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).

A randomised controlled trial to examine the effects of cinacalcet on bone and cardiovascular parameters in haemodialysis patients with advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism may lead to increased cardiovascular risk. The use of cinacalcet may improve bone and cardiovascular health with improved parathormone (PTH) and phosphate control. METHODS: This is an open-label prospective randomised controlled trial to compare progression of cardiovascular and chronic kidney disease mineral and bone disorder (CKD-MBD) parameters. Patients were randomised to receive cinacalcet alongside standard therapy or standard therapy alone. Thirty-six haemodialysis patients who had > 90 days on dialysis, iPTH > 300 pg/mL, calcium > 2.1 mmol/L and age 18-75 years were included. Following randomization, all 36 patients underwent an intensive 12-week period of bone disease management aiming for iPTH 150-300 pg/mL. The primary outcome was change in vascular calcification using CT agatston score. Secondary outcomes included pulse wave velocity (PWV), left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), augmentation index (Aix) and bone measurements. The above measurements were obtained at baseline and 12 months. RESULTS: There was no evidence of a group difference in the progression of calcification (median change (IQR) cinacalcet: 488 (0 to1539); standard therapy: 563 (50 to 1214)). In a post hoc analysis combining groups there was a mean (SD) phosphate reduction of 0.3 mmol/L (0.7) and median (IQR) iPTH reduction of 380 pg/mL (- 754, 120). Regression of LVMI and CIMT was seen (P = 0.03 and P = 0.001) and was significantly associated with change of phosphate on multi-factorial analyses. CONCLUSIONS: With a policy of intense CKD-MBD parameter control, no significant benefit in bone and cardiovascular markers was seen with the addition of cinacalcet to standard therapy over one year. Tight control of hyperphosphataemia and secondary hyperparathyroidism may lead to a reduction in LVMI and CIMT but this needs further investigation. Although the sample size was small, meticulous trial supervision resulted in very few protocol deviations with therapy.

Calciphylaxis in end-stage kidney disease: outcome data from the United Kingdom Calciphylaxis Study.

BACKGROUND AND AIMS: Calciphylaxis is a rare condition associated with very high mortality in patients with end-stage kidney disease. Data from country-based registries have been an invaluable resource for a better understanding of the natural history and management for this condition. This study aimed to investigate the current management strategies and outcomes of patients enrolled in the United Kingdom Calciphylaxis study (UKCS). METHODS: The study was conducted on 89 patients registered in the UKCS since 2012. The initial analysis included a description of the baseline characteristics, management strategies and outcomes on follow-up until May 2020. Further analysis included a comparison of the mortality outcome of the UKCS patients who were receiving haemodialysis with a propensity score matched cohort of haemodialysis patients from the Chronic Renal Insufficiency Standards Implementation Study- Haemodialysis (CRISIS-HD). RESULTS: Median age of the cohort was 59 years, with a predominance of females (61%) and Caucasian (95%) ethnicity. About 54% of the patients were diabetic and 70% were receiving haemodialysis at study entry. The skin lesions were mostly distributed in the lower extremities (48%). Sodium thiosulphate and calcimimetic were the most widely used management strategies. The mortality rate was 72 deaths per hundred patient-years (50 deaths observed in 69.5 patient years). Complete wound healing was noted in 17% and bacteraemia was reported in 26% of patients. In a comparative analysis of the matched haemodialysis patients, the presence of calciphylaxis in 62 patients showed a strong association with all-cause mortality (HR 6.96; p < 0.001), with annual mortality 67% versus 10.2% in haemodialysis patients without calciphylaxis. CONCLUSIONS: This UK wide study strengthens the evidence that calciphylaxis is a strong and independent risk factor associated with all-cause mortality; no significant benefit was shown with any individual treatment modality. Until further evidence becomes available, a multifaceted approach would be the appropriate treatment strategy in the management of this extremely serious condition.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

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.

Cardiac structure and function after revascularization versus medical therapy for renal artery stenosis: the ASTRAL heart echocardiographic sub-study.

BACKGROUND: The ASTRAL trial showed no difference in clinical outcomes between medical therapy and revascularization for atherosclerotic renal vascular disease (ARVD). Here we report a sub-study using echocardiography to assess differences in cardiac structure and function at 12 months. METHODS: ASTRAL patients from 7 participating centres underwent echocardiography at baseline and 12 months after randomisation. Changes in left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left atrial diameter (LAD), aortic root diameter (AoRD), E:A, and E deceleration time (EDT) were compared between study arms. Analyses were performed using t-tests and multivariate linear regression. RESULTS: Ninety two patients were included (50 medical versus 42 revascularization). There was no difference between arms in any baseline echocardiographic parameter. Comparisons of longitudinal changes in echocardiographic measurements were: δLVEF medical 0.8 ± 8.7% versus revascularization - 2.8 ± 6.8% (p = 0.05), δLVM - 2.9 ± 33 versus - 1.7 ± 39 g (p = 0.9), δLAD 0.1 ± 0.4 versus 0.01 ± 0.5 cm (p = 0.3), δAoRD 0.002 ± 0.3 versus 0.06 ± 0.3 cm (p = 0.4), δE:A - 0.0005 ± 0.6 versus 0.03 ± 0.7 (p = 0.8), δEDT - 1.1 ± 55.5 versus - 9.0 ± 70.2 ms (p = 0.6). In multivariate models, there were no differences between treatment groups for any parameter at 12 months. Likewise, change in blood pressure did not differ between arms (mean δsystolic blood pressure medical 0 mmHg [range - 56 to + 54], revascularization - 3 mmHg [- 61 to + 59], p = 0.60). CONCLUSIONS: This sub-study did not show any significant differences in cardiac structure and function accompanying renal revascularization in ASTRAL. Limitations include the small sample size, the relative insensitivity of echocardiography, and the fact that a large proportion of ASTRAL patient population had only modest renal artery stenosis as described in the main study.

Reducing acute kidney injury incidence and progression in a large teaching hospital.

Acute kidney injury (AKI) is a common syndrome that is associated with significant mortality and cost. The Quality Improvement AKI Collaborative at Salford Royal Foundation Trust was established to review and improve both the recognition and management of AKI. This was a whole-system intervention to tackle AKI implemented as an alternative to employing separate AKI nurses. Our aims were to reduce the overall incidence of AKI by 10%, to reduce hospital-acquired AKI by 25% and to reduce the progression of AKI from stage 1 to stage 2 or 3 by 50%. From 2014 to 2016, several multifaceted changes were introduced. These included system changes, such as inserting an e-alert for AKI into the electronic patient record, an online educational package and face-to-face teaching for AKI, and AKI addition to daily safety huddles. On 10 Collaborative wards, development of an AKI care bundle via multidisciplinary team (MDT) plan, do, study, act testing occurred. Results showed a 15.6% reduction in hospital-wide-acquired AKI, with a 22.3% reduction on the collaborative wards. Trust-wide rates of progression of AKI 1 to AKI 2 or 3 showed normal variation, whereas there was a 48.5% reduction in AKI progression on the Collaborative wards. This implies that e-alerts were ineffective in isolation. The Collaborative wards' results were a product of the educational support, bundle and heightened awareness of AKI. A number of acute hospitals have demonstrated impactful successes in AKI reduction centred on a dedicated AKI nurse model plus e-alerting with supporting changes. This project adds value by highlighting another approach that does not require a new post with attendant rolling costs and risks. We believe that our approach increased our efficacy in acute care in our front-line teams by concentrating on embedding improved recognition and actions across the MDT.

Improving CKD Diagnosis and Blood Pressure Control in Primary Care: A Tailored Multifaceted Quality Improvement Programme.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health issue. From 2009 to 2014, the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester (NIHR CLAHRC GM) in England ran 4 phased, 12-month quality improvement (QI) projects with 49 primary care practices in GM. Two measureable aims were set - halve undiagnosed CKD in participating practices using modelled estimates of prevalence; and optimise blood pressure (BP) control (<140/90 mm Hg in CKD patients without proteinuria; <130/80 mm Hg in CKD patients with proteinuria) for 75% of recorded cases of CKD. The 4 projects ran as follows: P1 = Project 1 with 19 practices (September 2009 to September 2010), P2 = Project 2 with 11 practices (March 2011 to March 2012), P3 = Project 3 with 12 practices (September 2012 to October 2013), and P4 = Project 4 with 7 practices (April 2013 to March 2014). METHODS: Multifaceted intervention approaches were tailored based on a contextual analysis of practice support needs. Data were collected from practices by facilitators at baseline and again at project close, with self-reported data regularly requested from practices throughout the projects. RESULTS: Halving undiagnosed CKD as per aim was exceeded in 3 of the 4 projects. The optimising BP aim was met in 2 projects. Total CKD cases after the programme increased by 2,347 (27%) from baseline to 10,968 in a total adult population (aged ≥18 years) of 231,568. The percentage of patients who managed to appropriate BP targets increased from 34 to 74% (P1), from 60 to 83% (P2), from 68 to 71% (P3), and from 63 to 76% (P4). In nonproteinuric CKD patients, 88, 90, 89, and 91%, respectively, achieved a target BP of <140/90 mm Hg. In proteinuric CKD patients, 69, 46, 48, and 45%, respectively, achieved a tighter target of <130/80 mm Hg. Analysis of national data over similar timeframes indicated that practices participating in the programme achieved higher CKD detection rates. CONCLUSIONS: Participating practices identified large numbers of "missing" CKD patients with comparator data showing they outperformed non-QI practices locally and nationally over similar timeframes. Improved BP control also occurred through this intervention, but overall achievement of the tighter BP target in proteinuric patients was notably less.

Effect of a Quality Improvement Program to Improve Guideline Adherence and Attainment of Clinical Standards in Dialysis Care: Report of Outcomes in Year 1.

BACKGROUND: Best practice in dialysis is synthesised in clear international guidelines. However, a large gap remains between the international guidelines and the actual delivery of care. In this paper, we report outcomes for the first year of a multifaceted dialysis improvement programme in our network. METHODS: One year collaborative involving 3 haemodialysis units and a peritoneal dialysis (PD) programme involving 299 dialysis patients. Each unit addressed a different indicator (unit A - catheter-related bloodstream infection [CRBSI], unit B - pre-dialysis blood pressure [BP], unit C - dialysis dose, unit D - anaemia) with a shared aim to match the top 10% in the UK. Tailored multifaceted approaches include a modified collaborative methodology with an aim, framework, driver diagram, learning sessions, facilitated meetings, plan-do-study-act cycles and continuous measurement. Analysis of outcomes, costings, erythropoietin stimulating agent and iron use, and safety culture attributes. RESULTS: Unit A reduced CRBSI from 2.65 to 0.5 per 1,000 catheter days (p = 0.02). Unit B improved attainment of target BP from 37.5 to 67.2% (p = 0.003). Unit C improved attainment of target urea reduction ratio from 75.8 to 91.4% (p = 0.04). PD unit D improved attainment of target haemoglobin from 45.5 to 62.7% (p = 0.01), with no significant change in the indicators in a non-intervention unit. Safety culture attributes improved. Costs associated with admission for fluid overload and infection, erythropoietin, iron and thrombokinase use decreased 36% (£415,620-£264,143). CONCLUSIONS: Units that took part in this collaborative improved guideline adherence compared both to their own pre-intervention performance and a non-intervention unit. Such multifaceted interventions are a useful methodology to improve dialysis care.

Effect of renal artery revascularization upon cardiac structure and function in atherosclerotic renal artery stenosis: cardiac magnetic resonance sub-study of the ASTRAL trial.

BACKGROUND: Cardiac abnormalities are frequent in patients with atherosclerotic renovascular disease (ARVD). The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial studied the effect of percutaneous renal revascularization combined with medical therapy compared with medical therapy alone in 806 patients with ARVD. METHODS: This was a pre-specified sub-study of ASTRAL (clinical trials registration, current controlled trials number: ISRCTN59586944), designed to consider the effect of percutaneous renal artery angioplasty and stenting on change in cardiac structure and function, measured using cardiac magnetic resonance (CMR) imaging. Fifty-one patients were recruited from six selected ASTRAL centres. Forty-four completed the study (medical therapy n = 21; revascularization n = 23). Full analysis of CMR was possible in 40 patients (18 medical therapy and 22 revascularization). CMR measurements of left and right ventricular end systolic (LV and RVESV) and diastolic volume (LV and RVEDV), ejection fraction (LVEF) and mass (LVM) were made shortly after recruitment and before revascularization in the interventional group, and again after 12 months. Reporting was performed by CMR analysts blinded to randomization arm. RESULTS: Groups were well matched for mean age (70 versus 72 years), blood pressure (148/71 versus 143/74 mmHg), degree of renal artery stenosis (75 versus 75%) and comorbid conditions. In both randomized groups, improvements in cardiac structural parameters were seen at 12 months, but there were no significant differences between treatment groups. Median left ventricular changes between baseline and 12 months (medical versus revascularization) were LVEDV -1.9 versus -5.8 mL, P = 0.4; LVESV -2.1 versus 0.3 mL, P = 0.7; LVM -5.4 versus -6.3 g, P = 0.8; and LVEF -1.5 versus -0.8%, P = 0.7. Multivariate regression also found that randomized treatment assignment was not associated with degree of change in any of the CMR measurements. CONCLUSIONS: In this sub-study of the ASTRAL trial, renal revascularization did not offer additional benefit to cardiac structure or function in unselected patients with ARVD.

Understanding the implementation of interventions to improve the management of chronic kidney disease in primary care: a rapid realist review.

BACKGROUND: Chronic kidney disease (CKD) is common and a significant marker of morbidity and mortality. Its management in primary care is essential for maintenance of cardiovascular health, avoidance of acute kidney injury (AKI) and delay in progression to end-stage renal disease. Although many guidelines and interventions have been established, there is global evidence of an implementation gap, including variable identification rates and low patient communication and awareness. The objective of this study is to understand the factors enabling and constraining the implementation of CKD interventions in primary care. METHODS: A rapid realist review was conducted that involved a primary literature search of three databases to identify existing CKD interventions in primary care between the years 2000 and 2014. A secondary search was performed as an iterative process and included bibliographic and grey literature searches of reference lists, authors and research groups. A systematic approach to data extraction using Normalisation Process Theory (NPT) illuminated key mechanisms and contextual factors that affected implementation. RESULTS: Our primary search returned 710 articles that were narrowed down to 18 relevant CKD interventions in primary care. Our findings suggested that effective management of resources (encompassing many types) was a significant contextual factor enabling or constraining the functioning of mechanisms. Three key intervention features were identified from the many that contributed to successful implementation. Firstly, it was important to frame CKD interventions appropriately, such as within the context of cardiovascular health and diabetes. This enabled buy-in and facilitated an understanding of the significance of CKD and the need for intervention. Secondly, interventions that were compatible with existing practices or patients' everyday lives were readily accepted. In contrast, new systems that could not be integrated were abandoned as they were viewed as inconvenient, generating more work. Thirdly, ownership of the feedback process allowed users to make individualised improvements to the intervention to suit their needs. CONCLUSIONS: Our rapid realist review identified mechanisms that need to be considered in order to optimise the implementation of interventions to improve the management of CKD in primary care. Further research into the factors that enable prolonged sustainability and cost-effectiveness is required for efficient resource utilisation.

Improving the identification and management of chronic kidney disease in primary care: lessons from a staged improvement collaborative.

QUALITY PROBLEM: Undiagnosed chronic kidney disease (CKD) contributes to a high cost and care burden in secondary care. Uptake of evidence-based guidelines in primary care is inconsistent, resulting in variation in the detection and management of CKD. INITIAL ASSESSMENT: Routinely collected general practice data in one UK region suggested a CKD prevalence of 4.1%, compared with an estimated national prevalence of 8.5%. Of patients on CKD registers, ∼ 30% were estimated to have suboptimal management according to Public Health Observatory analyses. CHOICE OF SOLUTION: An evidence-based framework for implementation was developed. This informed the design of an improvement collaborative to work with a sample of 30 general practices. IMPLEMENTATION: A two-phase collaborative was implemented between September 2009 and March 2012. Key elements of the intervention included learning events, improvement targets, Plan-Do-Study-Act cycles, benchmarking of audit data, facilitator support and staff time reimbursement. EVALUATION: Outcomes were evaluated against two indicators: number of patients with CKD on practice registers; percentage of patients achieving evidence-based blood pressure (BP) targets, as a marker for CKD care. In Phase 1, recorded prevalence of CKD in collaborative practices increased ∼ 2-fold more than that in comparator local practices; in Phase 2, this increased to 4-fold, indicating improved case identification. Management of BP according to guideline recommendations also improved. LESSONS LEARNED: An improvement collaborative with tailored facilitation support appears to promote the uptake of evidence-based guidance on the identification and management of CKD in primary care. A controlled evaluation study is needed to rigorously evaluate the impact of this promising improvement intervention.

A collaborative project to improve identification and management of patients with chronic kidney disease in a primary care setting in Greater Manchester.

PROBLEM: Research has demonstrated a knowledge and practice gap in the identification and management of chronic kidney disease (CKD). In 2009, published data showed that general practices in Greater Manchester had a low detection rate for CKD. DESIGN: A 12-month improvement collaborative, supported by an evidence-informed implementation framework and financial incentives. SETTING: 19 general practices from four primary care trusts within Greater Manchester. KEY MEASURES FOR IMPROVEMENT: Number of recorded patients with CKD on practice registers; percentage of patients on registers achieving nationally agreed blood pressure targets. STRATEGIES FOR CHANGE: The collaborative commenced in September 2009 and involved three joint learning sessions, interspersed with practice level rapid improvement cycles, and supported by an implementation team from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Greater Manchester. EFFECTS OF CHANGE: At baseline, the 19 collaborative practices had 4185 patients on their CKD registers. At final data collection in September 2010, this figure had increased by 1324 to 5509. Blood pressure improved from 34% to 74% of patients on practice registers having a recorded blood pressure within recommended guidelines. LESSONS LEARNT: Evidence-based improvement can be implemented in practice for chronic disease management. A collaborative approach has been successful in enabling teams to test and apply changes to identify patients and improve care. The model has proved to be more successful for some practices, suggesting a need to develop more context-sensitive approaches to implementation and actively manage the factors that influence the success of the collaborative.

Translating knowledge on best practice into improving quality of RRT care: a systematic review of implementation strategies.

Recent studies showed wide variation in the extent to which guidelines and other types of best practice have been implemented as part of routine health care. This is also true for the delivery of renal replacement therapy (RRT) for ESRD patients. Increasing uptake of best practice within such complex care systems requires an understanding of implementation strategies and specific quality improvement (QI) techniques. Therefore, we systematically reviewed over 5000 titles published since 1990 and included papers describing planned attempts to accelerate uptake of best RRT practice into daily care. This resulted in a list of 93 QI initiatives, categorized in order to expedite shared learning. The majority of the initiatives were executed within the domains of vascular access, nutrition, and anemia management. Strategies oriented at patients were most common and many initiatives pre-defined an improvement target before starting implementation. Of the 93 initiatives, 22 were sufficiently robust methodologically to be analyzed in more detail. Our results tend to support previous findings that multifaceted strategies are more effective than single strategies. Improving our understanding of how to successfully implement best practice can inform system-level change and is the only way to close the gap between knowledge on what works and the actual care delivered to ESRD patients. Research into implementation, using specific QI techniques, should therefore be given priority in future.

Serum phosphate and mortality in patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets. RESULTS: Mean (SD) eGFR was 32 (15) ml/min per 1.73 m(2), age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality. CONCLUSIONS: In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.

Factors associated with vascular stiffness: cross-sectional analysis from the Chronic Renal Insufficiency Standards Implementation Study.

BACKGROUND: Vascular stiffness is associated with increased cardiovascular risk. This study aimed to identify factors associated with vascular stiffness in a cohort of chronic kidney disease (CKD) patients. METHODS: The Chronic Renal Insufficiency Standards Implementation Study is a prospective epidemiological study of CKD patients not on dialysis, who are managed in a clinic setting. Phenotypic parameters were collected annually, and vascular stiffness was assessed using augmentation index (AI). Cross-sectional analysis was performed across quintiles of AI to evaluate factors associated with vascular stiffness. RESULTS: Mean patient age was 66.1 +/- 14.1 years and estimated glomerular filtration rate (eGFR) was 31.2 +/- 5.7 ml/min. Corrected calcium was 2.26 +/- 0.2 SD mmol/l, phosphate 1.2 +/- 0.4 SD mmol/l and intact parathyroid hormone 94 +/- 96 SD pg/ml; 18.3% of patients had cardiovascular disease. Increased age and systolic blood pressure were associated with increased AI (all p < 0.001). No statistical association was present between AI and eGFR, intact parathyroid hormone, phosphate or protein excretion. CONCLUSION: This study identified blood pressure as a potentially modifiable risk factor associated with AI, whereas eGFR was not associated with increased AI in a population of CKD stage 3-5 patients. Further knowledge of factors which influence progression of vascular stiffness will be important in risk quantification and management.

The effects of statins on the progression of atherosclerotic renovascular disease.

BACKGROUND/AIMS: The aim was to examine the influence of statin therapy on the natural history of atherosclerotic renal artery stenosis (RAS). METHODS: Our hospital atherosclerotic renovascular disease (ARVD) database was analysed for patients who underwent repeat renal angiography during clinical follow-up. Patients with >or=1 RAS lesion and >or=4 months between baseline and repeat renal angiography were analysed. 79 patients were included. Baseline renal arterial anatomy was classified as normal, 50% RAS or renal artery occlusion. RESULTS: Mean follow-up time between angiograms was 27.8 +/- 22.3 (4.0-101.9) months. Progression of RAS occurred in 28 (23%) vessels, regression in 14 (12%) and no significant change in 79 (65%). Multivariate regression analysis showed that baseline proteinuria >0.6 g/day increased the risk of progressive disease (relative risk, RR, 3.8; 95% confidence interval, CI, 1.2-12.1), treatment with statin reduced the risk of progression (RR 0.28; 95% CI 0.10-0.77). 14 renal arteries from 12 patients showed RAS regression with a greater proportion on statin [statin treatment 10 (83%) versus no statin treatment 2 (17%), p = 0.001]. Change in estimated glomerular filtration rate (eGFR) per year was not different between statin- and no-statin-treated groups. CONCLUSIONS: Progression or development of RAS was significantly less likely to occur with statin therapy. Delta eGFR did not correlate with progression of RAS, reflecting the importance of intrarenal injury in the aetiology of renal dysfunction. Our results suggest statin therapy can alter the natural history of ARVD.

The unrecognized prevalence of chronic kidney disease in diabetes.

BACKGROUND: Diabetes mellitus and chronic kidney disease (CKD) are common and exhibit synergistic associations with premature mortality. Current diabetes guidelines in the UK recommend annual urinary albumin and serum creatinine determinations to screen for diabetic kidney disease. The aim of this study was to estimate the burden of CKD in patients with diabetes and examine the ability of serum creatinine and albuminuria to detect clinically meaningful CKD compared with estimated glomerular filtration rate (eGFR). METHODS: All adults known to have diabetes in primary and secondary care in Salford, UK, alive with independent renal function on 1 January 2004 were included in this observational study (n=7596). Demographic and laboratory parameters were obtained from the Electronic Patient Record. eGFR was determined using the 4-variable modification of diet in renal disease (MDRD) formula. Clinically meaningful CKD was defined as an eGFR <60 ml/min/1.73 m(2). RESULTS: Creatinine and albuminuria were measured in the preceding 2 years in 82.3 and 55.2% of subjects, respectively. In patients with CKD, normoalbuminuria was present in 48.8%, and serum creatinine was normal (or=120 micromol/l) had a sensitivity and specificity of 45.3 and 100%, respectively, to identify CKD. The combination of abnormal creatinine and albuminuria had an improved performance but still failed to detect a large number with CKD (sensitivity 82.4%, specificity 75.4%). Serum creatinine failed to identify CKD more often in females (OR 8.22, CI 6.56-10.29). CONCLUSIONS: Undiagnosed CKD is common in diabetes. Current screening strategies, based on creatinine or albuminuria, fail to identify a considerable number of subjects with CKD. Incorporating eGFR into screening for CKD would identify individuals earlier in the natural history of the disease and enable early effective treatment to delay progression of CKD.