Death-censored Graft Survival Research Articles

Bisphosphonate Use After Kidney Transplantation Is Associated with Lower Fracture Risk.

Kidney transplant recipients are at higher risk of fractures compared to the general population. The use of bisphosphonates has been shown to increase bone mineral density after transplantation but has not been shown to lower fracture rates. Here, we aim to determine if exposure to bisphosphonates associates with lower incidence of non-vertebral fractures after kidney transplantation. We conducted a retrospective review for all Southern California Kaiser Permanente kidney transplant recipients with osteoporosis transplanted between 2000 and 2019. Baseline variables were collected. Those prescribed an oral bisphosphonate were compared to those who were not. The primary outcome was non-vertebral fracture. Chi square was used to evaluate categorical variables and Wilcoxson rank sum test for continuous variables. Propensity scores were generated to balance covariates in the bisphosphonate and non-bisphosphonate groups. Cause-specific hazard and sub distribution (Fine-Gray) methods were performed for competing risk analysis. Death censored graft survival was evaluated as a secondary outcome using standard Cox regression. There were 489 patients included in the study, 203 of which were in the bisphosphonate group. The cause specific hazard model suggested a 64% lower risk of non-vertebral fracture in the bisphosphonate group (p=0.02). The Fine-Gray hazard model treating death as a competing risk did not show lower relative incidence of non-vertebral fracture. Bisphosphonate treatment was associated with lower death censored graft failure (p=0.002). Bisphosphonate use after kidney transplantation may associate with lower risk of non-vertebral fracture after transplant. Bisphosphonate use in this study was also associated with lower death censored graft failure. Caution is advised when interpreting these results given the retrospective nature of the study.

Long-Term Outcomes of Induction Immunosuppression for Kidney Transplant Recipients With HIV Who Have Average Immunologic Risk: An Inverse Probability Treatment Weighting Analysis

We analyzed the Scientific Registry of Transplant Recipients (2004-2022) for primary kidney recipients with HIV who had average immunologic risk and were discharged on tacrolimus/mycophenolate mofetil (with or without corticosteroids). Recipients were grouped by induction type: rabbit antithymocyte globulin (r-ATG, n=688) and human interleukin-2 receptor antagonist (IL2Ra, n=467). Kaplan-Meier curves were generated to examine recipient and graft survival by induction type. We used mixed Cox proportional hazard models to determine associations between induction type and outcomes of interest, with adjustments for recipient and donor factors and transplant center as a random effect. Regression with propensity score weighting reduced selection bias from nonrandom induction allocation. The unadjusted 10-year survival rate was 57% for those receiving r-ATG and 64% for those receiving IL2Ra (P<.001). Adjusted risk of death was significantly lower for IL2Ra induction than r-ATG induction with Cox multivariable (hazard ratio, 0.65; 95% CI, 0.47-0.91; P=.01) and inverse probability treatment weighting (hazard ratio, 0.38; 95% CI, 0.29-0.50; P<.01) models. Death-censored kidney graft survival did not differ by induction type in either model. The 1-year rejection rate was 10.1% and 11.6% for r-ATG and IL2Ra recipients, respectively (P=.52). Overall, IL2Ra conferred better long-term survival than r-ATG without increased risk of graft loss.

Kidney Transplantation in Patients with Polycystic Kidney Disease: Increased Risk of Infection Does Not Compromise Graft and Patient Survival

Abstract Background Patients with autosomal dominant polycystic kidney disease (ADPKD) represent &amp;gt;10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear. Methods Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients we assessed the occurrence, frequency and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses. Results During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, p=0.022; 0.8±1.4 vs. 0.5±1.1 episodes, p&amp;lt;0.001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; p&amp;lt;0.001) and recipient age (RR 1.05; p=0.003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral: RR 0.60; p=0.088; bilateral: RR 0.45; p=0.020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients (HR 0.67; p=0.047) due to a lower risk of death-censored graft loss (HR 0.47; p=0.014). Donor age (HR 1.34; p=0.002) and rejection (HR 8.47; p&amp;lt;0.001) were risk factors for death-censored graft loss. Conclusions ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better.

Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database.

Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2±3.7 years (ESW) and 69.2±3.4 years (SCI, p=0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p=0.01) and 3 years (34.89% vs 44.29%, p=0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p=0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p=0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p<0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.

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.

Early and Late Microvascular Inflammation Have Differing Etiological Causes and Clinical Expression.

Microvascular inflammation (MVI) is an important pathological feature of antibody-mediated rejection (AMR). How posttransplant time affects its clinicopathological expression is little understood. This retrospective, single-center study screened 3398 kidney transplant biopsies and dichotomized 202 MVI ≥ 2 (Banff glomerulitis + peritubular capillaritis ≥ 2) samples by 9-mo median incidence time for comparison. The prevalence of MVI ≥ 2 was 12.4% in transplant kidneys, which failed more frequently than propensity-matched normal controls (n = 202; P < 0.001). Epidemiological risk factors for early MVI ≥ 2 were delayed graft function, prior AMR, and circulating donor-specific antibodies (DSAs+). Prior recipient sensitization occurred in 72.3%. Early MVI ≥ 2 was classified AMR in 65.3% and cellular rejection in 34.7%, and demonstrated excellent functional recovery and graft survival comparable to normal control kidneys. Late MVI ≥ 2 was predicted by younger (18 = 29 y) age, female recipient, living-donation, prior methylprednisolone, cyclosporine (versus tacrolimus, levels <5 ng/mL), absent antiproliferative therapy, and DSA+ using multivariable epidemiological modeling. Nonadherence caused 49.5%, with iatrogenic minimization responsible for 47.5%, usually for recipient infection. Late MVI ≥ 2 was because of AMR in 93.1%, and characterized by greater interstitial fibrosis, tubular atrophy, complement degradation split-product 4d (C4d) staining of peritubular capillaries+, endothelial C4d staining of glomerular capillaries+, transplant glomerulopathy and vasculopathy scores, DSA strength, and graft failure than early MVI ≥ 2 or normal transplant kidneys. Death-censored graft survival in 149 unique MVI ≥ 2 kidneys was independently determined by nonadherence, serum creatinine, proteinuria, DSA+, Banff C4d staining of peritubular capillaries+, and chronic interstitial fibrosis scores. MVI score and time lost significance using multivariable Cox regression. The changing expression of MVI ≥ 2 over time is best explained by differences in underimmunosuppression and microvascular injury from AMR impacting allograft function and survival.

Kidney Transplant Outcome Following Donation After Euthanasia.

In the Netherlands, organ donation after euthanasia (donation after circulatory death type V [DCD-V]) has been increasingly performed since 2012. However, the outcomes of DCD-V kidney grafts have not been thoroughly investigated. It is critical to assess the outcomes of these kidney grafts to ascertain whether DCD-V is a safe and valuable way to increase the kidney donor pool. To investigate the outcomes of DCD-V kidney transplantation and compare them with outcomes of kidney transplantation after circulatory death after withdrawal of life-sustaining therapies (DCD type III [DCD-III]) and donation after brain death (DBD). A retrospective cohort study was conducted using the database from the Dutch Transplant Foundation. All kidney transplants in the Netherlands between January 2012 (start of the euthanasia program) and July 2023 were included. Follow-up was obtained through 5 years after transplantation. Data analysis was performed from November 2023 until February 2024. Kidney transplantation with a DCD-V graft compared with DCD-III and DBD grafts. The primary outcome was death-censored graft survival until 5 years after transplantation. Secondary outcomes were the incidence of delayed graft function (DGF), permanent nonfunction (PNF), serum creatinine concentration, and patient survival until 5 years after kidney transplantation. A total of 145 DCD-V kidney transplants were compared with 1936 DCD-III and 1255 DBD kidney transplants. Median (IQR) recipient age was 59 (46-66) years in the DCD-V cohort, compared with 61 (50-68) years in the DCD-III cohort and 61 (50-68) years in the DBD cohort. The incidence of DGF with DCD-V kidney transplants (26%) was significantly less than that with DCD-III kidney transplants (49%; P < .001) and similar to that with DBD kidney transplants (22%; P = .46). PNF occurrence with DCD-V kidneys (6%) was similar to that with DCD-III kidneys (6%; P = .79) and higher than in DBD kidneys (4%; P < .001). There was no difference in 5-year death-censored graft survival between DCD-V grafts (82%) and DCD-III (86%; P = .99) or DBD (84%; P = .99) grafts. There was no difference in 5-year patient survival between DCD-V kidney transplants (69%) and DCD-III (76%; P = .45) or DBD (73%; P = .74) kidney transplants. A propensity score analysis was performed to match the DCD-V and DCD-III cohort, showing results similar to those of the unmatched cohort. This study found that DCD-V kidney transplantation yielded a lower incidence of DGF compared with DCD-III kidney transplantation and yielded long-term results similar to those of DCD-III and DBD kidney transplantation. The findings suggest that DCD-V is a safe and valuable way to increase the kidney donor pool.

Outcomes of Older Primary Kidney Transplant Recipients by Induction Agent and High-risk Viral Discordance Status in the United States.

The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients. We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics. Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival. In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.

Impact of single centre kidney-exchange transplantation to increase living donor pool in India: A cohort study involving non-anonymous allocation.

In India, 85% of organ donations are from living donors and 15% are from deceased donors. One-third of living donors were rejected because of ABO or HLA incompatibility. Kidney exchange transplantation (KET) is a cost-effective and legal strategy to increase living donor kidney transplantation (LDKT) by 25%-35%. We report our experience with 539 KET cases and the evolution of a single-centre program to increase the use of LDKT. Between January 2000 and 13 March, 2024, 1382 deceased donor kidney transplantations and 5346 LDKT were performed at our centre, including 10% (n = 539) from KET. Of the 539 KET, 80.9% (n = 436) were ABO incompatible pairs, 11.1% (n = 60) were compatible pairs, and 8% (n = 43) were sensitized pairs. There were 75% 2-way (n = 2 × 202 = 404), 16.2% 3-way (n = 3 × 29 = 87), 3% 4-way (n = 4 × 4 = 16), 1.8% 5-way (n = 5 × 2 = 10), 2.2% 6-way (n = 6 × 2 = 12), and 1.8% 10-way KET (n = 10 × 1 = 10). Of the recipients 81.2% (n = 438) were male and 18.8% (n = 101) were female, while of the donors, 78.5% (n = 423) were female and 21.5% (n = 116) were male. All donors were near relatives; wives (54%, n = 291) and mothers (20%, n = 108) were the most common donors. At a median follow-up of 8.2 years, patient survival, death censored graft survival, acute rejection, and median serum creatinine levels of functioning grafts were 81.63% (n = 440), 91% (n = 494), 9.8% (n = 53) and 1.3 mg/dL respectively. We credited the success to maintaining a registry of incompatible pairs, high-volume LDKT programs, non-anonymous allocation and teamwork. This is the largest single-centre KET program in Asia. We report the challenges and solutions to replicate our success in other KET programs.

Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36). In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide. Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

Long-term impact of immigration status on outcomes in pediatric kidney transplant recipients

This study aimed to investigate the effects of documentation status on pediatric kidney transplant outcomes in a single-center setting, emphasizing the significance of state insurance access for undocumented patients and federal policies like Deferred Action for Childhood Arrivals (DACA) on patient outcomes. A cohort of 283 patients, including 48 undocumented individuals, who received their first kidney transplant as children between 1998 and 2011 was analyzed. There was no significant difference in unadjusted all-cause (P = .91) and death-censored (P = .38) graft survival between undocumented patients and patients with permanent legal status, subsequently referred to as US residents. Additionally, in the Cox proportional hazards model, immigration status was not significantly associated with all-cause graft survival (hazard ratio 0.87, 95% CI 0.51-1.46, P = .6). Telephone interviews were conducted with the undocumented cohort. Forty-one of 48 of the undocumented recipients were contacted. Ninety-five percent had access to insurance with 68.3% on Medicaid or Medicare. DACA recipients exhibited higher employment rates (88% vs 67%, P = .11) and were more likely to complete a degree beyond high school (47.1% vs 12.5%, P = .01). Immigration status did not impact long-term graft survival, suggesting eligibility expansions for state-funded insurance and DACA may improve access to transplant care for undocumented patients. Moreover, DACA recipients showed trends toward increased employment and education compared to non-DACA recipients.

Anti-HLA Class II Antibodies Are the Most Resistant to Desensitization in Crossmatch-positive Living-donor Kidney Transplantations: A Patient Series.

In HLA-incompatible kidney transplantation, the efficacy of desensitization in terms of anti-HLA antibody kinetics is not well characterized. We present an overview of the course of anti-HLA antibodies throughout plasma exchange (PE) desensitization in a series of crossmatch-positive patients. All consecutive candidates in the Dutch HLA-incompatible kidney transplantation program between November 2012 and January 2022 were included. The eligibility criteria were a positive crossmatch with a living kidney donor and no options for compatible transplantation. Desensitization consisted of 5-10 PE with low-dose IVIg. A total of 16 patient-donor pairs were included. Patients had median virtual panel-reactive antibody of 99.58%. Cumulative donor-specific anti-HLA antibody (cumDSA) mean fluorescence intensity (MFI) was 31 399 median, and immunodominant DSA (iDSA) MFI was 18 677 for class I and 21 893 for class II. Median anti-HLA antibody MFI response to desensitization was worse in class II as compared with class I (P < 0.001), particularly for HLA-DQ. Class I cumDSA MFI decreased 68% after 4 PE versus 53% in class II. The decrease between the fifth and the 10th PE sessions was modest with 21% in class I versus 9% in class II. Antibody-mediated rejection occurred in 85% of patients, with the iDSA directed to the same mismatched HLA as before desensitization, except for 3 patients, of whom 2 had vigorous rebound of antibodies to repeated mismatches (RMMs). Rebound was highest (86%) in RMM-DSA with prior grafts removed (transplantectomy n = 7), lower (39%) in non-RMM-DSA (n = 30), and lowest (11%) for RMM-DSA with in situ grafts (n = 5; P = 0.018 for RMM-DSA transplantectomy versus RMM-DSA graft in situ). With a median follow-up of 59 mo, 1 patient had died resulting in a death-censored graft survival of 73%. Patients with class II DSA, and particularly those directed against HLA-DQ locus, were difficult to desensitize.

Risk Stratification Before Living Donor Kidney Transplantation in Patients With Preformed Donor-specific Antibodies by Different Crossmatch Methods.

Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce. DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS). Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM. Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA.

Kidney Transplant Outcomes in Amyloidosis: US National Database Study.

We aimed to assess contemporary transplant outcomes among kidney recipients with amyloidosis, as the treatment and prognosis of amyloidosis have shown improvement over time. Using the US Organ Procurement and Transplantation Network database, we initially evaluated the changes in patient and graft survival among kidney recipients with amyloidosis from 2002 to 2021. We then compared transplant outcomes between recipients with amyloidosis versus those with diabetic and nondiabetic causes of kidney failure, creating 1:4 matches with highly similar characteristics separately for deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) during the last decade (2012-2021). We identified 643 kidney recipients with amyloidosis during 2002-2021. Patient and death-censored graft survival improved over time. In the matching analysis for 207 DDKT and 166 LDKT recipients with amyloidosis during 2012-2021, patient survival was not significantly different between amyloidosis and diabetes groups in both DDKT (log-rank, P = 0.057) and LDKT (P = 0.99). Compared with the nondiabetes group, patient survival in the amyloidosis group was not significantly different for DDKTs (P = 0.56) but was significantly lower for LDKTs (P = 0.04). Death-censored graft failure risk was not significantly different between amyloidosis and diabetes or nondiabetes groups for both DDKTs (P = 0.78 and 0.75) and LDKTs (P = 0.40 and 0.24). In this well-matched cohort study, we found no significant differences in patient and graft survival between kidney recipients with amyloidosis and those with diabetes. Similarly, these outcomes were not significantly different between those with amyloidosis versus nondiabetic causes, except for patient survival of LDKT recipients.

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.

Long-Term Outcomes of Living Donor Liver Transplantation for Methylmalonic Acidemia.

Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations. We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications. The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Does Severity of Donor Acute Kidney Injury Influence Outcomes Following Kidney Transplantation?

The study purpose was to review retrospectively our single-center experience transplanting kidneys from deceased donors (DD) with acute kidney injury (AKI) according to terminal serum creatinine (tSCr) level. AKI kidneys were defined by a doubling of the DD's admission SCr and a tSCr ≥ 2.0mg/dL. From 1/07 to 11/21, we transplanted 236 AKI DD kidneys, including 100 with a tSCr ≥ 3.0mg/dL (high SCr AKI group, mean tSCr 4.2mg/dL), and the remaining 136 from DDs with a tSCr of 2.0-2.99mg/dL (lower SCr AKI group, mean tSCr 2.4mg/dL). These two AKI groups were compared to 996 concurrent control patients receiving DD kidneys with a tSCr < 1.0mg/dL. Mean follow-up was 69 months. Delayed graft function (DGF) rates were 51%versus 46%versus 29% (p < 0.0001), and 5-year patient and death-censored kidney graft survival rates were 96.8%versus 83.5%versus 82.2% (p=0.002) and 86.7%versus 77.8%versus 78.8% (p=0.18) in the high tSCr AKI versus lower tSCr AKI versus control groups, respectively. Despite a higher incidence of DGF, patients receiving kidneys from DDs with tSCr levels ≥3.0mg/dL have acceptable medium-term outcomes compared to either AKI DDs with a lower tSCr or DDs with a tSCr < 1.0mg/dL.

Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy.

Guidelines advise eculizumab prophylaxis for most kidney transplant recipients with atypical hemolytic uremic syndrome (aHUS). However, recurrence rates may be overestimated, and starting eculizumab at relapse ("rescue therapy") may prevent graft loss. Randomized controlled trials have not compared the efficacy, safety, and costs of different treatment strategies. We performed a comparative study, including a previously described Dutch cohort treated with rescue therapy and a UK cohort using eculizumab prophylaxis. In the Netherlands, we selected all adult patients with aHUS who received a kidney transplant between 2010 and 2021 in the Radboud University Medical Center (n = 30) and enriched this cohort with 8 patients who received rescue therapy in other centers. The UK cohort included all adult patients with aHUS at moderate or high risk of recurrence, transplanted between 2013 and 2017 with prophylactic eculizumab. We included 38 Dutch patients and 35 UK patients. Characteristics were comparable, although the UK cohort included more patients with a complement factor H SCR20 mutation or hybrid gene (31% versus 5%; P < 0.01), and more Dutch patients received living donor kidneys (66% versus 20%; P < 0.001). Follow-up was comparable (the Dutch patients 70.8 mo, range, 10-134; UK patients 55.4 mo, range, 2-95). Eighteen (47%) Dutch patients received rescue therapy. Death-censored graft survival was not significantly different (the Dutch patients 1 y, 3 y, and 6 y: 97.4%, 91.2%, and 87.1%, respectively; UK patients 1 y, 3 y, and 6 y: 97.1%, 88.2%, and 65.6%, respectively, log-rank P = 0.189). In a population characterized by low prevalence of "very high risk" genes, who were predominantly transplanted using an endothelial protective regime, death-censored graft survival with eculizumab rescue therapy was not inferior to prophylaxis.

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.

Long-Term Outcome after Early Mammalian Target of Rapamycin Inhibitor-Based Immunosuppression in Kidney Transplant Recipients.

Background: The use of mammalian target of rapamycin inhibitors (mTORis) in kidney transplantation increases the risk of donor-specific human leukocyte antigen (HLA) antibody formation and rejection. Here, we investigated the long-term consequences of early mTORi treatment compared to calcineurin inhibitor (CNI) treatment. Methods: In this retrospective single-center analysis, key outcome parameters were compared between patients participating in randomized controlled immunosuppression trials between 1998 and 2011, with complete follow-up until 2018. The outcomes of eligible patients on a CNI-based regimen (n = 384) were compared with those of patients randomized to a CNI-free mTORi-based regimen (n = 81) and 76 patients randomized to a combination of CNI and mTORi treatments. All data were analyzed according to the intention-to-treat (ITT) principle. Results: Deviation from randomized immunosuppression for clinical reasons occurred significantly more often and much earlier in both mTORi-containing regimens than in the CNI treatment. Overall patient survival, graft survival, and death-censored graft survival did not differ between the treatment groups. Donor-specific HLA antibody formation and BPARs were significantly more common in both mTORi regimens than in the CNI-based immunosuppression. Conclusions: The tolerability and efficacy of the mTORi treatment in kidney graft recipients are inferior to those of CNI-based immunosuppression, while the long-term patient and graft survival rates were similar.