Rapamycin Does Not Act as a Dietary Restriction Mimetic in the Protection against Ischemia Reperfusion Injury

Introduction: Short-term fasting protects against renal ischemia reperfusion injury (IRI). mTOR signaling is downregulated and may be involved in its protective effect. Rapamycin is considered a possible mimetic as it inhibits the mTOR pathway. This study examines the effect of rapamycin on renal IRI. Material and Methods: Mice were divided into four groups: ad libitum (AL), fasted (F), AL treated with rapamycin (AL+R), and F treated with rapamycin (F+R). Rapamycin was administered intraperitoneally 24 h before bilateral renal IRI was induced. Survival was monitored for 7 days. Renal cell death, regeneration, and mTOR activity were determined 48 h after reperfusion. Oxidative stress resistance of human renal proximal tubular and human primary tubular epithelial cells after rapamycin treatment was determined. Results: All F and F+R mice survived the experiment. Although rapamycin substantially downregulated mTOR activity, survival in the AL+R group was similar to AL (10%). Renal regeneration was significantly reduced in AL+R but not in F+R. After IRI (48 h), pS6K/S6K ratio was lower in F, F+R, and AL+R groups compared to AL fed animals (p = 0.02). In vitro, rapamycin also significantly downregulated mTOR activity (p &lt; 0.001) but did not protect against oxidative stress. Conclusion: Rapamycin pretreatment does not protect against renal IRI. Thus, protection against renal IRI by fasting is not exclusively mediated through inhibition of mTOR activity but may involve preservation of regenerative mechanisms despite mTOR downregulation. Therefore, rapamycin cannot be used as a dietary mimetic to protect against renal IRI.</p

What are the benefits of preemptive versus non-preemptive kidney transplantation? A systematic review and meta-analysis

Opting for a preemptive kidney transplant (PKT) can help avoid costs and morbidity associated with dialysis. However, while multiple studies have shown clinical benefits of PKT, other studies have not demonstrated this, leading to controversy in the literature regarding the exact benefits of PKT. Therefore, this study aimed to determine the clinical outcomes of PKT versus non-preemptive kidney transplantation (nPKT) in adult patients. Multiple databases were searched up to May 4, 2022. Independent reviewers selected studies for inclusion and extracted relevant data. Risk of bias was assessed using the Downs and Black checklist. Eighty-seven studies including 859,715 adult kidney transplant patients were included the review. The risk of patient death (relative risk [95% confidence interval] 0.74 [0.60–0.91]) was significantly lower in PKT versus nPKT patients for living donor (LD) transplants, whereas the risk of overall graft loss was significantly lower in PKT compared to nPKT patients for both LD (0.72 [0.62–0.83]) as well as deceased donor (DD) transplants (0.80 [0.69–0.92]). The evidence suggests that LD PKT patients have a lower risk of patient death and graft loss compared to nPKT patients, and DD PKT patients have a lower risk of graft loss than nPKT patients.</p

Surgical aspects of live kidney donation:An updated review

In the early 1990s, live kidney donation regained popularity to meet the demand of kidney transplantation. Significant developments in the field of live kidney donation have established live donation as the prime source of kidney transplants. Nowadays, management is focused on logistic and immunological innovations, and improvements in care of the live donor. However, a flawless surgical procedure in both donor and recipient is a prerequisite for further expansion of live kidney donor transplantation. From a surgical perspective, the introduction of the laparoscopic approach has been a major breakthrough. Less invasive techniques to procure live donor kidneys have been held responsible for a steep increase in the number of live donors. In addition, less invasive imaging, improvements in perioperative care, and novel insights in the follow-up have all improved the care of the live donor. Live kidney donation is developing as the most promising source of renal organs since artificial kidneys, xenografts and stem cell therapy for restoring intrinsic kidney function will probably not find application on a large scale in the near future.</p

Systematic Surgical Assessment of Deceased-Donor Kidneys as a Predictor of Short-Term Transplant Outcomes

Background: Short-term kidney graft dysfunction is correlated with complications and it is associated with a decreased long-term survival; therefore, a scoring system to predict short-term renal transplant outcomes is warranted. Aim: The aim of this study is to quantify the impression of the organ procurement surgeon in correlation with the following kidney transplant outcomes: immediate graft function (IGF), delayed graft function (DGF), and primary nonfunction (PNF). Results are compared to factors associated with the 1-year outcome. Methods: A regional prospective pilot study was performed using deceased-donor organ assessment forms to be filled out by procurement surgeons after procurement. Data were gathered on kidney temperature, perfusion, anatomy, atherosclerosis, and overall quality. Results: Included were 90 donors who donated 178 kidneys, 166 of which were transplanted. Variables that were significantly more prevalent in the DGF-or-PNF group (n = 65) are: large kidney size (length, p = 0.008; width, p = 0.036), poor perfusion quality (p = 0.037), lower diuresis (p = 0.039), fewer hypotensive episodes (p = 0.003), and donation-after-circulatory-death donors (p = 0.017). Multivariable analysis showed that perfusion quality and kidney width significantly predicted the short-term outcome. However multivariable analysis of long-term outcomes showed that the first measured donor creatinine, kidney donor risk index, IGF vs. DGF+PNG, and kidney length predicted outcomes. Conclusions: Results show that short-term graft function and 1-year graft function indeed are influenced by different variables. DGF and PNF occur more frequently in kidneys with poor perfusion and in larger kidneys. A plausible explanation for this is that these kidneys might be insufficiently washed out, or even congested, which may predispose to DGF. These kidneys would probably benefit most from reconditioning strategies, such as machine perfusion. A scoring system including these variables might aid in decision-making towards allocation and potential reconditioning strategies

Health Literacy and Official Websites about Deceased Organ Donation

Making informed decisions such as organ donation requires access to accurate, readily available and reliable information. One of the most easily accessible resources are the official national websites of countries around the topic of Deceased organ Donation (DOD). The content of the official organ donation websites in the UK (NHSBT), the Netherlands (ONT) and Spain (NTS) were analysed. This is a step towards finding the parameters of a health literacy agenda on organ donation and transplantation. Cross-comparative content analysis was employed and subsequently thematic analysis was used to locate themes and sub-themes in the sections of these websites and coverage of themes was assessed. The analysis was performed using Atlas.ti software in 2014-2016. The information provided in these websites were categorised in five themes consisting of Theme 1: Personal Values for Organ Donation, Theme 2: Facts on the Organ Donation Process, Theme 3: Registration Options, Theme 4: Communicating with Family Members and Theme 5: Promotional resources. Within themes 2 and 3, further sub themes were identified to explore the topic more fully. The information in the websites provides an overview of the main areas of organ donation in which the public is informed in different countries and highlights that changes need to be implemented in an individual, community and population level

Screening, Management, and Acceptance of Patients with Aorto-Iliac Vascular Disease for Kidney Transplantation: A Survey among 161 Transplant Surgeons

Introduction: Aorto-iliac vascular disease (AVD) is frequently found during the workup for kidney transplantation. However, recommendations on screening and management are lacking. We aimed to assess differences in screening, management, and acceptance of these patients for transplantation by performing a survey among transplant surgeons. Second, we aimed to identify center- A nd surgeon-related factors associated with decline or acceptance of kidney transplant candidates with AVD. Methods: A survey was sent to transplant surgeons and urologists. The survey contained general questions (part I) and 2 patient-based cases (part II) with Trans-Atlantic Inter-Society Consensus (TASC) D and B AVD supported with videos of their CT scans. Results: One hundred ninety-one (20.3%) participants responded; 171 were currently involved in kidney transplantation: 161 (94.2%) completed part I and 145 (84.8%) part II. Screening for AVD was often (38.5%) restricted to high-risk patients. The majority of respondents (67.7%) rated "technical problems"as the most important concern in case of AVD, followed by "increased mortality risk because of cardiovascular comorbidity"(29.8%). Pretransplant vascular interventions to facilitate transplantation were infrequently performed (71.4% mentioned <10 per year). Ninety (64.3%) respondents answered that an open vascular procedure should preferably be performed prior to kidney transplantation while 42 (30.0%) respondents preferred a simultaneous open vascular procedure. The decline rate was higher in the TASC D case compared to the TASC B case (26.9% and 9.7%, respectively). Respondents from centers with expertise in pretransplant vascular interventions were more likely to accept both patients with TASC D and B for transplantation. Conclusion: There is no uniformity in the screening, management, and acceptance of patients with AVD for transplantation. If a center declines a patient with AVD because of technical concerns, the patient should be referred for a second opinion to a tertiary center with expertise in pretransplant vascular interventions. Multidisciplinary meetings including a vascular surgeon and a cardiologist could help optimize these patients for transplantation