Deceased Donor Kidney Transplant Recipients Research Articles

Intraoperative central venous pressures related to early graft function in deceased donor kidney transplant recipients with low immunological risks

This study aims to analyze data from patients who received kidney transplantation from deceased donors to investigate the anesthetic factors influencing early and late graft outcomes, including the incidence of slow graft function (SGF), delayed graft function (DGF), and 3-year graft outcomes. We retrospectively analyzed 202 recipients who underwent deceased donor kidney transplantation from March 2010 to December 2020. Anesthetic monitoring data during the intraoperative period was analyzed at 5-minute intervals, and basic clinical parameters were evaluated. The mean recipient age was 46.6 ± 10.3 years, and the mean donor age was 41.7 ± 12.7 years. Anesthetic time averaged 285.8 ± 70.2 min, and operation time averaged 223.1 ± 44.0 min. The incidence of SGF was 11.8%, and the incidence of DGF was 3.9%. Mean central venous pressures (CVPs) were higher in recipients with SGF or DGF (11.7 mmHg) compared to those with immediate graft function (9.7 mmHg). Higher CVP was identified as an independent risk factor for SGF or DGF (odds ratio 1.219, p = 0.006). This study suggests that intraoperative monitoring of CVP is crucial for predicting short-term graft function in deceased donor kidney transplantation and should be managed to prevent excessive fluid intake.

Basiliximab vs. No Induction Therapy in Kidney Transplant Recipients with a Low Immunological Risk Profile Receiving Tacrolimus/Mycophenolate/Steroids Maintenance Immunosuppression.

Background: Induction therapy with basiliximab is recommended in kidney transplant (KT) recipients with a low immunological risk (LIR) profile. Whether basiliximab is associated with a decreased risk of acute rejection (AR) and graft loss is controversial. Methods: In our institution, LIR patients (absence of anti-HLA antibodies before KT) are inducted with basiliximab in case of living-donor KT, while deceased-donor KT recipients receive no induction. Maintenance immunosuppression is similar, including a combination of tacrolimus (Tac), mycophenolate (MPA) and steroids. In this single-center retrospective study, we included all adult LIR patients who underwent KT between 1 January 2015 and 31 December 2022. Results: Of the 471 patients included, 354 received no induction and 117 received basiliximab. The median (IQR) number of HLA A-B-DR mismatches was 3 (2-3) and 2 (2-4) in the no induction group and the basiliximab group, respectively. The cumulative incidences in the no induction group vs. the basiliximab group of acute rejection and graft loss over 5 years post-KT were similar at 8.9% vs. 7.8% (p = 0.8) and 8.5% vs. 4.2% (p = 0.063), respectively. In multivariable Cox regression analysis, delayed graft function emerged as an independent risk factor for acute rejection (hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.23-6.13, p = 0.014) and graft loss (HR 9.32, CI 4.10-21.1, p < 0.001). Conclusions: Basiliximab did not provide any advantage in terms of rate of acute rejection and graft survival within 5 years post KT compared with a strategy without induction therapy in patients with a low immunological risk profile receiving triple maintenance immunosuppression Tac/MPA/steroids.

Disseminated Toxoplasma Gondii Infection in a Deceased Donor Kidney Transplant Recipient: A Fatal Case Report

Abstract Introduction/Objective Post-transplant immunosuppression predisposes patients to severe complications from opportunistic infections, including Toxoplasma gondii. Typically asymptomatic and self-limited in immunocompetent individuals, Toxoplasma gondii can cause life-threatening disseminated disease in immunocompromised patients like solid organ transplant recipients. The challenge in diagnosing Toxoplasmosis is further exacerbated in patients receiving prophylactic therapy with agents such as Atovaquone, which may mask clinical suspicion. This case report describes a fatal presentation of disseminated Toxoplasmosis in a kidney transplant recipient. Methods/Case Report A 44-year-old male with a history of deceased donor kidney transplant presented to the emergency department two months post-transplant with symptoms of malaise, shortness of breath, hypoxemia, and hypotension. Despite medical interventions, the patient deteriorated rapidly, developing acute hypoxemic respiratory failure and septic shock requiring intubation. Subsequently, he succumbed to multisystem organ failure five days after admission. The autopsy revealed disseminated Toxoplasma gondii infection, with tachyzoites/bradyzoites identified in multiple organs, including the brain, bone marrow, and lymph nodes. Positive Toxoplasma immunohistochemical staining and PCR confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion Toxoplasma infection in post-transplant patients can manifest as a severe and potentially fatal complication. Dissemination can arise from the reactivation of latent infection, donor transmission, or new acquisition. In this case, the infection likely resulted from the reactivation of latent infection in the donor, compounded by immunosuppression in the recipient. Notably, the patient received Atovaquone prophylaxis due to a sulfa allergy. Nonetheless, the case highlights the potential for delayed diagnosis due to atypical presentations in immunocompromised patients. Clinicians should maintain a high index of suspicion for Toxoplasma infection in post- transplant patients, particularly in those with unexplained clinical deterioration. This case emphasizes the importance of maintaining a high index of suspicion for T. gondii infection in post-transplant patients, even in those receiving prophylaxis.

Renal transplantation in older adults: retrospective cohort study to examine the impact of the new 2019 kidney offering scheme on older adult transplant recipients.

In 2019, a new kidney offering scheme was launched in the United Kingdom, aiming to better match estimated patient survival and graft life expectancy. The scheme's impact on older patients undergoing kidney transplantation (KT) is unknown. This study aims to compare the outcomes of older adult KT recipients before and after introduction of the 2019 scheme. A retrospective observational cohort study of older adults who underwent KT was undertaken. Group 1 were transplanted between 1 September 2017 and 31 August 2019 (2006 allocation scheme) and group 2 between 1 September 2019 and 31 August 2021 (2019 offering scheme). An older adult was any person ≥60 years old at the time of KT. Univariable binary logistic regression analysis was performed to determine odds ratios (OR) and 95% confidence intervals (CI). There were 107 older adult deceased donor KT recipients, 62 from group 1 and 45 from group 2. Median age at transplantation was 68 (interquartile range [IQR] 62-71) and 67 (IQR 64-73) years, respectively. Univariable analysis showed that re-intervention (OR 6.486, 95% CI 1.306-32.216, p = 0.022) and critical care admission (OR 5.619, 95% CI 1.448-21.812, p = 0.013) were significantly more likely in group 2. Group 2 recipients were significantly more likely to have a level 4 human leucocyte antigen (HLA) mismatch (OR 4.667, 95% CI 1.640-13.275, p = 0.004) and to have undergone previous KT (OR 4.691, 95% CI 1.385-15.893, p = 0.013). The introduction of the 2019 offering scheme was associated with re-intervention and critical care admission for older KT recipients. We also observed less-favourable HLA matches but more KT in difficult-to-match groups.

Delayed graft function has comparable associations with early outcomes in primary and repeat transplant among deceased-donor kidney transplant recipients.

Delayed graft function (DGF) is a common complication and is associated with worse outcomes among kidney transplant recipients (KTRs). There are various risk factors for DGF including previous transplant. We hypothesized that DGF among KTRs undergoing repeat transplant has a greater impact on outcomes compared to primary KTRs. All deceased-donor KTRs between 01/2000 and 12/2020 at our center were included. Recipients were categorized as primary KTR or repeat KTR (any number of previous kidney transplants). Outcomes of interest included acute rejection, death-censored graft failure, and patient mortality within 12months post-transplant. A total of 3137 deceased-donor KTRs were included; 2498(80%) were primary KTRs and 639(20%) were repeat KTRs. The rates of DGF were similar between the groups at 29% and 28%, respectively. Compared to KTRs without DGF, DGF was associated with a greater incidence of death and graft failure in both primary and repeat transplants; however, the risk of rejection was not significantly higher in repeat KTRs (p = 0.72). Comparing primary and repeat KTRs, there were no significant differences in either acute rejection (p-interaction = 0.11), death-censored graft failure (p-interaction = 0.38), or death (p-interaction = 0.37). In subgroup analysis among repeat KTRs with DGF, a repeat transplant with no prior DGF was associated with increased risk for death-censored graft failure and death but not for acute rejection. DGF in the prior transplant was protective against death-censored graft failure (HR: 0.07, 95% CI 0.005-0.98, p = 0.05) (p-interaction = 0.04), but this was not significantly associated with acute rejection or death. DGF is associated with similar detrimental outcomes among primary and repeat KTRs.

Reexamining Transplant Outcomes in Acute Kidney Injury Kidneys Through Machine Learning.

Despite many people awaiting kidney transplant, kidney allografts from acute kidney injury (AKI) donors continue to be underutilized. We aimed to cluster kidney transplant recipients of AKI kidney allografts using an unsupervised machine learning (ML) approach. Using Organ Procurement and Transplantation Network-United Network for Organ Sharing (OPTN/UNOS) data, a consensus clustering cohort analysis was performed in 12356 deceased donor kidney transplant recipients between 2015 and 2019 in whom donors had a terminal serum creatinine ≥1.5mg/dL. Significant cluster characteristics were determined, and outcomes were compared. The median donor terminal creatinine was 2.2 (interquartile range [IQR] 1.7-3.3) mg/dL. Cluster analysis was performed on 12356 AKI kidney recipients, and three clinically distinct clusters were identified. Young, sensitized kidney re-transplant patients characterized Cluster 1. Cluster 2 was characterized by first-time kidney transplant patients with hypertensive and diabetic kidney diseases. Older diabetic recipients characterized Cluster 3. Clusters 1 and 2 donors were young and met standard kidney donor profile index (KDPI) criteria; Cluster 3 donors were older, more likely to have hypertension or diabetes, and meet high KDPI criteria. Cluster 1 had a higher risk of acute rejection, 3-year patient death, and graft failure. Cluster 3 had a higher risk of death-censored graft failure, patient death, and graft failure at 1 and 3 years. Cluster 2 had the best patient-, graft-, and death-censored graft survival at 1 and 3 years. Compared to non-AKI kidney recipients, the AKI clusters showed a higher incidence of delayed graft function (DGF, AKI: 43.2%, 41.7%, 45.3% vs. non-AKI: 25.5%); however, there were comparable long-term outcomes specific to death-censored graft survival (AKI: 93.6%, 93.4%, 90.4% vs. non-AKI: 92.3%), patient survival (AKI: 89.1%, 93.2%, 84.2% vs. non-AKI: 91.2%), and overall graft survival (AKI: 84.7%, 88.2%, 79.0% vs. non-AKI: 86.0%). In this unsupervised ML approach study, AKI recipient clusters demonstrated differing, but good clinical outcomes, suggesting opportunities for transplant centers to incrementally increase kidney utilization from AKI donors.

Graft Kidney Artery Stenosis in a Deceased Donor Kidney Transplant Recipient with Autosomal Dominant Polycystic Kidney Disease: A Case Report

Graft Kidney Artery Stenosis in a Deceased Donor Kidney Transplant Recipient with Autosomal Dominant Polycystic Kidney Disease: A Case Report

Time Course of Glycolytic Control Protein Expression in Urinary Extracellular Vesicles (UEV) of Deceased Donor Kidney Transplant Recipients

Time Course of Glycolytic Control Protein Expression in Urinary Extracellular Vesicles (UEV) of Deceased Donor Kidney Transplant Recipients

Association of early steroid withdrawal with kidney transplant outcomes in first-transplant and retransplant recipients.

Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR=1.04 [95% CI=1.00-1.09]), slightly higher hazard of graft failure (HR=1.09 [95% CI=1.05-1.12]), and slightly lower mortality (HR=0.93 [95% CI=0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR=1.42 [95% CI=1.29-1.57]; interaction p<0.001) and graft failure (HR=1.24 [95% CI=1.14-1.34]; interaction p=0.003), and similar mortality (HR=1.01 [95% CI=0.94-1.08]; interaction p=0.04). In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.

Urinary Extracellular Vesicles for Non-Invasive Quantification of Principal Cell Damage in Kidney Transplant Recipients.

The objective of the present study was to compare principal cell-specific aquaporin-2 (AQP2) abundances in urinary extracellular vesicles (uEVs) on the first postoperative day in deceased-donor kidney transplant recipients without and with acute kidney injury. We measured uEV markers (CD9 and CD63) and the abundances of proximal tubular sodium-glucose transporter 2, distal tubular sodium/chloride cotransporter, and principal cell-specific aquaporin-2 using Western blotting of urine. uEV-AQP2 levels were normalized to living donor controls. The validation cohort consisted of 82 deceased-donor kidney transplant recipients who had a median age of 50 years (IQR 43 to 57 years). A total of 32% of recipients had acute kidney injury. The median uEV-AQP2 was significantly higher in recipients with acute kidney injury compared to immediate allograft function (2.05; IQR 0.87 to 2.83; vs. 0.81; IQR 0.44 to 1.78; p < 0.01). The Youden index indicated a uEV-AQP2 threshold of 2.00. Stratifying uEV-AQP2 into quartiles showed that recipients with higher uEV-AQP2 levels had higher rates of acute kidney injury (Cochran-Armitage, p = 0.001). The discovery cohort showed elevated CD9, CD63, and uEV-AQP2 levels in urine from recipients with acute kidney injury compared to immediate allograft function. We were able to quantify the damage of principal cells after kidney transplant to predict acute kidney injury using uEV-AQP2.

407.2: Single-center observational study of 1,119 deceased donor kidney transplant recipients suggesting the removal of 5/13 individual components of the kidney donor risk index.

407.2: Single-center observational study of 1,119 deceased donor kidney transplant recipients suggesting the removal of 5/13 individual components of the kidney donor risk index.

Readmission Outcomes in Kidney Transplant Recipients With and Without Delayed Graft Function

Delayed graft function (DGF) is a common post-transplant event associated with increased resource utilization. As a center with experience in DGF, we aimed to assess differences in readmissions and post-transplant outcomes between patients with and without DGF. This was a retrospective review of deceased donor kidney transplant recipients at Mayo Clinic Arizona between 2015 and 2020. Recipients with at least one early readmission following kidney transplantation were included in the study. Two groups were identified: (1) recipients with DGF who required early readmission and (2) recipients without DGF who required early readmission. Among recipients with DGF, 43.9% (n = 405) required early readmission compared to 29.1% (n = 179) without DGF (P < .0001). There were no differences in the initial hospital length of stay (P = .08), and most recipients in both groups only required a single readmission (61.7% vs 72.1%, P = .02). Recipients with DGF were more likely to have ≥2 readmissions (P = .02) and a higher total readmission rate (P = .006). Recipients with DGF who required readmission also required more outpatient clinic visits (P = .003). When comparing recipients with and without DGF who required readmission, there were no differences in patient (P = .22) or death-censored (P = .72) graft survival. When comparing patients with and without DGF requiring one versus ≥2 readmissions, there were no differences in patient survival (P = .15), however patients with DGF and ≥2 readmissions had lower death-censored graft survival (P = .001). Recipients with DGF are at increased risk of readmission. Transplant center-level changes to reduce readmissions and infections could have an important impact on DGF outcomes.

The impact of donor hepatitis B virus infection on transplant outcomes in deceased donor kidney transplantation recipients.

The use of hepatitis B virus (HBV)-positive donor kidneys to expand the donor pool has been implemented, but limited evidence exists regarding their impact on transplant outcomes. This study aimed to investigate the effects of donor HBV infection on transplant outcomes. Donor and recipient data between 2015 and 2021 were collected. A total of 743 kidney transplant cases were screened, including 94 donor hepatitis B surface antigen (HBsAg)+/recipient HBsAg- (D+R-) and 649 donor HBsAg-/recipient HBsAg- (D-R-) cases. The analysis endpoints included recipient HBV infection, delayed graft function (DGF), peak estimated glomerular filtration rate (eGFR) within 12 months, recipient survival, and death-censored graft survival (DCGS). The D+R- group had a significantly higher risk of HBV infection compared to the D-R- group (6/72 vs. 3/231; relative risk, 6.4; p = 0.007). The risk of HBV transmission decreased significantly with increasing hepatitis B surface antibody (HBsAb) titer (p for trend = 0.003). Furthermore, the D+R- group did not exhibit an increased risk of DGF compared to the D-R- group (odds ratio, 0.70; p = 0.51) in the multivariable mixed model. Both groups had similar peak eGFR within 12 months (β = 1.01, p = 0.71), and this had no impact on patient survival (hazard ratio [HR], 0.36; p = 0.10) and DCGS (HR, 0.79, p = 0.59) in the shared-frailty Cox model. The use of HBsAg-positive donor kidneys appears relatively safe for HBV-immunized recipients in the short term. D+R- does not negatively affect graft function recovery and provides comparable posttransplant outcomes. Maintaining an HBsAb titer over 100 IU/L before transplantation is critical to reduce the risk of HBV transmission.

#2843 Urinary extracellular vesicles in after deceased donor kidney transplantation

Abstract Background and Aims Urinary extracellular vesicles (uEV) are membrane-bound organelles which contain several molecules from their host tissue, including proteins, membrane receptors, nucleic acids, and lipids. Currently it is unknown whether uEV can be used as a liquid biopsy tool to determine injuries of the allograft after kidney transplantation. The objective of the present study was to compare uEV early posttransplant in kidney transplant recipients with allografts from deceased male and deceased female donors. Method We measured the principal cell specific aquaporine 2 (AQP2) abundance in uEV with an Enzyme-linked immunosorbent assay (ELISA) using novel generated specific antibodies, 19-64-1. The AQP2 abundance in uEV was detected in urine samples from incident deceased donor kidney transplant recipients during two periods posttransplant, i.e., the first period was from 6 to 11 hours and the second period was from 12 to 23 hours posttransplant, respectively. The AQP2 abundance in uEV was normalized to urinary creatinine, i.e., abundance/mmol creatinine. Results Complete data were obtained from 71 kidney transplant recipients with median age, 50 years (IQR, 42 to 57 years), median weight 73 kg (IQR, 64 to 86 kg), median systolic blood pressure, 144 mmHg (IQR, 130 to 160 mmHg), median diastolic blood pressure, 87 mmHg (IQR, 78 to 98 mmHg), median time on dialysis 25 months (IQR, 10 to 44 months). In 43 kidney transplant recipients with deceased male donors the AQP2 abundance in uEV significantly decreased from median 0.12 (IQR, 0.06 to 0.29) at the first postoperative period to median 0.05 (IQR, 0.03 to 0.12; P = 0.0004 by Wilcoxon matched-pairs signed rank test). On the other hand, in 31 kidney transplant recipients with deceased female donors the AQP2 abundance in uEV did no change from median 0.09 (IQR, 0.05 to 0.24) at the first postoperative period to median 0.05 (IQR, 0.03 to 0.13; P = 0.09 by Wilcoxon matched-pairs signed rank test). Conclusion The larger postoperative decline of the AQP2 abundance in uEV from deceased male donors compared to deceased female donors in early periods posttransplant may point to a larger principal cell mass in males.

Is Lack of Consensus on the Management of Chronic Active Antibody-Mediated Rejection Harming Renal Transplant Recipients?

In 2022, over 92,000 kidney transplants were performed globally. With advancements in transplant science, 1-year graft survival rates have reached 94.3% for deceased donor kidney transplant recipients, and 97.8% for living recipients. However, 5-year graft survival remains at 76.3% and 86.5%. Antibody-mediated rejection (AMR) is one of the most common causes of immune-related allograft rejection. Chronic active AMR (CABMR) typically develops 6–12 months post-transplant; 76% of kidney transplant recipients with CABMR experience graft loss 1.9 years after diagnosis. Despite these alarming figures, consensus guidelines on the management of post-transplant patients have not been updated with advancements in testing and protocol biopsies, and there is currently no consensus in Europe on CABMR management.

Ensemble Clustering to Generate Phenotypes of Kidney Transplant Donors and Recipients.

In this paper we investigate the generation of phenotypes for kidney transplant donors and recipients to assist with decision making around organ allocation. We present an ensemble clustering approach for multi-type data (numerical and categorical) using two different clustering approaches-i.e., model based and vector quantization based clustering. These clustering approaches were applied to a large, US national deceased donor kidney transplant recipient database to characterize members of each cluster (in an unsupervised fashion) and to determine whether the subsequent risk of graft failure differed for each cluster. We generated three distinct clusters of recipients, which were subsequently used to generate phenotypes. Each cluster phenotype had recipients with varying clinical features, and the risk of kidney transplant graft failure and mortality differed across clusters. Importantly, the clustering results by both approaches demonstrated a significant overlap. Utilization of two distinct clustering approaches may be a novel way to validate unsupervised clustering techniques and clustering can be used for organ allocation decision making on the basis of differential outcomes.

Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.

The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty. We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age. Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days. The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.

Tacrolimus Interaction with Azole Antifungals in Kidney Transplant Recipients: Is Fluconazole or Clotrimazole a Worse Offender?

The utilization of rabbit ant thymocyte globulin induction with tacrolimus-based maintenance immunosuppression may increase the risk for opportunistic fungal infections, particularly oral-esophageal candidiasis. Both are commonly prescribed for deceased donor kidney transplant recipients Tacrolimus (TAC), a calcineurin inhibitor, is metabolized hepatically by cytochrome P450 3A4/5 enzymes. Due to this, a drug interaction can occur with TAC and either fluconazole (FCZ) or clotrimazole (CTMZ). Both are commonly used for antifungal prophylaxis. While both FCZ and CTMZ inhibit CYP3A4/5, systemic absorption of CTMZ is minimal, theoretically limiting the interaction with TAC and reducing the need for dose readjustments. Medical records for adult patients receiving a renal transplant between March 2009 and September 2011 were retrospectively reviewed for TAC dose adjustments following discontinuation of the antifungal agent required to maintain therapeutic TAC blood levels. The change in TAC dose: trough ratio 4-8 weeks after azole discontinuation was greater in patients receiving FCZ compared to CTMZ (FCZ +92.9% vs CTMZ +43.4%, p=0.004). In addition, the proportion of patients requiring ≥30% TAC dose increase was 70% with FCZ versus 45% with CTMZ (p=0.006). The choice of antifungal also did not affect the number of sub-therapeutic TAC levels, the number of patients with sub-therapeutic levels pre- or post-discontinuation, or incidence of biopsy-proven allograft rejection.

A2/A2B to B deceased donor kidney transplantation in the Kidney Allocation System era

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.192.332.47; P < .001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.780.941.13, P = .5). Moreover, there was no difference between A2→B vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.771.001.29, P > .9) or all-cause graft loss (wHR 0.820.961.12, P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.

The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.