Transplantation of kidneys retrieved from extended criteria donors is one of the options to expand the pool of available grafts, shorten the waiting time and increase the availability of this method of treatment. However, some factors (eg, donor age) may impair the results of transplantation. This study was a retrospective assessment of 327 patients who underwent renal transplants during the period 1995-2005, with kidneys harvested from expanded criteria donors (ECD) as defined by the United Network for Organ Sharing (UNOS). They formed 2 groups: group 1 (ECD - younger, n=255) consisted of recipients of kidneys obtained from donors aged 50-59 years; group 2 (ECD - older, n=72) consisted of patients who received kidneys from donors ≥ 60 years old. An analysis of the 1-, 3- and 5-year survival of grafts and patients and evaluation of graft function were performed. graft survival was significantly better in group 1 (ECD-younger) vs. group 2 (ECD-older), as was renal graft function. Survival 3 and 5 years after transplantation was 87.7% vs. 81.9%, 73.1% vs. 66.6%, and 60.1% vs. 51.7%, respectively. Delayed graft function occurred significantly more frequently in group 2 (group 1 vs. group 2-28.8% vs. 34.6%, p=0.0001). The transplantation of kidneys obtained from older donors fulfilling ECD definition is associated with shorter graft survival, deteriorated function and more frequent renal delayed graft function. However, this did not increase the mortality of recipients.

Background. Expression of acute kidney injury–associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in “failed repair” states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants. Methods. We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants. Results. In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. Both PC1 and PC3 correlated with reduced survival, with PC1 effects strongly increasing over time whereas PC3 effects were independent of time. In this model, we studied the expression of 12 “new” gene sets annotated in single-nucleus RNA-sequencing studies of epithelial cells with failed repair in native kidneys. The new gene sets reflecting epithelial-mesenchymal transition correlated with injury PC1 and PC3, lower estimated glomerular filtration rate, higher donor age, and future failure as strongly as any gene sets previously derived in transplants and were independent of nephron segment of origin and graft rejection. Conclusion. These results suggest 2 dimensions in the kidney transplant response to injury: PC1, AKI-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and PC3. Trial registration. INTERCOMEX (ClinicalTrials.gov NCT01299168); Trifecta-Kidney (ClinicalTrials.gov NCT04239703). Funding. Genome Canada; Natera, Inc.; and Thermo Fisher Scientific.

Introduction: Proper planning of laparoscopic radical prostatectomy (RP) in patients with prostate cancer (PCa) is crucial to achieving good oncological results with the possibility of preserving potency and continence. Aim: The aim of this study was to identify the radiological and clinical parameters that can predict the risk of extraprostatic extension (EPE) for a specific site of the prostate. Predictive models and multiparametric magnetic resonance imaging (mpMRI) data from patients qualified for RP were compared. Material and methods: The study included 61 patients who underwent laparoscopic RP. mpMRI preceded transrectal systematic and cognitive fusion biopsy. Martini, Memorial Sloan-Kettering Cancer Center (MSKCC), and Partin Tables nomograms were used to assess the risk of EPE. The area under the curve (AUC) was calculated for the models and compared. Univariate and multivariate logistic regression analyses were used to determine the combination of variables that best predicted EPE risk based on final histopathology. Results: The combination of mpMRI indicating or suspecting EPE (odds ratio (OR) = 7.49 (2.31–24.27), p < 0.001) and PSA ≥ 20 ng/mL (OR = 12.06 (1.1–132.15), p = 0.04) best predicted the risk of EPE for a specific side of the prostate. For the prediction of ipsilateral EPE risk, the AUC for Martini’s nomogram vs. mpMRI was 0.73 (p < 0.001) vs. 0.63 (p = 0.005), respectively (p = 0.131). The assessment of a non-specific site of EPE by MSKCC vs. Partin Tables showed AUC values of 0.71 (p = 0.007) vs. 0.63 (p = 0.074), respectively (p = 0.211). Conclusions: The combined use of mpMRI, the results of the systematic and targeted biopsy, and prostate-specific antigen baseline can effectively predict ipsilateral EPE (pT3 stage).

Background: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods: In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results: The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac (p < 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. −3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions: Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios.

Despite an increasing quality of life after renal transplantation, the number of recipients undertaking paid professional work remains relatively low. Employment after kidney transplantation became a new important marker of clinically significant health recovery. Furthermore, for social and economic reasons, returning to work and participation in social life may be considered as an objective parameter that demonstrate the effectiveness of transplantation. The objectives of the following study were to evaluate the factors that determine resuming paid work after renal transplantation, to assess a patient’s decision about returning to professional activity by comparative analysis of renal transplant recipients from Poland, Czech Republic and Germany, and to identify groups of patients exposed to professional exclusion in those EU countries. Five hundred renal transplant recipients from three EU countries were included into the study. The two main research methods used in the study were the SF-36 questionnaire, constructed and validated to assess the quality of life after kidney transplantation and a questionnaire constructed for the purposes of this study. Multifactorial analysis identified several risk factors associated with professional exclusions after kidney transplantation, namely young or advanced age, female gender, lack of education, place of residence in rural areas, long period of illness, and lack of occupational activity before transplantation. Despite the high standards of social care and rehabilitation support, patients in Germany failed to take up professional activity after kidney transplantation in more cases than those in Poland and Czech Republic. Surprisingly, the objective function of the kidney (creatinine level) and the multidimensional assessment of quality of life (SF-36 survey) did not have a significant association with the employment status after renal transplantation.