Impact of deceased donor with acute kidney injury on subsequent kidney transplant outcomes-an ANZDATA registry analysis.
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ABSTRACT: Background
The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature.Material and methods
This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection.Results
The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99-1.26), death-censored graft failure (HR 1.09, 95% CI 0.92-1.28), death (HR 1.15, 95% CI 0.98-1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91-1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92-2.68).Conclusion
Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.
SUBMITTER: Pei J
PROVIDER: S-EPMC7993825 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.
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Project description:Background and objectivesBK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.Design, setting, participants, & measurementsWe studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database.ResultsThe multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95).ConclusionsIn a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
| S-EPMC8259491 | biostudies-literature
Project description:BackgroundFavorable long-term and short-term graft survival and patient survival after kidney transplantation (KT) from deceased donors with acute kidney injury (AKI) have been reported. However, few studies have evaluated effects of donor AKI status on graft outcomes after KT in Asian population. Thus, the purpose of this study was to evaluate graft function after KTs from donors with AKI compared to matched KTs from donors without AKI using a multicenter cohort in Korea.MethodsWe analyzed a total of 1,466 KTs collected in Korean Organ Transplant Registry between April 2014 and December 2017. KTs from AKI donors (defined as donors with serum creatinine level ≥ 2 mg/dL) and non-AKI donors (275 cases for each group) were enrolled using a 1:1 propensity score matching. Graft outcomes including graft and patient survival, delayed graft function (DGF), rejection rate, and serially measured estimated glomerular filtration rate (eGFR) were evaluated.ResultsAfter propensity matching, KTs from AKI donors showed higher rate of DGF (44.7% vs. 24.0%, p < 0.001). However, the rejection rate was not significantly different between the two groups (KTs from AKI donors vs. KTs from non-AKI donors). eGFRs measured after 6 months, 1 year, 2 years and 3 years were not significantly different by donor AKI status. With median follow-up duration of 3.52 years, cox proportional hazards models revealed hazard ratio of 0.973 (95% confidence interval [CI], 0.584 to 1.621), 1.004 (95% CI, 0.491 to 2.054) and 0.808 (95% confidence interval [CI], 0.426 to 1.532) for overall graft failure, death-censored graft failure and patient mortality, respectively, in KTs from AKI donors compared to KTs from non-AKI donors as a reference.ConclusionsKTs from AKI donors showed comparable outcomes to KTs from non-AKI donors, despite a higher incidence of DGF. Results of this study supports the validity of using kidneys from deceased AKI donors in Asian population.
| S-EPMC8598029 | biostudies-literature
Project description:Rationale & objectiveDonor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation.Study designProspective cohort.Setting & participants862 deceased donors for 1,137 kidney recipients at 13 centers.ExposuresWe measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI.OutcomesThe primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year.Analytical approachMultivariable Fine-Gray models with death as a competing risk.ResultsMean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA.LimitationsBPAR was ascertained through for-cause biopsies, not surveillance biopsies.ConclusionsIn a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.
| S-EPMC9868058 | biostudies-literature
Project description:IntroductionExisting methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes.MethodsWe conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR.ResultsAKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml vs. 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m2 per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR.ConclusionDonor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.
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Project description:BACKGROUND:The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS:Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS:The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS:The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.
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Project description:We investigated the impact of acute kidney injury (AKI) in elderly deceased-donors (DDs) vs. AKI in young DDs on post-transplant clinical outcomes. A total of 709 kidney transplant recipients (KTRs) from 602 DDs at four transplant centers were enrolled. KTRs were divided into young-DDKT and elderly-DDKT groups according to the age of DD of 60 years. Both groups were subdivided into non-AKI-KT and AKI-KT subgroups according to AKI in DDs. We investigated short-term and long-term clinical outcomes of non-AKI-DDKT and AKI-DDKT subgroups within young-DDKT and elderly-DDKT groups. The incidence of DGF in the AKI-DDKT subgroup was higher and the allograft function within 12 months after KT in the AKI-DDKT subgroup was lower than those in the non-AKI-DDKT subgroup in both young-DDKT and elderly-DDKT groups. Death-censored allograft survival rate was significantly lower in the AKI-elderly-DDKT subgroup than that in the non-AKI-elderly-DDKT subgroup, but it did not differ between AKI-young-DDKT and non-AKI-young-DDKT subgroup. In multivariable analysis, AKI-elderly-DDKT was an independent risk factor for allograft failure (hazard ratio: 2.648, 95% CI: 1.170-5.994, p = 0.019) and a significant interaction between AKI and old age in DDs on allograft failure was observed (p = 0.001). AKI in elderly DDs, but not in young DDs, can significantly affect long-term allograft outcomes of KTRs.
| S-EPMC7048728 | biostudies-literature
Project description:BackgroundThis study evaluated the impact of acute kidney injury (AKI) on posttransplant clinical outcomes for deceased donor (DD) kidney transplantation (KT) using the Kidney Donor Profile Index (KDPI) system.MethodsOverall, 657 kidney transplant recipients (KTRs) receiving kidneys from 526 DDs from four transplant centers were included. We divided them into the high and low KDPI donor groups by 65%, the KDPI score, and both groups were subdivided into the AKI-DDKT and non-AKI-DDKT subgroups according to AKI in DDs.ResultsThere was no significant difference in the incidence of delayed graft function (DGF) between the high and low KDPI-KTR groups; however, the AKI-DDKT subgroup showed significantly higher incidence of DGF than the non-AKI-DDKT subgroup in both groups (p = 0.001, p < 0.001, respectively). The death-censored graft survival rate was significantly lower in the high KDPI-KTR group than in the low KDPI-KTR group (p = 0.005). Only in the high KDPI-KTR group, the death-censored graft survival rate was significantly lower in the KT from DDs with AKI stage 3 than KT from DDs with non-AKI or AKI stage 1 or 2 (p = 0.040). The interaction between AKI stage 3 in DDs and high KDPI on the allograft outcome was significant (p = 0.002).ConclusionKTs from DDs with AKI stage 3 showed an adverse impact on the allograft outcome in the high KDPI-KTR group. Therefore, DDs with a high KDPI score should be managed carefully so that severe AKI does not occur prior to KT.
| S-EPMC8041636 | biostudies-literature
Project description:Background and objectivesIn kidney transplantation, the relative contribution of donor versus other factors on clinical outcomes is unknown. We sought to quantify overall donor effects on transplant outcomes for kidney donations from deceased donors.Design, setting, participants, & measurementsFor paired donations from deceased donors resulting in transplants to different recipients, the magnitude of donor effects can be quantified by examining the excess of concordant outcomes within kidney pairs beyond chance concordance. Using data from the Organ Procurement and Transplantation Network between the years 2013 and 2017, we examined concordance measures for delayed graft function, death-censored 1-year graft failure, and death-censored 3-year graft failure. The concordance measures were excess relative risk, excess absolute risk, and the fixation index (where zero is no concordance and one is perfect concordance). We further examined concordance in strata of kidneys with similar values of the Kidney Donor Profile Index, a common metric of organ quality.ResultsIf the transplant of the kidney mate resulted in delayed graft function, risk for delayed graft function was 19% higher (95% confidence interval [95% CI], 18% to 20%), or 1.76-fold higher (95% CI, 1.73- to 1.80-fold), than baseline. If a kidney graft failed within 1 year, then the kidney mate's risk of failure was 6% higher (95% CI, 4% to 9%), or 2.85-fold higher (95% CI, 2.25- to 3.48-fold), than baseline. For 3-year graft failure, the excess absolute risk was 7% (95% CI, 4% to 10%) but excess relative risk was smaller, 1.91-fold (95% CI, 1.56- to 2.28-fold). Fixation indices were 0.25 for delayed graft function (95% CI, 0.24 to 0.27), 0.07 for 1-year graft failure (95% CI, 0.04 to 0.09), and 0.07 for 3-year graft failure (95% CI, 0.04 to 0.10). Results were similar in strata of kidneys with a similar Kidney Donor Profile Index.ConclusionsOverall results indicated that the donor constitution has small or moderate effect on post-transplant clinical outcomes.
| S-EPMC6895487 | biostudies-literature
Project description:Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ? 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.
| S-EPMC6331055 | biostudies-literature