Prophylactic Ureteric Stents in Renal Transplant Recipients: A Multicenter Randomized Controlled Trial of Early Versus Late Removal.

Prophylactic ureteric stenting in renal transplantation reduces major urological complications; however, morbidity is related to the indwelling duration of a stent. We aimed to determine the optimal duration for stents in this clinical setting. Patients (aged 2-75 years) from six UK hospitals who were undergoing renal transplantation were recruited and randomly assigned to either early stent removal at 5 days (without cystoscopy) or late removal at 6 weeks after transplantation (with cystoscopy). The primary outcome was a composite of stent-related complications defined as pain, visible hematuria, migration, fragmentation, and urinary tract infections (UTIs) within 3 mo of transplantation. Between May 2010 and Nov 2013, we randomly assigned 227 participants, with 205 included in the final analysis of the primary outcome. Stent-related complications were significantly higher in the late versus early stent removal groups (36 of 126 [28.6%] vs. 6 of 79 [7.6%]; p < 0.001). The majority of stent complications consisted of UTIs, with an incidence of 31 of 126 (24.6%) in the late group compared with 6 of 79 (7.6%) in the early group (p = 0.004). We found early stent removal on day 5 significantly reduced stent-related complications and improved quality of life in the first 3 mo after transplantation (ISRCTN09184595).

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

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.

Distributed expertise: qualitative study of a British network of multidisciplinary teams supporting parents of children with chronic kidney disease.

BACKGROUND: Long-term childhood conditions are often managed by hospital-based multidisciplinary teams (MDTs) of professionals with discipline specific expertise of a condition, in partnership with parents. However, little evidence exists on professional-parent interactions in this context. An exploration of professionals' accounts of the way they individually and collectively teach parents to manage their child's clinical care at home is, therefore, important for meeting parents' needs, informing policy and educating novice professionals. Using chronic kidney disease as an exemplar this paper reports on one aspect of a study of interactions between professionals and parents in a network of 12 children's kidney units in Britain. METHODS: We conducted semi-structured, qualitative interviews with a convenience sample of 112 professionals (clinical-psychologists, dietitians, doctors, nurses, pharmacists, play-workers, therapists and social workers), exploring accounts of their parent-educative activity. We analysed data using framework and the concept of distributed expertise. RESULTS: Four themes emerged that related to the way expertise was distributed within and across teams: (i) recognizing each other's' expertise, (ii) sharing expertise within the MDT, (iii) language interpretation, and (iv) acting as brokers. Two different professional identifications were also seen to co-exist within MDTs, with participants using the term 'we' both as the intra-professional 'we' (relating to the professional identity) when describing expertise within a disciplinary group (for example: 'As dietitians we aim to give tailored advice to optimize children's growth'), and the inter-professional 'we' (a 'team-identification'), when discussing expertise within the team (for example: 'We work as a team and make sure we're all happy with every aspect of their training before they go home'). CONCLUSIONS: This study highlights the dual identifications implicit in 'being professional' in this context (to the team and to one's profession) as well as the unique role that each member of a team contributes to children's care. Our methodology and results have the potential to be transferred to teams managing other conditions.

Mitochondrial disorders and general anaesthesia: a case series and review.

Patients with mitochondrial disease are at risk of metabolic decompensation and often require general anaesthesia (GA) as part of their diagnostic work up and subsequent management. However, the evidence base for the use of GA is limited and inconclusive. We have documented the practice and outcome in the use of GA in paediatric patients with mitochondrial disease using a retrospective case review study of 38 mitochondrial patients who had undergone 58 anaesthetics within the regional metabolic service for the period 1989-2005. A variety of anaesthetic agents were used and the pattern of use reflects that seen in standard paediatric practice. There were no episodes of malignant hyperthermia and no documented intraoperative events attributable to the GA. Three postoperative adverse events were noted; one episode of hypovolaemia, one episode of acute on chronic renal failure, and one episode of metabolic decompensation 12 h post-muscle biopsy. Despite theoretical concern about this group of patients, adverse events after GA are rare and in most cases unrelated to the anaesthesia. Further prospective studies of GA in mitochondrial disease are required to create evidence-based clinical guidelines for safe practice.

Measles-associated encephalopathy in children with renal transplants.

Two children, boys of 8 and 13 years, presented with measles-associated encephalopathy several years after kidney transplantation for congenital nephrotic syndrome. In the absence of prior clinical measles, the neurological symptoms initially eluded diagnosis, but retrospective analysis of stored samples facilitated the diagnosis of measles-associated encephalopathy without recourse to biopsy of deep cerebral lesions. Each had received a single dose of measles mumps and rubella vaccine before 12 months of age. Prior vaccination, reduction of immunosuppression and treatment with intravenous immunoglobulin and ribavirin may have contributed to their survival. Persistent measles virus RNA shedding, present in one child, was not controlled by treatment with i.v. ribavirin. Two years later, both patients continue to have functioning allografts with only minimal immunosuppression. These cases illustrate the difficulty in diagnosing measles-associated encephalopathy in the immunocompromised host, even in the era of molecular diagnostics, and highlight the renewed threat of neurological disease in communities with incomplete herd immunity.