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.
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Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of ...association.
In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes.
Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF aOR (95%CI); 4.83 (2.29, 10.22) and had lower 1-year eGFR adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI.
iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization.
Delayed graft function (DGF) is a common complication after kidney transplant. Despite extensive literature on the topic, the extant definition of DGF has not been conducive to advancing the ...scientific understanding of the influences and mechanisms contributing to its onset, duration, resolution, or long-term prognostic implications. In 2022, the National Kidney Foundation sponsored a multidisciplinary scientific workshop to comprehensively review the current state of knowledge about the diagnosis, therapy, and management of DGF and conducted a survey of relevant stakeholders on topics of clinical and regulatory interest. In this Special Report, we propose and defend a novel taxonomy for the clinical and research definitions of DGF, address key regulatory and clinical practice issues surrounding DGF, review the current state of therapies to reduce and/or attenuate DGF, offer considerations for clinical practice related to the outpatient management of DGF, and outline a prospective research and policy agenda.
There may be important transplant-related differences between right and left kidneys, including logistical/surgical considerations about vessel length for the right compared to the left kidney from ...the same donor. Because US centers choose between the right and left kidney when their recipient is ranked higher on a “match-run,” we sought to determine whether deceased-donor right kidneys have had worse posttransplantation outcomes than left kidneys.
Paired Organ Procurement and Transplantation Network analysis.
Deceased-donor kidney pairs transplanted during 1990 to 2016.
Right versus left kidney controlling for other significant factors.
Delayed graft function (DGF), all-cause and death-censored graft failure, and mortality.
Multivariable conditional logistic regression for DGF; proportional hazards models (conditional on same donor) for failure/mortality with right kidneys (operationalized as 6-month time-varying coefficients) adjusting for DGF and other confounders.
87,112 recipient pairs shared the following donor characteristics: mean age of 41 ± 14 years, 60% males, and 11% with cardiac death. Recipient characteristics were numerically similar by donor kidney side but with some statistical differences given the sample size. Right kidneys had slightly longer cold ischemia time. DGF occurred more often for right kidneys (28% vs 25.8%; P < 0.001; adjusted OR, 1.15 95% CI, 1.12-1.17). The adjusted hazard ratio (aHR) for all-cause graft failure with right kidneys within 6 months was 1.07 (95% CI, 1.03-1.11), and was 0.99 (95% CI, 0.97-1.01) thereafter. The aHRs for death-censored graft failure with right kidneys before and after 6 months were 1.11 (95% CI, 1.06-1.16) and 0.96 (95% CI, 0.93-0.99), respectively; the corresonding aHRs for mortality were 0.99 (95% CI, 0.93-1.04) and 1.00 (95% CI, 0.98-1.03), respectively.
Registry data, different transplant eras, reasons for kidney side unavailable.
There is modest association for transplantation of right kidneys with DGF and graft loss within the first 6 months, which is lost beyond this time point. These findings do not support the use of laterality of deceased-donor kidneys as an important factor in organ acceptance decisions.
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Biopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial.
...We compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (
=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (
=116 kidneys).
For kidneys on which more than one procurement biopsy was performed (
=116), category agreement was found in only 64% of cases (
=0.14). For all kidneys (
=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (
=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (
=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (
=0.13) and 80% (
=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure.
We found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.
Purpose
Urine oxygen partial pressure (PuO
2
) may be useful for assessing acute kidney injury (AKI) risk. The primary purpose of this study was to quantify the ability of a novel urinary oxygen ...monitoring system to make real-time PuO
2
measurements intraoperatively which depends on adequate urine flow. We hypothesized that PuO
2
data could be acquired with enough temporal resolution to provide real-time information in both AKI and non-AKI patients.
Methods
PuO
2
and urine flow were analyzed in 86 cardiac surgery patients. PuO
2
data associated with low (< 0.5 ml/kg/hr) or retrograde urine flow were discarded. Patients were excluded if > 70% of their data were discarded during the respective periods, i.e., during cardiopulmonary bypass (CPB), before CPB (pre-CPB), and after CPB (post-CPB). The length of intervals of discarded data were recorded for each patient. The median length of intervals of discarded data were compared between AKI and non-AKI patients and between surgical periods.
Results
There were more valid PuO
2
data in CPB and post-CPB periods compared to the pre-CPB period (81% and 90% vs. 31% of patients included, respectively; p < 0.001 and p < 0.001). Most intervals of discarded data were < 3 minutes during CPB (96%) and post-CPB (98%). The median length was < 25 s during all periods and there was no significant difference in the group median length of discarded data intervals for AKI and non-AKI patients.
Conclusions
PuO
2
measurements were acquired with enough temporal resolution to demonstrate real-time PuO
2
monitoring during CPB and the post-CPB period.
ClinicalTrials.gov Identifier:
NCT03335865, First Posted Date: Nov. 8th, 2017.
Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic ...utility of newer biomarkers or traditional markers (fractional excretion of sodium FeNa and urea FeUrea and microscopy) over clinical assessment alone.
This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death.
In 249 recipients, 57% were ≥65 years old, 48% were from intensive care, and mean baseline GFR was 69 ± 30 ml/min per 1.73 m(2). AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and "other" in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values <0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful.
On the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.
Kidney allocation trends from deceased donors with acute kidney injury (AKI) have not been characterized since initial Kidney Donor Profile Index reporting in 2012 and its use under the revised ...Kidney Allocation System (KAS) in 2014. We conducted a retrospective analysis of US registry data to characterize kidney procurement and discard trends in deceased donors with AKI, defined by ≥50% or ≥0.3 mg/dl (≥4.0 mg/dl or ≥200% for stage 3) increase in terminal serum creatinine from admission. From 2010 to 2020, 172 410 kidneys were procured from 93 341 deceased donors 16 years or older; 34 984 kidneys were discarded (17 559 from AKI donors). The proportion of stage 3 AKI donors doubled from 6% (412/6841) in 2010 to 12% (1365/11493) in 2020. Procurement of stage 3 AKI kidneys increased from 51% (423/824) to 80% (2183/2730). While discard of stage 3 AKI kidneys increased from 41% (175/423) in 2010 to 44% (960/2183) in 2020, this increase was not statistically significant in interrupted time‐series analysis following KAS implementation (slope difference −0.41 −3.22, 2.4, and level change 3.09 −6.4, 12.6). In conclusion, the absolute number of stage 3 AKI kidneys transplanted has increased. Ongoing high discard rates of these kidneys suggest opportunities for improved utilization.
Retrospective analysis of OPTN data from 2010 to 2020 shows increases in both the recovery and discard rates of kidneys from deceased donors with stage 3 acute kidney injury and a concurrent increase in the absolute number of transplants utilizing these kidneys.
Although hypothermic machine perfusion (HMP) is associated with improved kidney graft viability and function, the underlying biological mechanisms are unknown. Untargeted metabolomic profiling may ...identify potential metabolites and pathways that can help assess allograft viability and contribute to organ preservation. Therefore, in this multicenter study, we measured all detectable metabolites in perfusate collected at the beginning and end of deceased-donor kidney perfusion and evaluated their associations with graft failure. In our cohort of 190 kidney transplants, 33 (17%) had death-censored graft failure over a median follow-up of 5.0 years (IQR 3.0-6.1 years). We identified 553 known metabolites in perfusate and characterized their experimental and biological consistency through duplicate samples and unsupervised clustering. After perfusion-time adjustment and false discovery correction, six metabolites in post-HMP perfusate were significantly associated with death-censored graft failure, including alpha-ketoglutarate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, 1-carboxyethylphenylalanine, and three glycerol-phosphatidylcholines. All six metabolites were associated with an increased risk of graft failure (Hazard Ratio per median absolute deviation range 1.04-1.45). Four of six metabolites also demonstrated significant interaction with donation after cardiac death with notably greater risk in the donation after cardiac death group (Hazard Ratios up to 1.69). Discarded kidneys did not have significantly different levels of any death-censored graft failure-associated metabolites. On interrogation of pathway analysis, production of reactive oxygen species and increased metabolism of fatty acids were upregulated in kidneys that subsequently developed death-censored graft failure. Thus, further understanding the role of these metabolites may inform the HMP process and help improve the objective evaluation of allograft offers, thereby reducing the discard of potentially viable organs.
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