Decreased Graft Survival Research Articles

Intraoperative hypotension during critical phases of liver transplantation and its impact on acute kidney injury: a retrospective cohort study

IntroductionAcute Kidney Injury (AKI) following Liver Transplantation (LT) is associated with prolonged ICU and hospital stay, increased risk of chronic renal disease, and decreased graft survival. Intraoperative hypotension is a modifiable risk factor associated with postoperative AKI. We aimed to determine in which phase of LT hypotension has the strongest association with AKI: the anhepatic or neohepatic phase. MethodsThis retrospective cohort study included adult patients undergoing LT between January 2010 and June 2022. Exclusion criteria were re-do or combined transplantations, preoperative dialysis, and early graft failure or death. Primary outcome was AKI as defined by KDIGO. Hypotension was Mean Arterial Pressure (MAP) below predefined thresholds in minutes. Risk adjusted logistic regression analysis considered hypotension in 3 periods: the total procedure, anhepatic phase, and neohepatic phase. ResultsOur cohort included 1153 patients. The median MELD-NA score was 19 (IQR 11–28), and 412 (35.9%) were living-related donations. AKI occurred in 544 patients (47.2%). The unadjusted model showed an association with AKI for MAP < 60 mmHg (OR = 1.011 [1.0, 1.022], p = 0.047) and MAP < 55 mmHg (OR = 1.023 [1.002, 1.047], p = 0.040) in the anhepatic phase, and for MAP < 60 mmHg (OR = 1.032 [1.01, 1.056], p = 0.006) in the neohepatic phase. The adjusted model did not reach significance in the subgroups but did in the total procedure: MAP < 60 mmHg (OR = 1.005 [1.002, 1.008], p < 0.001) and MAP < 55 mmHg (OR = 1.008 [1.003–1.013], p = 0.004). ConclusionIntraoperative hypotension is independently associated with AKI following LT. This association is seen during the anhepatic phase. Maintaining MAP above 60 mmHg may improve kidney function after LT.

The Number of Episodes of Subtherapeutic Tacrolimus Blood Level Is Independently Associated With Reduced Kidney Graft Survival

ABSTRACTBackgroundTacrolimus blood level variability is associated with reduced graft survival among kidney transplant recipients. To date, no practical approach for reducing variability has been validated. We defined specific tacrolimus blood level patterns correlated with variability and evaluated their independent association with reduced graft survival.MethodsIn this single‐center retrospective study, we predefined 12 patterns that exhibited correlation with high tacrolimus blood level variability. Subsequently, we utilized a multivariate Cox proportional hazard model, in conjunction with the Akaike information criteria, to evaluate the association between the predefined patterns and decreased graft survival.ResultsOur cohort included 1305 kidney transplant recipients. The primary outcome of this trial was graft loss, defined as the initiation of chronic dialysis or the need for retransplantation. The secondary outcome was the combination of death‐censored graft loss and death with a functioning graft. During the study's follow‐up period, there were 131 events of graft loss. The number of episodes of subtherapeutic tacrolimus level during the first‐year posttransplantation was significantly associated with graft loss (HR 1.208 per episode, 95% CI 1.075–1.356, p = 0.001) and significantly improved the relative likelihood of the model compared to the multivariate model as demonstrated by the delta AIC value (8.256, p = 0.016).ConclusionIn addition to increased tacrolimus blood level variability, the number of episodes of subtherapeutic tacrolimus levels is independently associated with decreased graft survival among kidney transplant recipients.

Prophylactic treatment of FSGS recurrence in patients who relapsed in a previous kidney graft.

Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation and is classically associated with a significant decrease in graft survival. A major risk factor is a prior history of FSGS recurrence on a previous graft. This analysis reports the impact of a prophylactic treatment of FSGS recurrence in very high-risk patients who experienced a recurrence on a previous graft. We performed a retrospective multicentre observational study in 25 French transplantation centres. The inclusion criteria were patients aged more than 18 years who had undergone kidney transplant between December 31, 2004, and December 31, 2020, and who had a history of FSGS recurrence on a previous graft. We identified 66 patients: 40 received prophylactic treatment (PT+), including intravenous cyclosporine and/or rituximab and/or plasmapheresis, and 26 did not receive any prophylactic treatment (PT-). The time to progression to end-stage kidney disease was similar between groups. The PT+group was younger at FSGS diagnosis and at the time of kidney retransplantation and lost their previous graft faster. The overall recurrence rate was 72.7% (76.9% in the PT- group and 70.0% in the PT+group, P=0.54). At least partial remission was achieved in 87.5% of patients. The 5-year graft survival was 67.7% (95% CI: 53.4 to 78.4%): 65.1% (95%CI: 48.7 to 77.4%) in patients with FSGS recurrence vs. 77.3% (95% CI: 43.8 to 92.3%) in patients without recurrence (P=0.48). Our study suggests that prophylactic treatment should not be used routinely in patients receiving a second transplantation after recurrence of FSGS on a previous graft. The recurrence rate is high regardless of the use of prophylactic treatment. However, the 5-year graft survival remains satisfactory.

Detrimental impact of early biopsy-proven rejection in liver transplantation.

Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long-term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first-time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy-proven acute cellular rejection (EBPR) within the first 90 days post-transplant and compared outcomes between the groups. There were 896 liver transplants that met inclusion criteria with 112 cases (12.5%) of EBPR. Recipients who developed EBPR had higher biochemical Model for End-Stage Liver Disease scores (28vs. 24, p<.01), but other donor and recipient characteristics were similar. Recipients with EBPR had similar overall survival compared to patients without EBPR (p=.09) but had decreased graft survival (p<.05). EBPR was also associated with decreased time to first episode of late (>90 days post-transplant) rejection (p<.0001) and increased vulnerability to bacterial and viral infection (p<.05). In subgroup analysis of recipients with autoimmune indications for liver transplantation, EBPR had a more pronounced association with patient death (hazard ratio [HR] 3.9, p<.05) and graft loss (HR 4.0, p<.01). EBPR after liver transplant is associated with inferior graft survival, increased susceptibility to late rejections, and increased vulnerability to infection.

Liver transplantation for severe hepatic trauma: A multicenter analysis from the UNOS data set.

Orthotopic liver transplantation (OLT) is rarely indicated after hepatic trauma but it can be the only therapeutic option in some patients. There are scarce data analyzing the surgical outcomes of OLT after trauma. We used the UNOS data set to identify patients who underwent OLT for trauma from 1987 to 2022 and compared them to a cohort of patients transplanted for other indications. Cox proportional hazard and multivariable logistic regression analyses were performed to assess predictors of graft and patient survival. Seventy-two patients underwent OLT for trauma during the study period. Patients with trauma were more frequently on mechanical ventilation at the time of transplantation (26.4% vs. 7.6%, p < 0.001) and had a greater incidence of pretransplant portal vein thrombosis (12.5% vs. 4%, p = 0.002). Our 4:1 matched analysis showed that trauma patients had significantly shorter wait times, higher incidence of pretransplant portal vein thrombosis and prolonged length of stay. Trauma was associated with decreased overall graft survival (hazards ratio, 1.42; 95% confidence interval, 1.01-1.98), and increased length of stay ( p = 0.048). There were no significant differences in long-term patient survival. Unique physiological and vascular challenges after severe hepatic trauma might be associated with decreased graft survival in patients requiring liver transplantation. Prognostic and Epidemiological; Level III.

Delayed Graft Function in Kidney Retransplantation: United Network for Organ Sharing Data With Linked Primary and Retransplant

IntroductionThere are several articles exploring the risk factors for primary delayed graft function (DGF). However, current literature does not include many resources on the risk factors for DGF when it is a recipient's second kidney transplant or look at short-term graft and patient survival of DGF retransplants. MethodsUnited Network for Organ Sharing data from January 2008 to June 2021 were analyzed. Pancreas transplants, multi-organ transplants, and lost to follow-up transplants were excluded. Second transplant patients with DGF were identified. Multivariate logistic regression models based on the primary and second transplant characteristics were created. Survival analysis was performed with Kaplan-Meier methodology and assessed with log-rank test. ResultsA total of 2964 second kidney transplants were identified. Rate of DGF in the second transplant was 28.4% (843/2964) and 49.2% of them had a prior DGF in their first transplant (P < 0.001). Multivariate analysis confirmed that occurrence of DGF (odds ratio [OR] 1.5, P < 0.001) and graft loss due to acute rejection (OR 1.2, P < 0.005) in the primary transplant were predictors of reappearing DGF in the second transplant. Dialysis at transplant was the greatest risk factor from the second transplant (OR 3.539, P < 0.001). There was a decreased graft survival after 12 mo (77% versus 49% with log t-test <0.001) in the second transplant. However, DGF was not significantly associated with patient survival. ConclusionsThis study shows the interaction between primary and second transplant in developing DGF. Survival analysis shows lower graft survival for retransplants in the case of DGF. This study opens the possibility of identifying additional risk factors for patients undergoing retransplant surgeries.

Delayed Graft Function Among Kidney Transplant Recipients Is Associated With an Increased Risk of Urinary Tract Infection and BK Viremia.

Delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs) is a well-known risk factor for allograft rejection, decreased graft survival, and increased cost. Although DGF is associated with an increased risk of rejection, it is unclear whether it also increases the risk of infection. We reviewed all adult DDKTRs at our center between 2010 and 2018. The primary outcomes of interest were BK viremia, cytomegalovirus viremia, pneumonia, and urinary tract infection (UTI) within the first year of transplant. Additional analysis was made with censoring follow-up at the time of allograft rejection. A total of 1512 DDKTRs were included, of whom 468 (31%) had DGF. As expected, several recipient, donor, and baseline immunological characteristics differed by DGF status. After adjustment, DGF was significantly associated with an increased risk of BK viremia (hazard ratio: 1.34; 95% confidence interval, 1.0-1.81; P = 0.049) and UTI (hazard ratio: 1.70; 95% confidence interval, 1.31-2.19; P < 0.001) but not cytomegalovirus viremia or pneumonia. Associations were similar in models censored at the time of rejection. DGF is associated with an increased risk of early infectious complications, mainly UTI and BK viremia. Close monitoring and appropriate management are warranted for better outcomes in this unique population.

#3003 IMPACT OF FULL CORRECTION OF HEMOGLOBIN AMONG POST-TRANSPLANT ANEMIC KIDNEY TRANSPLANT RECIPIENTS: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL

Abstract Background and Aims Several studies have shown that post-transplant anemia (PTA) might be associated with increased mortality and decreased graft survival and de-novo congestive heart failure. So we aimed from this prospective randomized controlled study to assess the impact of full correction of PTA on the cardiovascular system of renal transplant recipients receiving erythropoietin stimulating agents (ESA). Method We recruited 247 kidney recipients with stable graft function in this RCT with 2 groups according to their target hemoglobin (11-12 g/dl, group 1, n=183) and (13:15 g/dl, group 2, n=64). After correction of deficiencies, the target hemoglobin was achieved using ESA. All patients were followed up clinically and Laboratory and radiologically for 12 months. Results Diabetic nephropathy was the main cause of ESKD in group 1. The studied groups were comparable regarding pre-transplant co-morbidities. Most patients received thymoglobulin as induction then cyclosporine based maintenance immunosuppression. We did not find any significant difference between the two groups concerning post-transplant diabetes, BK viremia or malignancies and even cardiovascular events (TIA, stroke, ACS), (p&amp;gt;0.05). Group 1 showed higher mean blood pressure (P = .003), lower LV internal dimensions, higher LVH, LV mass, IVSD and LV mass index after one year of the study (p&amp;lt; 0.05). MIVSD, mean ejection fraction and FS were comparable in both groups (p&amp;gt;0.05). Graft outcome was comparable between both groups (P = .125), meanwhile mortality cases were significantly higher among group 1 (16 cases, 8.7%) (P = .005). Conclusion Full correction of PTA is associated with stabilized cardiac dimensions indices without any significant cardiovascular comorbidities.

Low hepatic artery resistive index on Doppler ultrasound performed on the first post-liver transplant day is associated both with hepatic artery thrombosis and decreased graft survival.

Although liver transplantation (LT) outcomes have improved significantly over the last decades, early vascular complications are still associated with elevated risks of graft failure. Doppler ultrasound (DUS) enables detection of vascular complications, provides hepatic artery Resistive Index (RI). The aim of our study was to evaluate the association of the RI parameters of DUS performed in the first post-transplant week with post-transplant outcomes. All consecutive patients undergoing a first LT between 2001 and 2019 at a single center were included. Patients were divided into two groups: RI < 0.55 and RI ≥ 0.55. Patients were also divided according to the presence or absence of hepatic artery thrombosis (HAT). Graft survival was compared between groups. Overall, 338 patients were included. HAT occurred in 23 patients (6.8%), of which 7 were partial and 16, complete. Biliary complications were more common in patients with HAT (10 [43.5%]) vs. 38 [12.1%] [p < 0.001]). Graft survival was lower for patients with HAT (p = 0.047). Also, RI < 0.55 was associated with increased incidence of HAT (p < 0.001). Additionally, patients with RI < 0.55 on post-operative day 1 had decreased graft survival as compared to patients with RI > 0.55 (p = 0.041). RI on post-operative day 3 and 5 was not predictive of inferior graft outcomes. Intensive use of DUS in the early post-LT period offers the possibility of early diagnosis of vascular complications, guiding medical and surgical management of HAT. Additionally, according to our data, low RI (< 0.55) on the first postoperative day also is a predictor of HAT and decreased graft-survival.

Impact of ABO incompatibility and early antibody-mediated rejection on chronic antibody-mediated rejection in kidney transplant patients.

Early antibody-mediated rejection has been reported to increase chronic antibody-mediated rejection and decrease graft survival in kidney transplantation. However, the impact of early antibody-mediated rejection in ABO-incompatible kidney transplantation remains unclear. We retrospectively analyzed living-donor kidney transplantation patients from two Korean centers. Patients were categorized based on ABO compatibility and early antibody-mediated rejection within 1 year. The primary outcome was chronic antibody-mediated rejection. The secondary outcomes were production of de novo donor-specific antibody and composite kidney outcome, defined as graft loss or a decline in estimated glomerular filtration rate to below 30mL/min/1.73 m2. A total of 1639 patients were analyzed, including 1292 patients who underwent ABO-compatible kidney transplantation and 347 patients who underwent ABO-incompatible kidney transplantation. ABO-incompatible kidney transplantation had a lower risk of de novo donor-specific antibody production (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.95) and chronic antibody-mediated rejection (HR 0.33, 95% CI 0.12-0.92) with a comparable risk of the composite kidney outcome (HR 1.06, 95% CI 0.71-1.59) compared to ABO-compatible kidney transplantation. When outcomes of ABO-incompatible kidney transplantation were analyzed according to early antibody-mediated rejection, ABO-incompatible kidney transplantation without antibody-mediated rejection had a lower risk of de novo donor-specific antibody production (HR 0.60, 95% CI 0.41-0.88) and chronic antibody-mediated rejection (HR 0.28, 95% CI 0.09-0.91) than ABO-compatible kidney transplantation without antibody-mediated rejection. However, ABO-incompatible kidney transplantation with antibody-mediated rejection showed a higher risk of de novo donor-specific antibody production and similar risk of chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation without antibody-mediated rejection. ABO-incompatible kidney transplantation showed a lower risk of de novo donor-specific antibody production and chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation; however, early antibody-mediated rejection abrogated these beneficial effects of ABO-incompatible kidney transplantation.

Arterial hypertension in kidney transplantation: huge importance, but few answers.

Arterial hypertension (AH) after renal transplantation (RTX) is correlated with worse cardiovascular and renal outcomes, with loss of renal function, decreased graft survival and higher mortality. RTX recipients have discrepant blood pressure (BP) values when measured in the office or by systematic methodologies, such as Ambulatory Blood Pressure Monitoring (ABPM), with significant prevalence of no nocturnal dipping or nocturnal hypertension, white coat hypertension and masked hypertension. The aim of the present study was to review the issue of hypertension in RTX, addressing its multifactorial pathophysiology and demonstrating the importance of ABPM as a tool for monitoring BP in these patients. Treatment is based on lifestyle changes and antihypertensive drugs, with calcium channel blockers considered first-line treatment. The best blood pressure target and treatment with more favorable outcomes in RTX are yet to be determined, through well-conducted scientific studies, that is, in terms of AH in RTX, we currently have more questions to answer than answers to give.

The Effect of Topical Normobaric Oxygen Therapy on Composite Graft Survival in Fingertip Amputation

Background: Though composite grafting is an easy, simple treatment for fingertip amputation, it is known to have a low survival rate. To increase the likelihood of composite graft survival, various adjuvant therapies such as hyperbaric oxygen therapy, ice-cooling, or vasodilator agents have been used. In this study, we attempted to validate the hypothesis that topical normobaric oxygen therapy (tNBO) could improve composite graft survival in fingertip amputation.Methods: Patients who sustained fingertip amputations and who were treated with composite grafting between January 2015 and July 2020 were included. The patients (n=154) were divided into two groups: those who received tNBO (n=102) and those who had not (n=52). The effect of tNBO on graft survival, survival rate by level of amputation, and risk factors of graft survival (age, smoking, time to surgery, diabetes mellitus, and crush-avulsion injury type) were examined.Results: tNBO significantly increased composite graft survival (75.3% vs. 50%, P&lt;0.001) in amputations distal to the nail base area. Among risk factors, time to surgery &gt;5 hours (odds ratio, 48.6; P=0.001) and crush-avulsion injury type (odds ratio, 10.1; P&lt;0.001) significantly decreased graft survival in both groups. Smoking decreased graft survival only in the non-tNBO group (odds ratio, 28; P=0.015), not in the tNBO-treated group.Conclusion: tNBO increased composite graft survival in fingertip amputation distal to the nail base area. It can be helpful for composite graft survival in smokers.

Relapse of autoimmune diseases after liver transplantation

Background. The recurrence of autoimmune liver diseases can lead to reduced survival of recipients and grafts.Aim. To study the incidence and impact of the recurrence of autoimmune liver diseases on graft survival; the effect of maintenance immunosuppression on the recurrence of autoimmune diseases in liver transplant recipientsMaterial and methods. Transplantation outcomes in 111 recipients (21 recipients operated on for autoimmune hepatitis, 50 recipients operated on for primary biliary cirrhosis, and 40 recipients operated on for primary sclerosing cholangitis) were analyzed retrospectively.Results. The recurrence of autoimmune hepatitis is observed in 5%, the recurrence of primary biliary cirrhosis is in 10%, and the recurrence of primary sclerosing cholangitis is in 17% of cases. Among patients with recurrence of autoimmune diseases, men accounted for 54%, while for only 31% in the subgroup of patients without relapse (p=0.004). The followup for recipients with relapse (64.5 (42.8;82.0) months) was comparable to the follow-up for recipients without relapse (46.5 (17.9;103.5) months, p=0.54). A ten-year graft survival was significantly higher in the group of recipients with recurrent autoimmune diseases compared with recipients without autoimmune diseases recurrence (p&lt;0.0001).Conclusions. The recurrence of autoimmune diseases leads to a decrease in graft survival. The effect of immunosuppression components on the risk of recurrence of autoimmune diseases in the graft has not been established.

Transitional B cell cytokines risk stratify early borderline rejection after renal transplantation

Borderline rejection (BL) in renal transplantation is associated with decreased allograft survival, yet many patients with BL maintain stable graft function. Identifying patients with early BL at risk for shortened allograft survival would allow for timely targeted therapeutic intervention aimed at improving outcomes. 851/1187 patients transplanted between 2013-18 underwent early biopsy (0-4 mos). 217/851 (25%) had BL and were compared to 387/851 without significant inflammation (NI). Serial surveillance and for-cause biopsies and seven-year follow-up were used to evaluate histological and clinical progression. To identify high-risk patients, we examined clinical/histological parameters using regression and non-linear dimensionality reduction (tSNE) and a biomarker based on peripheral blood transitional-1 B cell (T1B) IL-10/TNFα ratio. Compared to NI, early BL was associated with increased progression to late acute rejection (AR; 5-12 mos), premature interstitial fibrosis and tubular atrophy (IFTA) and decreased seven-year graft survival. However, decreased graft survival was limited to BL patients who progressed to late AR or IFTA, and was not influenced by treatment. Although tSNE clustered patients into groups based on clinical factors, the ability of these factors to risk stratify BL patients was modest. In contrast, a low T1B IL-10/TNFα ratio at 3 months identified BL patients at high risk for progression to AR (ROC AUC 0.87) and poor 7-yr graft survival (52% vs. 92%, p=0.003), while BL patients with a high ratio had similar graft survival to patients with NI (91%, p=NS). Thus, progressive early allograft inflammation manifested as BL that progresses to late AR in the first post-transplant year represents a high-risk clinical state for poor allograft outcomes. Such high-risk status can be predicted by the T1B IL-10/TNFα ratio before irreversible scarring sets in, thus allowing timely risk stratification.

P8.045: Modern Medicine Needs Modern Technology Tools

Introduction: Early detection of subclinical rejection is critical to prevent the allograft loss. Currently used methods to detect subclinical rejection include surveillance biopsy protocol, serum creatinine level, eGFR or DSA; however, these methods have limited sensitivity and specificity to accurately detect subclinical rejection. Donor derived cell-free DNA (dd cf-DNA) is a non-invasive biomarker for allograft injury and has been shown to predict allograft rejection with higher sensitivity to detect subclinical rejection compare to some methods (1,2). Here, we show the value of dd cf-DNA in detecting early allograft rejection by presenting two cases where dd cf-DNA assay, AlloSure (CareDx) detected subclinical rejection while other indicators showed stable allograft function. Methods: Ochsner uses AlloSure (CareDx) for a surveillance for the high-risk patients. Results: Thirty-two years old Caucasian female with end stage kidney disease secondary to HIV infection underwent deceased-donor renal transplant in 2018 with KDPI 19% and cPRA 84%. Serum creatinine level had been stable at 1.1mg/dL to 1.2mg/dL post-transplant. This patient was monitored using AlloSure (CareDx) for 1-,2-,3-,4-,6- and 9-month post-transplant. AlloSure values for month 1 to 6 were <0.21, which indicates stable allograft function. However, at 9-month post-transplant, AlloSure value went up to 4.5%, which indicates possible allograft injury, while serum creatinine level remained stable at 1.2 mg/dL with low level of class 2 DSA (DR-1573). Despite stable creatinine level and low level DSA, we initiated biopsy because of sharp increase in AlloSure value. Biopsy revealed acute T-cell mediated rejection and acute vascular rejection. The second case is a 33 years-old Caucasian female with history of previous renal transplant. The first allograft failed in 2018 due to renal artery and vein thrombosis. The patient underwent deceased donor kidney transplant in 2019. Serum creatinine level was stable at 1.0 – 1.3 mg/dL and sharp increase in respectively. At month 3, AlloSure value went up to 0.78% but DSA was negative. We initiated biopsy based on increase in AlloSure value and it revealed acute antibody mediated rejection (ABMR) (Figure 1). The third case is a 56 years-old male with history of end-stage renal disease secondary to hypertension. The patient received deceased donor kidney transplant in 2017. He developed acute renal failure (Cr went up from 1.2 mg/dl to 1.7 mg/dL) few months after kidney transplant and his kidney biopsy showed acute antibody mediated rejection and T-cell mediated rejection which were treated. At 1-year post-transplant, serum creatinine level remained 1.2 mg/dL to 1.3 mg/dL. He was place on monthly Allosure surveillance. The first value was 1.9%, which indicate possible allograft injury. Monthly monitoring showed increase trend in AlloSure value up to 4.1% while Cr remained stable at 1.2 mg/dL-1.3 mg/dL. At that point, biopsy was performed, and it revealed acute antibody mediated rejection and chronic active antibody rejection. Patient was treated with for ABMR. In addition, monthly Tocilizumab was considered for chronic active antibody mediated rejection for 6 months. AlloSure values reflected the early detection of rejection in a patient with stable Cr as well as the efficacy of treatment with down trending values (Figure 2). Conclusion: For all 3 cases, biopsy would not have been initiated most likely due to stable creatinine level and weak or negative DSA. If this had gone untreated for long period of time, this would have led to significant decrease in graft survival. These cases demonstrate that normal serum creatinine does not mean patient has no active inflammatory process. When other indicators are normal/stable, AlloSure was able to detect early rejection. All three cases demonstrated the value of AlloSure as a monitoring tool for detection of early allograft rejection.

401.3: Microvascular Inflammation in Renal Transplant Recipients Without Antibody Mediated Rejection

Purpose: Microvascular inflammation (MVI) defined by glomerulitis (g) and peritubular capillaritis (ptc) is a hallmark of ABMR in renal transplantation. The prevalence and significance of MVI in patients without ABMR is less understood. Methods: Here, we analyzed MVI in the 1st post-transplant year, its relationship to DSA, and its clinical significance in a large cohort of patients without ABMR. Along with any for-cause biopsy (fcBx), patients underwent 2 protocol biopsies (pBx, 3 & 12mos). Bx were categorized as early (0-4mos) or late (5-12mos). Serum was screened for DSA at 0, 1, 3, 6, 9 & 12mos post-transplant. Results: MVI Prevalence: 956/1187 patients transplanted between 2013-18 underwent 1950 Bx (67% protocol, 33% for-cause). Of these Bx, 64 had either ABMR or GN and were excluded. MVI was noted in 23% (g+ptc score 1-1.5 in 13% & ≥2 in 10%) of the remaining 1887 Bx with greater prevalence in fcBx (fcBx 14% vs. pBx 7%) and late Bx (late Bx 29% vs. early Bx 17%). Of note, the MVI prevalence and its severity increased with increasing grades of tubulointerstitial inflammation (TII) (Fig 1A). Of note, 65% of patients with allograft infections (pyelonephritis & BKVN) had MVI. MVI & DSA: DSA was detected concurrently in 12% of all the 1887 Bx without ABMR. Although, MVI was associated with concurrent DSA detection in these Bx (OR 1.8, 95% CI 1.3-2.5, p<0.,001), ~60% of the biopsies never had DSA (concurrent/historic or future). Furthermore, in biopsies stratified by the grade of TCMR, there was no significant difference in concurrent DSA detection between patients with and without MVI (Fig.1B). Outcomes: MVI in patients without ABMR was associated with decreased 7yr-graft survival (Fig 1C, p<0.001). Importantly, the combination of MVI and TII was associated with worse graft survival when compared to either no inflammation or TII alone (Fig1C, p<0.001). Further, in a select sub-group of patients with allograft infection, MVI was associated with a trend towards decreased graft survival compared to no MVI (76% vs. 88%). Finally, MVI was associated with poor graft survival independent of potential confounders including DSA (HR 2.5, 95% CI 1.6-3.4, p<0.001). Conclusion: MVI is common even in the absence of ABMR or DSA and is a marker for the severity of allograft inflammation and subsequent poor clinical outcomes.

Cholecalciferol supplementation effectively improved tertiary hyperparathyroidism, FGF23 resistance and lowered coronary calcification score: a prospective study.

IntroductionTertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation.Materials and methodsTwo hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23–KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients.ResultsVitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12.ConclusionVitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

Second pregnancy following kidney transplantation is not associated with an increased risk of graft loss in a single center retrospective cohort study.

Previous studies on first pregnancy following kidney transplantation (KT) show no association with decreased graft survival. This study examined patients with multiple gestations compared to a single pregnancy following KT and evaluated the risk of graft function deterioration. A retrospective cohort study on fertile female kidney transplant recipients (KTRs) from Rabin Medical Center between January 2001 and December 2017 was performed. Data were collected on patients' comorbidities, pregnancy complications, graft loss, mortality, and lab results. Time-varying COX analysis was performed - second pregnancy being the time-related variable. Fifty-two KTRs split into 30 single pregnancy and 22 multiple pregnancy patients following KT. Single pregnancy patients were older during their first pregnancy and had a higher caesarian section rate. During a median follow-up period of 5.6 years, multiple pregnancies, compared to a single pregnancy, were not associated with an increased rate of graft loss. No significant difference was seen between first and second pregnancy in gestational age, birth weight, graft function, and proteinuria rates. Second pregnancy following KT was not shown to be associated with a decreased graft survival. In addition, obstetrical, maternal, and fetal complication rates are not increased in second compared to first pregnancy following KT.

Incidence of BK Viremia in Simultaneous Heart-Kidney Transplant Recipients: A Single-Center Experience

<h3>Purpose</h3> BK virus (BKV) after kidney transplant is associated with decreased graft survival, increased morbidity, and increased health-care costs. Management of BKV post-transplant remains difficult, especially in dual organ transplants where immunosuppression requirements are typically higher and limited evidence exists. Our aim was to describe our experience with simultaneous heart-kidney transplant (HKT) recipients who developed BKV. <h3>Methods</h3> This was a single-center case series of HKT recipients between 11/2015 and 11/2019. Data are presented as median (IQR) or percentages, as appropriate. The primary endpoint was the incidence of BK viremia within 12-months post-transplant. <h3>Results</h3> Of the 12 patients included, 5 (41.7%) developed BKV at a median time of 196 (85-258) days. Baseline demographics and clinical outcomes are included in Table 1. Patients who experienced BKV were more likely to receive rabbit anti-thymocyte globulin for induction (p=0.04). There was no statistical difference in maintenance immunosuppression; however, mycophenolate dose and tacrolimus troughs were numerically higher at 3 months post-transplant in patients with BKV. All 5 patients were treated with a reduction in maintenance immunosuppression. Additionally, three (60%) received intravenous immune globulin, three (60%) received cidofovir, and three (60%) were switched to sirolimus. Although not statistically significant, eGFR was numerically lower starting at 3-months post-transplant in patients with BKV. Only one (20%) patient developed biopsy-confirmed BK nephropathy. <h3>Conclusion</h3> BKV is an underappreciated complication post-HKT. The high incidence may be explained by lymphocyte-depleting induction and increased maintenance immunosuppression in this group. Although BKV did not impact patient or graft survival, added vigilance may be warranted. Long-term follow-up is required to help identify appropriate management strategies for this complication.

The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45–3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94–7.39; P < 0.001; HR, 9.92; 95% CI: 7.43–13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31–199.41; P = 0.002; HR, 82.67; 95% CI: 33.67–202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05–1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02–2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.