We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell–related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group—namely, the tolerant recipients—were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS‐independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross‐validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.
This study demonstrates that it is feasible to safely transplant potential PT recipients aged 50 and above. However, good medical assessment and careful patient selection is strongly recommended.
Study Type – Therapy (case series)
Level of Evidence 4
What’s known on the subject? and What does the study add?
The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation.
Post‐transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre‐transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre‐transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy.
OBJECTIVE
To analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation.
PATIENTS AND METHODS
A retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken.
RESULTS
There were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43–65).
Twenty patients were in the pre‐transplant nephrectomy group, 12 in the post‐transplant group, and three underwent the sandwich technique.
Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety).
Seven individuals in the pre‐transplant group and three in the post‐transplant group required critical care admission after nephrectomy.
Transient renal graft dysfunction occurred in two post‐transplant bilateral nephrectomy patients.
Two patients in the bilateral nephrectomy pre‐transplant group and one in the bilateral nephrectomy post‐transplant group died in the immediate post‐operative period.
No complications were noted in the sandwich technique group.
CONCLUSION
Native nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre‐transplant group.
Post‐transplant unilateral nephrectomy appears to be the safest approach with fewest complications.
TRAS is a recognized complication resulting in loss of renal allografts. Early Doppler ultrasound is a good primary diagnostic tool. Early intervention is associated with a good long-term graft function.
Type 1 diabetics with renal failure listed for pancreas transplantation are at a significant risk of mortality even without surgery. Transplantation offers considerable survival benefits, despite associated surgical and immunosuppressive risks. In selected patients, pancreas transplantation remains the benchmark treatment for type 1 diabetes mellitus.
the reperfusion phase of infrarenal aortic cross-clamping provokes a significant increase in pulmonary NOS metabolism. The increase in plasma TNF-alpha and MPO activity suggests that this response may be secondary to inducible NOS expression. Manipulation of this response may benefit patients at risk of acute injury following infrarenal aortic reconstruction.
Kidney transplantation is the treatment of choice for management of end-stage renal disease. However, in diabetic patients, the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation. Pancreatic transplantation in humans was first introduced in 1966. The initial outcome was disappointing. However, this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies. Combined kidney and pancreas transplantation will not only solve the problem of organ failure, but it will also stabilise or even reverse the metabolic complications of diabetes. Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure. Nevertheless, at the cost of an initial increase in morbidity and risk of mortality. Other transplantation options include pancreas after kidney transplantation and islet cell transplantation. We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease. Our work will provide a simplified, yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.