Are we on track to increase organ utilization? An analysis of machine perfusion preservation for liver transplantation in the United States.

BACKGROUND: Efforts to improve the quality of marginal grafts for transplantation are essential. Machine perfusion preservation appears as a promising solution. METHODS: The United Network for Organ Sharing (UNOS) database was queried for deceased liver donor records between 2016 and 2022. The primary outcome of interest was the organ nonutilization rate. Long-term graft and patient survival among extended criteria donors (ECDs) were also analyzed. RESULTS: During the study period, out of 54 578 liver grafts recovered for transplant, 5085 (9.3%) were nonutilized. Multivariable analysis identified normothermic machine perfusion (NMP) preservation as the only predictor associated with a reduction in graft nonutilization (OR = 0.12; 95% CI = 0.06-0.023, p < 0.001). Further analysis of ECD grafts that were transplanted revealed comparable 1-,2- and 3-years graft survival (89%/88%/82% vs. 90%/85%/81%, p = 0.60), and patient survival (92%/91%/84% vs. 92%/88%/84%, p = 0.65) between grafts that underwent MP vs. those who did not, respectively. CONCLUSIONS: Liver nonutilization rates in the United States are at an all-time high. Available data, most likely including cases from clinical trials, showed that NMP reduced the odds of organ nonutilization by 12% among the entire deceased donor pool and by 16% among grafts from ECD. Collective efforts and further evidence reflecting day-to-day clinical practice are needed to fully reach the potential of MP for liver transplant.

The Clinical Manifestation of Immunosuppressive Therapy as a Tool to Improve Immune Monitoring in Renal Transplant Recipients.

INTRODUCTION: Metrics for posttransplant immune monitoring to prevent over or under immunosuppression in renal transplant recipients (RTRs) are lacking. METHODS: We surveyed 132 RTRs, 38 in the first year posttransplant and 94 >1-year posttransplant, to study the clinical expression of immunosuppressive therapy. A questionnaire administered to these RTRs was divided into physical (Q physical) and mental (Q mental) symptoms. RESULTS: In multivariable models for the association between the calculated Q physical and Q mental scores and different clinical and biochemical variables in the 38 RTRs who filled out the questionnaire 130 times during the first year posttransplant, it was found that mycophenolic acid (MPA) and prednisone use increased the mean Q physical score by 0.59 (95% CI: 0.21-0.98, p = 0.002) and 0.53 (95% CI: 0.26-0.81, p = 0.00), respectively, while MPA use increased the mean Q mental score by 0.72 (95% CI: 0.31-1.12, p = 0.001). Among the 94 RTRs who each completed the questionnaire only once, the odds for the mean Q mental score to be above the median value were more than 3 times higher for RTRs treated versus non-treated with MPA (OR 3.38, 95% CI: 1.1-10.3, p = 0.03). MPA-treated RTRs had higher mean scores for questions related to sleep disorders (1.83 ± 1.06 vs. 1.32 ± 0.67 for not treated, p = 0.037), to difficulty falling asleep (1.72 ± 1.11 vs. 1.16 ± 0.5, p = 0.02), and to depression and anxiety. CONCLUSION: We concluded that prednisone and MPA use are associated with an increased Q physical and Q mental scores in RTRs. Routine monitoring of physical and mental status of RTRs should be implemented to improve the diagnosis of overimmunosuppression. Dose reduction or discontinuation of MPA should be considered in RTRs who report sleep disorders, depression, and anxiety.

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.

Bariatric surgery in solid organ transplant patients: Long-term follow-up results of outcome, safety, and effect on immunosuppression.

The surgical risk of transplanted patients is high, and the modified gastrointestinal anatomy after bariatric surgery (BS) may lead to pharmacokinetic alterations in the absorption of immunosuppressive drugs. Data on outcomes of BS and the safety and feasibility of maintaining immunosuppression and graft safety among solid organ transplanted patients are scarce. In the current study, weight loss, improvement in comorbidities, and changes in dosage and trough levels of immunosuppression drugs before and after BS were analyzed for all transplanted patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between November 2011 and January 2017. Thirty-four patients (13 females, 21 males, average age 53 years) were included in the study. A successful weight loss (>50% excess weight loss in 28 of them [82%]) was recorded at the last follow-up. Comorbidities improved significantly. Immunosuppressive stability increased from 39% to 47% among all patients. The tacrolimus blood trough levels declined slightly, but remained within therapeutic range. These data suggest that LSG and LRYGB ensure good immunosuppressive maintenance together with significant weight loss and improvement in comorbidities without serious graft rejection or dysfunction. The surgical risk is higher than in the regular BS population.

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.

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.

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.

Long-Term Results of Kidney Transplantation in the Elderly: Comparison between Different Donor Settings.

With scarce organ supply, a selection of suitable elderly candidates for transplant is needed, as well as auditing the long-term outcomes after transplant. We conducted an observational cohort study among our patient cohort >60 years old with a long follow up. (1). PATIENTS AND METHODS: We used our database to study the results after transplant for 593 patients >60 years old who underwent a transplant between 2000-2017. The outcome was compared between live donor (LD; n = 257) recipients, an old-to-old (OTO, n = 215) group using an extended criteria donor (ECD) kidney, and a young-to-old (YTO, n = 123) group using a standard-criteria donor. The Kaplan-Meir method was used to calculate the patient and graft survival and Cox regression analysis in order to find risk factors associated with death. (2). RESULTS: The 5- and 10-year patient survival was significantly better in the LD group (92.7% and 66.9%) compared with the OTO group (73.3% and 42.8%) and YTO group (70.9% and 40.6%) (p < 0.0001). The 5- and 10-year graft survival rates were 90.3% and 68.5% (LD), 61.7% and 30.9% (OTO), and 64.1% and 39.9%, respectively (YTO group; p < 0.0001 between the LD and the two DD groups). There was no difference in outcome between patients in their 60's and their 70's. Factors associated with mortality included: age (HR-1.060), DM (HR-1.773), IHD (HR-1.510), and LD/DD (HR-2.865). (3). CONCLUSIONS: Our 17-years of experience seems to justify the rational of an old-to-old allocation policy in the elderly population. Live-donor transplant should be encouraged whenever possible. Each individual decision of elderly candidates for transplant should be based on the patient's comorbidity and predicted life expectancy.

Survival benefit in bariatric surgery kidney recipients may be mediated through effects on kidney graft function and improvement of co-morbidities: A case-control study.

BACKGROUND: Data on the benefits of bariatric surgery for morbid obesity among kidney transplant recipients are scarce. OBJECTIVE: To examine the effect of bariatric surgery on graft function and survival and on obesity-related co-morbidities. SETTING: University hospital. METHODS: This case-control study used retrospectively collected data of all kidney recipients who underwent bariatric surgery in our institution between November 2011 and August 2016 (n = 30, 11 females). Nonbariatric operated kidney recipients matched for age, sex, and time elapsed since transplantation served as controls (n = 50, 23 females). Main outcomes were renal function, graft loss events, mortality, and obesity-related co-morbidities. RESULTS: The mean follow-up duration was 2.4 ± 1.3 years for both groups. At final follow-up, there was an increase in estimated glomerular filtration rates for the bariatric surgery group, and a decrease for the controls (13.4 ± 19.9 and -3.9 ± 15.8 mL/min/1.73 m2, respectively, P < .001). The chronic kidney disease classification improved in 9 bariatric surgery group patients and in 6 controls (P = .1). Two patients in the bariatric surgery group and 6 controls died. Total death or graft function loss during the follow-up was 6.7% and 16.7%, respectively (P = .3). The total numbers of co-morbidities and medications were lower in the bariatric surgery patients (-.7 and -2, respectively) and higher in the controls (+.3 and +1.1; P < .001) at study closure. CONCLUSIONS: There was an improvement in renal function, graft survival, and obesity-related co-morbidities among kidney transplant recipients who underwent bariatric surgery compared with those who did not. These findings support bariatric surgery in this population and warrant prospective studies.

Bariatric Surgery Is Efficacious and Improves Access to Transplantation for Morbidly Obese Renal Transplant Candidates.

BACKGROUND: The surgical risk of morbidly obese patients is high and even higher for kidney transplant candidates. A BMI > 35-40 kg/m2 is often a contraindication for that surgery. The safety, feasibility, and outcome of bariatric surgery for those patients are inconclusive. METHODS: We conducted a retrospective chart review of prospectively collected data on morbidly obese renal transplant candidates who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between January 2009 and September 2017. The reported outcome included body weight and graft status after a mean follow-up of 47 months (range 0.5-5 years). RESULTS: Twenty-four patients (8 females, 16 males, average age 54 years, average preoperative BMI 41 kg/m2 [range 35-51]) underwent LSG (n = 17) or LRYGB (n = 7). Sixteen of them (67%) proceeded to kidney transplantation. Of the 8 pre-transplant and post-bariatric surgery patients, 5 are on the waitlist, and 2 patients died (one of staple line leakage, and one from sepsis unrelated to the bariatric surgery). The average time from bariatric surgery to transplantation was 1.5 years (range 1 month to 4.3 years). The average pre-transplantation BMI was 28 kg/m2 (range 19-36). The mean percentage of excess weight loss was 66% (n = 21), and the total percentage of weight loss was 29% (n = 21). Comorbidities (type 2 diabetes, hypertension, and dyslipidemia) improved significantly following both surgical approaches. CONCLUSIONS: LSG and LRYGB appear to effectively address obesity issues before kidney transplantation and improve surgical access. Morbidly obese transplant candidates would benefit from prior bariatric surgery.

Long-Term Effectiveness of Laparoscopic Conversion of Sleeve Gastrectomy to a Biliopancreatic Diversion with a Duodenal Switch or a Roux-en-Y Gastric Bypass due to Weight Loss Failure.

BACKGROUND: Gastroesophageal reflux disease and inadequate weight loss (IWL) are long-term complications of laparoscopic sleeve gastrectomy (LSG) and indications for a laparoscopic conversion to an alternative bariatric procedure. The aim of this study is to report the long-term outcomes of biliopancreatic diversion with a duodenal switch (DS) or a Roux-en-Y gastric bypass (RYGB) as conversion procedures for weight loss failure after LSG. METHODS: The data of all patients who underwent post-LSG conversion to either a RYGB or a DS at our institution between November 2006 and May 2016 was retrospectively analyzed. Included were all patients with > 1-year follow-up who were operated due to IWL or weight regain. Patients with the indication of reflux were excluded. RESULTS: Sixty-six patients underwent conversion from LSG to RYGB, DS, or one-anastomosis gastric bypass during the study period. There were 21 revisions to DS and 18 to RYGB that met the inclusion criteria. The respective weight and body mass index (BMI) before and after LSG were 125 and 110 kg and 46 and 40.5 kg/m2 in the RYGB group and 148 and 126 kg and 53.7 and 46 kg/m2 in the DS group. At the last follow-up (> 2 years), 15 RYGB patients had a reduction in BMI of 8.5-31.9 kg/m2 and 18 DS patients had a reduction in BMI of 12.8-31.9 kg/m2. The mean follow-up was 48.5 months (range 24-76). All comorbidities improved or underwent complete remission. CONCLUSION: Conversion from SG to RYGB or DS is an efficient and effective treatment for IWL and improvement of comorbidities. Further studies are warranted to evaluate long-term weight regain.

Simultaneous Liver Transplantation and Sleeve Gastrectomy: Prohibitive Combination or a Necessity?

Previously, many morbidly obese (MO) patients were denied liver transplantation (LT) because of the higher operative risk. However, nowadays, 5 and 10 years graft survival is the rule, and patients whose lives can be prolonged with LT are dying of obesity-related comorbidities. Recent experience suggests that weight reduction in MO liver transplant recipients would improve their long-term survival. The bariatric surgery before LT is contraindicated for patients with decompensated cirrhosis, while post-transplant intervention is associated with increased technical difficulty. We present our experience with three patients who underwent simultaneous liver transplantation and sleeve gastrectomy. After a median 13 months follow-up, all patients are alive, having normal allograft function and significant weight loss. Combined liver transplantation with simultaneous sleeve gastrectomy appears technically feasible and relatively safe in selected patients.