Outpatient ureteric stent removal following kidney transplantation.

During a kidney transplant, a plastic tube (stent) is placed in the ureter, connecting the new kidney to the bladder, in order to keep the new join open during the initial phase of transplantation. The stent is then removed after a few weeks via a camera procedure (cystoscopy), as it is no longer needed. The present study compared performing this in the operating theatre or in clinic for transplanted patients using a new single-use type of camera with an integrated grasper system. The results have shown that it is safe and cost-effective to do this in clinic, despite patients being susceptible to infection after transplantation.

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation.

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002-2003 and 2011-2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.

Successful transplantation of kidneys from elderly circulatory death donors by using microscopic and macroscopic characteristics to guide single or dual implantation.

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.

Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys.

Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.

Early graft loss after kidney transplantation: risk factors and consequences.

Early graft loss (EGL) after kidney transplantation is a catastrophic outcome that is assumed to be more likely after the use of kidneys from suboptimal donors. We therefore examined its incidence, risk factors and consequences in our center in relation to different donor types. Of 801 recipients who received a kidney-only transplant from deceased donors, 50 (6.2%) suffered EGL within 30 days of transplantation. Significant risks factors for EGL were donation after circulatory death (DCD) (odds ratio [OR] 2.88; p = 0.006), expanded criteria donor (ECD) transplantation (OR 4.22; p = 0.010), donor age (OR 1.03; p = 0.044) and recipient past history of thrombosis (OR 4.91; p = 0.001). Recipients with EGL had 12.28 times increased risk of death within the first year, but long-term survival was worse for patients remaining on the waiting list. In comparison with patients on the waiting list but not transplanted, and with all patients on the waiting list, the risk of death after EGL decreased to baseline 4 and 23 months after transplantation, respectively. Our findings suggest that DCD and ECD transplantation are significant risk factors for EGL, which is a major risk factor for recipient death. However, long-term mortality is even greater for those remaining on the waiting list.

The generation and maintenance of serum alloantibody.

Donor-specific alloantibodies (DSA) mediate hyperacute and acute antibody-mediated rejection (AMR), which can lead to early graft damage and loss, and are also associated with chronic AMR and reduced long-term graft survival. Such alloantibodies can be generated by previous exposure to major histocompatibility (MHC) antigens (usually via blood transfusions, previous allografts or pregnancy) or can occur de novo after transplantation. Recent studies also suggest that non-MHC antibodies, including those recognising major histocompatibility complex class I-related chain A (MICA), MICB, vimentin, angiotensin II type I receptor may also have an adverse impact on allograft outcomes. In this review, we consider how the dose, route and context of antigen exposure influences DSA induction and describe factors which control the generation, maintenance and survival of alloantibody-producing plasma cells. Finally, we discuss the implications of these variables on therapeutic approaches to DSA.

Pancreas graft salvage using pancreatico-duodenectomy with enteric drainage.

As demand for donor pancreases increases, attempts are being made to utilize even marginal grafts for transplantation. Injury during pancreas recovery can predispose to posttransplant complications and graft loss. Early recognition and correction can salvage these grafts. The authors report an instance of poor segmental perfusion of the pancreas graft that was salvaged by pancreas head resection and enteric drainage through a Roux-en-Y pancreatico-jejunostomy.

Perioperative erythropoietin efficacy in renal transplantation.

BACKGROUND: There is no consensus on the usage of erythropoietin in the immediate postoperative period to prevent anemia and delayed graft function. METHODS: A retrospective case note audit of renal transplants included hemoglobin (Hb) and serum creatinine (Scr) values preoperatively as well as at days 7, 14, 30, 60, and 90. Patients were categorized as those receiving erythropoietin during the first 6 months posttransplant (Epo+ve) and those not receiving any erythropoietin (Epo-ve). RESULTS: Hb decreased from 12.4 +/- 1.6 g/L preoperatively to 9.5 +/- 1.5 g/L at day 14 and then rose to 10.5 +/- 1.6 g/L at 1 month and 12.4 +/- 1.7 g/L at 3 months. There was no difference in absolute Hb values in three transplant groups. Scr decreased from 597.0 +/- 200.1 mmol/L preoperatively to 254.1 +/- 196.9 mmol/L at day 14 and continued to fall to 163.8 +/- 98.9 mmol/L at 1 month and 147.8 +/- 66.9 mmol/L at 3 months. There was no difference in absolute Hb values and delayed graft function in the three transplant groups. CONCLUSION: With respect to anemia and delayed graft function, the use of erythropoietin in the first 3 months had little impact. We suggest that such an expensive medication may be safely omitted in the immediate postoperative period.

Oligodendroglial gliomatosis cerebri: (1)H-MRS suggests elevated glycine/inositol levels.

Oligodendroglial gliomatosis cerebri is very rare. We describe 42-year-old woman who had low-grade oligodendroglial gliomatosis cerebri confirmed on stereotactic biopsy. The diffuse nature of the tumour was apparent clinically, neurophysiologically, on MRI and on proton magnetic resonance spectroscopy (MRS). She also had an isolated, false-localising partial seventh nerve palsy. MRS, of which there are no previous reports, suggested elevated glycine/inositol levels. This might be explained by the cell lineage from which the tumour arose.

A Xenopus c-kit-related receptor tyrosine kinase expressed in migrating stem cells of the lateral line system.

The mammalian c-kit receptor tyrosine kinase gene is required during embryogenesis for the survival and/or proliferation of three migrating stem cell populations: primordial germ cells, haematopoietic stem cells and neural crest-derived melanoblasts. We have cloned a Xenopus gene, XKrk1, whose closest relative is c-kit. Differences in the expression pattern suggest that XKrk1 is not the Xenopus homologue of c-kit; however, it is expressed in a migrating stem cell population, the precursor cells for the mechanosensory lateral line system. XKrk1 is the first reported marker for lateral line stem cells.

Function of maternal cytokeratin in Xenopus development.

Intermediate filaments are ubiquitous in eukaryotic cells, but their functions are poorly understood. The Xenopus oocyte contains both messenger RNA and protein products of cytokeratin and vimentin genes in non-overlapping arrays. The cytokeratin filaments contain dimers of the type I (acidic) subunit XLK3a(19), and the type II (basic) subunit XCK1(8), polymerized to form a cortical network. These are homologues of the human simple epithelial keratins 19 and 8, respectively. After the first few cell cycles following fertilization these filaments become restricted to the superficial cells of the blastula. We have depleted the oocyte's store of the type II cytokeratin mRNA by injecting antisense oligodeoxynucleotides (oligos) and studied the effect on embryonic development. As zygotic transcription does not commence until the late blastula stage, there are at least 9 hours in which to see the effect of loss of function of this mRNA. We report here that the cytokeratin filaments become depleted in the cortical cells of the embryo. As a result, there is a loss of the 'compacted' epithelial surface of the blastula, an inability to close a wounded surface and defective gastrulation.

The role of intermediate filaments in early Xenopus development studied by antisense depletion of maternal mRNA.

The effects of depleting a maternal cytokeratin mRNA on the developing embryo are described. Cytokeratins are members of the intermediate filament family of cytoskeletal proteins, and are expressed in a cortical network of the superficial cytoplasm of the oocyte. After fertilisation, a new cortical network is built up, which comes to occupy only the most superficial cells of the blastula. The maternal cytokeratin mRNA is abundantly translated, both during oogenesis, and during oocyte maturation and after fertilisation. Depletion of the mRNA results in depletion of the cortical filaments at the blastula stage and leads to gastrulation abnormalities. We discuss the various possible control experiments required for antisense oligo depletion studies and the implications of these results for cytokeratin function.

Distinct distribution of vimentin and cytokeratin in Xenopus oocytes and early embryos.

We report the identity of a major component of Triton-insoluble extracts from Xenopus oocytes and early embryos. In a previous paper we showed that an antibody, Z9, cross-reacts with two polypeptides from such extracts (Mr 56,000 and 57,000) as well as Xenopus vimentin. Direct microsequencing of the Mr 57,000 protein shows near identity of three tryptic fragments with regions of the predicted amino acid sequence of XCK1(8), a basic cytokeratin whose mRNA is known to be expressed in Xenopus oocytes. We have raised an antibody, CK7, against a fusion protein generated from this cDNA. The specificity of this antibody has been tested using 1- and 2-dimensional immunoblotting, which show that it is specific for the Mr 56,000 and 57,000 proteins, suggesting that these two proteins may be the products of two non-allelic XCK1(8) genes. The antibody does not cross-react with vimentin. We have used CK7 to follow the distribution of XCK1(8) throughout development by immunoblotting and immunocytochemistry. In larval stages, strong staining is seen in the notocord, the apical epithelia of the gut, the mesentery, and a few cells in the spinal cord. In oocytes and early embryos, two distinct intermediate filament (IF) networks can be distinguished: a cortical cytokeratin network, and a deeper vimentin one. In addition, the oocyte germ plasm stains with Z9 but not CK7. We propose that such distinct distributions of each IF protein reflect functional differences during early development.

Identification of vimentin and novel vimentin-related proteins in Xenopus oocytes and early embryos.

We have made antibodies against fusion proteins of Xenopus vimentin. We show for the first time the distribution of vimentin in larval stages, where it is found in cells of mesenchymal origin, and in radial glial cells. In sections of Xenopus oocytes and early embryos, immunocytochemistry reveals the presence of an extensive cytoplasmic network, distributed in an animal-vegetal gradient. Germ plasm stains particularly strongly. The form of the IF proteins in this network is unusual. In immunoblot experiments the anti-vimentin antibodies detect a number of distinct proteins. We have identified those that are the products of the two known vimentin genes, by injection of synthetic mRNA transcribed from cloned vimentin cDNAs into oocytes, followed by two-dimensional Western blotting. This has demonstrated unambiguously that one Xenopus vimentin, Vim1, is present in oocytes and early embryos. However, two other immunoreactive proteins detected in Triton extracts of oocytes and early embryos are not the products of Vim1, since depletion of vimentin mRNA by antisense oligonucleotide injection has no effect on the synthesis of these proteins. These results suggest that novel IF-like proteins are expressed in Xenopus oocytes and early embryos.