Incidence Of Rejection Research Articles

Recent advances in fecal microbiota transplantation for Clostridium difficile infection-associated diarrhea after kidney transplantation

Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.

Immunosuppressive Induction Therapy Using the Antithymocyteglobulin Grafalon: A Single-Center Non-Interventional Study.

Background: Induction therapy with depleting antibodies in the setting of liver transplantation (LT) is discussed controversially to this day. The rabbit antithymocyteglobulin (ATG) Thymoglobulin (rATG) was introduced as early as 1984 and was frequently used as a standard regime for induction therapy after LT. There are no public reports characterizing Grafalon (ATG-F), a novel ATG, as an induction agent after LT. Objectives: The aim of this observational non-interventional study was to investigate the safety and efficacy of Grafalon induction therapy and characterize its clinical effects in the setting of LT. Methods: A cohort of 80 patients undergoing deceased donor LT at the Medical University of Vienna and receiving Grafalon as part of the clinical standard immunosuppressive regimen was prospectively included between March 2021 and November 2022. Patients were monitored closely for leukocytopenia and thrombocytopenia during the first postoperative week and followed up for incidence and severity of biopsy-proven acute rejection (BPAR), overall survival, and bacterial infections in the first year after LT. Results: The incidences of thrombocytopenia and leukocytopenia following Grafalon treatment peaked on postoperative day four, with 64% and 31%, respectively. However, there were no cases of severe leukocytopenia after the first postoperative week. Induction therapy with Grafalon resulted in a rate of localized bacterial infections and bacteremia of 28% and 21%, respectively. The rate of BPAR was 12.5% in the first year after LT; the one-year survival rate in this cohort was 90%. Conclusions: Overall, this study provides evidence of the safety and efficacy of Grafalon as an induction agent. Further studies investigating the potential long-term effects of Grafalon, as well as comparison studies with different immunosuppressive regimens, are needed in order to draw further conclusions.

Impact of Intravenous Immunoglobulin Replacement Therapy on Hypogammaglobulinemia and Infection in Lung Transplant Recipients

Secondary hypogammaglobulinemia (HGG) from immunosuppression therapy in lung transplant recipients has been associated with increased mortality, morbidity and higher risk of infection. Intravenous immunoglobulin (IVIG) for the treatment of HGG post-lung transplant is not well studied with conflicting evidence regarding efficacy. This single-center, retrospective cohort study analyzed adult lung transplant recipients with HGG receiving ≥1 dose of IVIG 0.3-0.5 g/kg. Resolution of HGG (IgG > 600 mg/dL within 30 days of IVIG) was evaluated for optimal dose and duration of IVIG therapy. Incidence of infection, patient survival, rejection, and chronic lung allograft dysfunction-free survival at 1 year were compared between resolved and persistent HGG. Results demonstrated majority of patients 46/58 (79.3%) achieved HGG resolution. Severe HGG (IgG < 400 mg/dL) was significantly associated with persistent HGG (50.5% vs 15.2%, p = 0.02), with comparable cumulative IVIG dose and duration between both groups (p = 0.96 and p = 0.39, respectively). No other variables correlated with HGG resolution. Overall infection rates were similar between groups (69.6% vs 58.3%, p = 0.50), suggesting HGG resolution did not correlate with incidence of infection. Lastly, use of IVIG for the treatment of HGG appears to be safe with minimal incidence of thrombosis found within each group.

Effect of Hydroxychloroquine Treatment on Kidney Allograft Rejection and Graft Failure

Kidney allograft rejection is a major issue because it causes graft failure and because immunosuppressive treatments used for its prevention increase the risk of infections and cancers. In systemic lupus patients, hydroxychloroquine is used to prevent immune flares with decreased doses of immunosuppressants. Hydroxychloroquine can be safely used in kidney transplant recipients when indicated for autoimmune disease, but its effect on allograft rejection is unknown. We hypothesized that it may prevent kidney allograft rejection. We conducted a nationwide retrospective propensity-matched study on kidney transplantations of patients treated with hydroxychloroquine in France between 2008 and 2018. We analyzed the incidence of allograft rejection or failure within the first year after transplantation. The rates of rejection or allograft failure were not different between the 188 patients treated with hydroxychloroquine at the time of transplantation and their propensity matched controls. Hydroxychloroquine treatment in association with standard immunosuppressive treatment does not prevent rejection in kidney allograft recipients.

The Pancreas After Kidney Transplant is a Competitive Option, Comparable to the Simultaneous Pancreas and Kidney Transplant

BackgroundSimultaneous pancreas and kidney transplant (SPK) is the most common type of pancreas transplant performed worldwide. In contrast, there are a few drawbacks to pancreas after kidney transplant (PAK), such as the requirement for an additional operation, the immunologic risk, etc. SPK is the best option, but because of a lack of deceased donors and a lengthy waiting period, it is not always possible to use it. MethodsFrom 2015 to 2022, we performed 23 SPKs and 21 PAKs at the Pusan National University Yangsan Hospital in Korea. We compared the findings of PAK and SPK conducted within the same time period. ResultsThe waiting time for pancreatic graft was significantly shorter in the PAK than SPK group (345 days vs 1350 days, P ≤ .001). Throughout the monitoring period, just 1 pancreatic graft was lost in patients who underwent PAK, and the 7-year graft survival was 95%, with no statistically significant difference compared to SPK (90.3%, P = .600). Moreover, the graft survival of SPK or PAK was superior to that of pancreatic transplant alone (63.7%, P = .016). Only 1 pancreatic graft loss was a case of mortality with a functioning graft. No additional kidney transplant loss was observed in PAK recipients. There was no variation in creatinine levels between the pretransplant and posttransplant periods. There were 2 incidents of pancreatic graft and kidney graft rejection, respectively, but the grafts entirely recovered following rejection treatment. ConclusionAccording to our experiences, PAK could be another best choice for individuals with diabetic end-stage renal disease, especially in cases where deceased donors were severely deficient but living donor kidney transplants were actively performed in countries like Korea.

Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p=1.00) and serious thromboembolic events (p=0.63) did not differ between study groups. We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Comparison of cardiac allograft vasculopathy incidence between simultaneous multiorgan and isolated heart transplant recipients in the United States

BackgroundPrior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multi-organ transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multi-organ heart transplants in the contemporary era. MethodsWe utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary endpoint was the development of angiographic CAV within 5 years of follow-up. ResultsAmong 20,591 patients included in the analysis, 1,279 (6%) underwent multi-organ heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ) and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years and 74% were male. There were no significant between-group differences in cold ischemic time between the groups. The incidence of acute rejection during the first year after transplant was significantly lower in the multi-organ group (18% vs. 33%, p<0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multi-organ group (p<0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multi-organ heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio=0.76, 95% confidence interval: 0.66-0.88, p<0.01). ConclusionsSimultaneous multi-organ heart transplantation is associated with significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.

Risk factors for corneal graft rejection after penetrating keratoplasty for keratoconus.

To evaluate the association between donor-related factors and the risk of rejection in patients undergoing penetrating keratoplasty (PKP) for keratoconus. A retrospective review was performed of keratoconus patients with no corneal neovascularization who underwent PKP from November 2014 to December 2016 and completed at least two years of follow-up. Preoperative, donor, operative, and postoperative data were collected and analyzed to identify factors leading to corneal graft rejection. A total of 201 eyes (of 201 patients) that underwent PKP for keratoconus were included. Of these, 22.9% (95% CI 17.6-29.2%) had an episode of graft rejection. The overall graft survival rate was 98.5%. Receipts with a history of corneal transplant in the fellow eye (IRR 1.69, 95% CI 1.01, 2.80; p = 0.044) and those with postoperative stromal neovascularization (IRR 2.51, 95% CI 1.49, 4.21; p = 0.001) had a significantly higher incidence of rejection than those without these features. In univariate analysis, death-to-surgery time and death-to-excision time (DET) showed a weak association with graft rejection (p 0.05 and 0.08 respectively); However, in the multivariable analysis, this significance was lost. Grafts with a death-to-excision time (DET) greater than 8 h had a 0.53X lower risk of rejection compared with grafts with DET within 8 h or less (p = 0.05). Rejection was higher in patients receiving grafts with a preservation time within 7 days or less compared with preservation time greater than 7 days (30.6% vs. 21.2%, respectively, p = 0.291). In the multivariable analysis, none of the donor-related factors were significantly associated with graft rejection; however, short death-to-surgery time may be associated with rejection after PKP. Recipients with a history of PKP in the fellow eye and those who developed corneal neovascularization were also at increased risk of developing rejection after keratoplasty.

An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis.

Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients. An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA). DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV- cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors. Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.

Topical tacrolimus for high-risk corneal transplantation: a randomized, clinical trial

BackgroundThe prevalence of rejection is 10–30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical corticosteroids is a standard method for management the rejection of post-PKP patients, it may not be sufficiently potent in high-risk patients. Topical administration of tacrolimus (TAC) may be effective in suppression rejection after corneal transplantation. This study aimed to investigate the efficacy and safety of topical TAC in high-risk PKP patients in Japan.MethodsThis study was a single centre, single-blinded, randomized controlled trial. Patients with a history of PKP, graft rejection, atopic dermatitis, or deep corneal neovascularisation who underwent PKP were enrolled. They were randomly assigned to receive 0.1% TAC ophthalmic suspension or artificial tear (AT) up to week 52 after surgery. All participants received 0.1% betamethasone up to week 13 after surgery then they received 0.1% fluorometholone up to week 52. The incidence of immunological rejection during the observation period was the main outcome measure in this study.ResultsThirty patients were enrolled in this study, and 12 eyes in the TAC group and 13 eyes in the AT group completed the study, respectively. Five out of 30 patients discontinued participation after providing informed consent. No serious adverse effects were developed in patients who received 0.1% TAC ophthalmic suspension. No rejection episodes occurred in the TAC group, while one eye in the AT group had rejection. Graft clarity, best spectacle-corrected visual acuity, intraocular pressure, and corneal endothelial cell density were not significantly different between the TAC and AT groups.ConclusionOur results demonstrated that good tolerability of 0.1% TAC ophthalmic suspension. However, we failed to demonstrate its efficacy in preventing immunological rejection in high-risk patients undergoing PKP.Trial registrationThis study was first registered in the University Hospital Medical Information Network (UMIN000029669, Date of registration: November 1, 2017). With the enforcement of the Clinical Trial Act in Japan, the study re-registered in the Japan Registry of Clinical Trials (jRCTs031180342, Date of registration: March 18, 2019).

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The ‘Reduction group’ involved dose reduction of tacrolimus while the ‘Conversion group’ included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3–4 and 4–5). In the iVL 4–5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3–4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.

Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BackgroundWith patients with congenital heart disease increasingly living into adulthood, there is a growing population of patients with adult congenital heart disease (ACHD) who have heart failure. Limited data exist on evaluating heart transplantation in this population. MethodsA retrospective review was performed of patients with ACHD who underwent heart transplantation from November 1990 to January 2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those patients with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range [IQR]) or counts (%). ResultsA total of 77 patients with a median age of 36 years (IQR, 27-45 years) were identified, including 57 (74%) BiV and 20 (26%) UniV patients. Preoperatively, UniV patients were more likely to have cirrhosis (9 of 20 [45.0%] vs 4 of 57 [7.0%]; P < .001) and protein losing enteropathy (4 of 20 [20.0%] vs 1 of 57 [1.8%]; P = .015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs 13 [23%]; P = .04). Operative mortality was 6.5%, 2 of 20 (10%) among UniV patients and 2 of 57 (4%) among BiV patients (P = .276). Median clinical follow-up was 6.0 years (IQR, 1.4-13.1 years). Survival tended to be lower among UniV patients compared with BiV patients, particularly within the first year (P = .09), but it was similar for survivors beyond 1 year. At 5 years, the incidence of rejection was 28% (IQR, 17%-38%) and that of coronary allograft vasculopathy was 16% (IQR, 7%-24%). ConclusionsUnderlying liver disease and the need for heart-liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV patients, particularly within the first year, but it was similar for survivors beyond 1 year.

#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.

#1156 Outcomes after kidney transplantation in ANCA-associated vasculitis

Abstract Background and Aims ANCA-associated vasculitis with glomerulonephritis (AAV-GN) can lead to end-stage kidney disease (ESKD), requiring replacement therapy with dialysis or kidney transplant (KT). Few large studies evaluated the outcome of these patients after KT. Our aim was to describe, in comparison with a control group, the occurrence of the following events: delayed graft function recovery, graft survival, relapse, acute rejection, overall survival; and to study the risk factors associated with these events. Method This was a retrospective, multicenter (6 French centers), observational study including patients who received a KT between 2005 and 2023 for ESKD secondary to AAV-GN. Each vasculitis case receiving a KT was matched with 2 controls, matched on gender, center, recipient age (±5 years) and transplant period (±1 year). Event-free survival and the associated risk factors were analyzed. Results 369 patients were included, including 123 with AAV-GN and 246 control patients. The median post-KT follow-up for all patients was 58 months. There was no difference in the occurrence of DGF between the groups (18 vs 17%, p = 0.9). In univariable analysis, graft survival was lower in the AAV-GN group compared to the controls (76% vs 81% at 10 years, p = 0.017) (Fig 1A). 10 patients experienced a relapse after KT. ANCA positivity at the time of transplantation appeared to be correlated with relapse. There was no difference in the incidence of acute rejection between the groups (p = 0.44). In univariable analysis, overall survival tended to be lower in AAV-GN patients compared to controls (62% vs 73% at 10 years, p = 0.084) (Fig. 1B). Conclusion Kidney transplantation is an interesting option for patients with AAV-GN: the relapse rate is low, and the occurrence of acute rejection is comparable to a population of control patients. However, in AAV-GN, graft survival and overall survival appear to be poorer than in control patients. Comparison with a matched AAV-GN population remaining on dialysis would be of interest to go further.

#1155 Outcomes after kidney transplantation in anti-glomerular basement membrane disease

Abstract Background and Aims Anti-glomerular basement membrane antibody disease-associated glomerulonephritis (anti-GBM-GN) can lead to end-stage kidney disease (ESKD), requiring replacement therapy with dialysis or kidney transplant (KT). Few studies evaluated the outcome of these patients after KT. Our aim was to describe, in comparison with a control group, the occurrence of the following events: delayed graft function recovery, graft survival, relapse, acute rejection, overall survival; and to study the risk factors associated with these events. Method This was a retrospective, multicenter (6 French centers), observational study including patients who received a KT between 2005 and 2023 for ESKD secondary to anti-GBM-GN. Each vasculitis case receiving a KT was matched with 2 controls, matched on gender, center, recipient age (±5 years) and transplant period (±1 year). Event-free survival and the associated risk factors were analyzed. Results 126 patients were included, including 42 with anti-GBM-GN and 84 control patients. The median post-KT follow-up for vasculitis patients was 95 months. There was no difference in the occurrence of DGF between the groups (24 vs 18%, p = 0.5). There was no difference in graft survival when comparing both groups (78% vs 82% at 10 years, p = 0.48) (Fig. 1A). Only one patient experienced a relapse after KT (being anti-GBM negative at the time of transplantation). There was no difference in the incidence of acute rejection between the groups (p = 0.82). There was no difference in overall survival when comparing both groups (83% vs 89% at 10 years, p = 0.76) (Fig. 1B). Conclusion Kidney transplantation is an interesting option for patients with anti-GBM-GN: outcomes are similar to those of a matched population with similar occurrence of acute rejection, graft loss or death. Moreover, relapse rate is low. Comparison with a matched anti-GBM-GN population remaining on dialysis would be of interest to go further.

Impact of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplant Outcomes.

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are acute, significant respiratory deteriorations in patients with IPF and can lead to increased morbidity and mortality. It remains unclear how AE-IPF impacts lung transplant (LTX) outcomes. All adult patients who were listed for LTX between July 2005 and October 2020 at the Loyola University Medical Center with a diagnosis of IPF were included. Pretransplant characteristics and posttransplant outcomes were gathered via retrospective chart review. The primary outcome was short- and long-term survival for patients transplanted during stable IPF versus those with AE-IPF. One hundred fifty-nine patients were included in this study, 17.6% of whom were transplanted during AE-IPF. AE-IPF patients were more likely to have higher oxygen needs pretransplant, have higher lung allocation score, and were more likely to be intubated or be on extracorporeal membrane oxygenation as compared with stable IPF patients. Survival by AE status at transplant did not differ at 90 d or 1 y posttransplantation. There were also no significant differences in rates of severe primary graft dysfunction or acute rejection within 1 y. Patients with AE-IPF were more likely to have higher oxygenation requirements and higher lung allocation score at the time of LTX than those with stable IPF. Despite this, there were no differences in survival at 90 d, 1 y, or 3 y, or differences in incidence of severe primary graft dysfunction or acute cellular rejection. Transplantation of patients with AE-IPF has clinical outcomes comparable with transplantation of patients with stable IPF. This contrasts with previous studies examining LTX in patients with AE-IPF.

#1103 Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients: a systematic review and meta-analysis

Abstract Background and Aims Delayed graft function (DGF) is more common in donors after cardiac death, especially expanded criteria donors and those with longer cold ischaemia time, older or with an increased serum creatinine. There is no agreement on the optimal immunosuppressive approach in patients at increased risk of DGF, with strategies including a delayed introduction of calcineurin inhibitors (CNI) or initial low dose CNI. Our aim was to evaluate the benefits and harms of delayed initiation of CNI or reduced CNI dose as initial immunosuppression therapy for kidney transplant (KT) recipients at high risk of DGF. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 07 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomized controlled trials (RCTs) and quasi-RCTs evaluating early vs delayed initiation of CNI or reduced vs standard initial dose of CNI in kidney transplant (KT) recipients at high risk of DGF. Three authors independently assessed study eligibility, and two assessed the risk of bias, certainty of evidence, extracted the data, and performed the analysis. Results were reported as risk ratios with 95% confidence intervals for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. Statistical analysis was performed using the random-effects model. Risk of bias was assessed with RoB2 and the certainty of the evidence according to GRADE methods. Results Thirteen studies were included (2386 randomized participants). Incidence of DGF (RR 1.09, 95% CI 0.89 to 1.32; I2 = 18%) and acute rejection (RR 0.98, 95% CI 0.72 to 1.33; I2 = 54%) were similar between early and delayed introduction of CNI, as well as between low vs standard dose of CNI (DGF: RR 1.16, 95% CI 0.90 to 1.50; I2 = 9%; acute rejection: RR 0.70, 95% CI 0.43 to 1.14; I2 = 58%). There were also no differences in secondary outcomes such as graft function, graft loss, risk of death, or infection. Conclusion In patients at high risk of DGF, the strategy of delaying CNI introduction or starting at a lower dose does not reduce the risk of DGF.

#2390 Does incompatible kidney transplantation provide a reliable alternative? An updated meta-analysis

Abstract Background and Aims The ABO system often poses one of the challenges to kidney transplantation, but due to the scarcity of organs, ABO incompatible kidney transplantation (ABOi-kTx) has gained the clinical attention. So, we aim in this study to evaluate the impact of ABO incompatible kidney transplantation on patients' clinical outcomes in comparison with ABO compatible kidney transplantation (ABOc-kTx). Method We searched six electronic databases: PubMed, Scopus, WOS, Cochrane, Embase, and Medline to identify relevant studies published until October 8th 2023, with no filters applied during the research process. After screening of 8562 studies, we included observational studies that compared any clinical outcomes of ABO incompatible kidney transplantation with ABO compatible kidney transplantation across various age groups. Synthesized odds ratios (ORs) with 95% confidence intervals (CIs) are used to present the differences between the two groups based on random-effects models. Results Our comprehensive search according to the eligible criteria of this study resulted in 102 studies including 254 496 patients in both groups. Due to the clinical heterogeneity, we used random effects models for quantitative synthesis of the eligible studies. Our meta-analysis showed that there was a statistically significant higher mortality ratio after one year, 3 years and 5 years (odds ratio [OR] 2.21 [95% CI 1.56–3.14], P &amp;lt; .00001; I² = 53%), (OR 1.86 [1.35–2.75], P = .0001; I² = 61%), (OR 1.69 [1.20–2.40], P = .003; I² = 75%), respectively. While there was no statistically significant difference at 8-years after transplantation (OR 1.05 [0.76–1.46], P = .77; I² = 58%). Pooled data of graft failure from our studies revealed higher incidence in ABOi-kTx group after one year (OR 2.44 [1.81–3.28], P &amp;lt; .00001; I² = 64%), 3 years (OR 1.57 [1.24–1.98], P &amp;lt; .00001; I² = 54%) and after 5 years (OR 1.57 [1.23–2.01], P = .0003; I² = 76%), There was not any statistically significant difference between both groups after 8 years. Acute anti-body mediated rejections were noticed to be statistically higher in ABOi-kTx group (OR 2.51 [2.12–2.97], (P &amp;lt; .00001); I² = 20%). Also, there was a significantly higher incidence of CMV infection in ABOi-kTx group (OR 1.27 [1.08–1.48], (P = .003); I² = 58%). Conclusion Although that ABOi-kTx is inferior to ABOc-kTx in the first 5 years after the transplantation in patient and graft mortality. Both groups are similar in both outcomes after 8 years post transplantation. Considering the higher incidence of acute rejection in the ABOi-kTx group and increased infection rate, desensitization techniques should be furtherly developed for better survival and complication outcomes.

#2084 Biologic effect evaluation of de novo long-term release tacrolimus on metabolizer phenotype and T cell composition after kidney transplantation

Abstract Background and Aims Kidney transplantation (KTX) is the current treatment of choice in patients with kidney failure. Since immunosuppressive medication to prevent acute rejection is still needed in high doses with frequent adverse events, new strategies to achieve risk-appropriate personalization of immunosuppression are needed. Calcineurin inhibitors are the cornerstone of T cell suppression, currently available in different release formulations including once daily long-term release tacrolimus (LCPT) and regular twice daily immediate release tacrolimus (IRT). Little is known about the temporal evolution of tacrolimus metabolism potentially influencing T cell composition and clinical endpoints between different tacrolimus formulations after KTX. Method To evaluate the influence of de novo LCPT on clinical endpoints, metabolizer phenotype and immune cell composition after KTX, subgroup analysis of a single-center, prospective, observational cohort study including 32 patients started on LCPT (0.1 mg/kg) and 55 patients started on IRT (0.1 mg/kg) was conducted. Peripheral blood mononuclear cells were isolated from whole blood samples drawn before KTX, 2 months and 12 months after KTX for flow cytometry analysis. Study visits were simultaneously conducted to obtain tacrolimus dosing, plasma levels, acute rejection and infection incidence. Statistical analysis was done using GraphPad Prism (v10), accepting significance for p &amp;lt; 0.05, and flow cytometry analysis was done using FlowJo (v10) software. Results The cohort represented KTX recipients with a median age of 60 years and similar distributions of gender, HLA-mismatches and induction therapy. Clinical outcome data showed a trend towards lower acute rejection rate, lower serum-creatinine values and increased incidence of BK-viremia in LCPT treated patients. Rejection rate was associated with a fast-metabolizer phenotype (HR 3.9; 1.1-6.8, p &amp;lt; 0.01) and HLA mismatch &amp;gt; 3 (HR 4.0; 1.2-7.3, p &amp;lt; 0.01) while this effect was blunted in the LCPT group (HR 1.9; 0.7-3.2, p = 0.67 and HR 0.9; 0.3-1.4, p = 0.38 respectively) in a multivariate Cox-regression model. Cluster exploration and tSNE analysis of flow cytometry data revealed diminution of activated-proliferative effector and regulatory T cell trajectories, with significant reduction in cell counts of CD4+CD15s+/CD45RA-Ki67+Foxp3+ Treg and in CD4+CD147high/CD45RA-LAP+HLADR+FcRL3+ effector T cells in LCPT treated patients after KTX. Conclusion Induction with de novo LCPT was associated with a blunted influence of metabolizer phenotype and HLA-mismatch on acute rejection in our cohort. Major changes were detected in peripheral T cell composition after transplantation, with signs of a stronger immunosuppressive effect of LCPT on circulating activated T cells. Therefore, LCPT may be considered for KTX recipients with higher HLA-mismatch (i.e. “old-for-old”) or fast-metabolizer phenotype. Inclusion of changes in T cell composition as biologic effect measures may be worthwhile in future studies evaluating biomarkers to guide immunosuppression and predict complications after KTX.