). The main goal of immunosuppressive therapy is to find a balance between the low incidence of acute rejection and infectious complications. Method We conducted a retrospective, monocentric analysis of transplant patients at the Transplant Center University Hospital Martin from 2011 to 2020 with various induction immunosuppressive therapies. We monitored the incidence of infections in terms of etiology, localization and severity at different intervals after KT. Results Our study included 39 patients on induction therapy with basiliximab to whom we paired 39 patients with induction therapy with thymoglobulin based on gender and age, in total our population consisted of 78 patients (56 men, 22 women), the mean age was 45 years. In the group of patients with induction therapy with thymoglobulin, we noted a higher proportion of fungal (P=0.0409), urogenital infections (P=0.0384), sepsis (P=0.0497) and leukopenia (0.0384) from 1st to 6th month after KTx, higher incidence of skin infections (P= 0.0218) and serious infections requiring hospitalization (P = 0.0269) from 6th-12th months to TO. On the other hand, in the basiliximab patient group, we identified a higher incidence of acute humoral and cellular rejection (P=0.0218) after 6 months of TO. From the perspective of recurrent infections, in the Thymoglobulin induction group, we noted a higher incidence of infections by localization, etiology and severity. Risk factors for recurrent bacterial infections from 1st to 6th month after KT are: history of respiratory diseases (P = 0.0108), thrombocytopenia (P = 0.0104) and infections caused by multi-resistant bacteria (P = 0.0003). Conclusion Patients on inductive immunosuppressive therapy with thymoglobulin are at a higher risk of recurrent, multidrug-resistant and severe infections after KT compared to induction with basiliximab with identical maintenance immunosuppressive therapy. On the other hand, patients on induction therapy with basiliximab have a higher risk of developing acute rejection. Therefore, it is essential to identify risk groups of patients benefiting from milder or more intensive inductive immunosuppressive therapy without a concomitant increased risk of infectious complications or acute graft rejection

#6011 VIRAL INFECTION AND DE NOVO PRODUCTION OF DONOR SPECIFIC ANTIBODIES IN KIDNEY TRANSPLANTATION: DCD VS DBD

Abstract Background and Aims Viruses are among the most common causes of opportunistic infection after transplantation and an accurate screening and follow-up is needed in order to prevent related complication as systemic damages and worsening of kidney function. On the other hand, in the first years after transplantation, antibody-mediated rejection (ABMR) is one of the first cause of graft lost and de novo production of donor specific antibody (dnDSAs) is the main source. In this monocentric study we analysed data of 255 patient transplanted from January 2016 to February 2022. We studied the incidence of viral infection and dnDSAs in the first one year after transplantation in different sub-groups of patients. Method Data was obtained from our monocentric registry, from January 2016 to February 2022. Starting from 299 kidney transplantation we obtained 255 patients with a complete annual follow-up for viral infection and DSA monitoring. We compared the incidence of viral infection and dnDSAs in different sub-group: transplanted from donation after brain-death treated with Basiliximab as induction therapy (DBDb), transplanted from donation after brain-death treated with rabbit anti-human thymocyte immunoglobulin (rATG) as induction therapy (DBDt), transplanted from donation after circulatory death treated with rATG as induction therapy (DCD) and transplanted treated with rATG as induction (DBDt+DCD). Results Global incidence of viral infection was 73% and dnDSAs formation was present in 12,5% of all patients. DBDs showed an incidence of 69% of viral infection and 10% of dnDSAs while in DBDt these values were 77,4% and 25%, respectively. In DCD data of viral infection was higher (96,7%) whereas dnDSAs was 14%. rATG (DBDt+DCD) displayed 87,1% of viral infection and 19% of dnDSAs. Conclusion Viral infection and dsDNAs are two paramount aspects in kidney transplantation and demonstrate different incidences depending on donation profile and immunosuppressive induction therapy. Specifically rATG seems to be associated to an higher rate of viral infection and DCD is the more relevant sub-group. Furthermore, rATG was associated with higher dsDNAs rate, especially in DBD treated with rATG. On the best of our knowledge, this data was never observed before. These data, due to the low number of cases, need to be confirmed from larger cohorts. Moreover our study underlines how significant is to develop a personalized approach in order to reduce complications associated to immunosuppressive therapies.

#5256 REACTIVATION OF HEPATITIS B VIRUS IN KIDNEY TRANSPLANT RECIPIENTS WITH RESOLVED INFECTION: A SINGLE-CENTER EXPERIENCE

Abstract Background and Aims Patients with end-stage renal disease (ESRD) frequently present serologic evidence of previous contact with hepatitis B virus (HBV). Although uncommon, HBV reactivation after kidney transplantation (KT) may cause serious complications and adverse outcomes in these patients. However, data regarding risk factors for reactivation are still scarce. This study aims to describe a cohort of patients with resolved HBV infection who showed reactivation of the virus after KT. Method Retrospective cohort study including patients with resolved HBV infection who underwent KT between August 2007 and December 2021. Resolved HBV infection was defined as being seronegative to HB surface antigen (HBsAg) and seropositive to HB core antibody (HBcAb), regardless of HB surface antibody (HBsAb) status. HBV reactivation after KT was defined as seropositivity to HBsAg or presence of HBV-DNA in the serum (viraemia). Preemptive prophylactic entecavir was not used. Demographic and clinical data were collected from the electronic records. Results A total of 104 patients (70.2% male) were included with a mean age of 52±10 years. Prior to KT, 93.3% were seropositive to HBsAb. Seropositivity to other viruses was present in 18 patients: human immunodeficiency virus (HIV) alone in 5 patients, hepatitis C virus (HCV) alone in 11 patients and coinfection in 2 patients. Deceased-donor KT was performed in 94.2% and only 9 patients had had a previous KT. Rituximab was used as induction immunosuppressive therapy in 13 patients. Median follow-up time after KT was 75 months (IQR 37-115). HBV reactivation occurred in 6 patients with a median time after KT of 5 months (IQR 3-11.5). At reactivation diagnosis, median HBsAg titer was 83.2 (IQR 34-784.5; reference range &amp;lt; 1) and median viral load was 6.7 × 106 copies/mL (IQR 0.4 × 106-378 × 106). Only one patient presented seropositivity to HBsAg without viraemia. Half of these patients were seropositive to HBsAb prior to KT and became seronegative at reactivation diagnosis. No liver enzyme elevation was registered at reactivation diagnosis. Donor HBcAb status, coinfection with HIV or HCV, Rituximab use and recipient HBsAb status were not associated to HBV reactivation after KT. Two patients with HBV reactivation lost kidney graft function and 2 died during follow-up. Conclusion Hepatitis B virus reactivation is possible after kidney transplantation and may pose major adjustments to the treatment, namely the immunosuppressive therapy. Careful monitoring of hepatitis B virus serology and viraemia could be particularly useful in early diagnosis and prompt approach to its reactivation. Larger and multi-center studies are warranted to identify specific risk factors in this population and prevent reactivation.

#5884 HLA COMPATIBILITY DOES NOT INFLUENCE KIDNEY GRAFT SURVIVAL AND DOES NOT IMPACT THE DEVELOPMENT OF POST-TRANSPLANT NEOPLASIA

Abstract Background and Aims HLA compatibility is a key issue in deceased and living kidney allocation, although the continuous improvement of immunosuppressive protocols might have reduced its relevance. However, an increased immunosuppression is associated with several adverse events, including the development of post-transplant neoplasia. Indeed, several reports demonstrated that the improvement in immunosuppressive drug efficiency corresponded to an increase incidence of malignancies after kidney transplantation. Thus, the aim of our study was to investigate the effect of HLA compatibility on kidney graft survival and incidence of post-transplant neoplasia. Method This is an observational, retrospective, multicenter center study including 1506 patients receiving a single kidney transplant at the Gemelli and Policlinico “Consorziale” kidney transplant centers from 1/1/2000 to 1/2/2022. The primary outcomes were death-censored graft survival and the development of post-transplant neoplasia. HLA compatibility was measured as the number of HLA mismatches (MM) at the three main class I (A and B) and class II (DR) loci. To this purpose, both donor and recipients were genotyped for HLA A, B and DR. We included in the analysis all deceased and living kidney donor transplants and excluded recipients from AB0 incompatible living kidney donors and with pre-transplant donor specific antibodies. Results Based on HLA compatibility, we divided our patients’ population in three groups (0-2 MM, 369 patients 3-4 MM, 856 patients and 5-6 MM, 281 patients). At univariate analysis (Kaplan-Meyer) number of MM were not associate with death-censored graft survival (Logrank p = 0.6) whereas we observed a significant association with the development of post-transplant neoplasia (Logrank p = 0.01). However, multivariate analysis (Cox model including recipient age, induction and maintenance immunosuppressive therapy) demonstrated that patients with 3-4 (HR 1.033, 95% CI 0.676-1.580, p = 0.9) and 5-6 MM (HR 1.342, 95% CI 0.853-2.111, p = 0.2) did not have any statistically significant increase in the risk to develop a post-transplant malignancy. Conclusion In this observational retrospective multicenter analysis, we demonstrated that HLA incompatibility, as indicated by the number of HLA A, B and DR MM, does not predict death-censored graft survival and does not impact the development of post-transplant neoplasia. Our observation would suggest that the missing effect of HLA compatibility on graft outcome is not associated with an increased long-term over-immunosuppression.

#6032 LONG-TERM OUTCOMES IN A COHORT OF PATIENTS WITH SYSTEMIC VASULITIDES (SV) AND KIDNEY INVOLVEMENT

Abstract Background and Aims Many randomized trials address the issue of SV therapy. Nevertheless, individualized treatment in patients with SV and renal involvement requires long term data and is often center specific. We present the experience of our center, a tertiary University hospital in Crete, Greece. Method Medical records were reviewed for clinical signs and symptoms. Statistical analysis was performed using SPSS 20 (IBM). Data were tested for normality, statistical significance was set at &amp;lt;0,05. Chi-Square test, Student's T-Test, Multiple-Regression analysis were utilized for statistical analysis. Results We examined 58 patients (37 females) with a mean follow-up of 5 years (Range 1-31) and a mean age of 66 years (Range 12-102). Serology revealed 46 pANCA+ve (79%), 8 cANCA+ve (14%) and 4 p/c ANCA negative patients (7%). Nine patients lost renal function and 16 patients died during follow-up. All patients received immunosuppressive induction therapy (Cyclophosphamide N = 42, Rituximab N = 7, Steroid monotherapy N = 9). All patients with pulmonary hemorrhage underwent plasmapheresis. The severity of clinical manifestation was associated with need for plasmapheresis and rapid renal function deterioration. Plasmapheresis resulted in the remission of pulmonary hemorrhage in all patients. Renal death was associated with renal function decline in months 1 and 6 post diagnosis. Treatment with cyclophosphamide or rituximab did not affect outcome (death or renal death). Number of relapses (14 patients), surprisingly, was not associated with renal function deterioration. Death was not associated with renal function deterioration in months 1 and 6 post diagnosis. Loss of Follow up was associated with increased mortality. Conclusion In this cohort either cyclophosphamide or Rituximab does not seem to affect prognosis. plasmapheresis efficiently contains pulmonary hemorrhage and, as expected, loss of follow-up is associated with poor outcomes.

#4251 KIDNEY TRANSPLANTATION WITH DONOR-SPECIFIC ANTIBODIES: A GROWING NEED

Abstract Background and Aims Preformed donor specific antibodies in kidney transplant (KT) recipients are associated with higher risk of antibody mediated rejection (ABMR) and poorer graft survival. However, remaining a long time on the waiting list is strongly related to worse patient outcomes. We aimed to analyze KT recipients with preformed DSA with mean intensity fluorescence (MFI) who received induction therapy adapted to their higher immunological risk. Method We conducted a cohort retrospective study. All KT with preformed DSA performed in our center since May 2010 until March 2021 were included in the analysis. The presence of DSA was evaluated through Luminex Single Antigen (SA®) technology. All KT were performed with cadaveric kidney donor and with previous negative test by CDC crossmatch. The induction therapy in the presence of DSA included steroids, thymoglobulin, rituximab, plasmapheresis and standard treatment with tacrolimus and mycophenolate. Results During the study period 27 KT with preformed DSA were carried out. Recipient median age was 49 (IQR 40-62) years and 70,2% were women. Dialysis vintage was 5.8 (IQR 2.3-10.2) years. 63% were blood group A and 29,5% blood group 0. 29.6% were also included in the Hypersensitized National Programme (PATHI). The main causes of sensitization were previous KT (55.6%), pregnancy (29.6%) and blood transfusions (3.7%). 63% received KT with preformed DSA class I (median MFI 2218) and 37% with preformed DSA class II (median MFI 1900). Median calculated PRA was 90.5% (IQR 80.6-98.3). Median follow up time was 32.5 (IQR 12.3-61.2) months. Seventeen kidney biopsies were carried out. The most frequent findings were acute tubular necrosis (35.3%) and active ABMR (23.5%). DSA disappeared in most of the cases in successive analysis (81%) without any differences between both DSA classes. Median serum creatinine was 1.25 (IQR 0.97-1.75) mg/dl at 12 months and 1.65 (IQR 1.1-1.81) mg/dl at 24 months. In the post-transplantation period 2 patients were diagnosed with malignant solid organ tumors, 3 developed BK nephropathy, 5 CMV asymptomatic reinfection, and 9 recurrent urinary tract infections. During the observation time, 8 grafts were lost (29.6%): 3 due to patient deaths with functioning grafts and 5 due to graft failure (3 chronic ABMR, 1 active ABMR and 1 BKV nephropathy). Graft survival was 98% and 12 months and 92% at 24 months, respectively. Conclusion DSA with MFI low levels must be considered as a risk factor of ABMR and not as a contraindication to perform KT. A reinforced induction immunosuppression therapy enables KT to patients with high immunological risk and avoid prolonged time on the waiting list.

Mycophenolate mofetil as induction and maintenance immunosuppressive therapy in adult primary central nervous system vasculitis: A prospective observational study.

To observe the clinical and angiographic effectiveness of mycophenolate mofetil (MMF) as induction and maintenance immunosuppressive therapy in primary central nervous system vasculitis (PCNSV). In this open-label prospective study done at a tertiary care neurology centre, adult patients with PCNSV, diagnosed by Calabrese's criteria, were recruited from 2017 to 2021 and treated with glucocorticoids, MMF and standard of care. Patients were followed-up and clinical and angiographic changes were recorded. Total 26 patients were recruited with median age 39years (34-49) with a slight female predilection (61.5%). Angiographic diagnoses were: small vessels disease 11.5%; large vessels disease 42.3% and both in 46.2%. Median duration of follow-up was 24.5months (14.25-38). Proportion of patients with severe disability (modified Rankin Score (mRS) 4-6) at baseline was 73.08% (19/26) which reduced to 7.69% (2/26) (p < 0.001). At the last follow-up mRS = 0 was achieved in 38.5% (10/26) and mRS of ≤ 1 was achieved in 69.2% (18/26). Median time to achieve a mRS ≤ 1 was 12months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13months (10.5-19.7), out of which 10 (62.5%) showed improvement and 5 (31.2%) showed non-progression of lesions. MMF may be an effective immunosuppressive therapy in adult PCNSV as both induction and maintenance. Serial DSA of brain may be useful to monitor the effect of treatment. Key Points • Mycophenolate mofetil is effective as induction and maintenance immunosuppressive therapy in PCNSV. • Repeat angiogram may be useful to monitor treatment response in PCNSV.

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management.

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management.