Long-Term Graft and Patient Survival After Re-Transplantation.

BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.

The association between hydrochlorothiazide use and non-melanoma skin cancer in kidney transplant recipients.

Background: hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of non-melanoma skin cancer (NMSC) and melanoma in the general population. Information is a scarce regarding this effect in kidney transplant recipients who are at increased risk of skin malignancies under immunosuppression. Methods: Single-center retrospective analysis of adult kidney transplant recipients between 1 January 2010 and 31 December 2015. The primary outcome of the study was the first diagnosis of skin cancer that was removed and pathologically analyzed. Exposure to thiazides was defined as HCTZ use daily for at least one year at a dose of 12.5 mg. Results: Among 520 kidney transplant recipients, 50 (9.4%) were treated with HCTZ. During a median follow-up of 9.8 years, 67 patients underwent surgical removal and pathological analysis of at least one skin cancer. Exposure to HCTZ during the 3 years following transplantation was associated with an increased risk of skin cancer (P = 0.004). In a multivariate model, there was a significant association between HCTZ exposure and NMSC (HR 2.54, 95%CI 1.26-5.15, P = 0.007). There was a higher rate of basal cell carcinoma with HCTZ exposure, according to both univariate and multivariate analyses (HR 2.61, 95%CI 1.06-6.43, P = 0.037) and (HR 3.03, 95%CI 1.22-7.55, P = 0.017, respectively). However, no significant association was observed between HCTZ exposure and squamous cell carcinoma. Conclusions: These findings suggest a benefit of increased frequency of dermatologist inspection in kidney transplant recipients receiving HCTZ especially in increased ultraviolet exposure area.

Improvement in Echocardiographic Indexes of Systolic Heart Failure Post Kidney Transplantation - a retrospective analysis.

INTRODUCTION: End-stage renal disease (ESRD) is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered as contraindication for kidney transplant although some patients demonstrate myocardial recovery post-transplant. We aim to identify and characterize the phenomenon of reverse myocardial remodelling in kidney transplanted patients. METHODS: The study is a retrospective cohort of patients undergoing kidney transplant between 2016-2019 (n=604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. RESULTS: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal or above 5%, whereas 36 (12%) patients had a LVEF improvement 10% or more post transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5% and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. Conclusion Renal transplantation might lead to improved LV systolic function in some patients.

Semidirected Living Donors in Israel: Sociodemographic Profile, Religiosity, and Social Tolerance.

Living kidney donations in Israel come from 2 sources: family members and individuals who volunteer to donate their kidney to patients with whom they do not have personal acquaintance. We refer to the first group as directed living donors (DLDs) and the second as semidirected living donors (SDLDs). The incidence of SDLD in Israel is ∼60%, the highest in the world. We introduce results of a survey among 749 living donors (349 SDLDs and 400 DLDs). Our data illustrate the sociodemographic profile of the 2 groups and their answers to a series of questions regarding spirituality and social tolerance. We find SDLDs to be sectorial: they are mainly married middle-class religious men who reside in small communities. However, we found no significant difference between SDLDs and DLDs in their social tolerance. Both groups ranked high and expressed tolerance toward different social groups. Semidirected living donation enables donors to express general preferences as to the sociodemographic features of their respected recipients. This stirs a heated debate on the ethics of semidirected living donation. Our study discloses a comprehensive picture of the profile and attitudes of SDLDs in Israel, which adds valuable data to the ongoing debate on the legitimacy of semidirected living donation.

Multi-phasic eGFR trajectory during follow up and long-term graft failure after kidney transplantation.

BACKGROUND: The prevailing assumption is that following kidney transplantation the pattern of kidney function decline is consistent. Nevertheless, numerous factors leading to graft loss may emerge, altering the trajectory of kidney function. In this study, we aim to assess alterations in estimated glomerular filtration rate (eGFR) trajectory over an extended period of follow-up and examine its correlation with graft survival. METHODS: We calculated eGFR using all creatinine values available from 1-year post transplantation to the end of follow-up. For pattern analysis, we used a piecewise linear model. RESULTS: Nine hundred eighty-eight patients were included in the study. After a median follow-up of 5.2 years, 297 (30.1%) patients had a multi-phasic eGFR trajectory. Change in eGFR trajectory was associated with increased risk for graft failure (HR 7.15, 95% CI 5.17-9.89, p < .001), longer follow-up time, younger age, longer cold ischemia time, high prevalence of acute rejection, longer hospitalization and a lower initial eGFR. Of the 988 patients included in the study, 494 (50.0%) had a mono-phasic stable trajectory, 197 (19.9%) had a mono-phasic decreasing trajectory, 184 (18.6%) had bi-phasic decreasing trajectory (initial stability and then decline, 46(4.7%) had a bi-phasic stabilized (initial decline and then stabilization) and 67(6.8%) had a more complex trajectory (tri-phasic). Out of the total 144 patients who experienced graft loss, the predominant pattern was a bi-phasic decline characterized by a bi-linear trajectory (66 events, 45.8%). CONCLUSIONS: Changes in eGFR trajectory during long-term follow-up can serve as a valuable tool for assessing the underlying mechanisms contributing to graft loss.

Perinatal Outcomes after Liver Transplantation: Is There a Role for Aspirin Treatment?

BACKGROUND: We aimed to describe perinatal outcomes and evaluate aspirin treatment effects in liver-transplanted pregnant women. METHODS: A retrospective study examining perinatal outcomes in liver transplant recipients at a single center (2016-2022). The effect of low-dose aspirin treatment on the risk of developing hypertensive disease in these patients was evaluated. RESULTS: Fourteen deliveries in 11 pregnant liver transplant recipients were identified. Primary liver disease was Wilson's in 50% of pregnancies. The median age was 23 years at transplant and 30 at conception. Tacrolimus was administered in all, steroids in 10 (71.43%), and aspirin (100 mg daily) in 7 (50.0%). Overall, two women (14.28%) developed preeclampsia, and one (7.14%) developed gestational hypertension. Median gestational age at delivery was 37 weeks (31-39 weeks), with six preterm births (between 31-36 weeks) and a median birthweight of 3004 g(range 1450-4100 g). None of those receiving aspirin developed hypertensive disease or suffered excessive bleeding during pregnancy, compared to two (28.57%) with pre-eclampsia in the non-aspirin group. CONCLUSION: Liver-transplanted pregnant women comprise a unique and complex patient population with overall favorable pregnancy outcomes. Based on our single-center experience and due to its safety profile and potential benefit, we recommend low-dose aspirin in all liver transplanted patients during pregnancy for preeclampsia prevention. Further large prospective studies are needed to corroborate our findings.

Bariatric Surgery in Severely Obese Kidney Donors Before Kidney Transplantation: A Retrospective Study.

BACKGROUND: Bariatric surgery (BS) is the optimal approach for sustained weight loss and may alter donation candidacy in potential donors with obesity. We evaluated the long-term effects of nephrectomy after BS on metabolic profile, including body mass index, serum lipids and diabetes, and kidney function of donors. METHODS: This was a single-center retrospective study. Live kidney donors who underwent BS before nephrectomy were matched for age, gender, and body mass index with patients who underwent BS alone and with donors who underwent nephrectomy alone. Estimated glomerular filtration rate (eGFR) was calculated according to Chronic Kidney Disease Epidemiology Collaboration and adjusted to individual body surface area to create absolute eGFR. RESULTS: Twenty-three patients who underwent BS before kidney donation were matched to 46 controls who underwent BS alone. At the last follow-up, the study group showed significantly worse lipid profile with low-density lipoprotein of 115 ± 25 mg/dL versus the control group with low-density lipoprotein of 99 ± 29 mg/dL ( P = 0.036) and mean total cholesterol of 191 ± 32 versus 174 ± 33 mg/dL ( P = 0.046). The second control group of matched nonobese kidney donors (n = 72) had similar serum creatinine, eGFR, and absolute eGFR as the study group before nephrectomy and 1 y after the procedure. At the end of follow-up, the study group had significantly higher absolute eGFR compared with the control group (86 ± 21 versus 76 ± 18 mL/min; P = 0.02) and similar serum creatinine and eGFR. CONCLUSIONS: BS before live kidney donation is a safe procedure that could increase the donor pool and improve their health in the long run. Donors should be encouraged to maintain their weight and avoid adverse lipid profile and hyperfiltration.

Effect of Age on Liver Transplantation Recipient Outcomes: Two Centers' Experience.

BACKGROUND: Liver diseases epidemiology has changed with advances in perioperative care. Transplantation at large centers is favorable among older and younger recipients. Local limitations on transplantation for recipients older than 65 years were cancelled in 2014. This study evaluates the effects of age on the transplantation outcome of Israeli patients in the era after removal of the limitations on recipient age. METHODS: This retrospective analysis examined prospective data on patients older than 18 years who underwent liver or liver-kidney transplantation between 2014 and 2019 at 2 transplantation centers. Patients were divided into 4 age groups (group 1: ≤59 years; group 2: 60-64 years; group 3: 65-69 years; and group 4: ≥70 years). Each group's associations of pretransplantation factors with outcome and survival were examined. RESULTS: Two hundred sixty-one recipients underwent 269 transplantations (mean age: 53 ± 12.61 y). There were 181 male (67.8%) and 88 female recipients (67.28%). Overall, 207 patients (79.6%) survived ≥12 months. One-year survival rates were 82.9%, 73.2%, 71.4%, and 93.8% for groups 1 to 4, respectively (not statistically significant; P = .11). One-year graft survival was similar between groups. More patients with chronic obstructive pulmonary disease, diabetes mellitus, or ischemic heart disease tended to survive <12 months. Cardiovascular complication was more common in older groups and affected survival. CONCLUSION: Patient age alone should not be used to deny access to transplantation, which could benefit older nonfrail individuals. However, risk factors such as male sex, chronic obstructive pulmonary disease, ischemic heart disease, diabetes mellitus, and concomitant kidney-liver transplantation should be carefully considered.

Exposure to tacrolimus trough levels below 6 ng/ml during the first year is associated with inferior kidney graft survival.

BACKGROUND: Accumulating data indicate that sub-therapeutic levels of tacrolimus are associated with long-term kidney graft loss. However, elevated doses increase the risk of infection and drug toxicity, which also threaten graft and patient longevity. We sought to determine the minimal tacrolimus level required to maintain graft survival. METHODS: We conducted a single-center historical cohort study. The first-year post-transplant exposure time was calculated for each of the five tacrolimus trough level intervals. This measure was adjusted to the exposure time below a given interval level, allowing us to define the threshold for the optimal tacrolimus level as the upper limit of the interval. We then determined the association between the adjusted exposure time at each tacrolimus level interval and our primary outcome, death-censored graft loss. RESULTS: One thousand four hundred and seventeen patients with a median follow-up of 5.3 years were included in the final cohort. The tacrolimus level interval of 5-6 ng/ml was the highest interval, which demonstrated a statistically significant association between adjusted exposure time and increased risk of graft loss (HR 1.58, per log days, p = .002). Cumulative exposure time above 14 days with a tacrolimus level below 6 ng/ml was associated with an increased rate of graft loss in most studied subgroups, except for recipients with pre transplant diabetes. CONCLUSIONS: Maintaining tacrolimus levels above 6 ng/ml during the first-year post-transplant might improve kidney graft survival.

The Role of Early Sequential Biopsies in Delayed Renal Graft Function of Transplanted Kidney Is Reduced in Modern Immunosuppression Era.

BACKGROUND: Delayed graft function (DGF) immediately after kidney transplantation is considered a risk factor for acute rejection. According to clinical guidelines, a weekly allograft biopsy should be performed until DGF resolves. Based on clinical evidence, the first biopsy is considered appropriate. However, the recommendation for further biopsies is based on sparse evidence from era of earlier immunosuppression protocols, and the benefit of the second and further biopsies remains uncertain. The aim of this study was to reevaluate this policy. METHODS: The database of a transplant medical center was retrospectively reviewed for all patients who underwent kidney transplantation in 2011-2020. Those with DGF who performed two or more graft biopsies within the first 60 days after transplantation were identified. Clinical data were collected from the medical files. The rates of diagnosis of acute rejection at the second and subsequent biopsies were analyzed relative to the previous ones. RESULTS: Kidney transplantation was performed in 1,722 patients during the study period, of whom 225 (13.07%) underwent a total of 351 graft biopsies within 60 days after transplantation, mostly due to DGF. A second biopsy was performed in 32 patients (14.2%), and a third biopsy in 8, at weekly intervals. In 2 patients (6.25%), the diagnosis changed from the first biopsy (acute tubular necrosis or toxic damage) to acute rejection in the second biopsy. In both, the rejection was borderline. Third and fourth biopsies did not add information to the previous diagnosis. CONCLUSIONS: The common practice of performing sequential biopsies during a postoperative course of DGF seems to be of low benefit and should be considered on a case-by-case basis.

The prognostic value of pre-operative coronary evaluation in kidney transplanted patients.

Aims: Non-invasive coronary assessment using single-photon emission computerized tomography (SPECT) testing for potential cardiac ischemia is an essential part of the evaluation of kidney transplant candidates. We aimed to examine the prognostic value of preoperative SPECT test results in kidney transplanted patients. Methods and results: We retrospectively analyzed the pre-surgical nuclear SPECT test results in a registry of kidney transplanted patients. Follow-up at 1 month and 1 year recorded major adverse cardiac events (MACE) including non-fatal myocardial infarction, all-cause mortality and hospitalization due to cardiovascular disease following the renal transplantation. Of 577 patients available for analysis, 408 (70.9%) patients underwent nuclear SPECT test pre-transplant and 83 (20.3%) had abnormal results with either evidence of ischemia or infarct. A significantly higher incidence of post-operative MACE at 1 month was evident among patients with abnormal SPECT test compared to patients with no evidence of ischemia (10.8 vs. 4.3% respectively; P = 0.019). Differences were mostly derived from significantly increased rates of myocardial infarction events (8.4 vs. 1.8%; P = 0.002). Yet, MACE rate was not statistically different at 1 year (20.5 vs. 13.1%; P = 0.88). Importantly, the prognostic impact of an abnormal SPECT was significantly attenuated for all outcomes following multivariable adjusting for conventional cardiovascular risk factors and coronary revascularization. Conclusion: Pre-surgical cardiac risk assessment of kidney transplant candidates with nuclear SPECT test was found to be predictive of post-operative MACE, yet apparently, its prognostic value was significantly attenuated when adjusted for cardiac risk factors.

Gender specific survival rates after deceased donor liver transplantation: A retrospective cohort.

Background: According to the literature, there are sex allocation inequalities in liver transplantation (LT). Sex disparities in outcomes after LT have been debated. This study aimed to evaluate sex-specific outcomes after LT, specifically short-term mortality and long-term survival rates. Methods: A retrospective cohort of the entire LT series from to 2010-2019 in a single center in which the inclusion criteria were adults ≥18 YO age who underwent primary deceased donor LT. Mortality rate was evaluated within 30 days and 6 months. Survival rate was evaluated at 1,3 and 5 years of age. Results: A total of 240 primary and deceased donor LTs (153 men and 87 women) were included. Mean age 55.2Y men and 51.6Y women (p = 0.02). Hepatocellular carcinoma (HCC) was the direct indication in 32.7% of the men and only 17.4% of the women. The leading primary liver morbidities were viral hepatitis (B, C, and D) in 38.3% (N = 92) and nonalcoholic steatohepatitis (NASH) in 20.8% (N = 50) of patients. Thirty-day mortality was 14%, which was significantly higher in men (18%) than in women (8%). Survival rates after 5 years were 64.9% and 78.3%, respectively. Multivariate analysis through logistic regression that included age, direct indication, MELD, and primary liver morbidity revealed statistically significant female to male Odds-Ratio of 0.4 in 30 days, 6 m mortality and a statistically significant higher long-term survival. Conclusions: Our observations revealed better female outcomes, namely, lower short-term mortality and higher long-term survival. Given the consistency after stratification and given the multivariate analysis, this is unlikely to be attributable to confounders. Such findings suggesting consistently better female outcomes have not been previously reported; hence, multi center study is encouraged.

The Impact of Obesity and Associated Comorbidities on the Outcomes after Renal Transplantation with a Living Donor vs. Deceased Donor Grafts.

Background: Obesity among kidney transplant (KT) recipients can lead to metabolic comorbidity-associated deaths. This study compares post-KT survival between obese and non-obese patients and outcomes of living donor (LD) and deceased donor (DD) grafts. Methods: Between January 2005−May 2019, 1403 KT recipients from a single center were included in the study, as well as 314 patients (22.4%) with obesity (BMI > 30 kg/m2), 137 DD transplants, and 177 LD transplants. Of the 1089 (77.6%) in the control group (BMI ≤ 30 kg/m2), 384 were DD transplants and 705 LD transplants. The Kaplan−Meier method was used for survival analysis and a Cox regression was used to identify risk factors for graft loss and mortality. Propensity score matching analysis adjusting for age, IHD, and T2DM was performed. Results: The study group had higher incidence of obesity related comorbidities, delayed graft function and primary non function (p < 0.001). One-, 5-and 10-year patient and graft survival were lower in the study group (p < 0.001). Subgroup analysis of graft survival according to type of graft shows a difference in the DD (p = 0.002) but not in the LD group (p = 0.220). However, mortality was higher in both groups (LD, p = 0.045; DD, p = 0.004). Risk factors for mortality were age, T2DM, IHD, and DD, and for graft failure: IHD, BMI, donor age, re-transplant, and DD. Propensity score analysis shows an odds ratio of 0.81 for graft failure and 0.93 for death in the study group (95% CI = 0.55, 1.21, p = 0.3 and CI = 0.59, 1.46, p = 0.7, respectively). Conclusions: Recipient age and metabolic comorbidities should be emphasized when evaluating patients with obesity. We suggest considering weight loss interventions using the new GLP-1 inhibitors and bariatric procedures in selected patients to prepare overweight patients for transplant.

Short versus prolonged antibiotic treatment for complicated urinary tract infection after kidney transplantation.

There is no consensus regarding the optimal duration of antibiotic therapy for urinary tract infection (UTI) following kidney transplantation (KT). We performed a retrospective study comparing short (6-10 days) versus prolonged (11-21 days) antibiotic therapy for complicated UTI among KT recipients. Univariate and inverse probability treatment weighted (IPTW) adjusted multivariate analysis for composite primary outcome of all-cause mortality or readmissions within 30 days and relapsed UTI 180 days were performed. Overall, 214 KT recipients with complicated UTI were included; 115 short-course treatment (median 8, interquartile range [IQR] 6-9 days), 99 prolonged course (median 14, IQR 12-21 days). The composite outcome occurred in 33 (28.6%) in the short-course group and 30 (30%) in the prolonged-course group; relapsed UTI occurred in 19 (16.5%) vs. 21 (21%), respectively. Duration of antibiotic treatment was not associated with any of these outcomes. The only risk factor for mortality/readmissions in multivariate analysis was deceased donor. No differences between groups were demonstrated for length of hospital stay, rates of bacteraemia, resistance development, and serum creatinine at 30 and 90 days. In conclusion, we found no difference in clinical outcomes between KT recipients treated for complicated UTI with short-course antibiotic (6-10 days) versus longer course (11-21 days).

The Association Between Exposure to Low Magnesium Blood Levels After Renal Transplantation and Cardiovascular Morbidity and Mortality.

Background: Serum magnesium levels are associated with cardiovascular disease and all-cause mortality in the general population and chronic kidney disease patients, but the association between serum magnesium levels and cardiovascular risk after kidney transplantation is not established. We sought to evaluate whether exposure to low serum magnesium levels after renal transplantation is related to cardiovascular morbidity and mortality. Methods: We conducted a single center retrospective study that included all transplanted patients who had a functioning graft for at least 6 months after transplantation between January 2001 and December 2013. We calculated exposure to magnesium using time weighted average for serum magnesium levels, using all values available during the follow-up. Several statistical methods were used, including liner regression analysis, χ2 test, and multivariate Cox proportional hazard model. Results: Four hundred ninety-eight patients were included. Median follow-up was 5.26 years. High time weighted average of serum magnesium was associated with a hazard ratio of 1.94 for all-cause mortality and major cardiovascular outcome compared to low levels (95% CI 1.18-3.19, p = 0.009). The high quartile of time weighted average of serum magnesium was associated with death censored major cardiovascular outcome (hazard ratio 2.13, 95% CI 1.17-3.86, p = 0.013) in multivariate analysis. Conclusions: Exposure to low serum magnesium levels in renal transplant recipients was associated with a lower risk for all-cause mortality and major cardiovascular outcome. These findings contrast the higher risk found in the general population.

Early post-liver transplantation infections and their effect on long-term survival.

BACKGROUND: Infections post-liver transplantation are major drivers for morbidity and mortality. However, the impact of infections within 180 days post-liver transplantation on long-term survival is not clear. METHODS: We present a retrospective cohort of 317 liver transplant patients for whom all infectious episodes were prospectively collected during a mean follow-up of 4.4 years. RESULTS: A total of 143/317 (45%) of patients suffered from any infectious episode during the first 6 months following liver transplantation. Patients with surgical site infections have a reduced survival compared to those with no infection (HR 0.33, 95% CI 0.172-0.636, P = .001), whereas infections from other sources, including pneumonia, UTI, and line-related infections, were not associated with increased mortality. Furthermore, even though the presence of any infection within 30 days or 6 months post-transplantation did not affect survival, more than a single infectious episode per patient was significantly associated with increased mortality (HR 1.70, CI 1.12-2.60, P = .013). In a multivariate analysis, the number of infectious episodes remained statistically significant (HR 1.58, 95% CI 1.03-2.43, P = .035) upon adjustment for other major variables associated with comorbidities and infection risk. CONCLUSIONS: Surgical site infections and the number of infectious episodes within 180 days post-liver transplantation are major determinants of long-term survival among these patients.

Generation of vascular chimerism within donor organs.

Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study.

OBJECTIVES: We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. METHODS: This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. RESULTS: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m2, 95% confidence interval (CI) 1.014-1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782-3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015-1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146-3.443, p 0.014). No serious adverse events resulting from the vaccine were reported. CONCLUSIONS: Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.

Long-term outcomes of Roux-en-Y gastric bypass or sleeve gastrectomy in patients with cirrhosis; before, during or after liver transplantation: A single center's experience.

BACKGROUND: The increasing prevalence of morbid obesity (MO) results in parallel growth of obesity-associated liver diseases necessitating liver transplantation (LT). OBJECTIVE: To examine the feasibility and safety of Roux-en-Y gastric bypass or sleeve gastrectomy in the setting of LT. METHODS: This retrospective chart review included the data on all the MO candidates before and after LT who underwent bariatric surgery (BS) in our institution between 04/2013-09/2016. The reported outcomes were weight change and early and late postoperative complications (mean follow-up: 43 ± 11.1 months). RESULTS: Eighteen MO peri-LT patients (10 females, 8 males, average age 48 years) were included in the study. Ten had cirrhosis (mean Model of End-stage Liver Disease [MELD] score of 12.5 ± 6.42), three underwent concurrent LT and BS (mean MELD score 23.7 ± 0.58), and five had LT (mean of 56 months from LT). The mean percentage of total and excess weight loss was 31% and 81%, respectively. Six of the eight patients with type 2 diabetes mellitus became normoglycemic after BS. Three patients sustained perioperative complications. Two cirrhotic patients died 1 and 4.5 years after BS with decompensation. CONCLUSIONS: Bariatric surgery appears to effectively address obesity in cirrhotic and LT patients. The surgical risk is higher than that of the regular BS population.