Extracellular vesicles in kidney transplantation: a state-of-the-art review.

Kidney transplantation is the optimal treatment for patients with kidney failure; however, early detection and timely treatment of graft injury remain a challenge. Precise and noninvasive techniques of graft assessment and innovative therapeutics are required to improve kidney transplantation outcomes. Extracellular vesicles (EVs) are lipid bilayer-delimited particles with unique biosignatures and immunomodulatory potential, functioning as intermediaries of cell signalling. Promising evidence exists for the potential of EVs to develop precision diagnostics of graft dysfunction, and prognostic biomarkers for clinician decision making. The inherent targeting characteristics of EVs and their low immunogenic and toxicity profiles combined with their potential as vehicles for drug delivery make them ideal targets for development of therapeutics to improve kidney transplant outcomes. In this review, we summarize the current evidence for EVs in kidney transplantation, discuss common methodological principles of EV isolation and characterization, explore upcoming innovative approaches in EV research, and discuss challenges and opportunities to enable translation of research findings into clinical practice.

Anastomosis of dual renal transplant veins.

As there is usually considerable overlap in the renal venous drainage, it is often possible to ligate supernumerary transplant renal veins in order to simplify the implantation procedure. Nonetheless, decisions about whether to implant multiple veins can be difficult and are usually made subjectively. Here, we describe the use of intraoperative Doppler ultrasound as an adjunct to decision-making when there are two renal veins and a novel technique for the sequential anastomosis of dual veins. The kidney was reperfused after anastomosis of the main renal vein with the second vein clamped. On-table Doppler ultrasound demonstrated reversed flow in diastole indicating that the second renal vein also needed to be anastomosed. By clamping the external iliac vein inferior to the first venous anastomosis it was possible to complete the lower polar renal vein anastomosis to the external iliac vein without interrupting the perfusion of the kidney.

Pre-emptive immunosuppression using tacrolimus monotherapy does not reduce the rate of early acute rejection in renal transplantation from live donors: a comparative cohort study.

The planned nature of live donor kidney transplantation allows for immunosuppression to be initiated in the pretransplant period. The aim of this study was to determine the effect of pre-emptive immunosuppression on acute rejection rates after live donor kidney transplantation. In two consecutive cohorts of live donor kidneys transplants, 99 patients received pre-emptive immunosuppression with tacrolimus monotherapy for 2 weeks prior to transplantation (PET group - first era) and 100 patients received tacrolimus-based immunosuppression commencing on the day of transplantation (control group - second era). The main outcome measure was the incidence of biopsy-proven acute rejection (BPAR) in the first 3 months post-transplantation. Tacrolimus levels were significantly higher in the PET group at day 4 post-transplant (PET 9.08 ± 4.57 vs. control 5.92 ± 3.64 ng/ml; P < 0.0001), but there were no significant differences in tacrolimus levels at day 7 (PET 8.22 ± 3.58 vs. control 7.63 ± 3.56 ng/ml; P = 0.2452). BPAR was numerically higher in the PET group, but this difference did not reach statistical significance (PET 13/99 vs. control 6/100; P = 0.097). There were no differences in allograft function measured by serum creatinine at 1 year (PET 130 ± 36 vs. control 142 ± 69 µmol/l; P = 0.6829). Graft survival at 1 year was equivalent in both groups (PET 96.9 vs. control 97.0%; P = 0.9915). This study suggests that there is little role for the use of pre-emptive tacrolimus monotherapy in ABO blood group and HLA-compatible live donor kidney transplantation in patients on triple maintenance immunosuppression.

Immediate Impact of Centralization on Abdominal Aortic Aneurysm Repair Outcomes for a Vascular Network in the South West of England: A Retrospective Cohort Study.

OBJECTIVE: Our aim was to assess the short-term impact of centralization on the outcomes of patients undergoing abdominal aortic aneurysm repair in a vascular network in the South West of England. BACKGROUND: The centralization of vascular services has been implemented nationally across the National Health Service to improve patient outcomes. The full impact of these major changes has not yet been fully analyzed. METHODS: A retrospective cohort study examining outcomes of patients undergoing abdominal aortic aneurysm repair, based on prospectively entered National Vascular Registry data, pre and post centralization in the South West of England. The primary outcome was mortality at 30 days. Secondary measures included 30-day morbidity, length of hospital stay, and length of intensive care unit stay. RESULTS: The 30-day mortality was unchanged pre and post-centralization (11% vs 12%, P = 0.84). The 30-day morbidity rate was also unchanged (24% vs 25%, P = 0.83), as was length of intensive care unit stay (3 vs 3 days, P = 0.74). Overall length of stay was not significantly different (8 vs 6 days, P = 0.76). Subgroup analysis of patients with elective, ruptured, and symptomatic aneurysm repair demonstrated no differences in 30-day mortality. There was a significantly shorter stay post-centralization for patients with symptomatic aneurysms (6 vs 12 days pre-centralization, P = 0.012). CONCLUSIONS: The process of centralization of abdominal aortic aneurysm repair in a vascular network was safe for patients and had no immediate impact on outcomes. Longer-term outcome measures and financial data will be required to further assess the benefit of centralization.

Sweet syndrome: a lesson in the management of the cutaneous lesions of malignancy.

We present the case of a lady with rapidly growing haemorraghic bullae in the digits of both hands. There was no effect of antibiotics and surgical debridement was detrimental. The lesions regressed following steroid therapy. We discuss the cutaneous complications of haematological malignancies. We emphasize the importance of avoiding surgery in these cases and explain that immunosuppressive therapy should form the basis of treatment.