Decisional Needs of People From Minority Ethnic Groups Around Living Donor Kidney Transplantation: A UK Healthcare Professionals' Perspective.

Despite improved patient and clinical outcomes, living donor kidney transplantation is underutilized in the United Kingdom, particularly among minority ethnic groups, compared to deceased donor kidney transplantation. This may in part be due to the way in which kidney services present information about treatment options. With a focus on ethnicity, semi structured interviews captured the views of 19 kidney healthcare professionals from two renal centres in West Yorkshire, about the decisional needs and context within which people with advanced kidney disease make transplant decisions. Data were analysed using thematic analysis. Themes were categorized into three groups: 1) Kidney healthcare professionals: language, cultural awareness, trusted personnel, and staff diversity, 2) Patient information resources: timing and setting of education and suitability of patient-facing information and, 3) People with advanced kidney disease: knowledge, risk perception, and cultural/religious beliefs. To our knowledge, this is the first study in the United Kingdom to investigate in depth, healthcare professionals' views on living donor kidney transplantation decision making. Six recommendations for service improvement/delivery to support decision making around living donor kidney transplantation among minority ethnic groups are described.

Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure. Methods: Prospective, open-labelled randomised biomarker-based strategy (hybrid) trial in 13 UK transplant centres [EudraCT (2012-004308-36) and ISRCTN (46157828)]. Patients were randomly allocated (1:1) to unblinded or double-blinded arms and screened every 8 months. Unblinded HLA Ab+ patients were interviewed to encourage medication adherence and had tailored optimisation of Tacrolimus, Mycophenolate mofetil and Prednisolone. The primary outcome was time to graft failure in an intention to treat analysis. The trial had 80% power to detect a hazard ratio of 0.49 in donor specific antibody (DSA)+ patients. Findings: From 11/9/13 to 27/10/16, 5519 were screened for eligibility and 2037 randomised (1028 to unblinded care and 1009 to double blinded care). We identified 198 with DSA and 818 with non-DSA. Development of DSA, but not non-DSA was predictive of graft failure. HRs for graft failure in unblinded DSA+ and non-DSA+ groups were 1.54 (95% CI: 0.72 to 3.30) and 0.97 (0.54-1.74) respectively, providing no evidence of an intervention effect. Non-inferiority for the overall unblinded versus blinded comparison was not demonstrated as the upper confidence limit of the HR for graft failure exceeded 1.4 (1.02, 95% CI: 0.72 to 1.44). The only secondary endpoint reduced in the unblinded arm was biopsy-proven rejection. Interpretation: Intervention to improve adherence and optimize immunosuppression does not delay failure of renal transplants after development of DSA. Whilst DSA predicts increased risk of allograft failure, novel interventions are needed before screening can be used to direct therapy. Funding: The National Institute for Health Research Efficacy and Mechanism Evaluation programme grant (ref 11/100/34).

Patient information about living donor kidney transplantation across UK renal units: A critical review.

BACKGROUND: Patient information about living donor kidney transplantation is used to supplement conversations between health professionals, people with advanced kidney disease and potential kidney donors. It is not known if the information is designed to support decision-making about renal replacement options and if it helps people discuss living kidney donation with family and friends. OBJECTIVE: Critical review of resources used in outpatient kidney consultations to support patients' decision-making about living kidney donor transplantation. DESIGN: Mixed methods including an audit questionnaire and critical analysis of patient information leaflets. PARTICIPANTS AND MEASUREMENTS: All kidney transplant centres and renal units in United Kingdom received a questionnaire to elicit by whom, how, and when information about living kidney donation is delivered. Copies of leaflets were requested. A coding frame was utilised to produce a quality score for each leaflet. RESULTS: Thirty-nine (54%) units participated. Patients discussed living donor kidney transplantation with nephrologists (100%), living donor nurse (94%), transplant co-ordinator (94%), and predialysis nurse (86%). Twenty-three leaflets were provided and reviewed, mean quality scores for inclusion of information known to support shared decision-making was m = 2.82 out of 10 (range = 0-6, SD = 1.53). Readability scores indicated they were 'fairly difficult to read' (M = 56.3, range = 0-100, SD = 9.4). Few included cultural and faith information. Two leaflets were designed to facilitate conversations with others about donation. CONCLUSIONS: Leaflets are unlikely to adequately support decision-making between options and discussions about donation. Services writing and updating patient leaflets may benefit from our six principles to guide their development.

Barriers and enablers to the implementation of a complex quality improvement intervention for acute kidney injury: A qualitative evaluation of stakeholder perceptions of the Tackling AKI study.

BACKGROUND: Acute kidney injury in hospital patients is common and associated with reduced survival and higher healthcare costs. The Tackling Acute Kidney Injury (TAKI) quality improvement project aimed to reduce mortality rates in patients with acute kidney injury by implementing a multicomponent intervention comprising of an electronic alert, care bundle and education in five UK hospitals across a variety of wards. A parallel developmental evaluation using a case study approach was conducted to provide the implementation teams with insights into factors that might impact intervention implementation and fidelity. The qualitative element of the evaluation will be reported. METHODS: 29 semi-structured interviews with implementation teams across the five hospitals were carried out to identify perceived barriers and enablers to implementation. Interviews were taped and transcribed verbatim and Framework analysis was conducted. RESULTS: Interviews generated four 'barriers and enablers' to implementation themes: i) practical/contextual factors, ii) skills and make-up of the TAKI implementation team, iii) design, development and implementation approach, iv) staff knowledge, attitudes, behaviours and support. Enablers included availability of specialist teams (e.g. educational teams), multi-disciplinary implementation teams with strong leadership, team-based package completion and proactive staff. Barriers were frequently the converse of facilitators. CONCLUSIONS: Despite diversity of sites, a range of common local factors-contextual, intervention-based and individual-were identified as potential barriers and enablers to fidelity, including intervention structure/design and process of/approach to implementation. Future efforts should focus on early identification and management of barriers and tailored optimisation of known enablers such as leadership and multidisciplinary teams to encourage buy-in. Improved measures of real-time intervention and implementation fidelity would further assist local teams to target their support during such quality improvement initiatives.

Update to the study protocol, including statistical analysis plan, for the multicentre, randomised controlled OuTSMART trial: a combined screening/treatment programme to prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies.

BACKGROUND: Chronic rejection is the single biggest cause of premature kidney graft failure. HLA antibodies (Ab) are an established prognostic biomarker for premature graft failure so there is a need to test whether treatment decisions based on the presence of the biomarker can alter prognosis. The Optimised TacrolimuS and MMF for HLA Antibodies after Renal Transplantation (OuTSMART) trial combines two elements. Firstly, testing whether a routine screening programme for HLA Ab in all kidney transplant recipients is useful by comparing blinding versus unblinding of HLA Ab status. Secondly, for those found to be HLA Ab+, testing whether the introduction of a standard optimisation treatment protocol can reduce graft failure rates. METHODS: OuTSMART is a prospective, open-labelled, randomised biomarker-based strategy (hybrid) trial, with two arms stratified by biomarker (HLA Ab) status. The primary outcome was amended from graft failure rates at 3 years to time to graft failure to increase power and require fewer participants to be recruited. Length of follow-up subsequently is variable, with all participants followed up for at least 43 months up to a maximum of 89 months. The primary outcome will be analysed using Cox regression adjusting for stratification factors. Analyses will be according to the intention-to-treat using all participants as randomised. Outcomes will be analysed comparing standard care versus biomarker-led care groups within the HLA Ab+ participants (including those who become HLA Ab+ through re-screening) as well as between HLA-Ab-unblinded and HLA-Ab-blinded groups using all participants. DISCUSSION: Changes to the primary outcome permit recruitment of fewer participants to achieve the same statistical power. Pre-stating the statistical analysis plan guards against changes to the analysis methods at the point of analysis that might otherwise introduce bias through knowledge of the data. Any deviations from the analysis plan will be justified in the final report. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN46157828 . Registered on 26 March 2013; EudraCT 2012-004308-36 . Registered on 10 December 2012.

An Organizational-Level Program of Intervention for AKI: A Pragmatic Stepped Wedge Cluster Randomized Trial.

BACKGROUND: Variable standards of care may contribute to poor outcomes associated with AKI. We evaluated whether a multifaceted intervention (AKI e-alerts, an AKI care bundle, and an education program) would improve delivery of care and patient outcomes at an organizational level. METHODS: A multicenter, pragmatic, stepped-wedge cluster randomized trial was performed in five UK hospitals, involving patients with AKI aged ≥18 years. The intervention was introduced sequentially across fixed three-month periods according to a randomly determined schedule until all hospitals were exposed. The primary outcome was 30-day mortality, with pre-specified secondary endpoints and a nested evaluation of care process delivery. The nature of the intervention precluded blinding, but data collection and analysis were independent of project delivery teams. RESULTS: We studied 24,059 AKI episodes, finding an overall 30-day mortality of 24.5%, with no difference between control and intervention periods. Hospital length of stay was reduced with the intervention (decreases of 0.7, 1.1, and 1.3 days at the 0.5, 0.6, and 0.7 quantiles, respectively). AKI incidence increased and was mirrored by an increase in the proportion of patients with a coded diagnosis of AKI. Our assessment of process measures in 1048 patients showed improvements in several metrics including AKI recognition, medication optimization, and fluid assessment. CONCLUSIONS: A complex, hospital-wide intervention to reduce harm associated with AKI did not reduce 30-day AKI mortality but did result in reductions in hospital length of stay, accompanied by improvements in in quality of care. An increase in AKI incidence likely reflected improved recognition.

Quality of life with conservative care compared with assisted peritoneal dialysis and haemodialysis.

BACKGROUND: There is little information about quality of life (QoL) for patients with end-stage kidney disease (ESKD) choosing conservative kidney management (CKM). The Frail and Elderly Patients on Dialysis (FEPOD) study demonstrated that frailty was associated with poorer QoL outcomes with little difference between dialysis modalities [assisted peritoneal dialysis (aPD) or haemodialysis (HD)]. We therefore extended the FEPOD study to include CKM patients with estimated glomerular filtration rate ≤10 mL/min/1.73 m2 (i.e. individuals with ESKD otherwise likely to be managed with dialysis). METHODS: CKM patients were propensity matched to HD and aPD patients by age, gender, ethnicity, diabetes status and index of deprivation. QoL outcomes measured were Short Form-12 (SF12), Hospital Anxiety and Depression Scale depression score, symptom score, Illness Intrusiveness Rating Scale (IIRS) and Renal Treatment Satisfaction Questionnaire. Frailty was assessed using the Clinical Frailty Scale. Generalized linear modelling was used to assess the impact of treatment modality on QoL outcomes, adjusting for baseline characteristics. RESULTS: In total, 84 (28 CKM, 28 HD and 28 PD) patients were included. Median age for the cohort was 82 (79-88) years. Compared with CKM, aPD was associated with higher SF12 physical component score (PCS) [Exp B (95% confidence interval) = 1.20 (1.00-1.45), P < 0.05] and lower symptom score [Exp B = 0.62 (0.43-0.90), P = 0.01]; depression score was lower in HD compared with CKM [Exp B = 0.70 (0.52-0.92), P = 0.01]. Worsening frailty was associated with higher depression scores [Exp B = 2.59 (1.45-4.62), P < 0.01], IIRS [Exp B = 1.20 (1.12-1.28), P < 0.01] and lower SF12 PCS [Exp B = 0.87 (0.83-0.93), P < 0.01]. CONCLUSION: Treatment by dialysis, both with aPD and HD, improved some QoL measures. Overall, aPD was equal to or slightly better than the other modalities in this elderly population. However, as in the primary FEPOD study, frailty was associated with worse QoL measures irrespective of CKD modality. These findings highlight the need for an individualized approach to the management of ESKD in older people.

Longitudinal Trends in Quality of Life and Physical Function in Frail Older Dialysis Patients: A Comparison of Assisted Peritoneal Dialysis and In-Center Hemodialysis.

BACKGROUND: In-center hemodialysis (HD) has been the standard treatment for older dialysis patients, but reports suggest an associated decline in physical and cognitive function. Cross-sectional data suggest that assisted peritoneal dialysis (aPD), an alternative treatment, is associated with quality of life (QoL) outcomes that are comparable to in-center HD. We compared longitudinal changes in QoL between modalities. METHODS: We enrolled 106 aPD patients, matched with 100 HD patients from 20 renal centers in England and Northern Ireland. Patients were assessed quarterly for 2 years using the Hospital Anxiety and Depression Scale (HADS), SF-12 physical and mental scores, symptom score, Illness Intrusiveness Rating Scale (IIRS), Barthel's score, and the Renal Treatment Satisfaction Questionnaire (RTSQ). Mixed model analysis was used to assess the impact of dialysis modality on these outcomes during follow-up. P values were adjusted for multiple significance testing. RESULTS: Multivariate analysis showed no difference in any of the outcome measures between aPD and HD. Longitudinal trends in outcomes were also not significantly different. Higher age at baseline was associated with lower IIRS and RTSQ scores during follow-up. One-hundred and twenty-five (60.6%) patients dropped out of the study: 59 (28.6%) died, 61 (29.6%) withdrew during follow-up, and 5 (2.5%) were transplanted. CONCLUSIONS: Quality of life outcomes in frail older aPD patients were equivalent to those receiving in-center HD. Assisted PD is thus a valid alternative to HD for older people with end-stage kidney disease (ESKD) wishing to dialyze at home.

Time, timing, talking and training: findings from an exploratory action research study to improve quality of end of life care for minority ethnic kidney patients.

Background. With an ageing and increasingly diverse population at risk from rising levels of obesity, diabetes and cardiovascular disease, including kidney complications, there is a need to provide quality care at all stages in the care pathway including at the end of life and to all patients. Aim. This study purposively explored South Asian patients' experiences of kidney end of life care to understand how services can be delivered in a way that meets diverse patient needs. Methods. Within an action research design 14 focus groups (45 care providers) of kidney care providers discussed the recruitment and analysis of individual interviews with 16 South Asian kidney patients (eight men, eight women). Emergent themes from the focus groups were analysed thematically. The research took place at four UK centres providing kidney care to diverse populations: West London, Luton, Leicester and Bradford. Results. Key themes related to time and the timing of discussions about end of life care and the factors that place limitations on patients and providers in talking about end of life care. Lack of time and confidence of nurses in areas of kidney care, individual attitudes and workforce composition influence whether and how patients have access to end of life care through kidney services. Conclusion. Training, team work and time to discuss overarching issues (including timing and communication about end of life) with colleagues could support service providers to facilitate access and delivery of end of life care to this group of patients.

Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research.

BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups.

Communication as care at end of life: an emerging issue from an exploratory action research study of renal end-of-life care for ethnic minorities in the UK.

South Asian people have a higher risk of developing kidney disease, are disproportionately represented in the patient population requiring renal replacement therapy and wait longer to receive a kidney transplant, compared with white Europeans. As a result, there is a demand for end-of-life care, which meets the needs of this group of patients. Providing end-of-life care to patients from different cultures is a challenge for renal services as there can be barriers to communication in the form of language, delegated decision-making within families and reluctance to discuss death. To explore end-of-life care for South Asians with kidney disease, 16 interviews with patients and 14 focus groups with care providers were conducted at four research sites in the UK with large South Asian populations. Using an action research design the data were analysed thematically and fed back to inform the research in a cyclical manner. If patients are not fully aware of their condition or of what end-of-life care is, it is less likely that they will be able to be involved in decision-making about their care and this is compounded where there are communication barriers. Variations in care provider awareness and experience of providing end-of-life care to South Asian patients, in turn, contributes to lack of patient awareness of end-of-life care. Communication as care at the end of life should be explored further. Researching the South Asian patient experience of end of life highlights many relevant and generalisable issues.

Improving the quality of communication and service provision for renal patients of South Asian origin: the contribution of a cultural and health improvement officer.

A large number of patients with advanced chronic kidney disease in Bradford, UK are of South Asian origin. Effective delivery of care for these patients demands a consistently high standard of communication between patients, their families and renal unit staff. Communication may be problematic for a number of reasons, including language barriers and an incomplete appreciation of important cultural or religious beliefs. In 2010, we received charitable funding for an Ethnic Liaison Support Worker, renamed Cultural and Health Improvement Officer (CHIO). The CHIO is able to engage with and support patients, relatives and other members of the multidisciplinary renal team. Core responsibilities include ensuring that patients and their families feel at ease whenever they are in communication with the renal services team in Bradford; contributing to formal discussion and explanation of important clinical issues in the patient's first language (typically Urdu or Punjabi), thereby encouraging patients to feel more involved in decisions about their care; listening to ad hoc patient queries and concerns and addressing these directly or indirectly through timely involvement of other members of the renal team; cultivating a greater awareness of and empathy towards the holistic needs of patients and their families within the renal MDT; and strengthening the links between renal and social care services. The involvement of the CHIO is especially important when discussing sensitive and complex issues such as conservative and end-of-life care with patients and their families, as communication needs to be detailed, precise and unequivocal. This is crucial to providing a bespoke supportive service for our all patients, especially those who have opted for conservative management. The significant contribution of the CHIO to the quality of renal services in Bradford has been recognised and a permanent CHIO post has now been established.

Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney.

BACKGROUND: Most cases of dialysis-dependent acute kidney injury due to myeloma cast nephropathy do not recover renal function. Renal biopsy typically shows cast formation, direct tubular injury and interstitial inflammation caused by nephrotoxic monoclonal free light chains (FLC). Established scarring at presentation is rarely severe. There is little data on in situ evolution of renal injury. AIMS: To conduct a detailed histological study of four patients with cast nephropathy. METHODS: Cast nephropathy was confirmed by renal biopsy. Treatment consisted of chemotherapy and high cut-off dialysis to maximise extracorporeal removal of FLC and reduce renal toxicity. All four patients remained dialysis dependent at 6 weeks, at which time they underwent a further biopsy. RESULTS: Three patients achieved independence from dialysis. Six-week biopsies showed differential changes in chronic damage from no progression, to accelerated progression of scarring from 10% to 42%, despite a rapid and sustained fall in FLC in all patients. In three patients there was a major reduction in intratubular cast numbers; these patients subsequently recovered renal function. In one patient who continued to have high cast formation at 6 weeks there was no subsequent renal recovery. CONCLUSIONS: Some FLC clones can promote rapid renal scarring. Significant reductions in cast formation on repeat biopsy may identify the potential for late renal recovery. Early diagnosis and treatment may prove crucial in determining renal recovery. Patients who have not recovered renal function after a period of treatment may be usefully reassessed by repeat biopsy for quantitative analysis of chronic damage and cast numbers.

Electronic consultation as an alternative to hospital referral for patients with chronic kidney disease: a novel application for networked electronic health records to improve the accessibility and efficiency of healthcare.

PROBLEM: Chronic kidney disease is increasingly recognised in the UK, leading to a greater demand for specialist services. Traditional means of meeting this demand rely on GP referral of patients to see a nephrologist. Hospital assessment may be inconvenient for patients and inefficient for health services. SETTING: 17 general practices and a secondary care nephrology service in Bradford, UK. DESIGN: A before and after evaluation comparing nephrology referrals from implementation and non-implementation practices following the introduction of electronic consultations (e-consultations) for chronic kidney disease. KEY MEASURES FOR IMPROVEMENT: The number, appropriateness and quality of new referrals (paper and electronic) from primary care, the timeliness of responses and the satisfaction of patients and health professionals with the new service. Strategies for change Electronic sharing of primary care electronic health records with the nephrology service was introduced to implementation practices. Participating GPs attended education workshops and received paper and e-guidance about the new service. EFFECTS OF CHANGE: There was a significant reduction in paper referrals from implementation practices. E-consultation provided nephrologists with access to more clinical information. GPs reported that the service was convenient, provided timely and helpful advice, and avoided outpatient referrals. Specialist recommendations were well followed, and GPs felt more confident about managing chronic kidney disease in the community. LESSONS LEARNT: E-consultation promotes effective management of patients with mild-to-moderate chronic kidney disease in primary care, allowing specialist resources to be directed towards supporting patients with more complex needs. There is a potential role for e-consultation in other chronic disease specialties.

Dietitian-led education program to improve phosphate control in a single-center hemodialysis population.

OBJECTIVE: We sought to analyze the effect of a structured, dietitian-led education program on patients' general knowledge of phosphate and phosphate binders, and its impact on serum phosphate concentrations in a single-center hemodialysis population. DESIGN: We compared subjects before and after intervention. SETTING: This study involved two dialysis units operated by a single center. PATIENTS: One hundred and fifteen hemodialysis patients consented to participate in this study (54% male; mean age, 61.1 years; 32% Asian). Patients acted as their own controls. One hundred and eight patients completed the study. INTERVENTION: All patients completed a questionnaire to assess their knowledge of phosphate and phosphate-binder therapy. Small group teaching sessions were then delivered to patients by a single dietitian, with the aid of a hospital interpreter as required. Patients also received information booklets or audio cassettes translated into Urdu. A second identical questionnaire was completed a month later. MAIN OUTCOME MEASURES: Outcome measures involved pre-education and posteducation knowledge scores, monthly measurements of serum phosphate, calcium, and mean Kt/V, and parathyroid hormone concentrations every 3 months during the 5 month run-in period and subsequent 5-month study period. RESULTS: The education program significantly improved patients' general knowledge of phosphate and of phosphate-binders (P < .001), especially in patients with a low pretest score and those of South Asian origin. This result was associated with a significant reduction in serum phosphate in patients with hyperphosphatemia (P = .032). CONCLUSIONS: These findings suggest that a combination of educational initiatives is effective in enhancing patients' knowledge of phosphate and phosphate-binders, and consequently in improving serum phosphate levels in patients with hyperphosphatemia.

A randomized controlled trial of immunosuppression conversion for the treatment of chronic allograft nephropathy.

BACKGROUND: This study was conducted to assess the effect of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). METHODS: Forty-two cyclosporin-treated renal transplant recipients were studied. Patients were included if they had a negatively sloping reciprocal of creatinine vs time (ROCT) plot for >6 months and biopsy-proven CAN. Patients were excluded if they had previously been treated with tacrolimus/mycophenolate mofetil (MMF) or their serum creatinine was >400 micromol/l. Subjects were randomly treated with either: (A) MMF/reduced dose cyclosporin [MMF for azathioprine 0.5-1.0 g bd; cyclosporin trough level (C(0)): 75-100 ng/ml]; (B) tacrolimus for cyclosporin (C(0): 5-10 ng/ml); or (C) continuation of standard therapy. Glomerular filtration rate (GFR) was measured at baseline and after 6 months. RESULTS: Two patients started dialysis within 6 months (one each from groups A and B). One patient in group A was intolerant of MMF, six others reported gastrointestinal symptoms and three developed anaemia. Cyclosporin dose was reduced by 24% [interquartile range (IQR): 14-27%] in group A [end-of-study C(0): 99 ng/ml (IQR: 90-113 ng/ml)]. In group B, the end-of-study tacrolimus C(0) was 7 ng/ml (5-9 ng/ml). The end-of-study cyclosporin C(0) in group C was 163 ng/ml (145-215 ng/ml). Comparison of ROCT slopes before and after intervention revealed a treatment advantage for group A (P<0.05). The GFR analysis was supportive (P = 0.05). When patients with GFR <20 ml/min/1.73 m(2) at enrollment were excluded from the analysis, the treatment advantage for group A reached statistical significance (n = 27, P<0.05). CONCLUSIONS: MMF/reduced dose cyclosporin is superior to tacrolimus-for-cyclosporin and standard dose cyclosporin in patients with CAN, at least in the short term. The cyclosporin dose reduction component is likely to be of particular importance. Other findings suggest that early intervention is beneficial.

Intravenous immunoglobulin-induced panel reactive antibody A reduction: not all preparations are created equal.

BACKGROUND: Use of intravenous (IV) immunoglobulin (Ig) to obtain panel reactive antibody (PRA) A reduction in sensitized patients has been widely reported. Because no IVIg preparation is formulated specifically for this purpose, the authors have sought to determine whether, through laboratory testing, they could guide the rational choice of product for clinical use. METHODS: Using a flow cytometric approach, the authors have quantitatively determined the capacity of 22 different IVIg preparations to cause PRA reduction. RESULTS: IVIg preparations showed considerable variability in their individual capacity to reduce serum PRA. Protein-A pretreatment of IVIg preparations was found to reduce their capacity to cause PRA reduction. CONCLUSION: Laboratory screening of IVIg preparations provides a rational basis for the selection of product for administration to patients in whom the aim is to produce a PRA reduction. Experiments involving protein-A treatment of IVIg preparations indicate that immunoglobulin G is the principal factor involved in the abrogation of serum reactivity.

Variability of cyclosporine exposure and its relevance to chronic allograft nephropathy: a case-control study.

BACKGROUND: Population data indicate that cyclosporine (CsA)-based immunosuppression has had relatively little effect on late renal allograft loss. For individual patients, however, the degree and variability of CsA exposure may be of prognostic importance. This case-control study has examined the contribution of these and other factors to the development of chronic allograft nephropathy (CAN) in patients receiving follow-up care in our unit. METHODS: The electronic record was interrogated to identify adult, CsA-treated renal transplant recipients with CAN (group A) and CsA-treated controls with stable graft function for a minimum of 4 years posttransplantation and serum creatinine less than 200 micromol/L (group B). Age at transplantation, gender, years posttransplantation, donor source and age, kidney preservation time, human leukocyte antigen match, occurrence of delayed graft function, immunosuppressive regimen, weight-adjusted maintenance CsA dose, and coefficient of variation (CvarC0 ) of dose-adjusted CsA trough blood levels (C0/dose) were recorded (CvarC0 =[SD (C0/dose)/mean (C0/dose)]x100). Statistical analysis included binary logistic regression analysis. RESULTS: Three transplant recipients were excluded because of known noncompliance with immunosuppressive medication, leaving a study population of 102 patients. Recipient age (AB, <0.01) and CsA dose (A>B, <0.02) were significantly different by univariate analysis. Only low recipient age ( P<0.001) and high CvarC0 ( P<0.02) were independent predictors of CAN in the regression model. CONCLUSION: Younger renal transplant recipients and those with highly variable CsA exposure are predisposed to developing CAN. Investigation of such patients may reveal correctable factors such as poor treatment compliance and lead to appropriate interventions.