Significance of steatosis in pancreatic transplantation.

The on-going success of whole organ pancreatic transplantation is dependent on overcoming the imbalance between demand and supply of optimal organs as well as tackling the vast comorbidity associated with the procedure. Pancreas steatosis is a common contributing factor to the problem and with obesity pandemics affecting the global population; the size and type of organs received from donors will only make steatosis more of an issue. The aim of this review is to highlight what is known about steatosis in the context of pancreas transplantation identifying potential methods to help its evaluation. Narrative review of literature from inception to June 2017, using OVID interface searching EMBASE and MEDLINE databases as well recent transplant conference data. All studies related to pancreas steatosis examined for clinical relevance with no exclusion criteria. Key ideas extracted and referenced. Pancreatic steatosis is not innocuous and is precariously regarded by transplant surgeons, however its associations with obesity, metabolic syndrome and long list of associated complications clearly show it needs more careful consideration. Radiologic and surgical advances now allow assessment of the fat content of organs, which could be used to quantify organs allowing better optimisation, but there is still much work to be done to refine the optimal method to achieve this.

Transplantation of Kidneys From Donors With Acute Kidney Injury: Friend or Foe?

The gap between supply and demand in kidney transplantation has led to increased use of marginal kidneys; however, kidneys with acute kidney injury are often declined/discarded. To determine whether this policy is justified, we analyzed outcomes of donor kidneys with acute kidney injury (AKI) in a large UK cohort. A retrospective analysis of the UK Transplant Registry evaluated deceased donors between 2003 and 2013. Donors were classified as no AKI, or AKI stage 1-3 according to Acute Kidney Injury Network (AKIN) criteria. Relationship of AKI with delayed graft function/primary nonfunction (DGF/PNF), estimated glomerular filtration rate (eGFR), and graft-survival at 90 days and 1 year was analyzed. There were 11 219 kidneys (1869 [17%] with AKI) included. Graft failure at 1 year is greater for donors with AKI than for those without (graft survival 89% vs. 91%, p = 0.02; odds ratio (OR) 1.20 [95% confidence interval (CI): 1.03-1.41]). DGF rates increase with donor AKI stage (p < 0.005), and PNF rates are significantly higher for AKIN stage 3 kidneys (9% vs. 4%, p = 0.04) Analysis of association between AKI and recipient eGFR suggests a risk of inferior eGFR with AKI versus no AKI (p < 0.005; OR 1.25 [95% CI: 1.08-1.31]). We report a small reduction in 1-year graft-survival of kidneys from donors with AKI. We conclude that AKI stage 1 or 2 kidneys should be used; however, caution is advised for AKI stage 3 donors.

Challenges in pancreas transplantation.

Whole-organ pancreas transplantation, either alone or combined with a kidney transplant, is the only definitive treatment for many patients with type 1 diabetes that restores normal glucose homoeostasis and insulin independence. Pancreas transplantation delays, or potentially prevents, secondary diabetes complications and is associated with improvement in patient survival when compared with either patients remaining on the waiting list or those receiving kidney transplant alone. Pancreas transplantation is safe and effective, with 1-year patient survival >97 % and graft survival rates of 85 % at 1 year and 76 % at 5 years in recent UK data. This review focuses on some current areas of interest in pancreas transplantation.

Realistic evaluation of Situation Awareness for Everyone (SAFE) on paediatric wards: study protocol.

INTRODUCTION: Evidence suggests that health outcomes for hospitalised children in the UK are worse than other countries in Europe, with an estimated 1500 preventable deaths in hospital each year. It is presumed that some of these deaths are due to unanticipated deterioration, which could have been prevented by earlier intervention, for example, sepsis. The Situation Awareness For Everyone (SAFE) intervention aims to redirect the 'clinical gaze' to encompass a range of prospective indicators of risk or deterioration, including clinical indicators and staff concerns, so that professionals can review relevant information for any given situation. Implementing the routine use of huddles is central to increasing situation awareness in SAFE. METHODS AND ANALYSIS: In this article, we describe the realistic evaluation framework within which we are evaluating the SAFE programme. Multiple methods and data sources are used to help provide a comprehensive understanding of what mechanisms for change are triggered by an intervention and how they have an impact on the existing social processes sustaining the behaviour or circumstances that are being targeted for change. ETHICS AND DISSEMINATION: Ethics approval was obtained from London-Dulwich Research Ethics Committee (14/LO/0875). It is anticipated that the findings will enable us to understand what the important elements of SAFE and the huddle are, the processes by which they might be effective and-given the short timeframes of the project-initial effects of the intervention on outcomes. The present research will add to the extant literature by providing the first evidence of implementation of SAFE and huddles in paediatric wards in the UK.

De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure.

This study assesses the role of posttransplant HLA antibody monitoring in the surveillance of pancreas transplant recipients. Four hundred thirty-three pancreas transplants were performed at the Oxford Transplant Centre 2006-2011 (317 simultaneous pancreas kidney [SPK] and 116 isolated pancreas [IP]). HLA antibody monitoring was performed at 0, 6 and 12 months and annually and during clinical events. There was no association between pancreas graft failure and recipient or donor characteristics. Posttransplant antibody status, available for 354 (81.8%) of recipients, demonstrated that 141 (39.8%) developed de novo HLA antibodies, of which 52 (36.9%) were de novo donor-specific HLA antibodies (DSA) (34 SPK, 18 IP). The development of antibodies to donor HLA, but not to nondonor HLA, was significantly associated with poorer graft outcomes, with 1- and 3-year graft survival inferior in SPK recipients (85.2% vs. 93.5%; 71.8% vs. 90.3%, respectively; log-rank p = 0.002), and particularly in IP recipients (50.0% vs. 82.9%; 16.7 vs. 79.4%, respectively; log-rank p = 0.001). In a multivariate analysis, development of de novo DSA emerged as a strong independent predictor of pancreas graft failure (hazard ratio 4.66, p < 0.001). This is the largest study to examine de novo HLA antibodies following pancreas transplantation and clearly defines a high-risk group in need of specific intervention.

Erythropoietin in experimental acute renal failure.

The haematopoietic factor erythropoietin (EPO) has recently been recognized to play a physiological role in the brain and other tissues. The EPO receptor is present in the glomerulus, mesangial and tubular epithelial cells in the kidney. We have reviewed the experimental use of EPO in animal models of acute renal failure. EPO attenuates the dysfunction and histological changes associated with ischaemia-reperfusion injury, with a reduction in apoptotic cell death. EPO has also shown benefit in animal models of systemic shock and cisplatin-induced nephrotoxicity. In vitro studies have shown that EPO has direct effects on proliferation and cell death in proximal tubular epithelial cells. There is increasingly strong experimental evidence that EPO may be of therapeutic use in acute renal failure, and clinical trials should be undertaken to determine its clinical applications in this field.

Sarcoid tubulo-interstitial nephritis: long-term outcome and response to corticosteroid therapy.

Sarcoidosis is a chronic relapsing multi-systemic disorder characterized by the development of non-caseating granulomas. Granulomatous tubulo-interstitial nephritis is an uncommon manifestation of this condition. We identified 39 patients with sarcoidosis and renal disease from a single center of whom 17 patients had biopsy-proven tubulo-interstitial nephritis. They were analyzed with respect to demographic and clinical features, including response to corticosteroids and length of follow-up. They all presented with significant renal impairment. At presentation the mean+/-s.d. estimated glomerular filtration rate (eGFR) was 26.8+/-14 ml/min by modification of diet in renal disease (MDRD) equation 7. With treatment there was a significant improvement in renal function with eGFR 49.6+/-5.2 ml/min (P<0.01) at 1 year, and 47.9+/-6.8 ml/min (P<0.05) at the last review. The median follow-up was 84 months (range 6-284 months). Patients with chronic kidney disease (CKD) 3, the mean eGFR was 38.30+/-2.4 ml/min at presentation and 60.2+/-7.4 ml/min at 1 year (P=0.02) and in CKD 4 it improved from 19+/-2 to 38+/-6.6 ml/min at 1 year (P<0.05). After the 1st year, the change in eGFR was +0.8 ml/min/year for CKD 3 and -2 ml/min/year for CKD 4 (P<0.05). Three patients ceased their therapy either due to complications or poor compliance and experienced a worsening of renal function which was then reversed on re-commencing corticosteroids. Corticosteroids are effective in advanced tubulo-interstitial nephritis due to sarcoidosis. Long-term treatment is necessary to preserve renal function and to delay the onset of end-stage renal disease.