Incidence Of Acute Rejection Research Articles

Valacyclovir versus valganciclovir for cytomegalovirus prophylaxis in kidney transplant recipients: a systematic review and comparative meta-analysis.

Valganciclovir (ValG) is the most widely used drug for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients (KTRs). However, it is associated with dose-limiting side effects and considerable costs. Some centers have identified valacyclovir (ValA) as an economically attractive alternative with a lower risk of bone marrow suppression. The comparative effectiveness of these two drugs is not well-established. This study aims to compare the efficacy and safety of ValA and ValG for CMV prophylaxis in KTRs. Searches were conducted of the Medline, Cochrane, Web of Science, Embase, and Ovid databases. Endpoints encompassed the incidence of CMV disease, CMV viremia, acute rejection, leukopenia/neutropenia, and other infections, including BK polyomavirus and non-CMV herpesviruses (HVs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Six studies, comprising 888 patients (438 receiving ValA), were included. The groups were comparable in CMV viremia incidence (RR, 0.70; 95% CI, 0.31-1.57; P=0.4) and the development of CMV disease (RR, 0.74; 95% CI, 0.09-5.97; P=0.8). No significant differences in acute rejection rates were observed (RR, 0.97; 95% CI, 0.50-1.91; P=0.8). However, the rate of leukopenia/neutropenia was significantly lower in the ValA group (RR, 0.57; 95% CI, 0.42-0.77; P<0.01). No significant differences were noted for BK viremia (RR, 0.67; 95% CI, 0.24-1.87; P=0.4) or other HV infections (RR, 1.43; 95% CI, 0.61-3.38; P=0.4). The drugs demonstrate comparable efficacy in preventing CMV infection following kidney transplantation. However, ValA may have a lower impact on bone marrow suppression.

Evaluation of Single Versus Two-Dose Basiliximab Induction Therapy in Live-Donor Liver Transplant.

Basiliximab is a high-cost induction agent typically given as two doses in liver transplant recipients. This study evaluated renal outcomes in live-donor liver transplant recipients (LDLTRs) with stable renal function at the time of transplant receiving one versus two doses of basiliximab. We retrospectively identified 231 adult LDLTR with a serum creatinine (SCr) <1.5mg/dL on post-transplant Day 5. The primary endpoint was a change in SCr from post-transplant Days 5 to 30 between the groups. Secondary endpoints included incidence of acute kidney injury (AKI), liver rejection, and culture-positive infections within 3 and 6 months of transplant. Basiliximab-related cost savings were also evaluated. Median change in SCr from post-transplant Days 5 to 30 was no different between the single-dose or two-dose groups (0.1 [IQR: -0.1-0.3] vs. 0.2 [IQR: -0.1-0.4], p = 0.08). Incidence of AKI was 56.9% in the two-dose group versus 39.0% in the single-dose group (p = 0.01). There was no difference in bacterial (p = 0.40), fungal (p = 0.59), or viral (p = 0.78) infections. Acute cellular rejection through 6 months post-transplant was noted in 9.7% of patients receiving two doses and 6.3% in the single-dose arm (p = 0.42). Basiliximab-related cost savings in the single-dose arm was ∼$697 863.72 over 159 transplants. Single-dose basiliximab appears to be safe and effective in place of two doses in LDLTR with stable renal function on post-transplant Day 5. Utilization of a single basiliximab dose significantly reduced medication-related costs.

Long-term outcomes in rapamycin on renal allograft function: a 30-year follow-up from a single-center experience

ObjectivesTo evaluate long-term renal graft prognosis and the role of rapamycin from a single-center in China over a 30-year follow-up.MethodsThis study enrolled a total of 654 patients who underwent kidney transplantation between 1989 and 2020. The basic characteristics of the included patients were collected. Graft survival was described and compared using Kaplan-Meier curves (K-M curves). Both continuous and categorical variables were included in a multivariate Cox proportional-hazards model. Patients were divided into rapamycin-based quadruple immunosuppression regimen group (rapa group, n = 41) and conventional tacrolimus-based triple immunosuppression regimen group (control group, n = 218). The indication biopsy results of the two groups were further reviewed to compare the incidence of rejection, acute rejection, and banff score.ResultsThe overall 5, 10, 15, 20-year graft survival rate of our center is 87.5%, 62.4%, 46.4% and 20.9%, respectively. The median survival time after surgery is 14 years. Multiple Cox regression analysis identified BMI (p = 0.035), dialysis type (p < 0.001), immunosuppressants (p < 0.01), urine albumen (p < 0.001), globulin (p = 0.041), and blood glucose (p = 0.002) as risk factors. The 20-year, 10-year and 5-year AUC is 0.78, 0.75 and 0.75. The combination of FK506 and rapamycin was further suggested by the model to effectively improve the graft prognosis (p < 0.01, HR = 0.763). The K-M curve showed that the long-term survival rate of renal grafts in the rapa group was significantly better than that in the conventional group (p < 0.001). In addition, indication biopsy records revealed a lower possibility of immune rejection in the rapa group than that in the conventional group (p < 0.001). Banff score indicated that rapa group had less vascular inflammation in the transplanted kidney.ConclusionsIn this study, a 30-year follow-up was performed in a single center, and a total graft 20-year survival rate of 20.9% was reported. The prognostic model and subgroup analysis suggested that FK506 combined with rapamycin could effectively improve the prognosis of renal transplantation, which could be explained by reduced acute rejection and less vascular inflammation.

Combined Whole Eye and Face Transplant: Microsurgical Strategy and 1-Year Clinical Course.

Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss.

The application of ERAS in the perioperative period management of patients for lung transplantation

ObjectiveTo explore the application of enhanced recovery after surgery (ERAS) in the perioperative period of lung transplantation. MethodsWe retrospectively collected the clinical data of 27 lung transplant patients who underwent ERAS during the perioperative period, while 12 lung transplant patients receiving routine treatment served as controls. General information was collected, including the specific implementation plan of ERAS, the incidence of complications and survival rate during the perioperative period (<30 d), postoperative hospitalization indicators, the postoperative length of stay, and numerical rating scale (NRS) scores. ResultsComparison of postoperative hospitalization indicators, the ERAS group compared with the control group, there were significant differences in postoperative ICU stay time (2.0(2.0,4.0) vs 4.5(3.0,6.0), p = 0.005), postoperative hospital stay time (18(15,26) vs 24(19.5,32.75), p = 0.016), duration of nasogastric tube (3(2,3) vs 4(2.25,4.75), p = 0.023), and first ambulation time (4(3,5) vs 5.8(4.5,7.5), p = 0.004). There was no significant difference in postoperative invasive mechanical ventilation time, time to eat after surgery, duration of urinary catheter and duration of chest tube between the ERAS group and the control group (p>0.05). The perioperative survival of the ERAS group was 81.5%, which was higher than the control group (66.7%), but there is no statistically significant difference. Comparison of post-extubation NRS scores, the ERAS group had lower NRS scores at 12 h (5.30 ± 0.14 vs 6.25 ± 0.75), 24 h (3.44 ± 0.64 vs 5.58 ± 0.9), 48 h (2.74 ± 0.66 vs 4.08 ± 0.79) and 72 h (1.11 ± 0.80 vs 2.33 ± 0.49) than the control group, the difference was statistically significant (p<0.01). Intra-group comparison, post-extubation 12 h comparison post-extubation 24 h, 48 h, 72 h, the NRS scores showed a gradual downward trend, the difference was statistically significant (p<0.01). In the comparison of perioperative complications, the ERAS group had a lower postoperative infection incidence than the control group, the difference was statistically significant (44.4% vs 83.3%, p = 0.037). The ERAS group had lower postoperative delirium incidence than the control group, the difference was statistically significant (11.1% vs 50%, p = 0.014). There was no significant difference in the incidence of acute rejection, primary graft loss (PGD), gastrointestinal (GI) complications and airway complications between two groups (p>0.05). ConclusionThe ERAS can be applied to lung transplant patients to relieve postoperative pain, shorten postoperative tube time, and shorten postoperative stay. Perioperative pulmonary rehabilitation exercises are beneficial to reducing the occurrence of postoperative pulmonary complications.

Impact of Dialysis Time on Long-term Outcomes in HLA-identical Living Donor Kidney Transplant Recipients.

Dialysis vintage is associated with worse outcomes after kidney transplantation. The reasons behind this observation include immunological and nonimmunological risk factors. To mitigate the influence of immunological factors, we examined the association between time on dialysis and clinical outcomes in a cohort of HLA-identical kidney transplant recipients. This retrospective study included 13 321 kidney transplant recipients between 1999 and 2016, of whom 589 were HLA identical followed for at least 5 y. Patient and graft survivals were compared according to dialysis time (<12 or >12 mo) using the log-rank test and Cox regression analysis. We compared surgical complications, cytomegalovirus infection, acute rejection, disease recurrence, and the trajectories of estimated glomerular filtration rate (eGFR). Median time on dialysis was 15 mo; 9.2% of patients received preemptive transplants, and 55.3% of patients were on dialysis for >12 mo. After a median follow-up time of 154 mo, there were no differences in unadjusted and adjusted patient and graft survivals (1, 5, 10, and 15 y) between the 2 groups. There were no differences in the incidence of surgical complications (6.2% versus 3.1%), acute rejection (6.1% versus 7.7%), cytomegalovirus infection (7.6% versus 4.0%), and disease recurrence (4.2% versus 4.0%), respectively. There were no differences in mean eGFR during 5 y or in the proportion of patients with an eGFR <30 mL/min at 5 y (9.9% versus 9.2%). In this low immunological risk cohort of HLA-identical kidney transplant recipients, we did not observe any association between dialysis vintage on patient survival and graft survival.

Pre-transplant Anemia as a Marker of Short-term Outcomes in Lung Transplant Recipients

BackgroundAnemia is a risk factor for increased morbidity and mortality in multiple medical conditions, yet the impact of pretransplant anemia in patients with advanced lung disease on post-transplant outcomes remains under-explored. We sought to determine whether pretransplant anemia serves as a marker of altered inflammation in the host and associates with short-term outcomes following lung transplantation. Study Design and MethodsWe performed a single-center, retrospective analysis of 238 lung transplant recipients. We assessed for risk factors of pretransplant anemia and identified associations with short-term post-transplant outcomes. ResultsPretransplant anemia was associated with increased intraoperative transfusion of packed red blood cells and a trend towards increased index hospital length of stay and 1-year mortality. Conversely, pretransplant anemia was associated with a decreased incidence of acute cellular rejection. ConclusionThese preliminary data suggest that anemia may be a biomarker of altered inflammation in the host recipient and influences post-transplant outcomes.

APOD: A biomarker associated with oxidative stress in acute rejection of kidney transplants based on multiple machine learning algorithms and animal experimental validation

BackgroundOxidative stress is an unavoidable process in kidney transplantation and is closely related to the development of acute rejection after kidney transplantation. This study aimed to investigate the biomarkers associated with oxidative stress and their potential biological functions during acute rejection of kidney transplants. MethodsWe identified Hub genes using five machine learning algorithms based on differentially expressed genes (DEGs) in the kidney transplant acute rejection dataset GSE50058 and oxidative stress-related genes (OS) obtained from the MSigDB database, and validated them with the datasets GSE1563 and GSE9493, as well as with animal experiments; Subsequently, we explored the potential biological functions of Hub genes using single-gene GSEA enrichment analysis; The Cibersort algorithm was used to explore the altered levels of infiltration of 22 immune cells during acute rejection of renal transplantation, and a correlation analysis between Hub genes and immune cells was performed; Finally, we also explored transcription factors (TFs), miRNAs, and potential drugs that regulate Hub genes. ResultsWe obtained a total of 57 genes, which we defined as oxidative stress-associated differential genes (DEOSGs), after intersecting DEGs during acute rejection of kidney transplants with OSs obtained from the MSigDB database; The results of enrichment analysis revealed that DEOSGs were mainly enriched in response to oxidative stress, response to reactive oxygen species, and regulation of oxidative stress and reactive oxygen species; Subsequently, we identified one Hub gene as APOD using five machine learning algorithms, which were validated by validation sets and animal experiments; The results of single-gene GSEA enrichment analysis revealed that APOD was closely associated with the regulation of immune signaling pathways during acute rejection of kidney transplants; The Cibersort algorithm found that the infiltration levels of a total of 10 immune cells were altered in acute rejection, while APOD was found to correlate with the expression of multiple immune cells; Finally, we also identified 154 TFs, 12 miRNAs, and 12 drugs or compounds associated with APOD regulation. ConclusionIn this study, APOD was identified as a biomarker associated with oxidative stress during acute rejection of kidney transplants using multiple machine learning algorithms, which provides a potential therapeutic target for mitigating oxidative stress injury and reducing the incidence of acute rejection in kidney transplantation.

Adverse Pregnancy Outcomes in Solid Organ Transplant Recipients

Transplant recipients experience high rates of adverse pregnancy outcomes; however, contemporary estimates of the association between solid organ transplantation and adverse pregnancy outcomes are lacking. To evaluate the association between solid organ transplantation and adverse pregnancy outcomes and to quantify the incidence of allograft rejection and allograft loss during pregnancy. PubMed/MEDLINE, EMBASE and Scopus databases were searched from January 1, 2000, to June 20, 2024, and reference lists were manually reviewed. Cohort and case-control studies that reported at least 1 adverse pregnancy outcome in pregnant women with solid organ transplantation vs without solid organ transplant or studies that reported allograft outcomes in pregnant women with solid organ transplantation were included following independent dual review of abstracts and full-text articles. Two investigators abstracted data and independently appraised risk of bias using the Newcastle Ottawa Scale. A random-effects model was used to calculate overall pooled estimates using the DerSimonian-Laird estimator. Reporting followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Primary pregnancy outcomes were preeclampsia, preterm birth (<37 weeks), and low birth weight (<2500 g). Secondary pregnancy outcomes were live birth rate, gestation, very preterm birth (<32 weeks), very low birth weight (<1500 g), and cesarean delivery. Allograft outcomes were allograft loss and rejection during pregnancy. Data from 22 studies and 93 565 343 pregnancies (4786 pregnancies in solid organ transplant recipients) were included; 14 studies reported adverse pregnancy outcomes, and 13 studies provided data for allograft outcomes. Pregnancies in organ transplant recipients were associated with significantly increased risk of preeclampsia (adjusted odds ratio [aOR], 5.83 [95% CI, 3.45-9.87]; I2 = 77.4%), preterm birth (aOR, 6.65 [95% CI, 4.09-12.83]; I2 = 81.8%), and low birth weight (aOR, 6.51 [95% CI, 2.85-14.88]; I2 = 90.6%). The incidence of acute allograft rejection was 2.39% (95% CI, 1.20%-3.96%; I2 = 68.5%), and the incidence of allograft loss during pregnancy was 1.55% (95% CI, 0.05%-4.44%; I2 = 69.2%). In this systematic review and meta-analysis, pregnancies in recipients of a solid organ transplant were associated with a 4 to 6 times increased risk of preeclampsia, preterm birth, and low birth weight during pregnancy. There was a low overall risk of graft rejection or loss during pregnancy.

Graft survival after percutaneous transluminal renal stenting for transplant renal artery stenosis (TRAS) is worse compared to matched cadaveric grafts without TRAS

Objectives Transplant renal artery stenosis (TRAS) is now recognized as a curable disease with a good prognosis if intervention occurs in the early stage. However, the mid-term outcomes of TRAS when treated by percutaneous transluminal angioplasty with stent placement have yet to be fully elucidated. The purpose of this study was to compare mid-term graft and patient survival of TRAS group with a control group. Patients and methods Ninety-two patients were diagnosed of TRAS between January 2016 and January 2022 in our center. Fifty-six pairs of recipients with grafts from the same donor were selected as a study group with TRAS and a control group without TRAS, respectively. All donor kidneys were from deceased organ donation rather than living donors. The primary endpoints were graft and patient survival. The secondary outcomes were changes in renal graft function. Results The mean follow-up time for the TRAS group was 43.6 months, while the mean follow-up time for the control group was 45.3 months. In the TRAS group, the age of patients ranged from 11 to 62 years with 39 males and 17 females. In the control group, the age of patients ranged from 18 to 67 years with 40 males and 16 females. In the TRAS group, there were more patients with diabetic nephropathy as the primary renal disease compared to the control group (5/56 vs 0/56), and the incidence of acute rejection was higher in the TRAS group than in the control group (12/56 vs 3/56). Eight patients in the TRAS group and one patient in the control group experienced graft loss (p = .019). Four patients in the TRAS group and four patients in the control group died with functional renal allograft during the follow-up time (p = .989). The levels of eGFR did not differ significantly between the two groups in the first three years after kidney transplant (p > .05). Patients in the TRAS group had worse graft functionality (eGFR, 44.96 ± 18.9 vs 54.9 ± 19.6 mL/min) in the fourth year when compared with the control group (p = .01). Conclusions The graft function deteriorated faster, and graft survival was lower in the TRAS group treated by stent placement when compared with a control group without TRAS over the mid-term.

Comparative outcomes of DSA positive, crossmatch negative living donor kidney transplants versus remaining on the waitlist for an HLA compatible deceased donor

IntroductionThe clinical relevance of preformed donor specific antibodies in the setting of a negative crossmatch (DSA + XM-) remains controversial. In this study we investigate the outcomes of patients with a DSA + XM- living donor (LDi) who proceeded with an HLA-incompatible (HLAi) transplant compared with those who waited for an HLA-compatible deceased donor (DDc). Materials and methodsWe investigated 359 patients on the transplant waiting list who had at least one potential HLAi living donor, from which 203 DSA + XM- pairs were identified and outcomes analysed. ResultsOut of 203 patients, 96 (47.3%) received a LD transplant: 52/96 (54.2%) a LDi, and 44/96 (45.8%) an alternative compatible LD. In addition, 107 patients out of 203(52.7%) waited for a DDc, of which 47(43.9%) were subsequently transplanted. Our adjusted analysis showed that the LDi transplantation did not offer a superior patient survival over waiting for a DDc transplant. For those transplanted, there was no difference in patient (p = 0.065) or death censored allograft survival (p = 0.37) between DDc and LDi recipients. However, there was a higher incidence of acute allograft rejection (p = 0.043) and antibody-mediated rejection (p = 0.005) in the LDi group. Having a high pre-transplant calculated reaction frequency and preformed DSA to both class I and class II antigens were associated with inferior outcomes in the LDi transplants. ConclusionsGiven the lack of difference in allograft survival between LDi and DDc transplants, in the absence of an alternative compatible living donor, proceeding with a LDi should be supported despite a higher rejection risk, providing individual risk assessment and shared decision making is undertaken.

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.

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.

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.

#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.

#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.