Clinical implications of early blood transfusion after kidney transplantation

Clinical implications of early blood transfusion after kidney transplantation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical implications of early blood transfusion after kidney transplantation Minyu Kang, Hwa-Hee Koh, Seung Hyuk Yim, Mun Chae Choi, Hyun Jeong Kim, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4978680/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Feb, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background Pre-transplantation red blood cell transfusion (RBCT) is a well-recognized cause of allosensitization. However, the effects of RBCT after kidney transplantation remain controversial. This study evaluates the impacts of RBCT within the first 30 days post-transplantation (early RBCT) with regard to long-term patient and graft outcomes. Methods We retrospectively analyzed 785 patients who underwent HLA- and ABO-compatible kidney transplantation between 2014 and 2020. Patients were categorized based on whether they received early RBCT. Results Overall, 18.9% of patients received early RBCT. On multivariable analysis, early RBCT was independently associated with increased risks of all-cause mortality (hazard ratio, 2.264; 95% CI, 1.186–4.324; P = 0.013) and death-censored graft loss (hazard ratio, 1.995; 95% CI, 1.045–3.810; P = 0.036). Cumulative incidence of antibody-mediated rejection was significantly higher in the early RBCT group ( P = 0.024). In the sensitivity analysis, the early RBCT significantly increased the risk of patient mortality ( P = 0.017), death-censored graft loss ( P = 0.018) and antibody-mediated rejection ( P = 0.05), regardless of the donor profile. Conclusions Early post-transplantation RBCT was associated with increased risks of all-cause mortality, graft loss, and antibody-mediated rejection, highlighting the need for reconsideration of transfusion practices following kidney transplantation. Health sciences/Diseases/Kidney diseases/Chronic kidney disease Health sciences/Medical research/Outcomes research Biological sciences/Immunology/Transplant immunology Biological sciences/Immunology/Transplant immunology/Allograft Health sciences/Nephrology Health sciences/Nephrology/Kidney diseases/Chronic kidney disease allosensitization graft survival kidney donor profile index kidney transplantation transfusion Figures Figure 1 Figure 2 Introduction At the time of kidney transplantation, the majority of patients with end-stage kidney disease have anemia secondary to reduced endogenous erythropoietin production and iron deficiency 1 . Anemia often worsens in the early post-transplantation period for various reasons, including intraoperative blood loss, allograft dysfunction, and the effects of immunosuppressive therapy 2 . Consequently, red blood cell transfusion (RBCT) is frequently administered as an effective and immediate intervention in the early post-transplantation period, with 20–60% of transplant recipients receiving post-transplantation RBCT 3 – 6 . While the risks of alloimmunization associated with pre-transplantation RBCT are well-established 7 , 8 , the implications of RBCT during the immunosuppressed, post-transplantation period are less clear 9 . The impact of RBCT on graft outcomes has been the subject of considerable debate, with previous studies reporting conflicting results 4 – 6 , 10 . This leads to considerable variability in RBCT practices across different transplantation centers and between different physicians, which is further compounded by the absence of a standardized target hemoglobin level for post-transplantation RBCT. The ongoing evolution of immunosuppressive therapies and changing indications for RBCT also add to the complexity of this issue 11 – 13 . Moreover, continuing advances in solid-phase assays and refinement of the criteria for diagnosing antibody-mediated rejection (AMR) further highlight the pressing need to explore the effects of post-transplantation RBCT considering contemporary clinical practices and emerging medical evidence 14 , 15 . The objective of this study was to evaluate the clinical implications of RBCT within the first month after kidney transplantation with regard to patient survival, graft survival, and biopsy-proven rejection. Results Baseline characteristics After applying the inclusion and exclusion criteria, 785 patients were included in this study, 148 (18.9%) of whom received early RBCT (within 1 month after transplantation). Baseline characteristics are summarized in Table S1 . No significant differences were observed between the early RBCT and no RBCT groups regarding recipient and donor age, number of HLA mismatches, and proportion of re-transplantation. Recipients in the early RBCT group were more frequently female, had a longer duration of pre-transplantation dialysis, and more frequently received a deceased donor graft, compared to those in the no RBCT group. The proportion of patients receiving anti-thymocyte globulin induction was significantly higher in the early RBCT group (44.6% vs. 19.0%, P < 0.001). The median follow-up duration of the entire study population was 66 months (IQR, 44.0–86.0 months). Transfusion characteristics A total of 469 packed red blood cells were administered to 148 recipients within 1 month after kidney transplantation. The median number of packed red blood cells among transfused recipients was 2 (IQR, 1.0–3.0), and the median time from transplantation to the first RBCT was 5.0 days (IQR, 2.0–12.0 days). Although pre-transplantation hemoglobin levels were comparable between the two groups, the lowest hemoglobin level during the first month after transplantation was significantly lower in the early RBCT group than in the no RBCT group (9.6 ± 1.2 vs. 7.6 ± 1.0 g/dL, P < 0.001). To investigate independent risk factors for requiring early RBCT after transplantation, we conducted multivariable logistic regression analysis ( Table S2 ). Recipient age, diabetes mellitus, body mass index, re-transplantation, dialysis vintage, and intraoperative RBCT did not exhibit significant associations with early RBCT after transplantation. In contrast, female recipient, lower pre-transplantation hemoglobin levels, and anti-thymocyte globulin induction were identified as significant risk factors associated with early RBCT. Graft and patient outcomes During the follow-up period, 43 (5.5%) of the 785 patients died, and 44 (5.6%) experienced death-censored graft loss. As depicted in Fig. 1 , both patient survival and death-censored graft survival were significantly lower in the early RBCT group than in the no RBCT group. The 1-year, 3-year, and 5-year patient survival rates were 95.8%, 92.3%, and 87.4% for the early RBCT group and 98.7%, 97.6%, and 96.2% for the no RBCT group ( P < 0.001). Multivariable Cox regression analysis confirmed the independent association between early RBCT and higher all-cause mortality (adjusted hazard ratio [aHR], 2.264; 95% confidence interval [CI], 1.186–4.324; P = 0.013; Table 1 ). Additionally, the amount of transfused packed red blood cells was associated with an increased risk of all-cause mortality when assessed as continuous variable (aHR, 1.130; 95% CI, 1.084–1.177; P < 0.001). The 1-year, 3-year, and 5-year death-censored graft survival rates were 97.3%, 94.4%, and 89.8% for the early RBCT group and 99.4%, 97.1%, and 95.6% for the no RBCT group ( P = 0.004). Early RBCT was significantly associated with an increased risk of death-censored graft loss on multivariable analysis (aHR, 1.995; 95% CI, 1.045–3.810; P = 0.036; Table 2 ). Table 1 Risk factor assessment for all-cause mortality Factors Univariable Multivariable cHR (95% CI) P value aHR (95% CI) P value Age (for 1 year increase) 1.075 (1.041–1.109) < 0.001 1.073 (1.035–1.114) < 0.001 Female 0.383 (0.184–0.799) 0.011 0.290 (0.133–0.634) 0.002 Diabetes mellitus 2.055 (1.121–3.769) 0.020 1.934 (0.950–3.938) 0.069 Re-transplantation 1.869 (0.789–4.431) 0.155 2.242 (0.929–5.408) 0.072 Dialysis duration (for 1 month increase) 1.009 (1.005–1.012) < 0.001 1.007 (1.001–1.012) 0.026 HLA mismatch 1.316 (1.080–1.603) 0.006 1.428 (1.133-1.800) 0.003 ATG induction 4.362 (2.390–7.959) < 0.001 1.777 (0.842–3.750) 0.131 Deceased donor KT 5.262 (2.652–10.439) 0.006 2.627 (0.957–7.206) 0.061 Donor age (for 1 year increase) 1.021 (0.996–1.047) 0.095 0.991 (0.968–1.014) 0.424 Female donor 1.082 (0.595–1.968) 0.796 Early RBCT 3.022 (1.640–5.571) < 0.001 2.264 (1.186–4.324) 0.013 aHR, adjusted hazard ratio; ATG, anti-thymocyte globulin; cHR, crude hazard ratio; CI, confidence interval; HLA, human leukocyte antigen; KT, kidney transplantation; RBCT, red blood cell transfusion Table 2 Risk factor assessment for death-censored graft loss Factors Univariable Multivariable cHR (95% CI) P value aHR (95% CI) P value Age (for 1 year increase) 1.013 (0.987–1.040) 0.332 1.002 (0.974–1.031) 0.895 Female 0.673 (0.357–1.269) 0.673 Diabetes mellitus 1.341 (0.711–2.530) 0.365 1.412 (0.712–2.801) 0.323 Re-transplantation 0.545 (0.132–2.254) 0.402 Dialysis duration (for 1 month increase) 1.001 (0.996–1.006) 0.673 HLA mismatch 1.233 (1.018–1.493) 0.032 1.249 (1.018–1.531) 0.033 ATG induction 2.186 (1.180–4.048) 0.013 1.661 (0.731–3.778) 0.226 Deceased donor KT 1.650 (0.913–2.981) 0.097 1.240 (0.548–2.806) 0.606 Donor age (for 1 year increase) 1.027 (1.002–1.053) 0.035 1.018 (0.992–1.044) 0.168 Female donor 0.949 (0.525–1.714) 0.862 Early RBCT 2.408 (1.291–4.493) 0.006 1.995 (1.045–3.810) 0.036 aHR, adjusted hazard ratio; ATG, anti-thymocyte globulin; cHR, crude hazard ratio; CI, confidence interval; HLA, human leukocyte antigen; KT, kidney transplantation; RBCT, red blood cell transfusion . Biopsy-proven allograft rejection A total of 245 biopsy-proven allograft rejection episodes (134 AMR and 111 TCMR) occurred in 165 recipients. The median time to the first biopsy-proven allograft rejection was 5 months (IQR, 2.0–23.0). Cumulative incidence for AMR was significantly higher in the early RBCT group than in the no RBCT group ( P = 0.024; Fig. 2 ), whereas cumulative incidence for TCMR between the two groups was not significantly different ( P = 0.641). Multivariable analysis confirmed the independent association between early RBCT and the development of AMR (aHR, 1.655; 95% CI, 1.054–2.598; P = 0.029). Number of HLA mismatches (aHR, 1.352; 95% CI, 1.181–1.547; P < 0.001) and donor age (aHR, 1.019; 95% CI, 1.002–1.036; P = 0.027) were also identified as independent risk factors for AMR. Graft renal function Mean eGFR values at various time points in the two groups are shown in Figure S4 . Mean eGFR at 1 month after kidney transplantation was significantly lower in the early RBCT group (58.2 ± 28.3 vs. 68.2 ± 21.0 mL/min/1.73 m 2 , P < 0.001). Mean eGFR was not significantly different between groups at 3 months post-transplantation and thereafter. Sensitivity analysis To address potential selection bias due to the inclusion of patients in poor condition in the transfusion group or those receiving kidneys from suboptimal donor, we performed a 1:2 propensity score matching for sensitivity analysis based on the donor type (Living or Deceased donor) and the donor profile (KDPI or LKDPI). This analysis resulted in a cohort of 398 kidney transplant recipients. 269 patients (68.1%) received early red blood cell transfusion (RBCT), while 139 patients (31.9%) did not ( Table S3 ). The matched group revealed differences only in preoperative hemoglobin levels and use of antithymocyte globulin. No statistical differences were observed in other variables. Patient survival and death-censored graft survival were considerably lower in the early RBCT group compared to the no RBCT group. The survival rates of patients at 1 year, 3 years, and 5 years were 94.9%, 91.9%, and 89.7% in the RBCT group, while in the no RBCT group, they were 97.4%, 96.6%, and 96.2%, respectively ( P = 0.017; Figure S2 a ). The death-censored graft survival rates at 1 year, 3 years, and 5 years were 97.0%, 96.1%, and 93.9% for the early RBCT group, compared to 98.9%, 98.4%, and 98.4% for the no RBCT group ( P = 0.018; Figure S2 b ). Also, cumulative incidence for AMR was higher in the early RBCT group compared to the no RBCT group ( P = 0.05; Figure S3 ), Importantly, in risk analyses, early RBCT was independently associated with an increased risk of death-censored graft loss, as shown by multivariable regression analysis (aHR 0.502; 95% CI, 1.150–2.372; P = 0.007; Table S4 ). Number of HLA mismatch also showed the risk, but types of induction agents were not associated with patient outcome. Discussion We had hypothesized that early red blood cell transfusion (RBCT) after kidney transplantation would be associated with adverse outcomes, including increased risks of all-cause mortality, graft loss, and antibody-mediated rejection. In this single-center study of 785 kidney transplant recipients, we investigated the clinical implications of early RBCT after transplantation. Our results revealed a significant, dose-dependent association between early RBCT and increased risk of all-cause mortality. Patients receiving early RBCT also had a higher risk of death-censored graft loss and AMR, compared to those who did not receive early RBCT. However, no significant associations were observed between early RBCT and TCMR or graft renal function after the first post-transplantation month. These results underscore the nuanced associations between early RBCT and specific clinical outcomes following kidney transplantation. Because donor profile was expected to affect posttransplantation outcomes, we performed subgroup analysis for sensitivity analysis. In the subgroup analysis, the early RBCT significantly increased the risk of patient mortality, death-censored graft loss and antibody-mediated rejection, regardless of the donor profile. Pre-transplantation RBCT is a well-recognized risk factor for developing anti-HLA antibodies 7 , 8 . To mitigate this risk, considerable efforts have been made to minimize pre-transplantation RBCT and to use leukocyte-depleted blood products 7 , 16 . Nevertheless, the effects of RBCT during the post-transplantation period, particularly during the period of intense immunosuppressive therapy, remain controversial 4 – 6 , 17 , 18 . In addition to the risk of alloimmunization, both anemia severe enough to require RBCT and RBCT itself may have detrimental effects, especially in the clinical setting of major surgery. Although a substantial proportion (20–60%) of kidney transplant recipients receive post-transplant RBCT, research on the long-term clinical implications of post-transplantation RBCT remains limited. Our study aimed to comprehensively investigate the associations between early post-transplantation RBCT on various long-term outcomes. Perioperative RBCT has been linked to higher mortality following major surgery 19 , 20 . This association is secondary not only to preoperative anemia or intraoperative bleeding but also to complications induced by RBCT itself, such as acute lung injury, circulatory overload, infection, and immunosuppression 21 . Kidney transplant recipients commonly experience anemia, leading to widespread use of RBCT in the early post-transplant period 3 – 6 , 21 . However, the impact of post-transplant RBCT on patient survival remains controversial, and there is a lack of clear indications for RBCT in this setting. In the current large-scale study of recent kidney transplant recipients, we found that 18.9% of recipients received early RBCT after transplantation, and receiving early RBCT was associated with a dose-dependent increase in all-cause mortality. These findings align with those of a previous single-center study, which also identified a dose-dependent relationship between post-transplantation RBCT and all-cause mortality 17 . However, this prior study included RBCT at any time after transplantation and did not provide specific indications for RBCT. Recent national cohort data from Korea also demonstrated a dose-dependent association between RBCT during hospitalization and all-cause mortality but did not distinguish between intraoperative and postoperative RBCT 22 . Overall, the findings of our study and others underscore the need to reconsider the effects of RBCT through further in-depth investigations into the specific effects of post-transplant RBCT on kidney transplantation outcomes. Our results revealed that postoperative RBCT was also significantly associated with not only mortality but also death-censored graft survival in the current study. Previous research on the impact of RBCT on graft outcomes has produced mixed results, with some studies reporting negative effects and others finding no significant impact 4 – 6 , 17 . These inconsistencies may be attributed to variations in transfusion practices over time and between institutions and practitioners, as well as a lack of clear transfusion guidelines. Our study, with its more recent and uniform cohort, provides updated insights that may be used to inform current transfusion protocols and highlights the need for a cautious approach to postoperative RBCT in the context of kidney transplantation. We identified early postoperative RBCT as an independent risk factor for developing AMR, but not TCMR. This association, while not proof of causality, offers a plausible explanation for the observed decrease in death-censored graft survival in our cohort. It suggests that RBCT specifically affects humoral immunity 23 . Moreover, previous studies have linked postoperative RBCT with the development of de novo donor-specific antibodies, further supporting the potential immunological implications of RBCT 4 , 9 . Together, our findings, although retrospective and requiring careful interpretation, underscore the need to revisit current transfusion practices in kidney transplantation. Although the Kidney donor profile index (KDPI) or Living kidney donor profile index (LKDPI) scores are a well-known predictor for post-transplant outcomes 24 , 25 , previous researches have not investigated the post-transplantation outcomes after transfusion while considering the donor profile 5 , 6 , 10 , 17 . Our research is significant in that we discovered transfusion remains a risk factor affecting patient outcomes even under similar donor profile conditions. It is important to emphasize that the relationship between RBCT and poor outcomes may be an association, as causation was confirmed with sensitivity analysis. This study has several limitations that deserve consideration. Firstly, future prospective studies with clear indications for RBCT are required to more conclusively determine the effects of early RBCT. Secondly, protocol biopsies were not routinely obtained in all patients, so episodes of subclinical rejection may have been missed. Nevertheless, we meticulously examined all indicated biopsies, and allograft rejection episodes were analyzed using the latest Banff criteria. In conclusion, our findings highlight a significant association between early post-transplantation RBCT and increased risk of all-cause mortality, death-censored graft failure, and AMR in kidney transplant recipients. These results warrant a critical reassessment of RBCT practices in the post-transplantation setting and emphasize the urgent need for further research and updated evidence-based clinical guidelines regarding transfusion practices. Methods Study design and participants We screened consecutive adults who underwent kidney transplantation between January 2014 and December 2020 at Severance Hospital, Seoul, Republic of Korea. We excluded patients who underwent multi-organ transplantation, received HLA- and/or ABO-incompatible kidneys, or experienced graft loss or death within 1 month after transplantation. After excluding ineligible patients, 785 recipients were included in this study ( Figure S1 ). To perform sensitivity analysis, all patients’ KDPI 26 or LKDPI 27 scores were collected, and a total of 398 matched cohorts were created. All study procedures were conducted in accordance with the Declaration of Helsinki and were approved by the Institutional Review Board of Severance Hospital (4-2022-1073). Informed consent was waived by the Institutional Review Board of Severance Hospital because of the study’s retrospective design. Exposure The main study exposure was “early RBCT”, which was defined as transfusion of packed red blood cells within 30 days after transplantation, starting on postoperative day 1. We selected this timeframe based on existing literature suggesting that a significant proportion of blood transfusions occur during the first month post-transplantation 3 , 4 . Patients were categorized into two groups: those who received early RBCT and those who did not. Throughout the study period, our institution exclusively used leukocyte-depleted packed red blood cells for transfusions. Data regarding transfusions were confirmed by comprehensively reviewing the blood bank records and each patient’s chart. RBCT decisions were guided by a general target hemoglobin level of 7.0 g/dL, although transfusion decisions were ultimately left to the discretion of the attending physician, who considered several other factors, such as the presence of heart disease, abnormal vital signs, or bleeding tendency. Immunosuppression Immunosuppressants were prescribed according to the standard protocol at our institution 28 . Most patients received induction therapy with basiliximab or anti-thymocyte globulin. Anti-thymocyte globulin was preferred in high-risk transplant recipients, such as those who underwent deceased donor kidney transplantation or received old-to-young grafts. Maintenance immunosuppression consisted of tacrolimus, prednisolone, and mycophenolate mofetil (MMF). The initial tacrolimus dosage was 0.1 mg/kg orally twice daily, with subsequent doses titrated to maintain a trough concentration of 5–8 ng/mL. The initial dose of intravenous methylprednisolone was 500–1000 mg, which was gradually reduced and converted to oral prednisolone (5–10 mg/day) during the first 3 weeks after transplantation. The initial dose of MMF was 1.0 g/day, which was subsequently adjusted to minimize adverse events (e.g., gastrointestinal side effects, neutropenia). Study endpoints and definitions The primary study endpoint was patient survival. The secondary endpoints included death-censored graft survival, biopsy-proven allograft rejection, and graft renal function. Patient survival was calculated from the date of transplantation to the date of death, loss to follow-up, or December 31, 2022 (the end of the study follow-up). Death-censored graft loss was defined as the return to dialysis or the need for re-transplantation. Graft survival was calculated from the date of transplantation to the date of graft loss or December 31, 2022. Renal biopsies were performed in patients with acute allograft dysfunction, which was defined as a > 30% increase in serum creatinine level above baseline or proteinuria of > 500 mg/day. Allograft biopsy samples were processed using light, immunofluorescent, and electron microscopy. All allograft rejections were confirmed by biopsy and classified as AMR or T-cell mediated rejection (TCMR) according to the most recent Banff criteria at the time of the biopsy 29 . Cases of mixed rejection (in which AMR and TCMR occurred simultaneously) were analyzed as AMR. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration Eq. 3 0 . Statistical analysis Depending on the type of variable, data were expressed as frequency, mean ± standard deviation, or median and interquartile range (IQR). Continuous variables were compared using Student’s t-test and Mann-Whitney test and categorical variables were compared using Chi-square or Fisher’s exact test. Multivariable logistic regression analysis was performed with early RBCT as the outcome variable. Patient survival, graft survival, and cumulative incidence of biopsy-proven allograft rejections were analyzed using Kaplan-Meier curves and the log-rank test. Associations between early RBCT and time-to-event outcomes were evaluated using Cox proportional hazard models, which included the following covariates: sex, age, dialysis duration, diabetes mellitus, re-transplantation, induction agent (anti-thymocyte globulin vs. basiliximab), type of donor (living vs. deceased), early RBCT, number of HLA mismatches, donor age, and donor sex. Clinically significant variables and variables with a p value ≤ .2 in univariable analyses were introduced in multivariable regression models. For sensitivity analysis, propensity score matching analysis was performed by matching donor profiles. Statistical analyses were performed using SPSS software (version 26.0; SPSS Inc., Chicago, IL, USA) and R (version 3.6.3; R Foundation for Statistical Computing, Vienna, Austria). All tests were performed two-tailed, and p values < .05 were considered significant. 31 Declarations Conflict of interest statement: The authors of this manuscript have no conflicts of interest to disclose as described by the Scientific Reports. Funding: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C1529). Author Contribution M.K. and J.L. drafted the manuscript. M.K., H-H.K., and J.L. conceived and designed the study. S.H.Y., M.C., H.J.K., H.W.K., J.Y., B.S.K., K.H.H., M.S.K., and J.L. collected the data. M.K. and J.L. performed the statistical analysis and interpreted the data. All authors read and approved the final version of the manuscript. Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. References Fishbane, S. & Spinowitz, B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am. J. Kidney Dis. 71 , 423–435 (2018). Vanrenterghem, Y. et al. Prevalence and management of anemia in renal transplant recipients: a European survey. Am. J. Transplant. 3 , 835–845 (2003). Scornik, J. C., Schold, J. D., Bucci, M. & Meier-Kriesche H.-U. Effects of blood transfusions given after renal transplantation. Transplantation . 87 , 1381–1386 (2009). Ferrandiz, I. et al. 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Shared alloimmune responses against blood and transplant donors result in adverse clinical outcomes following blood transfusion post–renal transplantation. Am. J. Transplant. 19 , 1720–1729 (2019). Gaiffe, E. et al. Early post-transplant red blood cell transfusion is associated with an increased risk of transplant failure: A nationwide French study. Front. Immunol. 13 , 854850 (2022). Halloran, P. F. Immunosuppressive drugs for kidney transplantation. N. Engl. J. Med. 351 , 2715–2729 (2004). Carson, J. L. et al. Red blood cell transfusion: 2023 AABB international guidelines. JAMA . 330 , 1892–1902 (2023). Babitt, J. L. et al. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney international 99, 1280–1295 (2021). Zhang, R. Donor-specific antibodies in kidney transplant recipients. Clin. J. Am. Soc. Nephrol. 13 , 182–192 (2018). Loupy, A., Mengel, M. & Haas, M. 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Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery. Ann. Surg. 252 , 11–17 (2010). Rohde, J. M. et al. Health care–associated infection after red blood cell transfusion: a systematic review and meta-analysis. Jama . 311 , 1317–1326 (2014). Lee, K. et al. The association between peri-transplant RBC transfusion and graft failure after kidney transplantation: a nationwide cohort study. J. Clin. Med. 10 , 3750 (2021). Refaai, M. A. & Blumberg, N. Transfusion immunomodulation from a clinical perspective: an update. Expert Rev. Hematol. 6 , 653–663 (2013). Kim, H. J. Clinical relevance of the Living Kidney Donor Profile Index in Asian kidney transplant recipients. Korean J. Transplantation . 36 , 140–140 (2022). Dahmen, M. et al. Validation of the Kidney Donor Profile Index (KDPI) to assess a deceased donor’s kidneys’ outcome in a European cohort. Sci. Rep. 9 , 11234 (2019). Rao, P. S. et al. A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation . 88 , 231–236 (2009). Massie, A. B. et al. A risk index for living donor kidney transplantation. Am. J. Transplant. 16 , 2077–2084 (2016). Lee, J. et al. The recovery status from delayed graft function can predict long-term outcome after deceased donor kidney transplantation. Sci. Rep. 7 , 13725 (2017). Loupy, A. et al. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell–and antibody-mediated rejection (Wiley Online Library, 2020). Inker, L. A. et al. New creatinine-and cystatin C–based equations to estimate GFR without race. N. Engl. J. Med. 385 , 1737–1749 (2021). Additional Declarations No competing interests reported. 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Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hwa-Hee","middleName":"","lastName":"Koh","suffix":""},{"id":357380138,"identity":"76d12bc6-0014-4027-8a1e-e3b7663c938e","order_by":2,"name":"Seung Hyuk Yim","email":"","orcid":"","institution":"Yongin Severance hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Seung","middleName":"Hyuk","lastName":"Yim","suffix":""},{"id":357380139,"identity":"da1fa97c-37ab-43cd-93c0-530554c63386","order_by":3,"name":"Mun Chae Choi","email":"","orcid":"","institution":"Armed Forces Capital Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mun","middleName":"Chae","lastName":"Choi","suffix":""},{"id":357380140,"identity":"efed97aa-9863-4381-b471-733d2c2ee2e7","order_by":4,"name":"Hyun Jeong Kim","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hyun","middleName":"Jeong","lastName":"Kim","suffix":""},{"id":357380141,"identity":"bb407d31-7bf5-4ee7-bab8-7171a1f7b83f","order_by":5,"name":"Hyung Woo Kim","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hyung","middleName":"Woo","lastName":"Kim","suffix":""},{"id":357380142,"identity":"d542cccc-d064-4ad1-9010-976fbc7778a1","order_by":6,"name":"Jaeseok Yang","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jaeseok","middleName":"","lastName":"Yang","suffix":""},{"id":357380143,"identity":"f17e768f-0709-4dfc-a748-8187f8353524","order_by":7,"name":"Beom Seok Kim","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Beom","middleName":"Seok","lastName":"Kim","suffix":""},{"id":357380144,"identity":"d3b367e1-b97f-48f6-b956-73feba685ff5","order_by":8,"name":"Kyu Ha Huh","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kyu","middleName":"Ha","lastName":"Huh","suffix":""},{"id":357380145,"identity":"4210d44d-3bb9-4de7-9de3-1625f27329d3","order_by":9,"name":"Myoug Soo Kim","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Myoug","middleName":"Soo","lastName":"Kim","suffix":""},{"id":357380146,"identity":"ea9b0423-4138-43b0-8cbb-b3003d8dc83c","order_by":10,"name":"Juhan Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIie2QoQoCQRRFrwhaBse4i6K/8JaFsfktI9ZRTCIYtFn8gP0PYfMsEyzaN1i2mBbzBoOrCMYZm+Cc8so73Pse4PH8IB2goUEAB1puynPtpYTb75Qa0s5K+6x1tbgM4lyJosJ4aFfYXGZ7usYiV6OYYRpt7cUUaUZmktYpPaAp7Sm8pOxOZnNIlAgrbByUQJGpUyQFSgQMxkW5SdMnEyWn67LH6Gi/hfNZVpR3M+S7aRpWq7X9YwB7z+6zEjkIH4Vrp3WPx+P5Qx4iZjiH5WJWNwAAAABJRU5ErkJggg==","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Juhan","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2024-08-26 14:28:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4978680/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4978680/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-90068-2","type":"published","date":"2025-02-25T15:57:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66869032,"identity":"779d9029-c18e-43b5-a6de-e22ec2867295","added_by":"auto","created_at":"2024-10-17 09:28:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":500246,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier curves for (A) patient survival and (B) death-censored graft survival in the early RBCT and no RBCT groups.\u003c/p\u003e\n\u003cp\u003eAbbreviations: RBCT, red blood cell transfusion\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4978680/v1/a80216be6bad407a8cde162f.png"},{"id":66869033,"identity":"7afb345c-90e7-45c8-a021-9213c420f62a","added_by":"auto","created_at":"2024-10-17 09:28:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":254680,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of antibody-mediated rejection in the early RBCT and no RBCT groups.\u003c/p\u003e\n\u003cp\u003eAbbreviations: AMR, antibody-mediated rejection; RBCT, red blood cell transfusion\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4978680/v1/bb83d7926d60ba457fe95bed.png"},{"id":77622706,"identity":"b546cde7-f0ec-42ef-a4c7-d07124b1dfc5","added_by":"auto","created_at":"2025-03-03 16:09:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1483712,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4978680/v1/d3146200-f192-44b7-9bb9-666eb939e2ff.pdf"},{"id":66869034,"identity":"6bd1095f-b2bc-408c-b4c7-8e7b78f821b6","added_by":"auto","created_at":"2024-10-17 09:28:10","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":564263,"visible":true,"origin":"","legend":"","description":"","filename":"RBCTinKTsupplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-4978680/v1/597f3723c2136f9bbaf28331.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical implications of early blood transfusion after kidney transplantation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAt the time of kidney transplantation, the majority of patients with end-stage kidney disease have anemia secondary to reduced endogenous erythropoietin production and iron deficiency \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Anemia often worsens in the early post-transplantation period for various reasons, including intraoperative blood loss, allograft dysfunction, and the effects of immunosuppressive therapy \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Consequently, red blood cell transfusion (RBCT) is frequently administered as an effective and immediate intervention in the early post-transplantation period, with 20\u0026ndash;60% of transplant recipients receiving post-transplantation RBCT \u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile the risks of alloimmunization associated with pre-transplantation RBCT are well-established \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, the implications of RBCT during the immunosuppressed, post-transplantation period are less clear \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The impact of RBCT on graft outcomes has been the subject of considerable debate, with previous studies reporting conflicting results \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. This leads to considerable variability in RBCT practices across different transplantation centers and between different physicians, which is further compounded by the absence of a standardized target hemoglobin level for post-transplantation RBCT. The ongoing evolution of immunosuppressive therapies and changing indications for RBCT also add to the complexity of this issue \u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Moreover, continuing advances in solid-phase assays and refinement of the criteria for diagnosing antibody-mediated rejection (AMR) further highlight the pressing need to explore the effects of post-transplantation RBCT considering contemporary clinical practices and emerging medical evidence \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe objective of this study was to evaluate the clinical implications of RBCT within the first month after kidney transplantation with regard to patient survival, graft survival, and biopsy-proven rejection.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eAfter applying the inclusion and exclusion criteria, 785 patients were included in this study, 148 (18.9%) of whom received early RBCT (within 1 month after transplantation). Baseline characteristics are summarized in \u003cb\u003eTable \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e. No significant differences were observed between the early RBCT and no RBCT groups regarding recipient and donor age, number of HLA mismatches, and proportion of re-transplantation. Recipients in the early RBCT group were more frequently female, had a longer duration of pre-transplantation dialysis, and more frequently received a deceased donor graft, compared to those in the no RBCT group. The proportion of patients receiving anti-thymocyte globulin induction was significantly higher in the early RBCT group (44.6% vs. 19.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The median follow-up duration of the entire study population was 66 months (IQR, 44.0\u0026ndash;86.0 months).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTransfusion characteristics\u003c/h2\u003e \u003cp\u003eA total of 469 packed red blood cells were administered to 148 recipients within 1 month after kidney transplantation. The median number of packed red blood cells among transfused recipients was 2 (IQR, 1.0\u0026ndash;3.0), and the median time from transplantation to the first RBCT was 5.0 days (IQR, 2.0\u0026ndash;12.0 days). Although pre-transplantation hemoglobin levels were comparable between the two groups, the lowest hemoglobin level during the first month after transplantation was significantly lower in the early RBCT group than in the no RBCT group (9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 vs. 7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 g/dL, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eTo investigate independent risk factors for requiring early RBCT after transplantation, we conducted multivariable logistic regression analysis (\u003cb\u003eTable \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/b\u003e). Recipient age, diabetes mellitus, body mass index, re-transplantation, dialysis vintage, and intraoperative RBCT did not exhibit significant associations with early RBCT after transplantation. In contrast, female recipient, lower pre-transplantation hemoglobin levels, and anti-thymocyte globulin induction were identified as significant risk factors associated with early RBCT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eGraft and patient outcomes\u003c/h2\u003e \u003cp\u003eDuring the follow-up period, 43 (5.5%) of the 785 patients died, and 44 (5.6%) experienced death-censored graft loss. As depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, both patient survival and death-censored graft survival were significantly lower in the early RBCT group than in the no RBCT group. The 1-year, 3-year, and 5-year patient survival rates were 95.8%, 92.3%, and 87.4% for the early RBCT group and 98.7%, 97.6%, and 96.2% for the no RBCT group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariable Cox regression analysis confirmed the independent association between early RBCT and higher all-cause mortality (adjusted hazard ratio [aHR], 2.264; 95% confidence interval [CI], 1.186\u0026ndash;4.324; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Additionally, the amount of transfused packed red blood cells was associated with an increased risk of all-cause mortality when assessed as continuous variable (aHR, 1.130; 95% CI, 1.084\u0026ndash;1.177; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The 1-year, 3-year, and 5-year death-censored graft survival rates were 97.3%, 94.4%, and 89.8% for the early RBCT group and 99.4%, 97.1%, and 95.6% for the no RBCT group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). Early RBCT was significantly associated with an increased risk of death-censored graft loss on multivariable analysis (aHR, 1.995; 95% CI, 1.045\u0026ndash;3.810; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factor assessment for all-cause mortality\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariable\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eaHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (for 1 year increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.075 (1.041\u0026ndash;1.109)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.073 (1.035\u0026ndash;1.114)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.383 (0.184\u0026ndash;0.799)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.290 (0.133\u0026ndash;0.634)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.055 (1.121\u0026ndash;3.769)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.934 (0.950\u0026ndash;3.938)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRe-transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.869 (0.789\u0026ndash;4.431)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.242 (0.929\u0026ndash;5.408)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis duration (for 1 month increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.009 (1.005\u0026ndash;1.012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.007 (1.001\u0026ndash;1.012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA mismatch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.316 (1.080\u0026ndash;1.603)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.428 (1.133-1.800)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eATG induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.362 (2.390\u0026ndash;7.959)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.777 (0.842\u0026ndash;3.750)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeceased donor KT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.262 (2.652\u0026ndash;10.439)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.627 (0.957\u0026ndash;7.206)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDonor age (for 1 year increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.021 (0.996\u0026ndash;1.047)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.991 (0.968\u0026ndash;1.014)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.424\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale donor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.082 (0.595\u0026ndash;1.968)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly RBCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.022 (1.640\u0026ndash;5.571)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.264 (1.186\u0026ndash;4.324)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eaHR, adjusted hazard ratio; ATG, anti-thymocyte globulin; cHR, crude hazard ratio; CI, confidence interval; HLA, human leukocyte antigen; KT, kidney transplantation; RBCT, red blood cell transfusion\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factor assessment for death-censored graft loss\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariable\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eaHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (for 1 year increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.013 (0.987\u0026ndash;1.040)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.002 (0.974\u0026ndash;1.031)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.895\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.673 (0.357\u0026ndash;1.269)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.341 (0.711\u0026ndash;2.530)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.365\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.412 (0.712\u0026ndash;2.801)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRe-transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.545 (0.132\u0026ndash;2.254)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis duration (for 1 month increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.001 (0.996\u0026ndash;1.006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLA mismatch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.233 (1.018\u0026ndash;1.493)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.249 (1.018\u0026ndash;1.531)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eATG induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.186 (1.180\u0026ndash;4.048)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.661 (0.731\u0026ndash;3.778)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeceased donor KT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.650 (0.913\u0026ndash;2.981)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.240 (0.548\u0026ndash;2.806)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.606\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDonor age (for 1 year increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.027 (1.002\u0026ndash;1.053)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.018 (0.992\u0026ndash;1.044)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale donor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.949 (0.525\u0026ndash;1.714)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.862\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly RBCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.408 (1.291\u0026ndash;4.493)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.995 (1.045\u0026ndash;3.810)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eaHR, adjusted hazard ratio; ATG, anti-thymocyte globulin; cHR, crude hazard ratio; CI, confidence interval; HLA, human leukocyte antigen; KT, kidney transplantation; RBCT, red blood cell transfusion\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eBiopsy-proven allograft rejection\u003c/h2\u003e \u003cp\u003eA total of 245 biopsy-proven allograft rejection episodes (134 AMR and 111 TCMR) occurred in 165 recipients. The median time to the first biopsy-proven allograft rejection was 5 months (IQR, 2.0\u0026ndash;23.0). Cumulative incidence for AMR was significantly higher in the early RBCT group than in the no RBCT group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), whereas cumulative incidence for TCMR between the two groups was not significantly different (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.641). Multivariable analysis confirmed the independent association between early RBCT and the development of AMR (aHR, 1.655; 95% CI, 1.054\u0026ndash;2.598; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029). Number of HLA mismatches (aHR, 1.352; 95% CI, 1.181\u0026ndash;1.547; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and donor age (aHR, 1.019; 95% CI, 1.002\u0026ndash;1.036; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027) were also identified as independent risk factors for AMR.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eGraft renal function\u003c/h2\u003e \u003cp\u003eMean eGFR values at various time points in the two groups are shown in \u003cb\u003eFigure \u003cspan refid=\"MOESM4\" class=\"InternalRef\"\u003eS4\u003c/span\u003e\u003c/b\u003e. Mean eGFR at 1 month after kidney transplantation was significantly lower in the early RBCT group (58.2\u0026thinsp;\u0026plusmn;\u0026thinsp;28.3 vs. 68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;21.0 mL/min/1.73 m\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Mean eGFR was not significantly different between groups at 3 months post-transplantation and thereafter.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003eTo address potential selection bias due to the inclusion of patients in poor condition in the transfusion group or those receiving kidneys from suboptimal donor, we performed a 1:2 propensity score matching for sensitivity analysis based on the donor type (Living or Deceased donor) and the donor profile (KDPI or LKDPI). This analysis resulted in a cohort of 398 kidney transplant recipients. 269 patients (68.1%) received early red blood cell transfusion (RBCT), while 139 patients (31.9%) did not (\u003cb\u003eTable \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e\u003c/b\u003e). The matched group revealed differences only in preoperative hemoglobin levels and use of antithymocyte globulin. No statistical differences were observed in other variables.\u003c/p\u003e \u003cp\u003ePatient survival and death-censored graft survival were considerably lower in the early RBCT group compared to the no RBCT group. The survival rates of patients at 1 year, 3 years, and 5 years were 94.9%, 91.9%, and 89.7% in the RBCT group, while in the no RBCT group, they were 97.4%, 96.6%, and 96.2%, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017; \u003cb\u003eFigure \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003ea\u003c/b\u003e). The death-censored graft survival rates at 1 year, 3 years, and 5 years were 97.0%, 96.1%, and 93.9% for the early RBCT group, compared to 98.9%, 98.4%, and 98.4% for the no RBCT group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018; \u003cb\u003eFigure \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003eb\u003c/b\u003e). Also, cumulative incidence for AMR was higher in the early RBCT group compared to the no RBCT group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05; \u003cb\u003eFigure \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e\u003c/b\u003e),\u003c/p\u003e \u003cp\u003eImportantly, in risk analyses, early RBCT was independently associated with an increased risk of death-censored graft loss, as shown by multivariable regression analysis (aHR 0.502; 95% CI, 1.150\u0026ndash;2.372; P\u0026thinsp;=\u0026thinsp;0.007; \u003cb\u003eTable \u003cspan refid=\"MOESM4\" class=\"InternalRef\"\u003eS4\u003c/span\u003e\u003c/b\u003e). Number of HLA mismatch also showed the risk, but types of induction agents were not associated with patient outcome.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe had hypothesized that early red blood cell transfusion (RBCT) after kidney transplantation would be associated with adverse outcomes, including increased risks of all-cause mortality, graft loss, and antibody-mediated rejection. In this single-center study of 785 kidney transplant recipients, we investigated the clinical implications of early RBCT after transplantation. Our results revealed a significant, dose-dependent association between early RBCT and increased risk of all-cause mortality. Patients receiving early RBCT also had a higher risk of death-censored graft loss and AMR, compared to those who did not receive early RBCT. However, no significant associations were observed between early RBCT and TCMR or graft renal function after the first post-transplantation month. These results underscore the nuanced associations between early RBCT and specific clinical outcomes following kidney transplantation. Because donor profile was expected to affect posttransplantation outcomes, we performed subgroup analysis for sensitivity analysis. In the subgroup analysis, the early RBCT significantly increased the risk of patient mortality, death-censored graft loss and antibody-mediated rejection, regardless of the donor profile.\u003c/p\u003e \u003cp\u003ePre-transplantation RBCT is a well-recognized risk factor for developing anti-HLA antibodies \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. To mitigate this risk, considerable efforts have been made to minimize pre-transplantation RBCT and to use leukocyte-depleted blood products \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Nevertheless, the effects of RBCT during the post-transplantation period, particularly during the period of intense immunosuppressive therapy, remain controversial \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. In addition to the risk of alloimmunization, both anemia severe enough to require RBCT and RBCT itself may have detrimental effects, especially in the clinical setting of major surgery. Although a substantial proportion (20\u0026ndash;60%) of kidney transplant recipients receive post-transplant RBCT, research on the long-term clinical implications of post-transplantation RBCT remains limited. Our study aimed to comprehensively investigate the associations between early post-transplantation RBCT on various long-term outcomes.\u003c/p\u003e \u003cp\u003ePerioperative RBCT has been linked to higher mortality following major surgery \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. This association is secondary not only to preoperative anemia or intraoperative bleeding but also to complications induced by RBCT itself, such as acute lung injury, circulatory overload, infection, and immunosuppression \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Kidney transplant recipients commonly experience anemia, leading to widespread use of RBCT in the early post-transplant period \u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, the impact of post-transplant RBCT on patient survival remains controversial, and there is a lack of clear indications for RBCT in this setting.\u003c/p\u003e \u003cp\u003eIn the current large-scale study of recent kidney transplant recipients, we found that 18.9% of recipients received early RBCT after transplantation, and receiving early RBCT was associated with a dose-dependent increase in all-cause mortality. These findings align with those of a previous single-center study, which also identified a dose-dependent relationship between post-transplantation RBCT and all-cause mortality \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. However, this prior study included RBCT at any time after transplantation and did not provide specific indications for RBCT. Recent national cohort data from Korea also demonstrated a dose-dependent association between RBCT during hospitalization and all-cause mortality but did not distinguish between intraoperative and postoperative RBCT \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Overall, the findings of our study and others underscore the need to reconsider the effects of RBCT through further in-depth investigations into the specific effects of post-transplant RBCT on kidney transplantation outcomes.\u003c/p\u003e \u003cp\u003eOur results revealed that postoperative RBCT was also significantly associated with not only mortality but also death-censored graft survival in the current study. Previous research on the impact of RBCT on graft outcomes has produced mixed results, with some studies reporting negative effects and others finding no significant impact \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. These inconsistencies may be attributed to variations in transfusion practices over time and between institutions and practitioners, as well as a lack of clear transfusion guidelines. Our study, with its more recent and uniform cohort, provides updated insights that may be used to inform current transfusion protocols and highlights the need for a cautious approach to postoperative RBCT in the context of kidney transplantation.\u003c/p\u003e \u003cp\u003eWe identified early postoperative RBCT as an independent risk factor for developing AMR, but not TCMR. This association, while not proof of causality, offers a plausible explanation for the observed decrease in death-censored graft survival in our cohort. It suggests that RBCT specifically affects humoral immunity \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Moreover, previous studies have linked postoperative RBCT with the development of \u003cem\u003ede novo\u003c/em\u003e donor-specific antibodies, further supporting the potential immunological implications of RBCT \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Together, our findings, although retrospective and requiring careful interpretation, underscore the need to revisit current transfusion practices in kidney transplantation.\u003c/p\u003e \u003cp\u003eAlthough the Kidney donor profile index (KDPI) or Living kidney donor profile index (LKDPI) scores are a well-known predictor for post-transplant outcomes \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, previous researches have not investigated the post-transplantation outcomes after transfusion while considering the donor profile \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Our research is significant in that we discovered transfusion remains a risk factor affecting patient outcomes even under similar donor profile conditions. It is important to emphasize that the relationship between RBCT and poor outcomes may be an association, as causation was confirmed with sensitivity analysis.\u003c/p\u003e \u003cp\u003eThis study has several limitations that deserve consideration. Firstly, future prospective studies with clear indications for RBCT are required to more conclusively determine the effects of early RBCT. Secondly, protocol biopsies were not routinely obtained in all patients, so episodes of subclinical rejection may have been missed. Nevertheless, we meticulously examined all indicated biopsies, and allograft rejection episodes were analyzed using the latest Banff criteria.\u003c/p\u003e \u003cp\u003eIn conclusion, our findings highlight a significant association between early post-transplantation RBCT and increased risk of all-cause mortality, death-censored graft failure, and AMR in kidney transplant recipients. These results warrant a critical reassessment of RBCT practices in the post-transplantation setting and emphasize the urgent need for further research and updated evidence-based clinical guidelines regarding transfusion practices.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eWe screened consecutive adults who underwent kidney transplantation between January 2014 and December 2020 at Severance Hospital, Seoul, Republic of Korea. We excluded patients who underwent multi-organ transplantation, received HLA- and/or ABO-incompatible kidneys, or experienced graft loss or death within 1 month after transplantation. After excluding ineligible patients, 785 recipients were included in this study (\u003cb\u003eFigure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eTo perform sensitivity analysis, all patients\u0026rsquo; KDPI \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e or LKDPI \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e scores were collected, and a total of 398 matched cohorts were created.\u003c/p\u003e \u003cp\u003e All study procedures were conducted in accordance with the Declaration of Helsinki and were approved by the Institutional Review Board of Severance Hospital (4-2022-1073). Informed consent was waived by the Institutional Review Board of Severance Hospital because of the study\u0026rsquo;s retrospective design.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eExposure\u003c/h2\u003e \u003cp\u003eThe main study exposure was \u0026ldquo;early RBCT\u0026rdquo;, which was defined as transfusion of packed red blood cells within 30 days after transplantation, starting on postoperative day 1. We selected this timeframe based on existing literature suggesting that a significant proportion of blood transfusions occur during the first month post-transplantation \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Patients were categorized into two groups: those who received early RBCT and those who did not. Throughout the study period, our institution exclusively used leukocyte-depleted packed red blood cells for transfusions. Data regarding transfusions were confirmed by comprehensively reviewing the blood bank records and each patient\u0026rsquo;s chart. RBCT decisions were guided by a general target hemoglobin level of 7.0 g/dL, although transfusion decisions were ultimately left to the discretion of the attending physician, who considered several other factors, such as the presence of heart disease, abnormal vital signs, or bleeding tendency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eImmunosuppression\u003c/h2\u003e \u003cp\u003eImmunosuppressants were prescribed according to the standard protocol at our institution \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Most patients received induction therapy with basiliximab or anti-thymocyte globulin. Anti-thymocyte globulin was preferred in high-risk transplant recipients, such as those who underwent deceased donor kidney transplantation or received old-to-young grafts. Maintenance immunosuppression consisted of tacrolimus, prednisolone, and mycophenolate mofetil (MMF). The initial tacrolimus dosage was 0.1 mg/kg orally twice daily, with subsequent doses titrated to maintain a trough concentration of 5\u0026ndash;8 ng/mL. The initial dose of intravenous methylprednisolone was 500\u0026ndash;1000 mg, which was gradually reduced and converted to oral prednisolone (5\u0026ndash;10 mg/day) during the first 3 weeks after transplantation. The initial dose of MMF was 1.0 g/day, which was subsequently adjusted to minimize adverse events (e.g., gastrointestinal side effects, neutropenia).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStudy endpoints and definitions\u003c/h2\u003e \u003cp\u003eThe primary study endpoint was patient survival. The secondary endpoints included death-censored graft survival, biopsy-proven allograft rejection, and graft renal function. Patient survival was calculated from the date of transplantation to the date of death, loss to follow-up, or December 31, 2022 (the end of the study follow-up). Death-censored graft loss was defined as the return to dialysis or the need for re-transplantation. Graft survival was calculated from the date of transplantation to the date of graft loss or December 31, 2022.\u003c/p\u003e \u003cp\u003eRenal biopsies were performed in patients with acute allograft dysfunction, which was defined as a\u0026thinsp;\u0026gt;\u0026thinsp;30% increase in serum creatinine level above baseline or proteinuria of \u0026gt;\u0026thinsp;500 mg/day. Allograft biopsy samples were processed using light, immunofluorescent, and electron microscopy. All allograft rejections were confirmed by biopsy and classified as AMR or T-cell mediated rejection (TCMR) according to the most recent Banff criteria at the time of the biopsy \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Cases of mixed rejection (in which AMR and TCMR occurred simultaneously) were analyzed as AMR. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration Eq.\u0026nbsp;3\u003csup\u003e0\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDepending on the type of variable, data were expressed as frequency, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, or median and interquartile range (IQR). Continuous variables were compared using Student\u0026rsquo;s t-test and Mann-Whitney test and categorical variables were compared using Chi-square or Fisher\u0026rsquo;s exact test. Multivariable logistic regression analysis was performed with early RBCT as the outcome variable. Patient survival, graft survival, and cumulative incidence of biopsy-proven allograft rejections were analyzed using Kaplan-Meier curves and the log-rank test. Associations between early RBCT and time-to-event outcomes were evaluated using Cox proportional hazard models, which included the following covariates: sex, age, dialysis duration, diabetes mellitus, re-transplantation, induction agent (anti-thymocyte globulin vs. basiliximab), type of donor (living vs. deceased), early RBCT, number of HLA mismatches, donor age, and donor sex. Clinically significant variables and variables with a p value\u0026thinsp;\u0026le;\u0026thinsp;.2 in univariable analyses were introduced in multivariable regression models. For sensitivity analysis, propensity score matching analysis was performed by matching donor profiles.\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using SPSS software (version 26.0; SPSS Inc., Chicago, IL, USA) and R (version 3.6.3; R Foundation for Statistical Computing, Vienna, Austria). All tests were performed two-tailed, and \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;.05 were considered significant.\u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest statement:\u003c/h2\u003e \u003cp\u003eThe authors of this manuscript have no conflicts of interest to disclose as described by the \u003cem\u003eScientific Reports.\u003c/em\u003e\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research was supported by a grant of the Korea Health Technology R\u0026amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health \u0026amp; Welfare, Republic of Korea (grant number: HI22C1529).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.K. and J.L. drafted the manuscript. M.K., H-H.K., and J.L. conceived and designed the study. S.H.Y., M.C., H.J.K., H.W.K., J.Y., B.S.K., K.H.H., M.S.K., and J.L. collected the data. M.K. and J.L. performed the statistical analysis and interpreted the data. All authors read and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFishbane, S. \u0026amp; Spinowitz, B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. \u003cem\u003eAm. J. Kidney Dis.\u003c/em\u003e \u003cb\u003e71\u003c/b\u003e, 423\u0026ndash;435 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVanrenterghem, Y. et al. Prevalence and management of anemia in renal transplant recipients: a European survey. \u003cem\u003eAm. J. Transplant.\u003c/em\u003e \u003cb\u003e3\u003c/b\u003e, 835\u0026ndash;845 (2003).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScornik, J. C., Schold, J. D., Bucci, M. \u0026amp; Meier-Kriesche H.-U. Effects of blood transfusions given after renal transplantation. \u003cem\u003eTransplantation\u003c/em\u003e. \u003cb\u003e87\u003c/b\u003e, 1381\u0026ndash;1386 (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerrandiz, I. et al. Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies. \u003cem\u003eAm. J. Transplant.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e, 2661\u0026ndash;2669 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhedjat, K. et al. Post-transplantation early blood transfusion and kidney allograft outcomes: a single-center observational study. \u003cem\u003eTranspl. Int.\u003c/em\u003e \u003cb\u003e35\u003c/b\u003e, 10279 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaloul, R., Braga, J. R., Diez, A., Logan, A. \u0026amp; Pesavento, T. Early posttransplant blood transfusion and risk for worse graft outcomes. \u003cem\u003eKidney Int. Rep.\u003c/em\u003e \u003cb\u003e6\u003c/b\u003e, 986\u0026ndash;994 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeffell, M. S. et al. Red blood cell transfusions and the risk of allosensitization in patients awaiting primary kidney transplantation. \u003cem\u003eTransplantation\u003c/em\u003e. \u003cb\u003e97\u003c/b\u003e, 525\u0026ndash;533 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScornik, J. \u0026amp; Meier-Kriesche, H. U. Blood transfusions in organ transplant patients: mechanisms of sensitization and implications for prevention. \u003cem\u003eAm. J. Transplant.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e, 1785\u0026ndash;1791 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHassan, S. et al. Shared alloimmune responses against blood and transplant donors result in adverse clinical outcomes following blood transfusion post\u0026ndash;renal transplantation. \u003cem\u003eAm. J. Transplant.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e, 1720\u0026ndash;1729 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaiffe, E. et al. Early post-transplant red blood cell transfusion is associated with an increased risk of transplant failure: A nationwide French study. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 854850 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHalloran, P. F. Immunosuppressive drugs for kidney transplantation. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cb\u003e351\u003c/b\u003e, 2715\u0026ndash;2729 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarson, J. L. et al. Red blood cell transfusion: 2023 AABB international guidelines. \u003cem\u003eJAMA\u003c/em\u003e. \u003cb\u003e330\u003c/b\u003e, 1892\u0026ndash;1902 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBabitt, J. L. et al. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. \u003cem\u003eKidney international\u003c/em\u003e 99, 1280\u0026ndash;1295 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, R. Donor-specific antibodies in kidney transplant recipients. \u003cem\u003eClin. J. Am. Soc. Nephrol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 182\u0026ndash;192 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoupy, A., Mengel, M. \u0026amp; Haas, M. Thirty years of the International Banff Classification for Allograft Pathology: the past, present, and future of kidney transplant diagnostics. \u003cem\u003eKidney Int.\u003c/em\u003e \u003cb\u003e101\u003c/b\u003e, 678\u0026ndash;691 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarpinski, M. et al. Leukocyte reduction of red blood cell transfusions does not decrease allosensitization rates in potential kidney transplant candidates. \u003cem\u003eJ. Am. Soc. Nephrol.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e, 818\u0026ndash;824 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMassicotte-Azarniouch, D. et al. Blood transfusion and adverse graft-related events in kidney transplant patients. \u003cem\u003eKidney Int. Rep.\u003c/em\u003e \u003cb\u003e6\u003c/b\u003e, 1041\u0026ndash;1049 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSullivan, H. C. \u0026amp; Gebel, H. M. Hurts So Good: Uncovering the Relationship Between Blood Transfusions and Allograft Outcome. \u003cem\u003eKidney Int. Rep.\u003c/em\u003e \u003cb\u003e6\u003c/b\u003e, 875\u0026ndash;877 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlance, L. G. et al. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. \u003cem\u003eJ. Am. Soc. Anesthesiologists\u003c/em\u003e. \u003cb\u003e114\u003c/b\u003e, 283\u0026ndash;292 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu, W. C. et al. Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery. \u003cem\u003eAnn. Surg.\u003c/em\u003e \u003cb\u003e252\u003c/b\u003e, 11\u0026ndash;17 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRohde, J. M. et al. 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The recovery status from delayed graft function can predict long-term outcome after deceased donor kidney transplantation. \u003cem\u003eSci. Rep.\u003c/em\u003e \u003cb\u003e7\u003c/b\u003e, 13725 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoupy, A. et al. \u003cem\u003eThe Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell\u0026ndash;and antibody-mediated rejection\u003c/em\u003e (Wiley Online Library, 2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInker, L. A. et al. New creatinine-and cystatin C\u0026ndash;based equations to estimate GFR without race. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cb\u003e385\u003c/b\u003e, 1737\u0026ndash;1749 (2021).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"allosensitization, graft survival, kidney donor profile index, kidney transplantation, transfusion","lastPublishedDoi":"10.21203/rs.3.rs-4978680/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4978680/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePre-transplantation red blood cell transfusion (RBCT) is a well-recognized cause of allosensitization. However, the effects of RBCT after kidney transplantation remain controversial. This study evaluates the impacts of RBCT within the first 30 days post-transplantation (early RBCT) with regard to long-term patient and graft outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 785 patients who underwent HLA- and ABO-compatible kidney transplantation between 2014 and 2020. Patients were categorized based on whether they received early RBCT.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOverall, 18.9% of patients received early RBCT. On multivariable analysis, early RBCT was independently associated with increased risks of all-cause mortality (hazard ratio, 2.264; 95% CI, 1.186\u0026ndash;4.324; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013) and death-censored graft loss (hazard ratio, 1.995; 95% CI, 1.045\u0026ndash;3.810; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036). Cumulative incidence of antibody-mediated rejection was significantly higher in the early RBCT group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024). In the sensitivity analysis, the early RBCT significantly increased the risk of patient mortality (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017), death-censored graft loss (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018) and antibody-mediated rejection (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05), regardless of the donor profile.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEarly post-transplantation RBCT was associated with increased risks of all-cause mortality, graft loss, and antibody-mediated rejection, highlighting the need for reconsideration of transfusion practices following kidney transplantation.\u003c/p\u003e","manuscriptTitle":"Clinical implications of early blood transfusion after kidney transplantation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-17 09:28:05","doi":"10.21203/rs.3.rs-4978680/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-29T17:21:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-27T15:08:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98427131116675558005420017834939695019","date":"2024-10-21T13:10:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-03T10:21:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211973659049573719449225504175430658912","date":"2024-09-03T09:27:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-02T08:58:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-02T08:27:26+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-29T19:08:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-28T05:48:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-26T14:26:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5f561bb6-f541-400b-b5f0-f346be5e6d85","owner":[],"postedDate":"October 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":38016942,"name":"Health sciences/Diseases/Kidney diseases/Chronic kidney disease"},{"id":38016943,"name":"Health sciences/Medical research/Outcomes research"},{"id":38016944,"name":"Biological sciences/Immunology/Transplant immunology"},{"id":38016945,"name":"Biological sciences/Immunology/Transplant immunology/Allograft"},{"id":38016946,"name":"Health sciences/Nephrology"},{"id":38016947,"name":"Health sciences/Nephrology/Kidney diseases/Chronic kidney disease"}],"tags":[],"updatedAt":"2025-03-03T16:05:35+00:00","versionOfRecord":{"articleIdentity":"rs-4978680","link":"https://doi.org/10.1038/s41598-025-90068-2","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-02-25 15:57:56","publishedOnDateReadable":"February 25th, 2025"},"versionCreatedAt":"2024-10-17 09:28:05","video":"","vorDoi":"10.1038/s41598-025-90068-2","vorDoiUrl":"https://doi.org/10.1038/s41598-025-90068-2","workflowStages":[]},"version":"v1","identity":"rs-4978680","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4978680","identity":"rs-4978680","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}