Slow Graft Function Research Articles

Impact of Post-Transplantation Hypomagnesemia on Long-Term Graft and Patient Survival after Transplantation

Background: Post-transplant hypomagnesemia is commonly observed among patients prescribed calcineurin inhibitor (CNIs). Methods: We conducted a retrospective single-center analysis (2000–2013, N = 726) to examine the association of hypomagnesemia with long-term patient and allograft outcomes in kidney transplant recipients. A median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year posttransplant was calculated. Results: For every increase in Mg of 0.1 mg/dL, the risk for either graft loss or death, overall mortality, and death with a functioning graft increased by 11%, 14%, and 12%, respectively (p < 0.01). In a multivariate model, patients with median Mg level ≥1.7 mg/dL had a reduced overall survival rate (HR 1.57, 95% CI: 1.04–2.38, p = 0.033) compared to those with median Mg level <1.7 mg/dL. This association was observed in subgroups of patients above 60 years old, in those who had a slow graft function (SGF) and in females. Conclusions: Posttransplant hypomagnesemia is associated with better patient and allograft survival up to 10 years posttransplant. This relationship remained significant after accounting for baseline allograft function, presence of SGF and CNI trough levels.

Creatinine reduction ratio on postoperative day 2 predicts long-term outcomes after living donor kidney transplantation.

To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post-transplantation clinical outcomes after living donor kidney transplantation. Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 - Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log-rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection-free survival, and the unpaired t-test and multivariate linear regression to assess post-transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor-specific antibody positivity and medically complex living donors as explanatory variables. Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death-censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post-transplantation did not differ within the groups. Post-transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant. The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long-term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.

Clinical significance of delayed or slow graft function in kidney transplantation recipients

Clinical significance of delayed or slow graft function in kidney transplantation recipients

Impact of SIRPα polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation.

Signal-regulatory protein α (SIRPα), a polymorphic inhibitory membrane-bound receptor, and its ligand CD47 have recently been implicated in the modulation of innate immune allorecognition in murine models. Here, we investigate the potential impact of SIRPα donor-recipient mismatches on graft outcomes in human kidney transplantation. To eliminate the specific role of HLA-matching in alloresponse, we genotyped the two most common variants of SIRPα in a cohort of 55 HLA-identical, biologically-related, donor-recipient pairs. 69% of pairs were SIRPα identical. No significant differences were found between donor-recipient SIRPα-mismatch status and T cell-mediated rejection/borderline changes (25.8%vs. 25%) or slow graft function (15.8%vs. 17.6%). A trend towards more graft failure (GF) (23.5%vs. 5.3%, P=.06), interstitial inflammation (50%vs. 23%, P=.06) and significant changes in peritubular capillaritis (ptc) (25%vs. 0%, P=.02) were observed in the SIRPα-mismatched group. Unexpectedly, graft-versus-host (GVH) SIRPα-mismatched pairs exhibited higher rates of GF and tubulitis (38%vs. 5%, P=.031 and .61 ± .88vs. 0, P=.019; respectively). Whether the higher prevalence of ptc in SIRPα-mismatched recipients and the higher rates of GF in GVH SIRPα-mismatched pairs represent a potential role for SIRPα in linking innate immunity and alloimmune rejection requires further investigation in larger cohorts.

ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study

We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function. We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF. The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P=.02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P=.006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation. ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months.

POS-770 “SLOW AND STEADY MAY NOT ALWAY WIN THE RACE “ –SHORT TERM OUTCOMES OF SLOW GRAFT FUNCTION POST RENAL TRANSPLANT - A SINGLE CENTRE EXPERIENCE

It is well established that delayed graft function (DGF), traditionally defined as the requirement of dialysis within the first week of transplant, is associated with poorer graft outcomes as compared to immediate graft function (IGF). A subset of patients do not have immediate graft function, but rather have a slower decrease in serum creatinine, not requiring dialysis, termed as slow graft function. Outcomes of this group of patients have not often been studied and most studies have classified this group of patients as having Immediate graft function (IGF) for comparison with patients with DGF. Our aim was to assess short term outcomes of these patients with slow graft function and to identify risk factors, if any among the cohort. Study setting: Kasturba Medical College, Manipal, a tertiary care centre in South India providing healthcare services to a predominantly rural population Type of study: Retrospective, ObservationalStudy Period: January 2016 to April 2018 Sample Size: 70 Renal allograft recipients Slow graft function was defined as per previous studies as follows 1)Creatinine > 3 mg/dl at Post-op day 5 or > 2.5mg/dl at day 72)Creatinine >1.5 and creatinine reduction ratio (CRR) < 20% between Post-op day 1 and post-op day 3Patients with DGF were not included in this study. Demographics related to recipient and donor, biopsy-proven acute rejections, short term outcomes in terms of graft function(serum creatinine and eGFR) at 1 year and 2 years follow up were documented and analysed. The transplants were predominantly living donor ( 88.6% ) and ABO compatible ( 97.1%) with a median follow up of 30 months (IQR 25-40) . 27 out of 70 transplanted patients (38.6%) were characterized as having slow graft function (SGF) as per the definitions and criteria used from earlier studies (Table 1: Baseline characteristics) . On univariate analysis, patients with SGF had lower GFR at 1 year (p-value – 0.028), higher number of biopsy-proven acute rejections over the median follow up period ( 48.1% versus 25.5 %; p-value – 0.039). The number of transplant patients with graft dysfunction at 1 year ( eGFR <60 ml/min) and 2 years were also statistically significant (Table 2: Univariate Analysis). Donor age and donor GFR ( measured by DTPA) were not significantly associated with SGF though numerically median donor age was higher and donor GFR was lower. The subset of patients with SGF may have adverse short term outcomes as compared to those with immediate graft function. A higher incidence of biopsy-proven rejection and higher number of patients with graft dysfunction at 2 years was seen in this cohort. Long term outcomes assessment and identification of risk factors leading to SGF needs to be studied and may help to better risk stratify and manage these patients for better outcomes.

Complex Surgical Reconstruction of Upper Pole Artery in Living-Donor Kidney Transplantation.

BackgroundThe use of allografts with multiple renal arteries has increased in the era of laparoscopic donor nephrectomy. Although several studies recommend reconstructing lower pole arteries (LPAs) to reduce risk of urologic complications, it is common opinion to ligate upper pole arteries (UPAs) with a diameter less than 2 mm because of increased risk of thrombosis related to their reconstruction. This retrospective study evaluates the feasibility and safety of reconstructing thin UPAs during living-donor kidney transplantation, with the goal of maintaining the integrity of the graft and assuring its maximal function.Material/MethodsData from 922 living-donor kidney transplants performed between 2009 and 2019 were reviewed. Six cases with UPAs were identified (0.65%). The study endpoints were incidence of allograft vascular and urologic complications, slow graft function, delayed graft function, graft failure, and graft and patient survival.ResultsThe UPAs had a mean diameter of 1.8±0.28 mm. Methods of reconstruction included: interposition graft (n=2), end-to-side anastomosis inside the renal hilum to a branch of the main renal artery (n=3), and side-to-side anastomosis with the main renal artery (n=1). Additional reconstruction of LPAs (n=2) and main renal arteries (n=2) was performed. During a median (range) follow-up of 14.5 (9–49) months no complications were observed.ConclusionsEx vivo reconstruction of UPAs with a diameter less than 2 mm is worth attempting, particularly in the setting of living-donor kidney transplantation.

Outcome of Kidney Transplantation With Transumbilical Laparoendoscopic Single-Site Donor Nephrectomy: A Single-Center Experience

AimThe aim of this study is to present the outcome of kidney transplantation after laparoendoscopic single-site donor nephrectomy (LESS DN) compared with conventional laparoscopic donor nephrectomy (LDN) in a single-center experience. MethodsThis retrospective study compares data from the initial experience with 110 consecutive LESS DN donors and their recipients (group A) with 205 consecutive conventional LDN donors and their recipients (group B). ResultsThis study compared 110 LESS DNs completed in an 18-month period with 205 LDNs completed in the immediately preceding 42-month period. All procedures were performed by the same surgeon. In groups A and B, respectively, the incidence of immediate graft function was 90% vs 91.2%, slow graft function was 9% vs 5.3%, delayed graft function was 0.9% vs 2.9%, graft loss was 0.9% vs 2.9%, and death with a functioning graft was 0.9% vs 1.5%. The mean serum creatinine levels were 1.3 ± 0.93 mg/dL vs 1.4 ± 1.2 mg/dL (P = .447), 1.1 ± 0.33 mg/dL vs 1.2 ± 0.75 mg/dL (P = .184), and 1.05 ± 0.25 mg/dL vs 1.1 ± 0.39 mg/dL (P = .224) at 7, 30, and 365 days after transplantation. The estimated glomerular filtration rate at 1 year was 88 ± 18.2 vs 83 ± 12.2 mL/min/1.73 m2 (P = .004). The mean donor operative times in groups A and B were 175.9 ± 24.9 minutes vs 199.88 ± 37.06 minutes (P = .0001), respectively, and the mean warm ischemia time was 5.2 ± 1.02 minutes vs 3.64 ± 1.38 minutes, respectively (P = .0001). The mean body mass index, the incidence of complex vascular anatomy, and the rate of complications were the same in the 2 donor groups. ConclusionsThe outcome of kidney transplantation after LESS DN is comparable to conventional LDN. LESS DN can be employed as the primary approach for kidney donation with low donor risk and without compromising recipient outcomes.

Plasma neutrophil gelatinase-associated lipocalin and Interleukin-18 as predictors of acute kidney injury in renal transplant recipients: A pilot study.

Urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL- 18) have shown promise for predicting renal graft recovery. However, urinary flow rate variations may cause variable biomarker dilution. Plasma NGAL and IL-18 may form a biomarker panel that may help predict delayed graft function and slow graft function (SGF) in renal transplant recipients within the first two postoperative days earlier than serum creatinine. There are only a few studies in the literature using plasma NGAL for predicting renal graft recovery. Hence, we planned this study. This observational single-center, prospective cohort study was conducted in renal transplant recipients above 18 years of age. In 22 consecutive renal transplant recipients, we collected ethylenediaminetetraacetic acid-plasma samples 1 h before surgery and subsequently at 6 h, 24 h, and 48 h after surgery for NGAL and IL-18 by sandwich enzyme-linked immuno-sorbent assay technique. Serum creatinine was measured as a part of routine transplant protocol. In renal transplant recipients, neither serum levels of NGAL and IL-18 nor their trends could reliably predict SGF. The only significant correlation existed between serum creatinine at day 2 and IL-18 at day 2 with P = 0.023. Serum NGAL did not correlate with serum creatinine in this setting of renal transplantation. Patients with immediate graft function had a greater percentage decrease of creatinine at day 1 and day 2 (P = 0.002 and 0.001) The percentage change in IL-18 at 24 h and 48 h after transplant from baseline could predict the occurrence of early graft loss (EGL) (P = 0.05, 0.04). The cutoffs were -4.12% at day 1 and +3.39% at day 2 with area under receiver operator characteristics of 0.82 and 0.83, respectively. The percentage change in IL-18 may be a useful marker of EGL in renal transplant recipients. Serum NGAL and creatinine were not able to predict EGL.

Kinetic GFR Outperforms CKD-EPI for Slow Graft Function Prediction in the Immediate Postoperative Period Following Kidney Transplantation.

Background: Rapid identification of patients at high risk for slow graft function (SGF) is of major importance in the immediate period following renal graft transplantation, both for early therapeutic decisions and long-term prognosis. Due to the high variability of serum creatinine levels after surgery, glomerular filtration rate (GFR) estimation is challenging. In this situation, kinetic estimated GFR (KeGFR) equations are interesting tools but have never been assessed for the identification of SGF patients. Methods: We conducted a single-center retrospective cohort study, including all consecutive kidney allograft recipients in the University Hospitals of Geneva from 2008 to 2016. GFR was estimated using both CKD-EPI and KeGFR formulae. Their accuracies for SGF prediction were compared. Patients were followed up for one year after transplantation. Results: A total of 326 kidney recipients were analyzed. SGF occurred in 76 (23%) patients. KeGFR estimation stabilized from the day following kidney transplantation, more rapidly than CKD-EPI. Discrimination ability for SGF prediction was better for KeGFR than CKD-EPI (AUC 0.82 and 0.66, p < 0.001, respectively). Conclusion: KeGFR computed from the first day after renal transplantation was able to predict SGF with good discrimination, outperforming CKD-EPI estimation. SGF patients had lower renal graft function overall at the one-year follow up.

Early persistent hyperparathyroidism post-renal transplantation as a predictor of worse graft function and mortality after transplantation.

Persistent hyperparathyroidism (pHPT) is frequently seen after transplantation contributing to post-transplant complications. We conducted a retrospective single center analysis to explore the relationship of early pHPT and long-term allograft outcome. Patients were divided into high (N=153) and low (N=252) PTH groups based on serum parathyroid hormone (PTH) level 3months post-transplant (PTH≥150 and<150pg/mL, respectively). High PTH was found to be an independent predictor for reduced kidney allograft function up to 3years post-transplant. eGFR decreased by 11.4mL/min (P<.001) and the odds of having an eGFR<60mL/min 3years post-transplant were sixfold higher (P<.01) in the high compared to the low PTH group. Subgroup analysis based on eGFR 1year post-transplant, presence of slow graft function (SGF), and transplant type revealed similar results. High PTH three months post-transplant was also independently associated with an increased risk for overall mortality and for death with a functioning graft (P<.05). pHPT three months post-renal transplantation is an independent predictor for a worse allograft function up to 3years post-transplant and a risk factor for mortality. This relationship remains statistically significant after accounting for baseline allograft function, presence of SGF and serum mineral levels abnormalities.

Protein and calorie restriction may improve outcomes in living kidney donors and kidney transplant recipients.

Previously, we and others showed that dietary restriction protects against renal ischemia-reperfusion injury in animals. However, clinical translation of preoperative diets is scarce, and in the setting of kidney transplantation these data are lacking. In this pilot study, we investigated the effects of five days of a preoperative protein and caloric dietary restriction (PCR) diet in living kidney donors on the perioperative effects in donors, recipients and transplanted kidneys. Thirty-five kidney donors were randomized into either the PCR, 30% calorie and 80% protein reduction, or control group without restrictions. Adherence to the diet and kidney function in donors and their kidney recipients were analyzed. Perioperative kidney biopsies were taken in a selected group of transplanted kidneys for gene expression analysis. All donors adhered to the diet. From postoperative day 2 up until month 1, kidney function of donors was significantly better in the PCR-group. PCR-donor kidney recipients showed significantly improved kidney function and lower incidence of slow graft function and acute rejection. PCR inhibited cellular immune response pathways and activated stress-resistance signaling. These observations are the first to show that preoperative dietary restriction induces postoperative recovery benefits in humans and may be beneficial in clinical settings involving ischemia-reperfusion injury.

Early graft function and intrarenal resistant index after kidney transplantation using Biolasol-A new solid organ preservation fluid.

Biolasol is a newly developed preserving solution for cold organ storage prior to transplantation. To date, only animal model experiments results are available. The aim of this single-center analysis was to summarize the clinical experience concerning the early post-transplant course of kidney grafts preserved with Biolasol in comparison with other preservation solutions. Before transplantation, 173 kidney grafts were preserved using Biolasol and 240 organs with other solutions (University of Wisconsin-UW, Institute Georges Lopez-IGL-1, or StoreProtect Plus solutions). Early graft function was defined based on serum creatinine concentration at day 3 (<3mg/dL-immediate graft function, IGF or >3mg/dL-slow graft function, SGF) or the need of dialysis therapy during first post-operative week (delayed graft function, DGF). The analysis included intrarenal resistive indices measured by Doppler sonography early after transplantation and before discharge from the hospital. IGF was more frequent in patients with organs preserved with IGL-1 (33.5%) and StoreProtect Plus (38.8%) than Biolasol (18.5%), whereas there was no difference in the occurrence of DGF. Both initial and discharge median resistance index values were significantly higher in the Biolasol subgroup (0.77 and 0.75) than in all three other subgroups (P values for all comparisons <.001), also after 1:1 propensity score matching for baseline characteristics. Multiple logistic regression analysis based on the propensity score-matched cohort revealed that the use of Biolasol solution [OR 0.59 (0.35-0.98); P<.05] independently decreased the occurrence of IGF. In our single-center clinical experience, kidney preservation using Biolasol solution was associated with significantly higher intrarenal resistant index in comparison with other preservation fluids, as well as worse early graft function than in the IGL-1 and the StoreProtect Plus subgroups. Long-term follow-up is needed in order to assess the kidney graft and patient survival.

P1671CHALLENGES AND OUTCOMES OF A KIDNEY TRANSPLANT PROGRAM IN LOW INCOME SETTINGS - THE EXPERIENCE OF THE REPUBLIC OF MOLDOVA

Abstract Background and Aims During the last decade, the development of kidney transplantation in the Republic of Moldova took a new course due to the adoption of the new transplantation law, and was strongly marked by the first transplant from a brain death donor. The implementation of a transparent organ allocation policy, the development of donation after brain death and the upgrade of the transplant infrastructure, based on European good practices, are the strengths of the new program. Method Since 2014, all the kidney grafts from deceased donors have been allocated based on the electronic allocation system (Renal Score), which includes the following variables: compatibility in ABO and HLA systems, dialysis vintage, time on waiting list, renal graft accessibility score, age difference between recipient and donor. All the living donors were evaluated based on a National Protocol. This is a retrospective analysis of the kidney transplant program during a period of five years, focused on recipient and donor demographics, donor-recipient matching, medical outcomes. Results During 2014-2018, there were performed 75 kidney transplantations: 23 (30,7%) from living donors and 52 (69,3 %) from brain-death donors. Among the kidney transplant recipients, there were 24 women (32,4%) and 50 men (67.6%). From 23 living kidney donors there were 10 (43,5%) males and 13 (56,5%) females, 21 (91,3%) were related donors and 2 (8,7%) emotionally related. The mean age of living donors was 50,45, ranging from 23 to 67, with 6 donors (20,1%) older than 60 years old. During this period, from 110 evaluated potential brain death donors 48 (43,6%) became effective brain-death donors and kidneys were procured in 36 (75%) cases (from 15 men (41,7%) and 21 women (58,3%)). The mean recipients age was 41,13, ranging from 23 to 67, while the mean donor age was 54,72, ranging from 19 to 72 years old. 18 donors (50%) were older than 60, the mean age of male donors were 49,4 and 59,14 for female donors. The mean donor-recipient age difference was 17,09 years (min- 0, max- 40). The mean cold ischemia time was 17,31 hours, with a minimum of 6,33 hours and a maximum of 25,8 hours. The majority of donors were blood type 0- 14 (38.8%) and A-13 (36,1%) and only 6 donors (16.6%) blood type B and 3 (8.3%) type AB. Regarding the outcomes, we noticed a rate of delayed graft function in 43,6% cases, 2,6% of slow graft function and 53,9% recipients with immediate graft function Conclusion Despite social and economic challenges in our country, the joint efforts of the kidney transplant team, the Transplant Agency and the government support ensure a growing kidney transplant program. The strengths of our program are the good legal framework and the respect for the main ethical and medical principals: transparency and traceability, ensured by the informational platform, equity and utility ensured by the use of the automated allocation system, accessibility ensured by the fool coverage of transplant related services by the public health insurance. We still face many challenges, as the high rate of marginal donors compared to younger recipients and donor-recipient age disparities, a long cold ischemia time and a sub-optimal organ discard rate, which is mainly due to the shortage of transplant professionals, the direct effect of the migration of health care personnel. Our next goal is to identify and to improve the factors impacting on kidney graft outcomes in order to achieve better results.

P1728FUROSEMIDE STRESS TEST PREDICTS DISCHARGE SERUM CREATININE AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Acute tubular necrosis is a common complication after kidney transplantation and is closely related to delayed graft function (DGF) and slower graft function recovery after surgery. The furosemide stress test (FST) uses a standardized dose of furosemide to evaluate the integrity of the renal tubule and determine which patients have developed severe tubular damage. We aimed to apply the FST to a sample of incident deceased-donor kidney transplant recipients and describe its association with DGF and serum creatinine (SCr) at discharge. Method Single-center prospective observational study of deceased-donor kidney transplant recipients. The FST, a standardized bolus dose of furosemide (1.5 mg/kg) was administered between the 3rd and 5th day after surgery. Patients were excluded if, during that time period, they presented evidence of active bleeding, obstructive uropathy or volume depletion. Urine output (UO) 60 and 120 min after FST was registered. To reduce the risk of hypovolemia, each ml of UO produced for six hours after FST was replaced with 1 ml of normal saline. Results 25 patients were included in the study. Mean 2h FST UO was 1012±570 ml. Demographic and clinical data are summarized in Table 1. Subjects that suffered DGF had a significantly lower 2h FST UO (534 vs 1164 ml; P=0.015). In adjusted linear regression analysis only a 2h FST UO&amp;lt;1000 ml (β=0.906; 95%CI: 0.04-1.772; P=0.041) and DGF (β=1.592; 95%CI: 0.488-2.696; P=0.008) were independent predictors of SCr at discharge (model adjusted for recipient age, cold ischemia time, number of HLA mismatches, donor SCr and donor hypertension). Conclusion Recipients with a 2h FST UO &amp;lt;1000 ml suffered DGF more frequently. FST and DGF were independent predictors of SCr at discharge. A standardized FST could help clinicians distinguish patients with more severe tubular dysfunction and higher risk of DGF.

Peri-transplant aminophylline in pediatric kidney transplant recipients of donation after brain death: a double-blinded placebo-controlled randomized clinical trial

During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF). Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels. Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9ml/min/1.73m2 vs. 80.48 ± 52.1ml/min/1.73m2p = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5ng/mg IQR 105.5-1464.5ng/mg vs. 425.4ng/mg IQR 140.3-1126.2ng/mg, p = 0.95; respectively). At 12months, there was 100% patient survival and 98% graft survival. eGFR at 12months was similar between the two arms. There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.

Recombinant Human Erythropoietin for Kidney Transplantation: A Systematic Review and Meta-Analysis.

The protective effect of recombinant human erythropoietin (rHuEPO) on kidney transplantation has not been established. Therefore, we conducted a systematic review and meta-analysis to evaluate the potential influence of rHuEPO on transplanted kidneys. To identify relevant studies, we searched electronic databases (PubMed, Medline, EMBASE, Ovid, the Cochrane Library, and major nephrology journals) from inception until June 15, 2018. Two independent reviewers assessed study quality. The systematic review and meta-analysis were performed with fixed- or random-effects models according to heterogeneity, and results are expressed as risk ratios (RR) or weighted mean differences. Six randomized controlled trials with a total of 435 patients met the inclusion criteria. rHuEPO, compared with placebo, had no statistically significant effect on delayed graft function (RR = 0.89, 95% confidence interval [CI] , 0.73 to 1.07; P = 0.22) and slow graft function (RR = 0.93, 95% CI, 0.60 to 1.43; P = 0.73). The rHuEPO and control groups did not differ in thromboembolic events, mortality, acute rejection, and blood transfusion. A significant difference was found in long-term estimated glomerular filtration rate (RR = 3.65, 95% CI, -4.45 to 11.75; P = 0.003). Our findings suggests that rHuEPO has a limited nephroprotective effect in patients undergoing kidney transplantation and does not increase the susceptibility to adverse events.

MP52-02 INITIAL EXPERIENCE WITH RENAL TRANSPLANTS AFTER MEDICAL ASSISTANCE IN DYING: FIRST SERIES IN NORTH AMERICA

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II (MP52)1 Apr 2020MP52-02 INITIAL EXPERIENCE WITH RENAL TRANSPLANTS AFTER MEDICAL ASSISTANCE IN DYING: FIRST SERIES IN NORTH AMERICA Samir Sami*, Max Levine, Andrew Rasmussen, Alp Sener, and Patrick Luke Samir Sami*Samir Sami* More articles by this author , Max LevineMax Levine More articles by this author , Andrew RasmussenAndrew Rasmussen More articles by this author , Alp SenerAlp Sener More articles by this author , and Patrick LukePatrick Luke More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000914.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In 2016, Canadian federal legislation was passed creating a regulatory framework for medical assistance in dying (MAiD) for individuals who were suffering from a medically futile condition and foreseeable death. As there is a paucity of literature on transplantation from MAiD donors, we report our unique experience and first reported outcomes in North America. METHODS: We retrospectively analyzed all renal transplant recipients from MAiD donors at London Health Sciences Centre, beginning in 2018. Patients eligible for MAiD underwent circulatory death after administration of life ending therapy and organ procurement was performed as per standard protocol. Ethics approval was obtained to review these outcomes. RESULTS: There were a total of 4 patients who became kidney donors and one kidney-pancreas donor. The indication for MAiD in the donors included 3 with debilitating neurological disease, 1 with heart failure and 1 who previously suffered a significant fall resulting in quadriplegia. Mean donor age was 53.66 ±13.17, median warm ischemia time (WIT) was 17 minutes, and median cold ischemia time (CIT) was 9 hours. One perioperative death occurred due to medical complication unrelated to renal graft function. No delayed graft function was encountered and only two patients experienced slow graft function. Median 30 day creatinine was 108 μmol. CONCLUSIONS: MAiD associated organ donation represents a potential means to increase the donor pool for those awaiting deceased donor organs. The controlled nature of MAiD associated circulatory death has the potential to minimize the deleterious effects of prolonged WIT that may be associated with standard donation after circulatory death. Our institution’s early experience is encouraging, with low WIT, and favorable early graft function results. Ongoing assessment of MAiD outcomes is required to better quantify the quality of these donation opportunities compared to conventional deceased donors. Source of Funding: N/A © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e772-e772 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Samir Sami* More articles by this author Max Levine More articles by this author Andrew Rasmussen More articles by this author Alp Sener More articles by this author Patrick Luke More articles by this author Expand All Advertisement PDF downloadLoading ...

Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial

ContextThymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established. ObjectiveDemonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppression Design, Setting, ParticipantsProspective randomized study in kidney transplant patients (12/2016-05/2018). Inclusion criteria: Recipients > 18 years, first living donor transplant. Exclusion criteria: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm3, platelets < 75,000 cells/mm3 and malignancy. InterventionGroup A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids. Main Outcome MeasuresBiopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months. Results100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns). ConclusionLow-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.

Posttransplantation Hypomagnesemia as a Predictor of Better Graft Function after Transplantation

Background: Hypomagnesemia is frequently seen after transplantation and is particularly associated with the use of calcineurin inhibitors (CNIs). Methods: We conducted a retrospective, single-center analysis (2000–2013, N = 726) to explore the relationship between hypomagnesemia and long-term allograft outcome in kidney transplant recipients. For this study, a median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year after renal transplantation was calculated. Results: For every increase in Mg by 0.1 mg/dL, the GFR decreased by 1.1 mL/min at 3 years posttransplant (p < 0.01) and by 1.5 mL/min at 5 years posttransplant. A median blood Mg level of ≥1.7 was found to be an independent predictor of a GFR <60 mL/min at 3 years posttransplant. The odds of having a GFR <60 mL/min 3 years posttransplant was almost 2-fold higher in the high Mg group than in the low Mg group. Conclusions: Hypomagnesemia from 1 to 12 months after renal transplantation is associated with a better allograft function up to 5 years posttransplant. This relationship was found to hold true after accounting for baseline allograft function and the presence of slow graft function.