Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.

The assessment of hypertension in kidney transplant patients: time to change our approach?

Kidney transplantation (KT) is an increasingly utilized treatment for end-stage kidney disease (ESKD). Hypertension either as a cause of kidney disease or a complication of chronic kidney disease (CKD) is the most frequently encountered comorbidity of KT patients. Hence, the management of hypertension in KT patients is crucial to prolong patient and graft survival. Ambulatory blood pressure monitoring (ABPM) appeared as a promising technique that has superiority over the office and home blood pressure (BP) monitoring to correctly diagnose and manage hypertension. A recent meta-analysis of Pisano et al including 42 studies with 4115 participants provided strong data for the comparison of ABPM with office BP monitoring in KT patients. In addition to the current literature knowledge, findings of Pisano et al filled the long-awaited evidence gap to suggest ABPM as a first-line BP monitoring technique for KT patients. Despite its disadvantages such as patient discomfort, cost-effectiveness, limited availability, ABPM has crucial advantages in the management of hypertension including the detection of abnormal circadian BP patterns, the assessment of effects of physical activity and short-term variability of BP, and the exclusion of masked and white-coat hypertension.

ABO Incompatible Liver Transplantation in Children: A 20 Year Experience from Centres in the TransplantChild European Reference Network

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multivariate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children.

The impact of sarcopenia and myosteatosis in liver transplant candidates on peritransplant course and patient and graft survival

Introduction: Sarcopenia (severe muscle depletion) and myosteaosis (pathological fat accumulation in muscle) are frequent muscle abnormalities in patients with cirrhosis associated with unfavorable prognosis. The aim of our study was to evaluate the impact of sarcopenia and myosteatosis in liver transplant (LT) candidates in our center on the peritransplant course and patient and graft survival. Methods: This prospective study included adult LT candidates who underwent clinical and laboratory examination. The skeletal muscle index (SMI) at L3 level and radiodensity of psoas major muscle (PM-RA) were evaluated by CT. Results: Pretransplant sarcopenia was found in 49 of 103 patients (47.6%) and myosteatosis in 53 (51.5%) patients. Patients with sarcopenia had lower BMI, waist circumference, occurrence of hypertension and metabolic syndrome and lower triglyceride and C-peptide levels than patients without sarcopenia. Patients with myosteatosis had higher Child-Pugh score and lower HDL-cholesterol levels than patients without myosteatosis. Pretransplant SMI negatively correlated with the amount of blood transfusions given during LT and occurrence of biliary complications. Patients with myosteatosis had higher need for blood transfusions during LT and after LT, and higher number of surgical revisions. Occurrence of sarcopenia had no significant effect on patient and graft survival. Patients with myosteatosis had worse long-term survival than patients without myosteatosis, the graft survival did not differ. Conclusion: Sarcopenia and myosteatosis are frequent muscle abnormalities in LT candidates with negative impact on peritransplant course. Myosteatosis was associated with a worse long-term survival in our study. Key words: sarcopenia – myosteatosis – liver transplantation – prevalence – complications – survival