Uncontrolled donation after circulatory death improves access to kidney transplantation: A decision analysis.

AIM: Uncontrolled donation after cardiac death (uDCD) remains an underutilized source of kidney allografts in the United States. The objective of this study was to estimate the impact of the implementation of a uDCD program on transplantation rates and long-term survival for patients with end-stage renal disease (ESRD) in the United States. METHODS: A decision-analytic Markov state transition model was created using medical decision-making software (DATA 3.5; TreeAge Software, Inc) to estimate the impact of an uDCD program on transplantation rates and patient survival. Additionally, sensitivity analysis of uDCD donor pool increase was modeled. All model statistic parameters were extracted from the literature. RESULTS: A uDCD program increased the rate of transplant at 10 years (37.8%, Accept uDCD group, vs 35.9%, Reject uDCD group). At 10 years, overall survival for Accept uDCD was 55.6% compared to 54.8% in the Reject uDCD. CONCLUSIONS: Uncontrolled DCD improves access to transplant for ESRD patients on the kidney transplant waitlist, thereby improving long-term survival.

Impact of Deceased-donor Acute Kidney Injury on Kidney Transplantation.

Even as record numbers of deceased donors are undergoing organ recovery, the global transplant community continues to struggle with a shortage of donor organs and a high organ discard rate. Acute kidney injury (AKI) occurs in many hospitalized patients, including up to 25% of patients in critical condition. Registry studies have shown a significant increase in nonrecovery or organ discard rates in AKI donors, despite most studies reporting similar clinical outcomes compared with non-AKI donors. This review aims to capture the salient information learned from these studies and to summarize the efforts that have been made to gain a more granular understanding of how kidneys from donors with AKI behave posttransplant. In particular, we reviewed the studies that analyzed the clinical outcomes in different stages of AKI and AKI in marginal donors, such as kidney donor profile index of >85%, older donors, and donation after circulatory death donors. We summarized studies investigating molecular biomarkers, transcriptomics, and possible future therapeutic targets for postdonation AKI.

COVID-19 and the Response of Transplant Centers: the Global Response with an Emphasis on the Kidney Recipient.

PURPOSE OF THE REVIEW: In response to the COVID-19 pandemic, vulnerable populations, such as transplant patients, were at greater risk than the regular population. In order to protect these populations, transplant centers enacted new guidelines. We approach this review by looking at how different transplant regions responded to COVID-19 and analyze the unifying themes that have proven invaluable in the subsequent waves. RECENT FINDINGS: We noticed that most elective surgeries including living donor transplant operations were suspended in most countries. The response to deceased donor transplants varied between countries: in some deceased donor transplants continued with modified donor and recipient criteria, while in other countries this surgery was suspended. There was a general trend of decreasing or holding antimetabolites, treating the virus with hydroxychloroquine and/or azithromycin, and converting outpatient clinics to virtual clinics. SUMMARY: We learned how to carefully select donors and recipients, tailor immunosuppressant regiments, and implement telemedicine. The kidney recipient population can be effectively managed in times of crisis with appropriate accommodations and measures. This review can be a model for the transplant community for future pandemics.

Reverse epidemiology and the obesity paradox for patients with chronic kidney disease: a Markov decision model.

BACKGROUND: Obesity has been associated with both increased progression of chronic kidney disease (CKD) as well as with a paradoxical improvement in survival among end-stage renal disease patients undergoing hemodialysis. As such, the optimal weight management strategy for obese CKD patients remains unclear. OBJECTIVE: To estimate the outcomes of obese, CKD stage 3b patients after 3 weight loss interventions, including medical weight management, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB), were followed to determine which strategy optimizes long-term survival. SETTING: University hospital, Aurora, Colorado. METHODS: A decision analytic Markov state transition model was created to simulate the life of 30,000 obese patients with CKD stage 3b, as they progressed to end-stage renal disease, transplantation, and death. Life expectancy after conservative medical weight management, RYGB, and SG were estimated. Base case patients were defined as being 50 years old and having a preintervention BMI of 40 kg/m2. Sensitivity analysis of initial BMI was performed. All Markov parameters were extracted from literature review. RESULTS: RYGB and SG were associated with improved survival for patients with preintervention body mass index of >38 kg/m2. Compared with conservative weight management, base case patients who underwent RYGB gained 10.6 months of life, and gained 8.3 months of life after SG. CONCLUSIONS: Balancing progression of CKD with improved survival on end-stage renal disease for obese patients requires selective use of weight management strategies. RYGB and SG improved survival for CKD patients with Class II and III obesity, but not for patients with Class I obesity. As such, aggressive weight loss interventions should be reserved for patients with Class II and III obesity, while more conservative methods should be offered to those with Class I obesity.

Offspring Versus Nonoffspring to Parent Living Donor Liver Transplantation: Does Donor Relationship Matter?

BACKGROUND: Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation. METHODS: A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly 3 HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling. RESULTS: A total of 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% versus 72%; P < 0.001) and patient survival (52% versus 81%; P < 0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered among male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR = 2.87; P = 0.04) and mortality (hazard ratio = 3.89; P = 0.03). Again, this association was not seen with male recipients. CONCLUSIONS: Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection.

Detection of early allograft dysfunction at 30 min of reperfusion in liver transplantation: An intraoperative diagnostic tool with real time assessment of graft function.

INTRODUCTION: During the anhepatic phase of liver transplantation (LT), fibrinolytic activity increases, since the liver clears tissue plasminogen activator (tPA). We hypothesize that patients who fail to reduce fibrinolytic activity following graft reperfusion will have an increased rate of early allograft dysfunction (EAD). METHODS: Assessment of fibrinolysis in liver transplant recipients was quantified with thrombelastography (TEG) LY30. Changes in LY30 were assessed after graft reperfusion. The 30-min post-reperfusion LY30 was subtracted from the anhepatic LY30 quantifying fibrinolytic changes (delta-LY30). RESULTS: Seventy-three primary LT patients were included in the analysis. Receiver operating characteristic curve (ROC) analysis identified an inflection point of delta-LY30-5.3% as a risk factor for EAD. EAD occurred in 44% of these patients compared to 5% in high delta-LY30 (p = 0.002). CONCLUSION: LT recipients that develop hyperfibrinolysis who fail to reduce fibrinolytic activity 30 min after graft reperfusion had an EAD rate 8-fold higher than patients who had a large reduction in LY30 following reperfusion.

A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation.

BACKGROUND: An NIH clinical coagulopathy score has been devised for trauma patients, but no such clinical score exists in transplantation surgery. We hypothesize that that this coagulopathy score can effectively identify laboratory defined coagulopathy during liver transplantation and correlates to blood product utilization. METHODS: TEGs were performed and coagulopathy scores (1, normal bleeding - 5, diffuse coagulopathic bleeding) were assigned by the surgeons at 5 intra-operative time points. Blood products used during the case were recorded between time points. Statistical analyses were performed to identify correlations between coagulopathy scores, TEG-detected abnormalities, and blood product utilization. RESULT: Transfusions rarely correlated with the appropriate TEG measurements of coagulation dysfunction. Coagulopathy score had significant correlation to various transfusions and TEG-detected coagulopathies at multiple points during the case. High aggregate coagulopathy scores identified patients receiving more transfusions, re-operations, and longer hospital stays CONCLUSION: The combination of viscoelastic testing and a standardized clinical coagulopathy score has the potential to optimize transfusions if used in tandem as well as standardize communication between surgery and anesthesia teams about clinically evident coagulopathy.

The use of thromboelastography to assess post-operative changes in coagulation and predict graft function in renal transplantation.

BACKGROUND: End stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery. METHODS: Kidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining "good" graft function. Follow up was done at 6, 12, and 24 months. RESULTS: Percent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30. CONCLUSIONS: Post-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant.

Non-Invasive Targeted Hepatic Irradiation and SPECT/CT Functional Imaging to Study Radiation-Induced Liver Damage in Small Animal Models.

Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the liver, which in turn may lead to the development of more effective cancer treatments. Previous models of hepatic irradiation are limited by either invasive laparotomy procedures, or the need to irradiate the whole or large parts of the liver using external skin markers. In the setting of modern-day radiation oncology, a truly translational animal model would require the ability to deliver RT to specific parts of the liver, through non-invasive image guidance methods. To this end, we developed a targeted hepatic irradiation model on the Small Animal Radiation Research Platform (SARRP) using contrast-enhanced cone-beam computed tomography image guidance. Using this model, we showed evidence of the early development of region-specific RILD through functional single photon emission computed tomography (SPECT) imaging.

Early Readmission After Kidney Transplantation: Examination of Discharge-Level Factors.

BACKGROUND: Early rehospitalization after kidney transplantation (KTx) is common and is considered a quality metric. Recipient and donor risk factors for early readmission after KTx are well studied. Little data exist on discharge-level factors associated with readmission. METHODS: We performed a single-center, retrospective cohort study between 2011 and 2015 of adult KTx recipients to examine readmission indication, risk factors, and opportunities for reduction. RESULTS: Of 462 KTxs, 145 (31.4%) were readmitted within 30 days of discharge. The primary reason for readmission was surgery-site specific in 30 cases (20.7%). Of 115 recipients with nonsurgical indications for readmission 25 (21.7%) were related to infection, 24 (20.9%) graft dysfunction, 25 (21.7%) gastrointestinal, 25 (21.7%) metabolic, and 16 (13.9%) other reasons. On multivariate analysis significant independent predictors of early readmission were electrolyte abnormalities on the day of discharge (odds ratio [OR], 1.77; 95% confidence interval [95% CI], 1.17-2.69), 3 or more comorbidities (OR, 2.01; 95% CI, 1.04-3.86), delayed graft function at the time of discharge (OR, 1.65; 95% CI, 1.00-2.70), and post-KTx hospitalization complication (OR, 1.70; 95% CI, 1.10-2.61). Among 11.7% of patients, readmission may have been attenuated by addressing the medical issue before discharge from index hospitalization. In 28.3% of patients, readmission rates may have been reduced with continued management as an outpatient or provision of observational or same-day diagnostic resources. CONCLUSIONS: Specific discharge level factors correlate with readmission irrespective of comorbidities and transplant complications. These findings may have important implications on discharge practice by aiding to identify which KTx recipients could be targeted for enhanced care transitions. Overall, potential opportunities for readmission reduction exist on multiple process levels.

Should functioning AV fistulas be ligated after renal transplantation?

PURPOSE: There is limited literature available to guide physicians on a course of action when they are approached by renal transplant recipients regarding the status of their vascular accesses. However, this is a frequent topic of discussion with these patients and there should be guidelines available to assist in the decision of whether to maintain or ligate an arteriovenous fistula (AVF) in a successful renal transplant patient. This review intends to present some of the literature, as well as to establish guidelines for management. METHODS: The medical literature was reviewed and anecdotal information from our clinical experience was collected. RESULTS: Taking into account 10-year adjusted renal transplant graft survival rates, and the relative paucity of donors, it is possible that a successfully transplanted patient will have to return to dialysis at some point. After review of the literature, the impact of AVF ligation on the transplant patient's cardiac morphology and function is not clear. Patient and graft survival do not appear to be impacted by persistent AVFs. Emergent closure of the AVF might be required in cases of severe venous hypertension, risk of rupture from pseudoaneurysm, significant high output cardiac failure or ischemic hand. CONCLUSIONS: We recommend that following successful renal transplantation, functioning AVFs should almost never be ligated. Many patients require return to dialysis and the physiologic impact of the patent AVF on these patients does not strongly advocate routine ligation following transplant.

Intraoperative mapping and monitoring of the corticospinal tracts with neurophysiological assessment and 3-dimensional ultrasonography-based navigation. Clinical article.

OBJECT: Preserving motor function is a major challenge in surgery for intraaxial brain tumors. Navigation systems are unreliable in predicting the location of the corticospinal tracts (CSTs) because of brain shift and the inability of current intraoperative systems to produce reliable diffusion tensor imaging data. The authors describe their experience with elaborate neurophysiological assessment and tractography-based navigation, corrected in real time by 3D intraoperative ultrasonography (IOUS) to identify motor pathways during subcortical tumor resection. METHODS: A retrospective analysis was conducted in 55 patients undergoing resection of tumors located within or in proximity to the CSTs at the authors' institution between November 2007 and June 2009. Corticospinal tract tractography was coregistered to surgical navigation-derived images in 42 patients. Direct cortical-stimulated motor evoked potentials (dcMEPs) and subcortical-stimulated MEPs (scrtMEPs) were recorded intraoperatively to assess function and estimate the distance from the CSTs. Intraoperative ultrasonography updated the navigation imaging and estimated resection proximity to the CSTs. Preoperative clinical motor function was compared with postoperative outcome at several time points and correlated with incidences of intraoperative dcMEP alarm and low scrtMEP values. RESULTS: The threshold level needed to elicit scrtMEPs was plotted against the distance to the CSTs based on diffusion tensor imaging tractography after brain shift compensation with 3D IOUS, generating a trend line that demonstrated a linear order between these variables, and a relationship of 0.97 mA for every 1 mm of brain tissue distance from the CSTs. Clinically, 39 (71%) of 55 patients had no postoperative deficits, and 9 of the remaining 16 improved to baseline function within 1 month. Seven patients had varying degrees of permanent motor deficits. Subcortical stimulation was applied in 45 of the procedures. The status of 32 patients did not deteriorate postoperatively (stable or improved motor status): 27 of them (84%) displayed minimum scrtMEP thresholds > 7 mA. Six patients who experienced postoperative deterioration quickly recovered (within 5 days) and displayed minimum scrtMEP thresholds > 6.8 mA. Five of the 7 patients who had late (> 5 days postoperatively) or no recovery had minimal scrtMEP thresholds < 3 mA. An scrtMEP threshold of 3 mA was found to be the cutoff point below which irreversible disruption of CST integrity may be anticipated (sensitivity 83%, specificity 95%). CONCLUSIONS: Combining elaborate neurophysiological assessment, tractography-based neuronavigation, and updated IOUS images provided accurate localization of the CSTs and enabled the safe resection of tumors approximating these tracts. This is the first attempt to evaluate the distance from the CSTs using the threshold of subcortical monopolar stimulation with real-time IOUS for the correction of brain shift. The linear correlation between the distance to the CSTs and the threshold of subcortical stimulation producing a motor response provides an intraoperative technique to better preserve motor function.