Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Reversal of Roux-en-Y Gastric Bypass for Successful Salvage of Renal Allograft.

Enteric hyperoxaluria (EH) is a known complication of Roux-en-Y gastric bypass (RYGB) and can lead to nephrolithiasis, oxalate-induced nephropathy, and end-stage renal disease. Recurrent EH-induced renal impairment has been reported after kidney transplantation and may lead to allograft loss. EH occurs in up to one quarter of patients following malabsorption-based bariatric operations. We present a report of medically refractory EH in a renal transplant recipient with allograft dysfunction that was successfully managed with reversal of RYGB. The patient developed renal failure 7 years following gastric bypass requiring renal transplant. Following an uneventful living donor kidney transplant, the patient developed recurrent subacute allograft dysfunction. A diagnosis of oxalate nephropathy was made based on biopsy findings of renal tubular calcium oxalate deposition in conjunction with elevated serum oxalate levels and elevated 24-hr urinary oxalate excretion. Progressive renal failure ensued despite medical management. The patient underwent reversal of her RYGB, which resulted in recovery of allograft function. This report highlights an under-recognized, potentially treatable cause of renal allograft failure in patients with underlying gastrointestinal pathology or history of bariatric surgery and proposes a strategy for management of patients with persistent hyperoxaluria based on a review of the literature.

Early Effect of the Circular Model of Kidney Allocation in the United States.

BACKGROUND: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. METHODS: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after the onset of COVID-19 and the implementation of KAS250 were evaluated using an interrupted time-series model. Changes in allocation practices (biopsy, machine perfusion, and virtual cross-match) were also evaluated. RESULTS: Post-KAS250 saw a two-fold increase in kidneys imported from nonlocal organ procurement organizations (OPO) and a higher proportion of recipients with calculated panel reactive antibody (cPRA) 81%-98% (12% versus 8%; P <0.001) and those with >5 years of pretransplant dialysis (35% versus 33%; P <0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards after KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased, whereas reliance on virtual cross-match increased, which was associated with shorter CIT. CONCLUSIONS: Early trends after KAS250 show an increase in transplant access to patients with cPRA>80% and those with longer dialysis duration, but this was accompanied by an increase in CIT and a suggestion of worsening kidney discards.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

The combination of exposure to Tacrolimus, mycophenolic acid, Inosine 5'-Monophosphate Dehydrogenase activity and inhibition in the first week define early histological outcomes in renal transplant recipients.

Therapeutic drug monitoring is routine for Tacrolimus, while levels are not routinely monitored for mycophenolic acid (MPA). This study investigated the effect of early post-transplant pharmacokinetics (PK) of MPA and Tacrolimus along with the pharmacodynamics (PD) of MPA on biopsy-proven acute rejection (BPAR) after renal transplantation. A prospective PK/PD study with limited sampling (three blood samples) was conducted in renal transplant recipients on week 1, around Day 6 (n = 42) and at the 3rd-month biopsy on Day 90 (n = 23). The partial exposures (area under curve [AUC]0-3.5 h ) of both MPA and Tacrolimus obtained during the first week were more predictive of rejection (combined clinical and subclinical rejection) by Day 90 than their trough concentrations or Day 90 exposures. Patients with rejection had significantly worse renal function (eGFR) and a comparatively lower exposure to MPA during the first post-transplant week. The lower MPA exposure was also associated with sub-optimal inosine monophosphate dehydrogenase (IMPDH) inhibition in patients with rejection, and the probability of rejection was higher in the presence of an increased pre-transplant IMPDH activity. A composite of parameters, including MPA exposure and IMPDH activity was found to predict acute rejection and may be beneficial along with tacrolimus monitoring early after renal transplantation.

Long-term immunological outcomes of early subclinical inflammation on surveillance kidney allograft biopsies.

The long-term impact of early subclinical inflammation (SCI) through surveillance biopsy has not been well studied. To do this, we recruited a prospective observational cohort that included 1000 sequential patients who received a kidney transplant from 2013-2017 at our center. A total of 586 patients who underwent a surveillance biopsy in their first year post-transplant were included after excluding those with clinical rejections, and those who were unable to undergo a surveillance biopsy. Patients were classified based on their biopsy findings: 282 with NSI (No Significant Inflammation) and 304 with SCI-T (SCI and Tubulitis) which was further subdivided into 182 with SC-BLR (Subclinical Borderline Changes) and 122 with SC-TCMR (Subclinical T Cell Mediated Rejection, Banff 2019 classification of 1A or more). We followed the clinical and immunological events including Clinical Biopsy Proven Acute Rejection [C-BPAR], long-term kidney function and death-censored graft loss over a median follow-up of five years. Episodes of C-BPAR were noted at a median of two years post-transplant. Adjusted odds of having a subsequent C-BPAR was significantly higher in the SCI-T group [SC-BLR and SC-TCMR] compared to NSI 3.8 (2.1-7.5). The adjusted hazard for death-censored graft loss was significantly higher with SCI-T compared to NSI [1.99 (1.04-3.84)]. Overall, SCI detected through surveillance biopsy within the first year post-transplant is a harbinger for subsequent immunological events and is associated with a significantly greater hazard for subsequent C-BPAR and death-censored graft loss. Thus, our study highlights the need for identifying patients with SCI through surveillance biopsy and develop strategies to prevent further alloimmune injuries.

Function and longevity of renal grafts from high-KDPI donors.

BACKGROUND: High kidney-donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. METHODS: We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I-KDPI ≤ 25% (n = 151), Group II-KDPI 26-50% (n = 182), Group III-KDPI 51-75% (n = 176), and Group IV-KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5-years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group. FINDINGS: High-KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups (P = .06). Although patient survival was signigicantly lower for recipients of high-KDPI grafts, death-censored graft survival was similar among the four KDPI groups (P = .33). CONCLUSIONS: The shorter functional survival of high-KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.

Sequential liver and kidney living donors: Making the ultimate gift twice.

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation.

The Clinical Impact of Anti-HLA Donor Specific Antibody Detection Through First Year Screening on Stable Kidney Transplant Recipients.

Anti-HLA Donor Specific Antibody (DSA) detection post kidney transplant has been associated with adverse outcomes, though the impact of early DSA screening on stable patients remain unclear. We analyzed impact of DSA detection through screening in 1st year stable patients (n = 736) on subsequent estimated glomerular filtration rate (eGFR), death censored graft survival (DCGS), and graft failure (graft loss including return to dialysis or re-transplant, patient death, or eGFR < 20 ml/min at last follow up). Patients were grouped using 1st year screening into DSA+ (Class I, II; n = 131) or DSA- (n = 605). DSA+ group were more DR mismatched (p = 0.02), more sensitized (cPRA ≥90%, p = 0.002), less Caucasian (p = 0.04), and had less pre-emptive (p = 0.04) and more deceased donor transplants (p = 0.03). DSA+ patients had similar eGFR (54.8 vs. 53.8 ml/min/1.73 m2, p = 0.56), DCGS (91% vs. 94%, p = 0.30), and graft failure free survival (76% vs. 82%, p = 0.11). DSA timing and type did not impact survival. Among those with a protocol biopsy (n = 515), DSA detected on 1st year screening was a predictor for graft failure on multivariate analysis (1.91, 95% CI 1.03-3.55, p = 0.04). Overall, early DSA detection in stable patients was an independent risk factor for graft failure, though only among those who underwent a protocol biopsy.

Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation.

Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5-6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R-) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group (n = 56) received <5 mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG (P < .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12-3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.

Outcomes and factors leading to graft failure in kidney transplants from deceased donors with acute kidney injury-A retrospective cohort study.

Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.

Positive flow cytometry crossmatch with discrepant antibody testing results following COVID-19 vaccination.

The impact of COVID-19 vaccination on the alloimmunity of transplant candidates is unknown. We report a case of positive B cell flow cytometry crossmatch in a patient waiting for second kidney transplantation, 37 days after receiving the COVID-19 vaccine. The preliminary crossmatch, using sample collected before COVID-19 vaccination, was negative. The antibodies to mismatched donor HLA-DR7 were detected only with multi-antigen beads but not with single-antigen beads, excluding possible prozone effects in solid-phase antibody assays. The crossmatches were positive with HLA-DR7-positive surrogates (n = 2) while negative with HLA-DR7-negative surrogates (n = 3), which confirms the HLA-DR7 alloreactivity. The antigen configurations on B lymphocytes are similar to that on the multi-antigen beads while distinct from the single-antigen beads. HLA-DR7 was the repeating mismatched antigen with the failing first kidney allograft. The newly emerged antibody to HLA-DR7 probably is the consequence of bystander activation of memory response by the COVID-19 vaccination. This case highlights the importance of verifying allo-sensitization history and utilizing multiple assays, including cell-based crossmatch and solid-phase assays with multi-antigens. COVID-19 immunization may deserve special attention when assessing the immunological risk before and after organ transplantation.

Donation after circulatory death is associated with increased fibrosis on 1-year post-transplant kidney allograft surveillance biopsy.

AIM: The use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here, we investigated the effect of DCD on fibrotic changes on 1 1-year post 1-transplant surveillance kidney allograft biopsy. METHODS: Recipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]). Banff scores for interstitial fibrosis and tubular atrophy were summed as IFTA and compared between the groups. RESULTS: DCD and DBD groups were comparable for baseline characteristics. Delayed graft function was 39% in DCD versus 19% in DBD, P = .0002. Patient and graft survival were comparable for DCD and DBD cohorts. IFTA scores were higher in DCD compared to DBD (2.43±..13 vs. 2.01±..08, P = .0054). On multivariate analysis, the odds of IFTA > 2 in the DCD group was 2.5× higher (95%CI: 1.354.63) than in the DBD group. Within the DCD group, kidneys with IFTA > 2 had inferior 5-year graft survival (P = .037). CONCLUSION: Compared to DBD kidneys, DCD kidneys developed a greater degree of fibrotic changes on 1-year post-transplant surveillance biopsy, which affected graft longevity within the DCD cohort.

Impact of Subclinical and Clinical Kidney Allograft Rejection Within 1 Year Posttransplantation Among Compatible Transplant With Steroid Withdrawal Protocol.

Early acute kidney rejection remains an important clinical issue. METHODS: The current study included 552 recipients who had 1-2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell-mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. RESULTS: The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant. CONCLUSIONS: The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.

Kidney allograft rejection: Diagnosis and treatment practices in USA- A UNOS survey.

We studied diverse rejection management strategies across centers by conducting a UNOS survey of kidney transplant program directors in 2017. There were 104 total responses from 235 kidney transplant programs representing 88 unique transplant programs (response rate 37%). Information was collected on center-specific management practices. Pertinent center-specific data were obtained from the OPTN database. Of the respondents, 33% were considered large centers (>100 transplants/year). Thymoglobulin was the most commonly used induction agent at 84%, 72% responders do rapid steroid withdrawal, and mycophenolic acid (MPA) is the major antimetabolite (100%). For diagnosing TCMR, 100% used indication biopsy, 28% used protocol biopsy, 2% used serum biomarkers, and none used urine cytokines. For ABMR, 99% used indication biopsy, 34% used protocol biopsy, 72% used DSA, 21% used C1q positive DSA, and none used gene profiling (ENDATS). The treatment of subclinical and clinical TCMR included iv/PO steroids. PP/IVIG were the commonest treatments for ABMR. The use of rituximab, bortezomib, and eculizumab increased from C4D-ABMR to recurrent ABMR. There are diverse management practices for diagnosing and treating rejection. An effort to harmonize these diverse practices for management of TCMR and ABMR will give an opportunity to pool data for evaluating clinical outcomes.

Evaluation of Renal Anionic Secretion Following Living-donor and Deceased-donor Renal Transplantation: A Clinical Pharmacokinetic Study of Cefoxitin Microdosing.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs). METHODS: The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation. RESULTS: No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls. CONCLUSIONS: These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.

Early subclinical tubulitis and interstitial inflammation in kidney transplantation have adverse clinical implications.

This prospective observational cohort study compared the impact of subclinical tubulitis with or without interstitial inflammation to interstitial inflammation alone and to no inflammation in early post kidney transplant biopsies. A study cohort of 415 patients (living and deceased donor recipients) was divided into three groups on the basis of their three-month biopsy: 149 patients with No Inflammation (NI), 83 patients with Isolated Interstitial Inflammation (IIF), and 183 patients with Tubulitis [(with or without interstitial inflammation) (TIF) but not meeting criteria for Banff IA]. TIF was further divided into 56 patients with tubulitis without interstitial inflammation (TIF0) and 127 patients with tubulitis alongside interstitial inflammation (TIF1). TIF was significantly associated with higher incidence of subsequent T-cell mediated rejection (clinical or subclinical) at one year compared to IIF (31% vs 15%) and NI (31% vs 17%). Chronicity on one-year biopsy was significantly higher in TIF compared to IIF (22% vs 11%) and NI (22% vs 7%). De novo donor-specific antibody development was significantly higher in TIF compared to NI (6% vs 0.7%). Tubulitis subgroups (TIF0 and TIF1) revealed comparable effects on de novo donor-specific antibody and interstitial fibrosis/tubular atrophy development. However, tubulitis with interstitial inflammation had a significantly higher incidence of subsequent rejection and posed an increased hazard for the composite end point (subsequent acute rejection and death censored graft loss) compared to other groups [adjusted hazard 2.1 (95% confidence interval 1.2-3.5)]. Thus, subclinical tubulitis is a marker of adverse immunological events, but tubulitis with interstitial inflammation has a worse prognosis. Hence, the Banff 1997 (TIF1) and Banff 2005 classifications (TIF) for borderline change may have different implications.

Donor acute kidney injury and its effect on 1-year post-transplant kidney allograft fibrosis.

Transplantation of kidneys from deceased donors with acute kidney injury (AKI) can expand the donor pool. We investigated the effect of donor AKI on renal function and chronic changes on protocol biopsies at 1-year post-transplant. Donor AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. Between 2013 and 2017, 333 kidneys were transplanted and subsequently biopsied after 1 year. Fifty-three kidneys from AKI donors (AKIN stage I n = 42, stage II n = 8, stage III n = 3) were compared to 280 kidneys from non-AKI donors. At 1-year follow-up, patient and graft survival were comparable. Donor AKI was not predictive of IFTA (Banff interstitial fibrosis plus tubular atrophy scores) at 1-year post-transplant biopsy (2.10 ± 1.28 in AKI, 2.09 ± 1.22 in non-AKI, P = .95). Donor AKI was also not associated with progression of IFTA from 3 to 12 months (P = .69), or inferior glomerular filtration rate (eGFR, P = .94). In a multivariate analysis, the odds of IFTA >2 were comparable between AKI and non-AKI groups. In conclusion, the transplantation of kidneys from donors with predominantly stage I AKI results in comparable function and degree of fibrosis on protocol biopsies 1-year post-transplant. Selected grafts from donors with AKI are a valuable tool for expanding the donor pool for kidney transplantation.

Post-transplant donor specific antibody is associated with poor kidney transplant outcomes only when combined with both T-cell-mediated rejection and non-adherence.

Post-transplant donor specific antibody (DSA) is associated with poor renal allograft outcomes. However, variable timing of DSA assessment and inclusion of patients who undergo desensitization treatments have hindered our understanding of its consequences and limited its predictive value. Here we prospectively studied non-desensitized patients to determine factors associated with poor four-year outcomes in patients who developed post-transplant DSA. Using serial monitoring, 67 of 294 patients were found to develop DSA by one year. Compared to patients who do not develop DSA, those with DSA exhibit an increased incidence of both clinical and subclinical T-cell-mediated rejection (TCMR). The combination of TCMR plus DSA led to an almost three-fold increase in graft loss compared to either DSA or TCMR alone. Moreover, DSA was associated with higher Banff grade TCMR and chronic changes at one year. Antibody-mediated rejection was uncommon and always associated with TCMR. Amongst factors independently associated with DSA plus TCMR; non-adherence is potentially modifiable. Non-adherence, measured as intra-patient variability of calcineurin trough levels during the first post-transplant year, further risk-stratified patients with DSA plus TCMR such that about 75% of these patients had impending graft loss by four years, whereas adherent patients with DSA plus TCMR had outcomes comparable to other patient groups. Thus, early post-transplant DSA, especially in non-adherent patients, is associated with increased incidence of TCMR and represents a high-risk group of patients who might benefit from targeted therapeutic interventions.