Andrew Connor

Consensus guidelines for the safe prescription and administration of oral bowel-cleansing agents

Oral bowel-cleansing preparations are used before colonic surgery and endoscopic and radiological assessment of the intestine to minimise faecal contamination. In February 2009, the UK National Patient Safety Agency issued a Rapid Response Report highlighting the potential risk of harm associated with the use of these preparations and instructing local NHS Trusts to implement safeguards to reduce this risk. This guidance has been prepared to help NHS Trusts to respond to these concerns, as the risk of complications is influenced by both individual patient risk factors and the choice of bowel preparation, for which definitive guidance was not previously available. This document provides an outline of the different available oral bowel-cleansing agents and the complications that may arise. This is followed by recommendations for their use in different patient groups and circumstances. The recommendations are based on consensus between the authors, each of whom circulated drafts to members of their specialist society. The evidence for these recommendations has been assessed using the modified GRADE system. The recommendations cover the choice, administration and complications (relative and absolute) of the different oral bowel-cleansing agents, with specific guidance provided for different patient groups.

Clinical transformation: the key to green nephrology.

Climate change represents a major global public health threat. The very provision of healthcare itself has a significant untoward effect on the environment, to which kidney care is likely to contribute disproportionately. In this article we describe the four principles we believe will underpin a successful transformation to lower carbon kidney care: disease prevention, patient empowerment, lean service delivery and the preferential use of low-carbon technologies. We illustrate their application and their co-benefits, such as improvements in patient care and reductions in cost, with examples.

THE GREEN NEPHROLOGY SURVEY OF SUSTAINABILITY IN RENAL UNITS IN ENGLAND, SCOTLAND AND WALES

The impact of unmitigated climate change upon global health is predicted to be disastrous. However, the very provision of healthcare itself has a significant environmental impact, and the contribution of kidney care to the carbon footprint of the NHS is likely to be disproportionately high. Furthermore, the current economic climate will ensure that healthcare systems face unprecedented reductions in resources (or, at the very least, diminished expansion in the face of ongoing increases in demand). Improvements in the way that renal services use resources will address both issues. This survey was designed to identify a baseline for sustainability in kidney care, to support a clinical transformation to lower carbon kidney care by identifying fruitful areas for attention, and to act as an educational tool. The survey identified measures for improvement across the different areas of the provision of kidney care, including building energy use, patient and staff transport, water use and the consumption and procurement of resources. The results of the survey, which was completed by 58 adult and paediatric renal units across England, Scotland, and Wales, are reported here and potential changes are discussed.SUMMARY The impact of unmitigated climate change upon global health is predicted to be disastrous. However, the very provision of healthcare itself has a significant environmental impact, and the contribution of kidney care to the carbon footprint of the NHS is likely to be disproportionately high. Furthermore, the current economic climate will ensure that healthcare systems face unprecedented reductions in resources (or, at the very least, diminished expansion in the face of ongoing increases in demand). Improvements in the way that renal services use resources will address both issues. This survey was designed to identify a baseline for sustainability in kidney care, to support a clinical transformation to lower carbon kidney care by identifying fruitful areas for attention, and to act as an educational tool. The survey identified measures for improvement across the different areas of the provision of kidney care, including building energy use, patient and staff transport, water use and the consumption and procurement of resources. The results of the survey, which was completed by 58 adult and paediatric renal units across England, Scotland, and Wales, are reported here and potential changes are discussed.

Generic tacrolimus in renal transplantation: trough blood concentration as a surrogate for drug exposure.

The use of generic formulations of immunosuppressive drugs in place of brand-name drugs offers considerable cost savings. Adoport (Sandoz, Camberly, Surrey, United Kingdom), an immediaterelease, twice-daily, oral tacrolimus preparation (1), was introduced to the United Kingdom in August 2010. Although both pharmaceutical and bioequivalence with the originator product, Prograf (Astellas Pharma US, Inc., Deerfield, IL), have been demonstrated for licensing purposes (2), recent guidance on the substitution of generic immunosuppressant drugs has highlighted the possibility that the relationship between the exposure to the drug and the surrogate marker may vary between formulations (3), particularly in routine clinical practice. The narrow therapeutic index of tacrolimus (4) and the potential adverse consequences of subtherapeutic and toxic concentrations necessitate close monitoring of patients’ exposure to the drug. Twelve-hour pharmacokinetic profiles are the most exact method for monitoring the area under the concentration-time curve (AUC) and hence the total tacrolimus exposure. However, they require that the tacrolimus concentration is measured at a minimum of six different time points (5). Instead, tacrolimus trough concentrations (C0) are commonly measured as a surrogate for the AUC, although there have been conflicting reports regarding the correlation of C0 with AUC and systemic exposure (6Y10). For cost reasons, the South West Transplant Centre switched from administering Prograf to Adoport for de novo transplant recipients on November 1, 2010. We sought to evaluate the relationship between C0 and the AUC in patients receiving Adoport during the acute phase after renal transplantation. Serial tacrolimus concentrations were measured on day 4 or 5 after transplantation in 16 sequential patients (11 men and 5 women) not receiving medications known to interact with tacrolimus. The mean age was 56 years (range, 31Y72 years). Thirteen patients received donation after cardiac death organs, and three patients received living-donor transplants. Thirteen patients received basiliximab at induction, for whom Adoport was commenced on day 0 at 0.10 mg/kg in two divided doses with a target C0 of 8 to 10 ng/mL. Three patients received alemtuzumab at induction, for whom Adoport was commenced on day 3 after transplantation at a dose of 2 mg twice daily with a target C0 of 5 to 7 ng/mL. It was intended that patients fasted overnight before administration of Adoport to control for the effects of food on tacrolimus absorption (11). Whole-blood samples were collected before administration and at 0.5, 1, 2, 4, 8, and 12 hr after administration of Adoport. Tacrolimus concentrations were determined in ethylenediaminetetraacetic acid whole blood using liquid chromatographyYmass spectrometry. The lower limit of quantification was 2.0 ng/mL. The AUC was calculated from the timeversus-tacrolimus plot, using the linear trapezoid rule. The C0 values were determined by using the whole-blood tacrolimus concentration measured at 12 hr. The mean dose of Adoport was 0.09 (T0.03) mg/kg per day, and the mean AUC was 136.0 (T78.2) ng hr/mL. The mean C0 was 7.9 (T4.8) ng/mL. The linear regression coefficient of multiple determination (r) for the relationship between C0 and the AUC was 0.92. The mean dose-normalized AUC was 3327 (T2389) ng hr/mL. The mean dosenormalized C0 was 196 (T146) ng/mL. The 12-hr pharmacokinetic profiles for these patients, and the correlation between the AUC and the C0, are shown in Figure 1. The coefficient of determination for the relationship between C0 and AUC for Prograf has been reported to lie between 0.125 and 0.86 (7, 8, 10, 12Y14). The variability in these correlations may be attributable to a number of factors, including differences in the

Renal impairment resulting from hypothyroidism

We describe two cases of reversible renal impairment secondary to hypothyroidism. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

A reliable method for avoiding false negative results with Luminex single antigen beads; evidence of the prozone effect

Luminex single antigen bead (SAB) assays have become an essential tool in monitoring the status of antibody to the Human Leucocyte Antigen (HLA) of patients both before and after transplantation. In addition SAB data is used to aid risk stratification to assess immunological risk of humoral rejection in solid organ transplantation (CTAG/BTAG guidelines) [1]. Increasingly laboratories are reporting false negative results at high antibody titre due to a prozone effect. Here we report a case study where the prozone effect led to a false negative antibody result that could have resulted in adverse outcome. We describe a method to reliably remove the prozone effect through heat inactivation and the addition of Ethylenediaminetetraacetic acid (EDTA) to the Luminex wash buffer.

A single-centre comparison of the clinical outcomes at 6 months of renal transplant recipients administered Adoport ® or Prograf ® preparations of tacrolimus

Background The use of generic formulations of immunosuppressive drugs in place of brand name drugs offers considerable cost savings. Brand name tacrolimus (Prograf®) came off patent in April 2008. However, published evidence supporting therapeutic equivalence of generic formulations of tacrolimus in solid organ transplantation is lacking. The South West Transplant Centre switched from administering Prograf® to a generic formulation (Adoport®) for de novo transplant recipients in November 2010. This study sought to compare the clinical outcomes of renal transplant recipients administered Prograf® with those receiving Adoport®. Methods Data regarding patient characteristics and clinical outcomes were collected retrospectively for all patients undergoing renal transplantation at the South West Transplant Centre between 8 November 2009 and 8 November 2011 to whom tacrolimus was prescribed. Results A total of 48 patients received Prograf® and 51 received Adoport®. At 6 months, no statistically significant differences were identified in the rates of patient survival, graft survival, acute allograft rejection, delayed graft function, calcineurin inhibitor toxicity or cytomegalovirus infection occurring within the two groups. Conclusions This is the first study to compare the clinical outcomes of patients receiving Adoport® with those receiving brand name tacrolimus. We report comparable clinical outcomes at 6 months in patients receiving either Prograf® or Adoport® from the time of renal transplantation. These early outcome data therefore support the use of Adoport® in place of Prograf® as a potential cost-saving measure.

Outlook: Implications of climate change for nephrology

It is now accepted that climate change is occurring as a result of human activity and that it will have potentially devastating effects on health. Nephrologists are likely to see a changing spectrum of disease as a consequence of climate change and are ideally placed to lead mitigating strategies in health-care provision.

Transplantation of a Gitelman Syndrome Kidney Ameliorates Hypertension: A Case Report

Gitelman syndrome is caused by inactivating mutations of the gene that encodes the renal sodium/chloride cotransporter (NCC; encoded by SLC12A3), resulting in hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Renal salt wasting commonly provokes mild hypotension. The paucity of previous kidney transplants from donors with known tubulopathies suggests that such conditions may be considered contraindications to donation. A 76-year-old man received a live unrelated kidney transplant from a donor with known Gitelman syndrome secondary to a pathogenic mutation of SLC12A3. Immediate graft function preceded the emergence of the Gitelman syndrome biochemical phenotype and blood pressure subsequently improved. The recipient developed unexpected hyponatremia. Potential causes are discussed, including the possibility that it paralleled the physiologic changes seen in the high-volume state of thiazide-induced hyponatremia. Transplanted kidneys are subject to nephrotoxicity from the use of calcineurin inhibitors. Acquired Gitelman syndrome may confer a potential long-term advantage to the recipient through both improved blood pressure control and protection against the calcineurin inhibitor-induced side-effect profile caused by NCC overactivation. Both the donor and recipient remain well. In conclusion, Gitelman syndrome need not preclude kidney donation and transference of the phenotype may have benefits for the recipient.