Marginal Donors Research Articles

Histological Evaluation of Extended Criteria Donors: Donor’s Kidney Biopsy and Graft Outcome after 5 Years of Transplantation

Pre-transplant kidney biopsy is routinely used to decide whether kidneys from marginal donors should be transplanted as single or double trans-plantation. This is a 5-year extension of the follow-up of a previous study. In that study, graft outcomes were compared retrospectively between a group of 44 recipients of a single kidney graft from an extended criteria donor and a Karpinski histological score of 3 or less, and another group of 56 recipients of a single transplant with a Karpinski histological score of 4 or 5. After 5 years of transplantation, there was no difference between the two groups in terms of recipient’s serum creatinine levels (1.8 ± 0.5 vs 1.9 ± 0.6 mg/dL, P = 0.5), creatinine clearance (53 ± 23 vs 49 ± 27.0 mL/min, P = 0.6), or the rates of graft loss (41% vs 49%,P = 0.5). Therefore, the choice between single and double transplant should not be made only on the basis of histological score but should be done together with the evaluation of donor’s clinical parameters, especially the renal function.

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion.

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.

Isolated Lung Perfusion in the Management of Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.

Preservation by cold storage vs ex vivo normothermic perfusion of marginal donor hearts: clinical, histopathologic, and ultrastructural features

The aim of this study was to match clinical outcomes of heart transplantation (HTx) against histopathologic and ultrastructural characteristics of marginal grafts preserved by cold storage (CS) or ex vivo normothermic perfusion. Since 2011, 100 patients had undergone HTx at our institution by using marginal donors (aged ≥55 years, expected ischemic time of >4 hours, left ventricular ejection fraction of ≤50%, interventricular septum thickness of ≥14 mm, drug abuse history, episodes of cardiac arrest, and presence of mild coronary artery disease). CS was utilized in 79 cases (Group 1, 79%), and ex vivo perfusion was utilized in 21 (Group 2, 21%). Pre-operative data, survival, and complications in the first 5 years after HTx were analyzed. Myocardial biopsies were collected at graft harvesting, just before implantation, and immediately after aortic declamping. Pre-operative demographics were similar in the 2 groups. Graft utilization rate with ex vivo perfusion was 81%. Ischemic, cardiopulmonary bypass, and surgical times were shorter in Group 2 patients, who showed a lower incidence of overall complications (33% vs 13%, p = 0.04) and better 5-year survival (log-rank, p = 0.04). Moreover, restoration of hypertrophy-related sarcomere changes and mitigation of reperfusion-dependent myocardium injuries were more frequently observed in Group 2 hearts. Ex vivo perfusion allows for continuous evaluation of marginal donor hearts, favoring exclusion of unsuitable grafts, reduction of complications, and optimal survival of up to 5 years. Such results, supported by consistent histopathologic and ultrastructural findings, suggest better myocardial preservation.

Strategies in Organ Preservation-A New Golden Age.

Strategies in Organ Preservation-A New Golden Age.

OPCR DBD, “ORGAN PRESERVING CARDIOPULMONARY RESUSCITATION IN DECEASED BRAIN DEAD DONOR” TO MINIMIZE WASTAGE OF ORGANS

Introduction: Although lot of advances in the management of brain dead patients are undergoing, but in a resource limited country with an incipient deceased donation program there practicality is difficult. In such situations, Organ preserving cardiopulmonary resuscitation (OP-CPR) is an excellent cost-effective way to minimize organ wastage. OP-CPR is defined as the use of CPR in cases of cardiac arrest to preserve organs for transplantation, rather than to revive the patient. The implementation of OP-CPR in various countries are controversial, but in our country we don’t have any legal barriers for this practice. This would be the first study which highlights the characteristics of renal transplant recipient with deceased kidney from OP-CPR. We would try to solve lot of research questions like immediate and long-term outcome with OP-CPR, comparison with marginal donors and standard criteria donors, ethical issues to be addressed, applicability of OP-CPR and hurdles involved. Materials and Methods: This was a prospective institutional and ethical board approved case control single center study. All organ donation and retrieval procedure are done as per rules of Transplantation of Human Organs and Tissues Act (THOTA 2014). Informed consent for OP-CPR was taken. We discarded all DCD, and DBD converted to DCDs. If patient relatives didn’t consent for OPCPR then we followed do not attempt cardiopulmonary resuscitation (DNACPR). We compared the outcome of OP-CPR DBD with marginal donors and standard criteria donors in terms of BPAR, infections, patient and graft survival. Result: A total of 109 OPCPR-DBD transplant cases were done. The patient and graft survival in OPCPR with or without AKI showed no statistical difference. OPCPR outcome with non OPCPR group as well as SCD group were also similar. Rejection rate were similar in all group. Discussion: Previously only few cases of OPCPR has been reported, we describe the maximum no of cases so far. Few countries don’t accept OPCPR while some don’t use defibrillation in OPCPR. We don’t have any restriction in our nation. OP- CPR can help a family from fulling there last wish to be an organ donor but OP- CPR could also prove to be a distressing event, It can feel like stretching the agony before death. How long OP CPR can be continued, what should be the cutoff for DNACPR, long-term outcome of OP CPR recipients are some of the research questions which further needs consideration. Small sample size, and short followup was the limitation of our study. Conclusion: OPCPR proved to be a successful cost effective procedure in expanding the donor poll in our study. With promising results in our center we recommend to follow OPCPR in all institutions which are linked to transplant centers nationwide. Trainings like ALS, BLS should be incorporated to all medical strata, and intensive care should be more strengthened so that more lives can be saved, even after death.

THE PREVENTIVE EFFECT OF SIROLIMUS ON URETERAL STRICTURE FORMATION

Introduction: Stricture of the transplant kidney ureter occurs in approximately 3% of transplant recipients. Risk factors for ureteral stricture include kidneys coming from marginal donors with advanced age and multiple comorbidities. Additionally, delayed graft function, presence of multiple renal arteries and direct injury during retrieval may increase the risk of this complication. Its clinical presentation is typical with elevated serum creatinine accompanied by hydronephrosis. Although several open and endoscopic techniques have been described to manage this condition, ureteral stricture still increases short and long-term graft loss significantly. An M-TOR inhibitor Sirolimus has been shown to reduce fibrosis. Since the mechanism of stricture formation is also through fibrosis, we analyzed the effect of this immunosuppressive drug on the prevention of ureteral strictures. Methods: 32 New Zealand White rabbits (2500-3000grams) were used in the study. The rabbits were randomly assigned into four groups (n=8). Group 1: A unilateral nephrectomy and subsequent full transection of the contralateral ureter was performed. The transected ureter was reconstructed over a double J ureteral stent by using interrupted 7/0 PDS stitches. Group 2: Same procedure with group 1 with Sirolimus- impregnated (1mg) stent placement Group 3: A unilateral nephrectomy and subsequent full transection of the contralateral ureter was performed. The transected ureter was reconstructed without a stent and 1 ml of saline was instilled over the anastomosis. Group 4: Same with group 3 with 1ml (1mg/ml) of Sirolimus solution instilled over the ureteric anastomosis (Figure 1). On postoperative day 3, serum creatinine levels were measured. On postoperative day 7, an ultrasound of the kidney was performed to evaluate hydronephrosis. On postoperative day 21, all rabbits were explored to evaluate the ureteral anastomosis. Subsequently, all subjects were terminated, and full segment of the ureter was removed for histopathology assessments and tissue hydroxyproline level measurements. Results: Severe hydronephrosis and creatinine elevation were observed in group 3 compared to other groups (Figure 2). Histopathological evaluation of the specimens showed increased fibrosis scores in groups 1 and 3 (Figures 3&4). Tissue hydroxyproline levels in group 4 were found to be lower compared to other groups. Conclusion: Sirolimus-impregnated double J stents may decrease ureteric stricture formation. This effect can be beneficial both in both kidney transplant and endourology practice.Fig. 1.Fig. 2.Fig. 3.

EXTERNAL VALIDATION OF CURRENT INTERNATIONAL SHORT- AND LONG-TERM PROGNOSTIC MODELS FOR SURVIVAL IN HEART TRANSPLANT RECIPIENTS USING MARGINAL DONOR HEARTS AT SINGLE JAPANESE CENTER

Introduction: Current prognostic models to predict survival in heart transplant (HTx) recipients, which are ‘Index for Mortality Prediction After Cardiac Transplantation (IMPACT) model’ using the recipient-factor and ‘International Heart Transplantation Survival Algorithm (IHTSA) model’ using both recipient- and donor-factors, have been verified the good adaptation on the global registry data in HTx recipients. In Japan, extremely serious donor shortages will necessitate a long waiting period, and using more marginal donor hearts. But several donor risk factors for HTx were not included enough in these prognostic models. It is unclear whether these prognostic models can be adapted with HTx using more marginal donor hearts. This study aimed to validate the usefulness of IMPACT and IHTSA models for the prediction of long-term mortality in recipients transplanted marginal hearts. Materials and Methods: Consecutive 126 adult HTx recipients who underwent HTx between May 1999 and February 2020 were included in this study. The risk score based on IMPACT model was calculated for each recipient. And we entered the clinical data of each recipient and donor into the web-based calculator of the IHTSA model and calculated predicted 5-year mortality rate based on the IHTSA model. The discrimination for survival in our subjects was evaluated using Harrell’s concordance index (C-index). Survival analysis was conducted to evaluate the actual mortality rate in our subjects. Results and Discussion: Over median follow-up of 4.9 years [interquartile range (IQR); 2.6-9.0 years] after HTx, 8 recipients (6.3%) died during follow-up. The IMPACT score was median of 6.0 (IQR; 3.0-8.0), and the estimated 5-year mortality rate based on IHTSA model was median of 0.25 (IQR; 0.21-0.29). The predicted versus actual 5-year survival rates were 73.7% versus 95.8%. The discrimination (C-index) for survival using IMPACT score and 5-year mortality rate based on the IHTSA model were 0.689 and 0.720, respectively. Conclusion: This study validated a usefulness of two current prognostic models, IMPACT and IHTSA, for survival in HTx recipients using marginal donor hearts. Our results suggest that these models might be useful even in HTx recipients using highly marginal donor hearts. Further validation is needed to adapt an appropriate prognostic model in such clinical situation as serious donor shortages.

ASSOCIATION OF HAEMOGLOBIN LEVELS DURING NORMOTHERMIC MACHINE PERFUSION OF PORCINE DONATION AFTER CARDIAC DEATH KIDNEYS WITH RENAL METABOLISM AND FUNCTION

Introduction: The shortage of kidneys for transplantation remains. Therefore, kidneys of suboptimal quality are used more often. These derive from expanded criteria donors (ECD) and donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) of these marginal donor kidneys is used to preserve and assess renal function. Although perfusion fluids are all based on red blood cells or alternative oxygen carriers, haemoglobin levels are mostly below 6 mmol/L. It is unknown to which extent oxygen carrying capacity is required to support kidney function during NMP. The aim of this study was to retrospectively evaluate the effect of haemoglobin levels on renal metabolism and function during NMP. Methods: Porcine kidneys obtained from a local slaughterhouse were considered eligible for this retrospective cohort study and were included when subjected to a warm ischemic time (WIT) ranging from 30 to 35 minutes and were subsequently preserved with oxygenated hypothermic machine perfusion (HMP) ranging from 3 to 24 hours. For all kidneys a 4 hours observation period with oxygenated NMP with an oxygen carrier was required. Kidneys were stratified according to haemoglobin concentrations (per 1 mmol/L increment). Variables measured were creatinine clearance, oxygen consumption, and fractional sodium reabsorption rates. Results: In total, 101 (84%) of 120 eligible kidneys were included. Preliminary results show that groups containing a haemoglobin level over 5 mmol/L or more result in higher oxygen consumption rates and increased reabsorption of sodium. Creatinine clearance seems to be improved in these groups as well.Conclusion: In this preliminary study, a minimum haemoglobin level of 5 mmol/l seems to be essential to effectively asses renal metabolism and function. It is unclear if lower haemoglobin levels result in renal injury.

Valvular surgery in donor hearts before orthotopic heart transplantation

Donor heart shortage has extended the waiting time and increased the mortality of patients on the transplant waiting list. Widening old standard donor criteria has successfully increased the number of heart transplantations, but for many years, a valve disease in a donor heart has been considered a primary contraindication for organ donation. To analyse the results of aortic and mitral valvular surgery in marginal donor hearts with valvulopathy before orthotopic heart transplantation. Between January 2012 and November 2015, we performed 53 heart transplantations in our department. In four donors, echocardiography performed at the time of organ procurement showed a valvular disease: three had moderate-to-severe mitral regurgitation; and one had moderately severe aortic valve stenosis. The mean bench mitral repair and aortic replacement time, aortic cross-clamp time and total ischaemic time were: 18 (range 7-25) minutes, 78.7 (range 57-98) minutes and 184 (range 89-255) minutes, respectively. Intraoperative transoesophageal echocardiography showed good mitral repair or aortic prosthetic valve function, and good right and left ventricular function. One patient died of infectious pneumonia after 1 month. The mean duration of follow-up for the patients discharged home was 75±13 months, and all have returned to an active unrestricted lifestyle. Our limited series demonstrates that conventional valvular procedures performed on otherwise healthy donor hearts with mitral and aortic valve pathology can efficaciously expand the donor pool for orthotopic cardiac transplantation and decrease the mortality rate on the waiting list.

A single-center long-term experience with marginal donor utilization for heart transplantation.

To evaluate the early and late outcome of heart transplantation (HT) using marginal (MDs) and optimal donors (ODs). Clinical records of recipients transplanted between July 2004 and December 2014 were retrospectively reviewed. MDs were defined as follows: age >55years, high-dose inotropic support, left ventricular ejection fraction <45%, left ventricular hypertrophy, donor to recipient predicted heart mass ratio <0.86, ischemic time >4hours. A total of 412 (55%) recipients received an organ from a MD; recipients who received an organ from an OD had less primary graft dysfunction (PGD) (25% vs 38%; P<.001), less acute renal failure (23% vs 34%; P<.001), and higher survival rates (90.2% vs 81.8% at 30days, 79.5% vs 71.1% at 1year, 51.8% vs 45.4% at 12years; P=.01) than recipients who received an organ from a MD. There was no statistically significant difference in 30-day conditional survival between the two groups (survival rates 57.4% vs 55.5% at 12years; P=.43). PGD, perioperative hemodialysis, and sepsis were independent risk factors of mortality at multivariate analysis. Utilization of MDs for HT is associated with a higher incidence of PGD and acute renal failure, and a reduction of 30-day survival.

Cell-free DNA in human ex vivo lung perfusate as a potential biomarker to predict the risk of primary graft dysfunction in lung transplantation

BackgroundCell-free DNA (cfDNA), such as mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA), are known to be released from injured cells and as such have been explored as biomarkers for tissue injury in different clinical settings. Ex vivo lung perfusion (EVLP) has been developed as an effective technique for marginal donor lung functional assessment. We hypothesized that the level of cfDNA in EVLP perfusate may reflect tissue injury and thus can be developed as a biomarker to quantify the degree of donor lung injury or predict the development of primary graft dysfunction (PGD) after lung transplantation (LTx). MethodsThe perfusate from 62 donor lungs transplanted at our institution between May 2010 and December 2015 was sampled for cfDNA at 1 and 4 hours of perfusion. Sequences of genes encoding nicotinamide adenine dinucleotide dehydrogenase 1 (NADH-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were used to represent mtDNA and nuDNA, respectively. Levels were quantified by real-time polymerase chain reaction and correlated with clinical outcome after LTx. ResultsIn our entire cohort, 14 patients developed PGD grade 3 (PGD3) within 72 hours after LTx. The non-PGD group included 48 patients (PGD0-1). Concentrations of mtDNA in the perfusate of the PGD3 group were significantly higher than those in non-PGD group at 1 hour of EVLP (1874 ± 844 vs 1259 ± 885 copies/μL; P = .011). The perfusate of the PGD3 group had significantly higher levels of nuDNA compared with the non-PGD group at both 1 hour (1498 ± 1895 vs 675 ± 391 copies/μL; P = .008) and 4 hours (4521 ± 5810 vs 1764 ± 1494 copies/μL; P = .001). In donation after cardiac death (DCD) cases, mtDNA levels were significantly higher in the PGD3 group compared with the non-PGD group at 1 hour of EVLP (2060 ± 997 vs 1184 ± 782 copies/μL; P = .040), and the levels of nuDNA were significantly higher in the PGD3 group compared with the non-PGD group at both 1 hour (1021 ± 495 vs 606 ± 305 copies/μL; P = .041) and 4 hours (2358 ± 1028 vs 1185 ± 967 copies/μL; P = .006). In donation after brain death (DBD) cases, cfDNA scores did not show a significant difference. ConclusionsWe found that the amount of cfDNA, especially nuDNA, in EVLP perfusate was higher in the severe PGD group (PGD3) compared with the non-PGD group. This proof-of-concept study supports the concept that the analysis of cfDNA levels in EVLP perfusate can help estimate the damage to donor lungs before implantation. Larger studies are needed to validate this concept.

Heterotopic heart transplant: relevance as Bio-VAD in emerging economies.

Despite the introduction of mechanical circulatory assist systems in India two decades ago, there has not been their wide usage due to two main reasons: (1) economic-financial unaffordability and (2) lack of social support. There have been a number of significant steps taken by the government and by the media for augmenting awareness for organ donation. A sizeable donor pool in India falls into the category of marginal donors, due to a variety of reasons like geographical distances, lack of rapid transport, suboptimal donor management due to the lack of resources, and trained manpower in hospitals where donor harvest is done. Consequently, the usage of the heart as a donor organ is less than 20% in India. There is a lack of statistical data regarding the usage of heterotopic heart transplants, due to the absence of a registry, since the procedure is rarely performed, and comparative results are difficult to obtain due to different subsets of both donors and the recipients. The original papers by Barnard and Cooper cannot be extrapolated in the modern context, as these publications were in the pre-cyclosporin era. Orthotopic heart transplantation (OHT) is a well-established and commonly utilized procedure for patients with end-stage heart failure. Heterotopic heart transplantation (HHT) is a surgical procedure that allows the graft to be connected to the native heart in a parallel fashion to provide a kind of biological biventricular or univentricular (left ventricular support). It was performed first in human beings by Barnard in 1974 [S, J., 49:, Afr, Med, 1975, 303-12].

There are no best practices in a pandemic: Organ donation within the COVID-19 epicenter.

LiveOnNY, the organ procurement organization (OPO) for the greater New York metropolitan area, suspended several best practices to manage the rising referrals of deaths from hospitals during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic. On April 2, 2020 hospitals in the donor service area were notified that coronavirus disease 2019 (COVID‐19) referrals should be deferred. Still, only 2% of referred patients to the OPO in April 2020 were on ventilators and considered possible organ donors, versus a baseline of 11% in 2019. Few of these deaths were unrelated to COVID‐19. Accordingly, organ donors declined to 10 in April (from 26 in March). Despite the exclusion of marginal donors and organs, the implementation of COVID‐19 donor testing, and the availability of local procurement surgeons, only 1 organ (a liver) was accepted by a transplant center outside of New York State and 8 organs (5 livers, 4 kidneys) were transplanted in state; 11 organs (1 liver, 10 kidneys) were discarded. Allocation was unsuccessful for 11 additional organs (1 liver, 4 kidneys, 4 hearts, 2 lungs). Despite the obstacles, organ donation remained an important model of collaboration and satisfaction for the health care community in the pandemic's US epicenter. Declining COVID‐19 deaths led to the resumption of the comprehensive referral policy on May 6, 2020, with improvement to 18 donors in May.

A Low-Cost Perfusate Alternative for Ex Vivo Lung Perfusion

BackgroundNormothermic ex vivo lung perfusion (EVLP) has been used successfully to evaluate and recondition marginal donor lungs; however, multiple barriers continue to prevent its widespread adoption. We sought to develop a common hospital ingredient-derived perfusate (CHIP) with equivalent functional and inflammatory characteristics to a standard Krebs–Henseleit buffer with 8% serum albumin-derived perfusate (KHB-Alb) to improve access and reduce costs of ex vivo organ perfusion. MethodsSixteen porcine lungs were perfused using negative pressure ventilation (NPV) EVLP for 12 hours in a normothermic state and were allocated equally to 2 groups: KHB-Alb vs CHIP. Physiological parameters, cytokine profiles, and edema formation were compared between treatment groups. ResultsPerfused lungs in both groups demonstrated equivalent oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen ratio >350 mm Hg) and physiological parameters. There was equivalent generation of tumor necrosis factor-α and IL-6, irrespective of perfusate solution used, when comparing CHIP vs KHB-Alb. Pig lungs developed equivalent edema formation between groups (CHIP: 15.8 ± 4.8%, KHB-Alb 19.5 ± 4.4%, P > .05). ConclusionA perfusate derived of common hospital ingredients provides equivalent results to a standard Krebs–Henseleit buffer with 8% serum albumin-based perfusate in NPV-EVLP.

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.

Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P=.009), decreased expression of injury biomarker NGAL (P=.012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P=.019, medulla P=.001), downregulation of interleukin (IL)-1β (P=.050), and upregulation of IL-10 (P<.047) and Indolamine-2, 3-dioxygenase (P=.050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P<.001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

P1648CLINICAL OUTCOMES OF LIVING DONOR KIDNEY TRANSPLANTATION FROM MARGINAL DONORS

Abstract Background and Aims Evidence demonstrating the outcomes of living donor kidney transplantation (LDKT) from marginal donors (MDs) is limited. We retrospectively investigated the clinical outcomes of LDKT from MDs in both recipients and donors. Method Clinical data on patients who received LDKT in Jichi Medical University Hospital between 2006 and 2019 were extracted from the medical records. Based on the Japanese guideline for preoperative conditions of donors, they were classified as standard donors (SDs) or MDs, the latter including the elderly and patients with obesity, hypertension, diabetes mellitus, and reduced renal function. Multivariate Cox proportional hazard regression analysis for graft survival was performed using explanatory variables of the donor conditions (MD vs SD) and recipient conditions, including age, gender, duration of dialysis, ABO compatibility, and presence of donor specific antibodies. The estimated glomerular filtration rates (eGFRs) of the donors were compared using an unpaired t-test. Results Of the 293 donors, 195 were SDs and 98 were MDs. Demographics and baseline characteristics of recipients and donors Recipients of kidney transplants from MDs were associated with a higher incidence of death-censored graft loss than recipients of kidney transplants from SDs. Kaplan-Meier plots for overall and death-censored graft survival. Multivariate Cox proportional hazard regression analyses for overall and death-censored graft survival The eGFRs of MDs before transplantation were significantly lower than those of SDs, while no significant differences were observed between the two groups 3- and 5-years after transplantation. Comparison of estimated glomerular filtration rates of donors Conclusion While the renal prognosis of recipients of kidneys from MDs is poorer than that of recipients from SDs, donating a kidney has no adverse effects on the renal health of MDs. The present study is the most comprehensive study that examined that the outcomes of LDKT from MDs according to the Japanese guideline.

P1629THE COMBINATION OF KDRI AND THE HISTOLOGICAL SCORE IMPROVES THE RISK STRATIFICATION OF MARGINAL ORGANS IN KIDNEY TRANSPLANTATION

Abstract Background and Aims The organ shortage has led to increase the procurement of kidneys from marginal donors, but the risk of graft failure is still object of debate. The aim of the study is to assess whether using both clinical and histological scores can better assess the risk for worse outcome for marginal organs. Method We analyzed 210 kidney transplant recipients from donors aged &amp;gt;50 years. We retrospectively calculated the Kidney Donor Risk Index (KDRI) for each donor and we divided the population according to the KDRI (-, if KDRI ≤ median; +, if KDRI &amp;gt; median) and the histological score (HS, -, if HS ≤ 3; +, if HS &amp;gt; 3) in 4 groups: KDRI-HS- (low KDRI and HS), KDRI-HS+ (low KDRI and high HS), KDRI+HS-(high KDRI and low HS) and KDRI+HS+ (high KDRI and HS). We compared graft function between groups at 2 years and Cox regression analysis was performed to assess the risk for end stage renal disease (ESRD) between groups. Results Overall, median KDRI was 1.44 (1.25-1.65), while mean total HS was 3.04±1.62. Median follow-up was 51.9 (26.4 – 99.4) months. Graft function at 2 years was significantly worse in groups with high KDRI (KDRI+HS- and KDRI+HS+) compared to those with low KDRI (p&amp;lt;0.001), while no differences were found according to the HS. By contrast, the best ROC curve in predicting the development of ESRD is for the model that included both KDRI and histological score (AUC 0.81, 95%CI 0.708-0.914, p&amp;lt;0.001). A Cox model adjusted for recipient age, gender, acute rejection, DGF and chronic allograft dysfunction, patients with high KDRI and high HS are more likely to develop ESRD compared to the other groups (OR 5.6, 95%CI 1.3 to 24.5, p=0.02)(Figure 1). Conclusion Patients with high KDRI and HS have worse outcome compared to patients with high KDRI but better histology. The integration of histology to clinical score may improve the assessment of the risk for graft failure in patients receiving organs from marginal donors.

P1684MULTI-NATIONAL SURVEY AMONG NEPHROLOGISTS AND TRANSPLANT SURGEONS ABOUT THE SUITABILITY AND ACCEPTANCE OF MARGINAL LIVE KIDNEY DONORS WITH HEAVY SMOKING OR INTERMITTENT DRUG ABUSE

Abstract Background and Aims Potential kidney donors who actively smoke heavily or had intermittent illegal drug use (IIDU) are mostly excluded from donating a kidney. Tobacco use in kidney donor has been linked to worse outcomes for donors and while less evidence exists for IIDU as they mostly excluded from donation. We conducted a short survey about the suitability of these marginal living kidney donors. The purpose of this survey is to form a consensus on live kidney donor with using smoking or illegal drugs. Method This is a cross-sectional survey of nephrologists and transplant surgeons about suitability and acceptance of marginal live kidney donors. We asked physicians about accepting kidney donors who are actively smoking or using illegal drugs. The survey was mainly distributed through AST and ERA-EDTA. The role of these organization is limited to facilitate the distribution of the survey as an external study. We excluded in-training nephrologists or transplant surgeons. Results One hundred twenty-two physicians from 22 countries (80% nephrologists and 20% transplant surgeons (TS)) participated in the survey. Most physicians were experienced in pre-transplant evaluation (72% over 6 years’ experience and 68.5% of responders perform donors’ evaluation on weekly or monthly bases). Interestingly, most physicians would allow donation in active smoker with advice to quit later (56.2%) (62% of nephrologists versus only 29% of TS (p=0.002). TS would decline active smoker patients than nephrologists (42% versus 25%, p=0.09). Less physicians considered donors with IDU (after psychiatric counselling) than active smoking (30% versus 56.2%, p=0.00003). There was no difference in acceptance rate for donors with IIDU between TS and nephrologists (33.3% versus 29% respectively, p=NS) or in declining these donors (37.5% versus 45.3%, p=0.4). TS would accept more active smokers to donate if no alternative donor available than nephrologists (29.2% vs. 12.3%, p=0.04) but not IDU (29.2% vs. 25.8%, p=ns). Conclusion Active heavy smoking and intermittent illegal drug use are not viewed as solo contraindications for kidney donation by most physicians. Nephrologists and TS did not differ in attitude regarding donors with IIDU. Nephrologist seems more confident to accept donors who are actively smoking with advice to quit afterward while TS would accept them more if no alternative donor available or would decline them completely.