Explore the vast range of titles available.

Better understanding of the contribution of donor aging and comorbidity factors of expanded criteria donors (ECD) to the clinical outcome of a transplant is a challenge in kidney transplantation. We investigated whether the features of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF) could be indicative of the deleterious impact of the ECD microenvironment on a renal transplant. A comparative analysis of cellular components, transcriptomic and vasculogenic profiles was performed in PRAT-SVF obtained from 22 optimal donors and 31 ECD deceased donors. We then investigated whether these parameters could be associated with donor aging and early allograft dysfunction. When compared with the PRAT-SVF of non-ECD donors, ECD PRAT-SVF displayed a lower proportion of stromal cells, a higher proportion of inflammatory NK cells. The global RNA sequencing approach indicated a differential molecular signature in the PRAT-SVF of ECD donors characterized by the over-expression of CXCL1 and IL1-β inflammatory transcripts. The vasculogenic activity of PRAT-SVF was highly variable but was not significantly affected in marginal donors. Periorgan recruitment of monocytes/macrophages and NK cells in PRAT-SVF was associated with donor aging. The presence of NK cell infiltrates was associated with lower PRAT-SVF angiogenic activity and with early allograft dysfunction evaluated on day 7 and at 1 month post-transplant. Our results indicate that human NK cell subsets are differentially recruited in the periorgan environment of aging kidney transplants. We provide novel evidence that PRAT-SVF represents a non-invasive and timely source of donor material with potential value to assess inflammatory features that impact organ quality and function.

Shortage of kidney donor is still a major limitation for renal transplantation programs. This review focuses on the emerging practices, adopted to increase transplant activities, of expanding the criteria for donor and recipient selection without exposing the recipient to the drawbacks of a graft with inadequate nephron mass. Expanding the donor pool inevitably led to consideration for kidney transplantation of organs from older donors or from donors with hypertension, diabetes or other renal diseases. To fit the reduced performance of these suboptimal organs with the renal requirement of the recipient, selection of recipients with reduced metabolic requirements or increase of nephron mass by simultaneous transplantation of two suboptimal kidneys in the same recipient have been pursued. However, a critical aspect of both approaches is to quantify functioning nephron mass provided to the recipient by pre-transplant kidney biopsies. Morphological parameters assessed on kidney biopsies at the time of donor evaluation may serve to quantify the preserved tissue and to discriminate chronic irreversible lesions from acute changes that may account for a transiently impaired renal function in the donor, but that may recover after transplant.

Background We investigated the roles of renal volumetry and histological features in the assessment of preoperative and postoperative renal function in living kidney donors (LKDs) including high-risk marginal donors (MDs). Methods We included 128 LKDs who underwent donor nephrectomy at our institution between 2006 and 2022. Clinical and radiographic data were retrospectively obtained from medical charts. Renal volume parameters were calculated using preoperative computed tomography images. Tissues obtained from allograft biopsies were examined. MDs were defined according to the Japanese guidelines and compared with standard donors (SDs). Results LKDs were divided into 89 SDs and 39 MDs. Renal volumetry parameters did not differ significantly between the two groups, while interstitial inflammation and interstitial fibrosis/tubular atrophy were significantly higher in MDs ( P  = 0.031 and P  = 0.041). In the multivariate analysis, age < 60 years ( P  = 0.036), body mass index > 25 ( P  = 0.031), and residual kidney volume/body surface area (RKV/BSA; P  = 0.002) were independent factors for poor preservation of renal function. Subgroup analysis of the MDs revealed that RKV/BSA ( P  = 0.0096), residual measured glomerular filtration rate (GFR) ( P  = 0.0005), and arteriosclerosis ( P  = 0.045) were associated with poor preservation of renal function. Furthermore, the risk of graft loss was significantly higher for kidneys donated from MDs ( P  = 0.0019). Conclusions RKV/BSA can be a reliable screening and prognostic tool for selection of LKDs, including MDs, and RKV/BSA, measured GFR, and histological findings such as arteriosclerosis can be used to establish clearer MD criteria for optimal personalized follow-up after surgery.

The persistent organ shortage has led to the consideration of “marginal” donors, including those of advanced age, but the outcomes of using living kidney donors aged 70 years or older remain debated. This multicenter retrospective cohort study aimed to evaluate the propriety of kidney donation from older adult donors by analyzing the association between transplant outcomes and recipient age. Using data from 633 adult living-donor kidney transplants, we compared an elderly donor group (age ≥ 70 years, n  = 75) with a non-elderly donor group (age < 70 years, n  = 558). After 1:1 propensity score matching, the elderly donor group showed significantly lower death-censored graft survival. However, this disadvantage disappeared entirely in recipients aged 50 years or older, who exhibited comparable death-censored graft survival to those with non-elderly donors ( p  = 0.743). In contrast, recipients younger than 50 years who received grafts from elderly donors had markedly inferior death-censored graft survival ( p  = 0.008). In conclusion, using living kidney donors aged ≥ 70 years is a viable strategy to expand the donor pool, but its success is influenced by recipient age. These results support an age-sensitive approach in counseling and decision-making for kidney transplantation.

Proprotein Convertase Subtilisin/Kexin type 9 PCSK9 inhibitors (PCSK9i) are a novel class of cholesterol-lowering agents that also offer protection against tissue ischemia by reducing apoptosis, pyroptosis, and myocardial infarct size. This study evaluated the effects of the PCSK9 inhibitor PEP 2-8 during hypothermic perfusion (HP) in a rat model of donation after circulatory death (DCD) kidney transplantation. DCD kidneys were perfused at 4 °C for six hours with either Perf-Gen solution alone (control) or Perf-Gen supplemented with PEP 2-8. Glucose and lactate dehydrogenase (LDH) levels were measured at baseline and after six hours (T6h). At T6h, kidneys were evaluated for ischemic injury, tubular cell proliferation, apoptosis, nitrotyrosine (N-Tyr) staining, tissue ATP and LDH levels, and gene expression of PCSK9 and NOX4. Metabolomic profiling was also performed. PEP 2-8 treatment significantly reduced PCSK9 expression, decreased tubular ischemic injury and necrosis, and lowered LDH release. Treated kidneys showed enhanced tubular cell proliferation, reduced apoptosis, and diminished oxidative stress, indicated by decreased N-Tyr staining and NOX4 expression. Energy metabolism was improved, with higher tissue ATP and glucose levels observed in the PEP 2-8 group. Metabolomic analysis further supported the antioxidant effects of PEP 2-8. This is the first study to demonstrate that PEP 2-8 administered during pre-transplant hypothermic perfusion provides renal protection by improving energy metabolism and reducing oxidative stress in the context of ischemic injury.

Background and Objectives: Considering the growing shortage of grafts available for kidney transplantation (KT) due to the increase in the number of end-stage renal disease patients, it is essential to utilize all transplantation options. The Karpinski score is a histological scoring system utilized for the evaluation of pre-implantation kidney biopsies from deceased donors. In contrast with Remuzzi Criteria, there has recently been a tendency to perform single KT using grafts with a Karpinski score of 4 or 5. This strategy allows two score 4 or 5 grafts to be used for two different recipients instead of a double-graft KT on one patient. The aim of this study was to analyze the outcomes of single-graft KT with a score of 4 versus 5, and to investigate possible correlations with the clinical characteristics of donors and recipients. Materials and Methods: Retrospective single-centre analysis of 100 KTs performed with a single Karpinski score 4 or 5 graft between January 2014 and December 2022. Results: Grafts with a Karpinski score of 5 harvested from donors older than 70 years of age had a statistically significant (p = 0.014) worse 5-year survival rate (50.0 +/− 18.6%) compared to younger donors (100% for score 5 grafts from donors aged 31–60, and 100% for score 5 grafts from donors aged 61–70). Conversely, donor’s age did not significantly affect the survival of score 4 grafts. Conclusions: The results suggest that a single-graft KT with a Karpinski score 5 graft may be a viable procedure with favourable outcomes. However, for Karpinski score 5 grafts, the use of an older donor beyond the age of 70 seems to be a significant negative factor for the long-term outcome. In such cases, a double KT would potentially be the optimal approach.

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the \"Collaborative Transplant Study\" were analyzed using Kaplan-Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997-2006 and 2007-2016 with the donor age categories 18-49, 50-59, 60-69, and ≥70 years were considered. From 1997-2006 to 2007-2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997-2006 and 2007-2016, the 5-year graft survival improved in all donor age categories. During 2007-2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997-2006. This was true both for younger recipients (18-64 years) and older recipients (≥65 years). Among the younger recipients, 45-64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007-2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997-2006. Our analysis indicates that within only one further decade (1997-2006 vs. 2007-2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.

Background Despite organ shortages, the discard rate of deceased donor kidneys is high. Risk factors for this trend warrant further study. Methods We investigated reasons for discard in a cohort of brain death donors with marginal kidneys and procurement biopsies. Paraffin embedded procurement biopsies were systematically reevaluated and graded for the purpose of the study. Assessment included percentage of global glomerulosclerosis, Banff Lesion scores and tubular epithelial damage. Donor-, transplant process-, perfusion quality-, histopathology-, and recipient-related parameters were compared between discarded and transplanted organs. Results Although most clinical characteristics were similar between donors whose kidneys were transplanted and those whose kidneys were procured but discarded, discarded kidneys were more likely to be from donors with hepatitis C, to have undergone wedge biopsies, to show changes of acute and chronic injury and to be deemed poor quality. Except for obvious anatomic abnormalities, kidneys were often discarded due to the findings of procurement biopsies. Donors of kidneys discarded for histologic reasons more often had hypertension, coronary artery disease, stroke, and increased serum creatinine. The reason for discard was unknown in 20% of cases. Discarded kidneys came from donors who appeared to be clinically similar to donors whose kidneys were utilized for transplant. Conclusion A considerable proportion of discarded kidneys were of acceptable quality. The analysis of the outcome of every recovered organ could help to overcome this problem. Procurement biopsies more often lead to discard than to transplantation of recovered organs. Proper handling during allocation has to be determined. Graphical abstract

Organ transplantation is undergoing profound changes. Contraindications for donation have been revised in order to better meet the organ demand. The use of lower-quality organs and organs with greater preoperative damage, including those from donation after cardiac death (DCD), has become an established routine but increases the risk of graft malfunction. This risk is further aggravated by ischemia and reperfusion injury (IRI) in the process of transplantation. These circumstances demand a preservation technology that ameliorates IRI and allows for assessment of viability and function prior to transplantation. Oxygenated hypothermic and normothermic machine perfusion (MP) have emerged as valid novel modalities for advanced organ preservation and conditioning. prolonged lung preservation has resulted in successful transplantation of high-risk donor lungs. Normothermic MP of hearts and livers has displayed safe (heart) and superior (liver) preservation in randomized controlled trials (RCT). Normothermic kidney preservation for 24 h was recently established. Early clinical outcomes beyond the market entry trials indicate bioenergetics reconditioning, improved preservation of structures subject to IRI, and significant prolongation of the preservation time. The monitoring of perfusion parameters, the biochemical investigation of preservation fluids, and the assessment of tissue viability and bioenergetics function now offer a comprehensive assessment of organ quality and function . Gene and protein expression profiling, investigation of passenger leukocytes, and advanced imaging may further enhance the understanding of the condition of an organ during MP. In addition, MP offers a platform for organ reconditioning and regeneration and hence catalyzes the clinical realization of tissue engineering. Organ modification may include immunological modification and the generation of chimeric organs. While these ideas are not conceptually new, MP now offers a platform for clinical realization. Defatting of steatotic livers, modulation of inflammation during preservation in lungs, vasodilatation of livers, and hepatitis C elimination have been successfully demonstrated in experimental and clinical trials. Targeted treatment of lesions and surgical treatment or graft modification have been attempted. In this review, we address the current state of MP and advanced organ monitoring and speculate about logical future steps and how this evolution of a novel technology can result in a medial revolution.

Background The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. Methods We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) ( n  = 41), middle-aged (aged 46–69 years) ( n  = 239), and young donors (aged <46 years) ( N  = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. Results Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor ( p  < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02–20.6), p  = 047, 0.95 (0.94–0.96), p  ≤ 0.01, respectively]. However, recovery of eGFR 4–5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. Conclusions Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation.