Search Results (9)

This pictorial essay aims to navigate through the complexities and challenges of renal transplantation (RT), by weaving together visual imagery with clinical insights within a comprehensive illustrative surgical guide. Herein, we provide a detailed visual exploration of the intricate anatomy and surgical processes necessary for both renal graft retrieval from the donor and also for an adequate implantation in the recipient. Regarding graft retrieval, after reviewing the relevant retroperitoneal surgical anatomy, and donor nephrectomy techniques, graft preservation and optimal backbench graft dissection principles were meticulously analyzed. Thereafter, the recipient surgical strategy for graft implantation was addressed, focusing on preoperative preparations, the site of implantation selection, exposure, operative bed dissection, graft revascularization, and urinary tract reconstruction. Careful donor and recipient selection, meticulous surgical execution, and rigorous postoperative management clearly hold a pivotal role in optimizing patient outcomes. Fostering a deeper understanding of the surgical nuances and clinical management practices that contribute to successful results post-RT, we hope to provide a useful practical tool for clinicians about to embark on the treacherous road of RT surgery. Innovative technologies and surgical practices that have already significantly improved the safety and effectiveness of RT stand testament to the importance of further scientific inquiry, conceptual developments, and clinical integration. Moving forward, it is essential that the medical community continues to refine these strategies and advocate for equitable access to transplantation, ensuring that advancements in the field translate into real-world benefits for all patients grappling with ESRD. The collaborative efforts of multidisciplinary teams are essential in addressing the complex clinical challenges associated with RT, with the ultimate goal of improving patient survival, enhancing graft longevity, and reducing healthcare disparities. Full article

Fetal organs and organoids are important tools for studying organ development. Recently, porcine organs have garnered attention as potential organs for xenotransplantation because of their high degree of similarity to human organs. However, to meet the prompt demand for porcine fetal organs by patients and researchers, effective methods for producing, retrieving, and cryopreserving pig fetuses are indispensable. Therefore, in this study, to collect fetuses for kidney extraction, we employed cesarean sections to preserve the survival and fertility of the mother pig and a method for storing fetal kidneys by long-term cryopreservation. Subsequently, we evaluated the utility of these two methods. We confirmed that the kidneys of pig fetuses retrieved by cesarean section that were cryopreserved for an extended period could resume renal growth when grafted into mice and were capable of forming renal organoids. These results demonstrate the usefulness of long-term cryopreserved fetal pig organs and strongly suggest the effectiveness of our comprehensive system of pig fetus retrieval and fetal organ preservation, thereby highlighting its potential as an accelerator of xenotransplantation research and clinical innovation. Full article

Background and objectives: For patients with end-stage renal disease (ESRD), the best replacement therapy is renal transplant (RTx) to ensure life with good quality. Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder and a common cause of ESRD. Different from ESRD of other causes, ADPKD patients need careful pre-RTx evaluations like detecting the presence of intracranial aneurisms, cardiac manifestations, and complications of liver and renal cysts. Materials: We retrieved a total of 1327 RTx patients receiving 1382 times RTx (two recipients with three times, 48 recipients with two times) over the last 35 years. Only 41 of these patients were diagnosed with ADPKD. Results: At the first RTx, patients’ ages were 42.9 ± 12.6 (mean ± SD) years. Ages of the ADPKD group (52.5 ± 10.1 years) were older than the non-ADPKD group (42.7 ± 12.7 years, p = 0.001). We found more cell mediated and antibody mediated rejection (29.3% vs. 26.0%, and 22.0% vs. 7.0%; both p < 0.001), new onset diabetes after transplant (NODAT) (21, 51.2% vs. 326, 25.3%; p = 0.005), and worse graft survival (p < 0.001) in the ADPKD group, and with the development of more malignancies (18; 43.9% vs. 360; 28.0%; p = 0.041). The long-term patient survivals were poorer in the ADPKD group (38.9% vs. 70.3%; p = 0.018). ADPKD was found as an independent risk factor for long-term patient survival (HR = 2.64, 95% CI 1.03–6.76, p = 0.04). Conclusions: Patients with ADPKD-related ESRD developed more NODAT, and also more malignancies if not aggressively surveyed before surgery. Due to poor long-term graft and patient survivals, regular careful examinations for NODAT and malignancies, even in the absence of related symptoms and signs, are highly recommended in the follow-ups. Full article

Background: Warm reperfusion after previous cold storage has been shown to have a negative impact on mitochondrial function of organ grafts. Here, we wanted to investigate whether a more controlled warming up of the cold graft by ex vivo machine perfusion with gradually elevated temperature from cold to normothermia (including comparison of two warming up protocols) prior to implantation would be effective in preventing mitochondrial dysfunction upon reperfusion. Methods: All experiments were conducted on porcine kidneys retrieved 15 min after cardiac arrest. After 18 h of cold storage in HTK solution (CS, n = 6), kidneys (n = 6) were subjected to 2 h of reconditioning machine perfusion starting with a hypothermic period followed by a gradual increase in perfusion temperature up to 35 °C (controlled oxygenated rewarming—COR). For a second group (n = 6), the slow warming up was begun instantly after connecting the graft onto the machine (iCOR). Functional recovery of all grafts was then observed upon normothermic reperfusion in vitro. At the conclusion of the experiments, tissue specimens were taken for immediate isolation and analysis of renal mitochondria. Results: COR resulted in a significantly and more than 3-fold increased glomerular filtration rate upon reperfusion, along with a significant higher tubular sodium reabsorption and lesser loss of glucose in comparison to the controls. Enzyme release (AST) was also massively reduced during the reperfusion period. Specific analysis at the mitochondrial level revealed significantly better coupling efficiency and spare respiratory capacity in the COR group compared to the cold storage group. Interestingly, additional experiments revealed that the omission of a hypothermic perfusion period did not deteriorate any of the results after COR, provided that the instant temperature increase from 10 to 35 °C was effectuated in the same controlled manner. Conclusion: Controlled rewarming after extended cold preservation effectively improves mitochondrial recovery upon reperfusion and early functional outcome of kidney grafts. Full article

Background and Aims: Recipient demographics affect outcomes after kidney transplantation. The aim of this study was to assess, for kidneys retrieved from living donors, the effect of recipient sex, ethnicity, and body mass index (BMI) on delayed graft function (DGF) and one-year graft function, incidence of acute rejection (AR), and recipient and graft survivals. Methods: A systematic review and meta-analysis was performed. EMBASE and MEDLINE databases were searched using algorithms through Ovid. Web of Science collection, BIOSIS, CABI, Korean Journal database, Russian Science Citation Index, and SciELO were searched through Web of Science. Cochrane database was also searched. Risk of bias was assessed using the NHBLI tools. Data analysis was performed using Revman 5.4. Mean difference (MD) and risk ratio (RR) were used in analysis. Results: A total of 5129 studies were identified; 24 studies met the inclusion criteria and were analysed. Female recipients were found to have a significantly lower serum creatinine 1-year-post renal transplantation (MD: −0.24 mg/dL 95%CI: −0.18 to −0.29 p < 0.01) compared to male recipients. No significant difference in survival between male and female recipients nor between Caucasians and Africans was observed (p = 0.08). However, Caucasian recipients had a higher 1-year graft survival compared to African recipients (95% CI 0.52−0.98) with also a lower incidence of DGF (RR = 0.63 p < 0.01) and AR (RR = 0.55 p < 0.01). Recipient obesity (BMI > 30) was found to have no effect on 1-year recipient (p = 0.28) and graft survival (p = 0.93) compared to non-obese recipients although non-obese recipients had a lower rate of DGF (RR = 0.65 p < 0.01) and AR (RR = 0.81 p < 0.01) compared to obese recipients. Conclusions: Gender mismatch between male recipients and female donors has negative impact on graft survival. African ethnicity and obesity do not to influence recipient and graft survival but negatively affect DGF and AR rates. Full article

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol^® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol^® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI. Full article

Background: Failed kidney transplant recipients benefit from a new graft as the general incident dialysis population, although additional challenges in the management of these patients are often limiting the long-term outcomes. Previously failed grafts, a long history of comorbidities, side effects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplantation population, leading to significant complex immunological and technical aspects and often compromising the short- and long-term results. Although recipients’ factors are acknowledged to represent one of the main determinants for graft and patient survival, there is increasing interest in expanding the donor’s pool safely, particularly for high-risk candidates. The role of living kidney donation in this peculiar context of repeated kidney transplantation has not been assessed thoroughly. The aim of the present study is to analyse the effects of a high-quality graft, such as the one retrieved from living kidney donors, in the repeated kidney transplant population context. Methods: Retrospective analysis of the outcomes of the repeated kidney transplant population at our institution from 1968 to 2019. Data were extracted from a prospectively maintained database and stratified according to the number of transplants: 1st, 2nd or 3rd+. The main outcomes were graft and patient survivals, recorded from time of transplant to graft failure (return to dialysis) and censored at patient death with a functioning graft. Duration of renal replacement therapy was expressed as cumulative time per month. A multivariate analysis considering death-censored graft survival, decade of transplantation, recipient age, donor age, living donor, transplant number, ischaemic time, time on renal replacement therapy prior to transplant and HLA mismatch at HLA-A, -B and -DR was conducted. In the multivariate analysis of recipient survival, diabetic nephropathy as primary renal disease was also included. Results: A total of 2395 kidney transplant recipients were analysed: 2062 (83.8%) with the 1st kidney transplant, 279 (11.3%) with the 2nd graft, 46 (2.2%) with the 3rd+. Mean age of 1st kidney transplant recipients was 43.6 ± 16.3 years, versus 39.9 ± 14.4 for 2nd and 41.4 ± 11.5 for 3rd+ (p < 0.001). Aside from being younger, repeated kidney transplant patients were also more often males (p = 0.006), with a longer time spent on renal replacement therapy (p < 0.0001) and a higher degree of sensitisation, expressed as calculated reaction frequency (p < 0.001). There was also an association between multiple kidney transplants and better HLA match at transplantation (p < 0.0001). A difference in death-censored graft survival by number of transplants was seen, with a median graft survival of 328 months for recipients of the 1st transplant, 209 months for the 2nd and 150 months for the 3rd+ (p = 0.038). The same difference was seen in deceased donor kidneys (p = 0.048), but not in grafts from living donors (p = 0.2). Patient survival was comparable between the three groups (p = 0.59). Conclusions: In the attempt to expand the organ donor pool, particular attention should be reserved to high complex recipients, such as the repeated kidney transplant population. In this peculiar context, the quality of the donor has been shown to represent a main determinant for graft survival—in fact, kidney retrieved from living donors provide comparable outcomes to those from single-graft recipients. Full article

(1) Background: Little is currently known about the health impacts of daily-life moderate-to-vigorous physical activity (MVPA) in relation to the development of post-transplant diabetes mellitus (PTDM) and the long-term survival of renal transplant recipients (RTRs). (2) Methods: We analyzed self-reported data on MVPA within non-occupational and occupational domains, estimated with the SQUASH questionnaire, from a prospective cohort study of RTRs (n = 650) with a functioning graft exceeding 1 year. PTDM diagnoses were based on plasma glucose levels (≥126 mg/dL), HbA1c (≥6.5%), and the use of antidiabetic medication. Mortality data were retrieved from patient files up to the end of September 2015. (3) Results: During a median follow-up period of 5.3 years, 50 patients (10%) developed PTDM and 129 (19.8%) died. Of these deaths, 53 (8.9%) were caused by cardiovascular disease. Cox regression analyses showed that higher MVPA levels among patients were associated with a lower risk of PTDM (hazard ratio (HR); 95% confidence interval (95%CI) = 0.49; 0.25–0.96, p = 0.04), cardiovascular- (0.34; 0.15–0.77, p = 0.01), and all-cause mortality (0.37; 0.24–0.58, p < 0.001) compared with No-MVPA patients, independently of age, sex, and kidney function parameters. Associations of MVPA with cardiovascular and all-cause mortality remained significant and materially unchanged following further adjustments made for transplant characteristics, lifestyle factors, metabolic parameters, medication use, and creatinine excretion (muscle mass). However, the association between MVPA and PTDM was no longer significant after we adjusted for metabolic confounders and glucose levels. (4) Conclusion: Higher MVPA levels are associated with long-term health outcomes in RTRs. Full article

The aim of this study was to determine whether anti-angiotensin type 1 receptor antibodies (AT1R-Abs) are related to acute rejection (AR) and kidney graft failure in renal transplantation. We searched electronic databases including MEDLINE, EMBASE, and the ISI Web of Science databases for all studies on the association between anti-angiotensin type 1 receptor antibodies and kidney allograft outcomes updated to November 2016. Reference lists from included articles were also reviewed. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were extracted or calculated using a random-effects model. The potential sources of heterogeneity and publication bias were estimated. Nine studies enrolling 1771 subjects were retrieved in the meta-analysis. AT1R-Abs showed significant associations with increased risk of AR (RR = 1.66; 95% CI, 1.23–2.09). In addition, a significant relationship was found between AT1R-Abs and kidney graft failure compared with AR (RR = 3.02; 95% CI, 1.77–4.26). The results were essentially consistent among subgroups stratified by participant characteristics. These results demonstrated that the AT1R-Abs were associated with an elevated risk of kidney allograft outcomes, especially with kidney graft failure. Large-scale studies are still required to further verify these findings. Full article