Brain Stem Death Research Articles

Can you die twice? In India you can! Paradox and ambiguities in the legal determination of brainstem death in India

Can you die twice? In India you can! Paradox and ambiguities in the legal determination of brainstem death in India

Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during Hypothermic Machine Perfusion in Rat Model.

Transplanted organs are subjected to harmful conditions through stopping blood flow, hypothermic storage of the graft, and subsequent reperfusion. In particular, kidneys donated from patients after cardiac arrest (DCD) are classified as more vulnerable to ischemia-reperfusion injury (IRI). Hypothermic machine perfusion is proposed as a solution for better kidney storage before transplantation, and it is a good platform for additional graft treatment. Antioxidants have gained interest in regenerative medicine due to their ability to scavenge reactive oxygen species (ROS), which play a key role in IRI. We evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted antioxidant, administered directly to the perfusing buffer. Rat kidneys were isolated, randomly classified into one of the following groups, donation after brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a hypothermic machine perfusion system. Subsequently, we detected levels of kidney injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and mitochondrial integrity) markers. We compared the activation of the apoptosis pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt ratio after drug administration. The length of warm ischemia time negatively impacts the graft condition. However, MitoQ added to the perfusing system as an 'on pump' therapy mitigates injury to the kidney before transplantation by inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential drug for DCD graft preconditioning.

Case Report: Cerebellar Stroke with Acute Vestibular Syndrome

The posterior circulation accounts for around 20% of cerebral ischemic strokes. According to estimates, 20% of these individuals appear with solitary vertigo. This symptom is incorrectly classified as peripheral vestibular in roughly one-sixth to one-third of these patients [1]. As a result, therapeutic and secondary preventive treatment is deferred from these missing stroke patients, potentially resulting in avoidable morbidity and mortality. Based on a careful evaluation of the literature, we suggest a diagnostic method for clinical differentiating of individuals with acute vestibular syndrome [2]. A stroke involving the inferior cerebellum must be recognized because it can cause cerebellar enlargement, which can lead to brain stem compression and death unless surgery is performed [1]. We report a case of 45-year-old female who had vertigo for 4-5 months and it is not associated with vomiting and posture or climate change, imbalance while walking for 6 months. She is known case of diabetes for 2 years with ongoing Antidiabetic treatment. Evaluating a central origin vertigo or dizziness is the main consequence here.

Hypothermic machine perfusion for uterus transplantation

To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context. This video article shows all the technical details of using the HMP for uterine transplantation. University. Porcine model. Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient. The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus. This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of femalerecipients. Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context.

SP3.6 Does a novel preservation solution improve organ performance in an ex-vivo perfusion of porcine liver?

Abstract Aims This project aims to compare LS-A (Leeds solution for abdomen) to a gold standard solution, IGL-1 (Institute George-Lopez solution) at clinically acceptable CIT (Cold ischaemic time) in a DCD (Donation after cardiac death) model of porcine liver transplant. An ex-vivo Perfusion device will then provide normothermic machine perfusion to simulate the immediate post-transplant stage. Methods DCD livers retrieved from landrace pigs, were preserved at 4-hours CIT in LS-A or IGL-1. They were re-perfused on a normothermic machine perfusion device, using autologous blood as a perfusate. Biochemical analysis was performed hourly for various markers of tissue and hepatocyte damage. Results Livers stored in LS-A (n=6) and IGL-1 (n=6) have no significant differences when compared for ALT, AST, ALP, LDH and glucose. Perfusate lactate was significantly lower in the LS-A group (p=0.008) as was the perfusate potassium(p=0.001) across the perfusion period. Conclusions Analysis has shown significantly lower lactate and potassium in LS-A preserved livers, in DCD retrieval, with 4-hours CIT. There are no other observed significant differences between LS-A and IGL-1 when comparing liver function tests and LDH production. This suggests better tissue preservation with LS-A in the setting of very high risk donor livers. The next stage of the project will look at LS-A vs IGL-1 in an extended preservation period (>14 hours) in a DBD (Donation after brainstem death) model.

WTP2.9 Early Deceased Donor Kidney Transplant outcomes: Results from a Prospective National Transplant Access to Theatre (NTACT) Audit

Abstract Background Renal transplantation is increasing, yet there is a paucity of data describing post-operative complications. Therefore, this national audit aims to identify the incidence of early complications that impact patient outcomes. Methods We conducted a multicentre, prospective audit of adult deceased donor kidney-only transplants across 14 UK transplant centres between February and September 2022. Data was collected on significant checkpoints pre, intra and post-operatively, assessing for 30-day complication and mortality rates. Data was recorded on RedCap and analysed using descriptive statistics. Results 476 kidney-only transplants were recorded, (59 excluded for incomplete/incorrect data). Of 417, 215 were donation after brainstem death (DBD) organs and 202 were donation after circulatory death (DCD) organs. The 30-day mortality was 0.47% (n=2/417). The primary graft function rate was 81%. The 30-day readmission rate was 18%, and median number of readmissions was 1 (IQR: 1-3). Of the readmitted recipients, 92% were readmitted once and 8% were readmitted more than. The 30-day reoperation rate was 12%, and median number of reoperations was 1 (IQR: 1-2), of these, 91% had 1 reoperation and 9% had more than 1 reoperation. Most common indications for reoperations were bleeding 49% (n=25), assessment of graft perfusion 17% (n=9), and wound dehiscence 10% (n=5). We noted a difference in rates of reoperations between DCD and DBD organs, 16% and 9% respectively, however, this was not significant. There was no significant difference in the readmission and mortality rate between DBD and DCD organs. Conclusion The overall early postoperative complication rates and 30-day mortality following deceased donor kidney transplantation are low.

SP3.4 Barriers to deceased donor kidney organ utilisation: Results of a National Transplant ACcess to Theatre (NTACT) Audit

Abstract Aims Various barriers to deceased-donor kidney utilisation exist, however, there is a lack of data on these; therefore, this national audit aims to identify the barriers to prompt kidney utilisation after the arrival of organs at the implanting centre (IC). Methods We conducted a multicentre, prospective audit of adult deceased-donor kidney-only transplants across 14 UK centres between February and September 2022. Data was collected on time-intervals between significant checkpoints before transplantation and perceived reasons for delays. Data was recorded on RedCap and analysed using descriptive statistics. Results 476 kidney-only transplants were recorded (59 excluded-incomplete/incorrect data). There were 215 donations after brainstem death (DBD) organs and 202 donation after circulatory death (DCD) organs. The median cold ischaemia time (CIT) for DBD organs was 10:51 (IQR: 08:07-14:44), and for DCD organs was 11:09 (IQR: 08:13-14:50). The national CIT recommendations were exceeded by 40% of DCD and 14% of DBD organs. The median time-interval between the organ’s arrival at IC and knife-to-skin was 04:16 (IQR 02:46-07:52). The median time-interval between anaesthetic induction and knife-to-skin was 00:55 (IQR: 00:39-01:10). In 17% of cases, crossmatch results arrived after organ arrival at IC, median delay was 02:30 (IQR: 00:56-04:27). Delays were reported in 34% of cases, availability of the surgical team, anaesthetic team, porters, and the operating theatre were the most common causes of delay. Conclusions A significant proportion of kidneys were implanted beyond nationally recommended CIT. This audit delineated the current timings of each stage of the transplantation process and will be used in future to set realistic targets to optimise current practice.

Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis.

The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types. A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death. Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT. HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.

Kidneys recovered from brain dead cardiac arrest patients resuscitated with ECPR show similar one-year graft survival compared to other donors

IntroductionAmong patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) as a second line of treatment for refractory out-of-hospital cardiac arrest (OHCA), some may develop brain death and become eligible for organ donation. The objective of this study was to evaluate long-term outcomes of kidney grafts recovered from these patients. Material and methodsWe conducted a retrospective monocentric observational study between January 1, 2011, and December 31, 2017. We exclusively included patients eligible for planned donation after brainstem death and from whom at least one organ graft was retrieved and transplanted. We compared two groups of brain dead patients: those treated with ECPR for refractory OHCA (ECPR group) and a diverse group of patients who did not receive ECPR, from which only 5/23 (22%) had OHCA (control group). The primary outcome was one-year kidney graft survival. ResultsWe included 45 patients, 23 in the control group and 22 in the ECPR group. Although patients in the ECPR group were younger and had a lower prevalence of chronic renal disease (p = 0.01), their kidney function was more severely impaired upon admission in the ICU. A total of 68 kidney grafts were retrieved, transplanted, and studied, 34 in each study group. There was no significant difference between the two groups in terms of one-year kidney graft survival (p = 0.52). ConclusionOrgan transplantation from patients treated with ECPR after refractory OHCA showed one-year kidney graft survival rates comparable to those of patients not treated with ECPR.

Successful Kidney Transplantation of Two Patients with Donors Positive for Severe Acute Respiratory Syndrome Coronavirus Infection

Despite preventative measures, including vaccination, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection may result in severe illness, particularly in immunosuppressed transplant recipients. This has had a negative impact on organ donation and transplantation rates. However, the risk of transmission from SARS-CoV-2 positive donors to kidney transplant recipients is unknown. We describe 2 cases of successful kidney transplantation from SARS-CoV-2 positive donors. Case 1: 38-year old unvaccinated female, established on haemodialysis for 1 year, with underlying reflux nephropathy. Donor tested SARS-CoV-2 positive on polymerase chain reaction testing with a cycle threshold (CT) value of 29 initially. Sequential testing demonstrated a rise in CT value (37.8), aiding the decision to proceed. The recipient was high immunological risk and received a controlled category 3 donation after circulatory death (DCD) kidney transplant. She had immediate graft function and did not develop SARS-CoV-2 infection. Case 2: 63-year old female, with diabetes mellitus and hypertension. She was low immunological risk and for pre-emptive transplantation. The donor was SARS-CoV-2 positive with a CT value of 41.5 and was subsequently negative. Decision was made to proceed with a donation after brainstem death (DBD) transplant. The recipient had immediate graft function and did not develop SARS-CoV-2 infection. We report 2 cases of successful transplantation from SARS-CoV-2 positive donors, without severe infection, with no transmission seen in the recipients post-operatively. Decisions to proceed were primarily made on clinical grounds with assistance from RT-PCR CT values, making this a useful additional tool in determining suitability of organ donation in people who are SARS-CoV-2 positive.

Metabolic Outcomes After Pancreas Transplant Alone From Donation After Circulatory Death Donors-The UK Transplant Registry Analysis.

Extrapolating data from early DCD (donation after circulatory death) kidney transplantation, pancreas transplants from DCD grafts were feared to have worse metabolic outcomes. Hence, we aimed to address the question of pancreas transplant alone (PTA) from DCD donors-are our concerns justified? A UK transplant registry analysis of 185 PTA performed between 2005 and 2018 was done. All early graft losses (<3months) were excluded to allow focus on the metabolic outcomes (HbA1c, weight gain and incidence of secondary diabetic macrovascular complications). The aim was to compare the metabolic outcomes, rejection rates (including the need for steroids), patient and graft survival between DBD (Donation after brainstem death) and DCD groups. After excluding early graft losses, data from 162 PTA (DBD = 114 and DCD = 48) were analyzed. Body mass index of the donor was less in DCD group (DBD = 23.40 vs. DCD = 22.25, p = 0.006) and the rest of the baseline transplant characteristics were comparable. There were no significant differences in the HbA1c, weight gain, rejection rate, and incidence of secondary diabetic macrovascular complications post-transplant between DBD and DCD recipients. The 1-, 5-, and 10-year patient and graft survival were similar in both the groups. PTA from DCD donors have equivalent metabolic outcomes and survival (patient/graft) as that of DBD donors.

Guillain-Barré Syndrome Mimicking Brainstem Death Following Traumatic Intracerebral Hemorrhage (P12-7.006)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 73-year-old man attended the ED following an assault where he sustained multiple traumatic blows to the head. He was alert, complained of headache but provided a detailed account. There were facial injuries but no clinical signs of cranial or skull base fractures. There was injury to the right eye, in which he had pre-existing visual impairment from previous injury. Vision was normal in the left. Right pupillary light reflex was absent but left was normal. The remainder of the neurological examination was unremarkable. CT-Head identified a small traumatic subarachnoid hemorrhage over the left cerebral convexity and a small contusion in the left temporo-parietal region. Vitreous hemorrhage was evident in the right eye. Clinically stable, follow-up CT on day 3 showed small intra-cerebral haemorrhage within the contusion, with minimal mass effect. However, on day 8, his GCS dropped and he was admitted to the ITU for airway management. Both pupils were non-responsive to light. Expansion of haemorrhage was suspected, however repeat CT was stable. EEG showed slowing over the left hemisphere without epileptiform activity. MRI excluded alternative causes for his neurological status such as brainstem ischaemia. With no clinical improvement, formal brainstem death testing was initiated. No potential confounders were recognised. The pupillary, corneal, oculocephalic, cough and gag reflexes were absent. Unexpectedly, deep tendon reflexes were absent in all limbs. A peripheral nerve stimulator using a train-of-four test protocol found no response. Post-traumatic Guillain-Barré syndrome (GBS) was suspected. Intravenous immunoglobulin was commenced. Nerve conduction studies found absent motor and sensory responses in all limbs. EMG showed fibrillation potentials and sharp waves. These findings were consistent with acute motor-sensory axonal neuropathy (AMSAN) variant of GBS. Serum Anti-GM1 antibodies were identified. After multiple rounds of plasmapheresis the patient was weaned from the ventilator. Nevertheless, severe neurological disability remained. <h3>Conclusions:</h3> NA <b>Disclosure:</b> Dr. Finegan has nothing to disclose. Dr. Ryan has nothing to disclose. Michael J. Hennessy has nothing to disclose. Kevin Murphy has nothing to disclose. Dr. Crowley has nothing to disclose. Dr. Elamin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche .

Isolated Brainstem Death is Rare and is Associated with Infratentorial Stroke Among Patients Suspected of Death by Neurologic Criteria (P1-7.004)

Isolated Brainstem Death is Rare and is Associated with Infratentorial Stroke Among Patients Suspected of Death by Neurologic Criteria (P1-7.004)

Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study.

Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor "liver blood tests" on transplant outcomes. This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019); adjusted regressions models were used to assess the effect of donor "liver blood tests" on outcomes. A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044). Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.

Intensive care unit deaths among neurosurgery patients in a tertiary hospital in South Western Nigeria

Background: Neurosurgical patients are the most critical ICU admissions. While advancements in neurosurgical ICUs (NICU) have improved outcomes of care globally, ICU mortality remains a major clinical issue in developing nations. This study evaluates ICU mortalities of neurosurgical patients in a general ICU setting at the UNIOSUN Teaching Hospital, Osogbo, Nigeria.&#x0D; Method: Case records of neurosurgery patients who died in the ICU of UNIOSUN Teaching Hospital, Osogbo, South-Western, Nigeria from June 2012 to May 2022 were reviewed. Simple descriptive statistics of data on demographics, clinical diagnoses, management and outcome were done.&#x0D; Results: Mortality rate was 38.9% (84 of 216 admissions). Males were 67(79.8%) and the mean age was 41.5years (Range: 2-85years). The average duration of ICU stay was 3.5days (Range: 30minutes-20days). Most patients had severe traumatic brain injury (TBI) (62, 73.8%). This was followed by cerebrovascular diseases (12, 14.3%) and brain tumours (6, 7.1%). Two had brain abscess. One patient each had mixed subacute/chronic subdural haematoma and severe cervical spondylotic myelopathy. Of the 69 whose case files were found, 7(10.1%) had a diagnosis of brainstem death before eventual 'final' death after an average of 13.5 additional hours on mechanical life support. The identified secondary causes of death included raised ICP, sepsis, primary surgical haemorrhage, seizures, acute kidney injury, malignant hypertension, poor glycaemic control and aggressive blood pressure lowering. Only 1 patient had autopsy.&#x0D; Conclusion: Most ICU mortalities among neurosurgical patients were from severe TBI. The establishment of NICU is necessary to improve outcome of care of neurosurgical patients.

What does "brainstem death" mean? A review of international protocols.

The term "brainstem death" is ambiguous; it can be used to refer either exclusively to loss of function of the brainstem or loss of function of the whole brain. We aimed to establish the term's intended meaning in national protocols for the determination of brain death/death by neurologic criteria (BD/DNC) from around the world. Of 78 unique international protocols on determination of BD/DNC, we identified eight that referred exclusively to loss of function of the brainstem in the definition of death. Each protocol was reviewed to ascertain whether it 1) required assessment for loss of function of the whole brain, 2) required assessment only for loss of function of the brainstem, or 3) was ambiguous about whether loss of function of the higher brain was required to declare DNC. Of the eight protocols, two (25%) required assessment for loss of function of the whole brain, three (37.5%) only required assessment for loss of function of the brainstem, and three (37.5%) were ambiguous about whether loss of function of the higher brain was required to declare death. The overall agreement between raters was 94% (κ = 0.91). There is international variability in the intended meaning of the terms "brainstem death" and "whole brain death" resulting in ambiguity and potentially inaccurate or inconsistent diagnosis. Regardless of the nomenclature, we advocate for national protocols to be clear regarding any requirement for ancillary testing in cases of primary infratentorial brain injury who may fulfill clinical criteria for BD/DNC.

MP31-12 ASSOCIATION OF INITIAL POST-TRANSPLANT DONOR-DERIVED CELL-FREE DNA LEVELS WITH PERI-TRANSPLANT OUTCOMES AND DONOR CHARACTERISTICS IN DECEASED DONOR KIDNEY TRANSPLANT RECIPIENTS: A SINGLE-CENTER RETROSPECTIVE STUDY

You have accessJournal of UrologyCME1 Apr 2023MP31-12 ASSOCIATION OF INITIAL POST-TRANSPLANT DONOR-DERIVED CELL-FREE DNA LEVELS WITH PERI-TRANSPLANT OUTCOMES AND DONOR CHARACTERISTICS IN DECEASED DONOR KIDNEY TRANSPLANT RECIPIENTS: A SINGLE-CENTER RETROSPECTIVE STUDY Conner Lombardi, Jacob Lang, Emile Garcia, Mary Lee Brown, Dinkar Kaw, Deepak Malhotra, Shobha Ratnam, Michael Rees, and Obi Ekwenna Conner LombardiConner Lombardi More articles by this author , Jacob LangJacob Lang More articles by this author , Emile GarciaEmile Garcia More articles by this author , Mary Lee BrownMary Lee Brown More articles by this author , Dinkar KawDinkar Kaw More articles by this author , Deepak MalhotraDeepak Malhotra More articles by this author , Shobha RatnamShobha Ratnam More articles by this author , Michael ReesMichael Rees More articles by this author , and Obi EkwennaObi Ekwenna More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003264.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Donor-derived cell-free DNA has been demonstrated as an accurate biomarker and risk predictor for acute rejection in kidney transplantation, but it’s association with other clinical variables implicated in rejection have been mixed. The aim of this study was to assess the clinical association of dd-cfDNA levels that have been associated with peri-transplant outcomes including development of delayed graft function, cold ischemia time (CIT), use of machine perfusion, and donor characteristics, including deceased donor mode of death, kidney donor profile index (KDPI), and donor age. METHODS: Retrospective data from a cohort of 84 deceased donor kidney recipients transplanted from November 2019 to December 2020 with initial dd-cfDNA (ProsperaÔ, Natera, Inc.) levels collected within six months (Median date of collection 19 days; IQR 16-31 days) of undergoing transplantation were included in the study. Pearson’s C2, Wilcoxon rank-sum tests, and linear regression with Pearson’s correlation coefficient were used to measure association with significance determined at p<0.05. RESULTS: When examining peri-transplant characteristics, mean levels of dd-cfDNA were significantly higher in those with DGF (n=20) than non-DGF (n=64) [1.02% (95% CI 0.65-1.39%) vs. 0.65 (95% CI 0.42-0.88%); p=0.002]. Dd-cfDNA levels were not significantly associated with CIT (mean p=.744, r=.036), or machine perfusion (n=45) versus no machine perfusion(n=39) (0.85% (95% CI 0.52%-1.19%) vs. 0.60% (95% CI 0.41%-0.78%); p=.32). When examining donor characteristics, dd-cfDNA levels in were significantly higher in recipients with donation after cardiac death (DCD) kidneys versus donation after brainstem death (DBD) kidneys [1.26% (95% CI 0.75%-1.76%) vs. 0.53% (95% CI 0.36%-0.69%); p=0.000]. Donor age (p=.271, r=0.12) and KDPI (p=0.15, r=0.16) were not significantly associated with dd-cfDNA levels. CONCLUSIONS: Dd-cfDNA levels were significantly elevated in patients who had DGF and in recipients of DCD kidneys in our single center cohort. Notably, machine perfusion, donor age, KDPI, and CIT were not associated with increased levels with of dd-cfDNA. As associations of these variables in the literature are thus far varied, studies with increased sample size are necessary to determine the true associations. Source of Funding: The authors declare no sources of funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e434 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Conner Lombardi More articles by this author Jacob Lang More articles by this author Emile Garcia More articles by this author Mary Lee Brown More articles by this author Dinkar Kaw More articles by this author Deepak Malhotra More articles by this author Shobha Ratnam More articles by this author Michael Rees More articles by this author Obi Ekwenna More articles by this author Expand All Advertisement PDF downloadLoading ...

Editors' Note: Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria: A Systematic Review and Meta-analysis.

In “Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria: A Systematic Review and Meta-analysis,” Briard et al. report that based on a review of 21 studies, the prevalence of (1) infratentorial brain injury among patients with suspected death by neurologic criteria (DNC) was 2%–16% and (2) isolated brainstem death was 1%–4%. Machado pointed out that a series of 4 patients with infratentorial brain injury who initially had isolated brainstem death subsequently progressed to whole-brain death. The study on these patients was included in Briard's review. He also commented that Jahi McMath, who was declared dead by neurologic criteria based on both clinical evaluation and ancillary testing after hypoxic-ischemic brain injury, had a lesion in her pons and was not dead by neurologic criteria because she did not have a complete intracranial circulatory arrest. This case has been discussed extensively in the literature, but Briard and Chassé did not offer comments on it. However, they agree with Machado that additional research is needed to understand the determination of DNC in patients with infratentorial brain injury. In “Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria: A Systematic Review and Meta-analysis,” Briard et al. report that based on a review of 21 studies, the prevalence of (1) infratentorial brain injury among patients with suspected death by neurologic criteria (DNC) was 2%–16% and (2) isolated brainstem death was 1%–4%. Machado pointed out that a series of 4 patients with infratentorial brain injury who initially had isolated brainstem death subsequently progressed to whole-brain death. The study on these patients was included in Briard's review. He also commented that Jahi McMath, who was declared dead by neurologic criteria based on both clinical evaluation and ancillary testing after hypoxic-ischemic brain injury, had a lesion in her pons and was not dead by neurologic criteria because she did not have a complete intracranial circulatory arrest. This case has been discussed extensively in the literature, but Briard and Chassé did not offer comments on it. However, they agree with Machado that additional research is needed to understand the determination of DNC in patients with infratentorial brain injury.

Author Response: Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria: A Systematic Review and Meta-analysis.

We thank Dr. Machado for the interest in our article on the prevalence, characteristics, and evolution of infratentorial brain injury and isolated brainstem death among patients suspected of death by neurologic criteria (DNC).1

Reader Response: Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria: A Systematic Review and Meta-analysis.

The article by Briard et al.1 affirmed that infratentorial brain injury is relatively uncommon among patients suspected of death by neurologic criteria (DNC) and that isolated brainstem death seems to progress to whole-brain death in most cases.