A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies.

BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer. CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome. DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.

Scaling Hemodialysis Target Dose to Reflect Body Surface Area, Metabolic Activity, and Protein Catabolic Rate: A Prospective, Cross-sectional Study.

BACKGROUND: Women and small men treated by hemodialysis (HD) have reduced survival. This may be due to use of total-body water (V) as the normalizing factor for dialysis dosing. In this study, we explored the equivalent dialysis dose that would be delivered using alternative scaling parameters matching the current recommended minimum Kt/V target of 1.2. STUDY DESIGN: Prospective cross-sectional study. SETTING & PARTICIPANTS: 1,500 HD patients on a thrice-weekly schedule, recruited across 5 different centers. PREDICTORS: Age, sex, weight, race/ethnicity, comorbid condition level, and employment status. OUTCOMES: Kt was estimated by multiplying V by 1.2. Kt/body surface area (BSA), Kt/resting energy expenditure (REE), Kt/total energy expenditure (TEE) and Kt/normalized protein catabolic rate (nPCR) equivalent to a target Kt/V of 1.2 were then estimated by dividing Kt by the respective parameters. MEASUREMENTS: Anthropometry, HD adequacy details, and BSA were obtained by standard procedures. REE was estimated using a novel validated equation. TEE was calculated from physical activity data obtained using the Recent Physical Activity Questionnaire. nPCR was estimated using a standard formula. RESULTS: Mean BSA was 1.87m2; mean REE, 1,545kcal/d; mean TEE, 1,841kcal/d; and mean nPCR, 1.03g/kg/d. For Kt/V of 1.2, there was a wide range of equivalent doses expressed as Kt/BSA, Kt/REE, Kt/TEE, and Kt/nPCR. The mean equivalent dose was lower in women for all 4 parameters (P<0.001). Small men would also receive lower doses compared with larger men. Younger patients, those with low comorbidity, those employed, and those of South Asian race/ethnicity would receive significantly lower dialysis doses with current practice. LIMITATIONS: Cross-sectional study; physical activity data collected by an activity questionnaire. CONCLUSIONS: Current dosing practices may risk underdialysis in women, men of smaller body size, and specific subgroups of patients. Using BSA-, REE-, or TEE-based dialysis prescription would result in higher dose delivery in these patients.

Membranous nephropathy: a retrospective observational study of membranous nephropathy in north east and central London.

BACKGROUND: Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. MN is a clinically heterogeneous disease and it is difficult to accurately predict outcomes (including end stage renal failure) at presentation and whom to treat with potentially toxic therapies. We aimed to identify factors predicting outcome in MN in our cohort from two large tertiary London units by undertaking a retrospective data analysis of 148 biopsy-proven MN patients from North East and Central London between 1995 and 2015. METHODS: Review of clinical and biochemistry databases. RESULTS: Surprisingly, patients that reached end stage renal failure (ESRF) had a less severe nephrosis compared to those that did not develop ESRF; serum albumin 33 g/L (3.3 g/dL) versus 24 g/L (2.4 g/dL), p = 0.002 and urinary protein creatinine ratio (uPCR) 550 mg/mmol (5500 mg/g) versus 902 mg/mmol (9020 mg/g), p = 0.0124. The correlation with ESRF was strongest with the presenting creatinine; 215 µmol/L (2.43 mg/dL) compared to 81 µmol/L (0.92 mg/dL), p < 0.0001. Patients presenting with creatinine of >120 µmol/L (1.36 mg/dL; corresponding to an eGFR of ≤60 ml/min in non-Black males) had an increased rate of ESRF and a faster decline. Other traditional risk factors for progression were not significantly associated with ESRF. Black patients presented with higher serum creatinine but no statistically significant difference in the estimated glomerular filtration rate, a higher rate of progression to ESRF and had a poorer response to treatment. CONCLUSIONS: This ethnically diverse cohort does not demonstrate the traditional risk profile associated with development of ESRF. Thus, careful consideration of therapeutic options is crucial, as current risk modelling cannot accurately predict the risk of ESRF. Further studies are required to elucidate the role of antibodies and risk genes.

Major bleeding in hemodialysis patients using unfractionated or low molecular weight heparin: a single-center study.

BACKGROUND: Successful hemodialysis (HD) requires circuit anticoagulation, with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) - it is not clear if differences in risk or benefit between these agents exist. We report our experience of major bleeding in patients on hemodialysis receiving either LMWH or UFH for anticoagulation of the dialysis circuit. We also examined any effect of anti-platelet agents or oral anticoagulants on bleeding rates. METHODS: An observational, retrospective, single-center study. Bleeding episodes are described using the International Society of Thrombosis and Hemostasis (ISTH) definition of a major bleeding event, and by extending this group to include all bleeds that led to a hospital admission (clinically significant). Incident event rates are reported per 100 at risk patient years, and event-free survival calculated using multivariate analysis by Cox-proportional hazard ratio. RESULTS: We report on 522 patients (792 years of exposure) in the UFHHD cohort and 889 patients (1,200 years of exposure) in the LMWH-HD cohort. The incidence of a major bleed was 1.33%, and 1.92% bleeds respectively. The incidences of clinically significant bleeding rates were 3.33% and 3.96% respectively. There was no significant difference in bleed free survival between UFH compared to LMWH (OR 0.904, CI 0.557 – 1.468, p = 0.684). Warfarin or anti-platelet usage did not increase the risk of bleeding when comparing patients not on any anticoagulants. CONCLUSIONS: There is no difference in bleeding rates between hemodialysis patients treated with either UFH or LMWH for anticoagulation of the extracorporeal circuit. We believe that both heparins have similar safety profiles when used for extracorporeal anticoagulation and that bleeding risk should not determine the choice of anticoagulation.

Anti-Xa activity supports using a simple dosing algorithm for tinzaparin for anticoagulation in hemodialysis.

BACKGROUND: Unfractionated heparin has been traditionally used for anticoagulation during hemodialysis (HD), but more recently low-molecular-weight heparin (LMWH) is being used as an alternative. Anti-Xa activity can be measured as a surrogate of LMWH efficacy. We present 52 patients treated with tinzaparin anticoagulation on HD, confirming that fixed dosing is safe and efficacious with sound pharmacodynamic reason in relation to anti-Xa profiling. METHODS: We undertook a prospective audit in a single dialysis unit. All patients were established on a simple anticoagulation protocol for at least 1 month prior to the audit. Blood anti-Xa activity was measured at time 0, 30, 60 and 120 min into and at the end of HD. Efficacy and safety data were collected on the study day and the two sessions before and after it. RESULTS: Fifty-two patients were included in the efficacy and safety analysis with 43 patients undergoing anti-Xa analysis (9 sampling errors). Using current consensus (an end-HD anti-Xa activity of <0.4 IU/ml), our fixed-dose protocol resulted in satisfactory safety in all patients tested. Of 260 HD sessions, 10 (4%) had reduced tinzaparin efficacy. During 105 dialysis sessions (21 patients) using an arteriovenous fistula, 4 patients had one episode of minor bleeding and there were 6 episodes (2 patients) of post-needle-compression time greater than 15 min. CONCLUSION: Tinzaparin administered thrice weekly as a fixed dose has good efficacy and is well tolerated as an anticoagulant during HD when used according to our protocol.

Characteristics and outcomes of dialysis patients with infective endocarditis.

BACKGROUND: The incidence of infective endocarditis (IE) in dialysis patients is higher than the general population. Dialysis patients who develop endocarditis are thought to have a poorer prognosis than other patients with IE. AIM: To examine the risk profiles, clinical features, and outcomes of patients on dialysis who developed IE in a large cohort. DESIGN AND METHODS: A retrospective analysis of all patients developing IE on dialysis (using the modified Duke criteria) was undertaken between 1998 and 2011. Patients were identified from a prospectively collected clinical database. RESULTS: 42 patients developed IE out of a total incident dialysis population of 1,500 over 13 years. 95% of the patients (40/42) were on long-term haemodialysis (HD) and 5% (2/42) on peritoneal dialysis. Mean patient age was 55.2 years (IQR: 43-69), and mean duration of HD prior to IE was 57.4 months. Primary HD access at the time of diagnosis was an arteriovenous fistula in 35% (14/40), a dual-lumen tunnelled catheter in 55% (22/40), and a dual-lumen non-tunnelled catheter in 10% (4/40). Staphylococcus aureus (including methicillin-resistant S. aureus) was present in 57.1% (24/42). The aortic valve was affected in 42.8% of the patients (18/42), the mitral valve in 30.9% (13/42), and both valves in 9.5% (4/42). 33.3% of the patients had an abnormal valve before the episode of IE. In 21.4% (9/42), valve surgery was performed and mortality was lower in the surgical group compared to the group managed medically during hospitalisation (11.1 vs. 15.2%, p = 0.892), at 3 months (13.1 vs. 19.6%, p = 0.501), and during follow-up (p = 0.207), but this difference did not reach statistical significance. Age >60 years, septic emboli, and methicillin-resistant S. aureus were all adverse prognostic factors. Patients receiving surgery were younger (mean 47.1 ± 14.4 years vs. 57.4 ± 14.3, p = 0.049) and less likely to be infected with S. aureus (surgery 33.3% vs. antibiotics 63.6%, p = 0.046). CONCLUSION: This is one of the largest reported series of IE in dialysis patients. The incidence of IE remains high and the prognosis poor in dialysis patients, although patients selected for early valve surgery have good 1-year survival.

A Genetic Risk Score Distinguishes Different Types of Autoantibody-Mediated Membranous Nephropathy.

Introduction: Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults and is characterized by detectable autoantibodies against glomerular antigens, most commonly phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain containing 7A (THSD7A). In Europeans, genetic variation in at least five loci, PLA2R1, HLA-DRB1, HLA-DQA1, IRF4, and NFKB1, affects the risk of disease. Here, we investigated the genetic risk differences between different autoantibody states. Methods: 1,409 MN individuals were genotyped genome-wide with a dense SNV array. The genetic risk score (GRS) was calculated utilizing the previously identified European MN loci, and results were compared with 4,929 healthy controls and 422 individuals with steroid-sensitive nephrotic syndrome. Results: GRS was calculated in the 759 MN individuals in whom antibody status was known. The GRS for MN was elevated in the anti-PLA2R1 antibody-positive (N = 372) compared with both the unaffected control (N = 4,929) and anti-THSD7A-positive (N = 31) groups (p < 0.0001 for both comparisons), suggesting that this GRS reflects anti-PLA2R1 MN. Among PLA2R1-positive patients, GRS was inversely correlated with age of disease onset (p = 0.009). Further, the GRS in the dual antibody-negative group (N = 355) was intermediate between controls and the PLA2R1-positive group (p < 0.0001). Conclusion: We demonstrate that the genetic risk factors for PLA2R1- and THSD7A-antibody-associated MN are different. A higher GRS is associated with younger age of onset of disease. Further, a proportion of antibody-negative MN cases have an elevated GRS similar to PLA2R1-positive disease. This suggests that in some individuals with negative serology the disease is driven by autoimmunity against PLA2R1.

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease.

Background: People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric and social care) and physical rehabilitation management is variable across England, as well as the rest of the UK. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The National Health Service (NHS) England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Methods: A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results: Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the 'Systems' section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic wellbeing assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking Therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognize psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion: There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the 'Systems' section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.

Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis.

Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.

Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease.

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of Mycobacterium tuberculosis infection and disease in patients with all grades of renal impairment.

HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol.

INTRODUCTION: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment. METHODS AND ANALYSIS: HEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.

Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice--the ECHO observational study.

BACKGROUND: The use and effectiveness of cinacalcet in 'real-world' clinical practice was investigated in a pan-European observational study in dialysis patients with secondary hyperparathyroidism (SHPT) of varying severity. METHODS: Adult patients with chronic kidney disease on dialysis who had initiated cinacalcet treatment were enrolled. Data were collected 6 months before initiating cinacalcet, at baseline (initiation of cinacalcet) and up to 12 months after cinacalcet initiation. RESULTS: A total of 1865 patients [mean (SD) age 58 (15) years] were enrolled from 187 sites in 12 countries. Most patients had a dialysis vintage of > or =1 year (1-5 years, n = 833; >5 years, n = 748 versus <1 year, n = 265). The patients generally had severely uncontrolled intact parathyroid hormone (iPTH) serum levels (median 721 pg/ml) and elevated phosphorus (median 5.9 mg/dl) and calcium (median 9.6 mg/dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI(TM) (KDOQI(TM))] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium-phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received <60 mg/day cinacalcet at Month 12. Vitamin D sterol use remained fairly stable throughout the study. There was a 13% decrease in prescribed sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns. CONCLUSION: This analysis of current European clinical practice shows that-consistent with findings from randomized controlled trials and retrospective observational studies-cinacalcet improves attainment of KDOQI bone metabolism targets in dialysis patients with various stages of SHPT.

Statins do not affect mineral metabolism in chronic kidney disease: a retrospective analysis.

It has recently been proposed that statins act as vitamin D analogs in binding the ubiquitously expressed vitamin D receptor, accounting for the perceived pleiotropic effects of statins (a reduction in cancer risk, prevention of organ transplant rejection and autoimmune disease). Chronic kidney disease (CKD) offers a useful test of this hypothesis: serum 25-hydroxyvitamin D levels are insufficient (<75 nmol/l) in as many as 76% of patients with advanced CKD, associated with secondary hyperparathyroidism and reduced bone mineralization. Vitamin D suppresses parathyroid hormone (PTH) secretion in part through its action on the vitamin D receptor. If statins act as vitamin D analogs, they may then be able to suppress PTH secretion in CKD. We examined data on 714 vitamin D analog naïve patients with stage 3-4 CKD. 404 patients were treated with a statin indicated almost exclusively for primary prevention of coronary heart disease, and 310 patients were not. Both groups were similar in characteristics. Statins had no effect on the intact PTH concentration, the percentage of patients achieving K/DOQI PTH targets, or on calcium or phosphate concentrations. In patients with stage 3-4 CKD, statins had no effect on secondary hyperparathyroidism. If the hypothesis contending that statins act as vitamin D analogs to exert pleiotropic effects is true, this is of no clinical benefit in the prevention of secondary hyperparathyroidism in CKD.

Predictors of late presentation to renal dialysis: a cohort study of linked primary and secondary care records in East London.

OBJECTIVES: The outcomes and experience of care for patients who start renal replacement therapy (RRT) in an unplanned manner are worse than for those who have planned care. The objective of this study was to examine the primary care predictors of unplanned starts to RRT. DESIGN: Retrospective cohort study with linked primary care and hospital data. SETTING: 128 general practices in East London with a combined population of 1 043 346 people. PARTICIPANTS: 999 consecutive patients starting dialysis at Barts Health National Health Service Trust between September 2014 and August 2017. PRIMARY OUTCOME MEASURES: Unplanned versus a planned start to dialysis among the cohort of 389 patients with a linked primary care record. An unplanned start to dialysis is defined as receiving nephrology care in the low clearance clinic (or equivalent) for less than 90 days. A planned start is defined as access to pre-dialysis counselling and care for at least 90 days prior to commencing dialysis. RESULTS: The adjusted logistic regression analysis showed that the most important modifiable risk factors for unplanned dialysis were the absence of a chronic kidney disease (CKD) code in the general practice (GP) record (OR 8.02, 95% CI 3.65 to 17.63) and the absence of prescribed lipid lowering medication (OR 2.37, 95% CI 1.05 to 5.34). Other contributing factors included male gender and a greater number of long-term conditions. CONCLUSIONS: Improving CKD coding in primary care and the additional review and clinical scrutiny associated with this may contribute to a further reduction in unplanned RRT rates.

Improving coding and primary care management for patients with chronic kidney disease: an observational controlled study in East London.

BACKGROUND: The UK national chronic kidney disease (CKD) audit in primary care shows diagnostic coding in the electronic health record for CKD averages 70%, with wide practice variation. Coding is associated with improvements to risk factor management; CKD cases coded in primary care have lower rates of unplanned hospital admission. AIM: To increase diagnostic coding of CKD (stages 3-5) and primary care management, including blood pressure to target and prescription of statins to reduce cardiovascular disease risk. DESIGN AND SETTING: Controlled, cross-sectional study in four East London clinical commissioning groups (CCGs). METHOD: Interventions to improve coding formed part of a larger system change to the delivery of renal services in both primary and secondary care in East London. Quarterly anonymised data on CKD coding, blood pressure values, and statin prescriptions were extracted from practice computer systems for 1-year pre- and post-initiation of the intervention. RESULTS: Three intervention CCGs showed significant coding improvement over a 1 year period following the intervention (regression for post-intervention trend P<0.001). The CCG with highest coding rates increased from 76-90% of CKD cases coded; the lowest coding CCG increased from 52-81%. The comparison CCG showed no change in coding rates. Combined data from all practices in the intervention CCGs showed a significant increase in the proportion of cases with blood pressure achieving target levels (difference in proportion P<0.001) over the 2-year study period. Differences in statin prescribing were not significant. CONCLUSION: Clinically important improvements to coding and management of CKD in primary care can be achieved by quality improvement interventions that use shared data to track and monitor change supported by practice-based facilitation. Alignment of clinical and CCG priorities and the provision of clinical targets, financial incentives, and educational resource were additional important elements of the intervention.

Trisodium citrate 46.7% selectively and safely reduces staphylococcal catheter-related bacteraemia.

BACKGROUND: Trisodium citrate (TSC) 30% has been shown in a randomized control trial to be an effective antimicrobial catheter locking solution, able to significantly reduce catheter-related bacteraemia (CRB) in haemodialysis patients. Since that report, the formulation in Europe has been changed to 46.7% TSC without confirmatory data on efficacy. We report a 55 915 patient-day at risk experience in tunnelled lines of 46.7% TSC, emphasizing efficacy and changes in microbiology seen. METHODS: On 1 July 2006, inter-dialytic catheter locking solution was changed from 5000 IU/ml heparin to Citra-lock(TM) (46.7% TSC) in all haemodialysis patients at Barts and the London Renal Unit dialysing through an incident or prevalent tunnelled catheter. Prospectively collected blood culture data for the 6 months prior to the switch and 3 months at the end of the first year of TSC use were analysed. TSC tolerability was excellent with only a single withdrawal for intolerance of the agent. No major adverse events were reported. RESULTS: A major fall in CRB rates was noticed with a change from heparin (2.13/1000 catheter-days) in 2006 to TSC (0.81/1000 catheter-days) in 2007. This was due to significant reductions in staphylococcal CRB, true for sensitive, methicillin-resistant and coagulase-negative staphylococci. No increase in catheter malfunction was observed. CONCLUSIONS: We found that 46.7% TSC is a safe, convenient and highly effective catheter locking solution, leading to significant reduction in CRB largely by preventing staphylococcal bloodstream infections. Given that Staphylococcus aureus in particular is associated with serious and often disseminated infection, TSC seems to be a powerful tool for dialysis units.

Nephrotic Syndrome: Oedema Formation and Its Treatment With Diuretics.

Oedema is a defining element of the nephrotic syndrome. Its' management varies considerably between clinicians, with no national or international clinical guidelines, and hence variable outcomes. Oedema may have serious sequelae such as immobility, skin breakdown and local or systemic infection. Treatment of nephrotic oedema is often of limited efficacy, with frequent side-effects and interactions with other pharmacotherapy. Here, we describe the current paradigms of oedema in nephrosis, including insights into emerging mechanisms such as the role of the abnormal activation of the epithelial sodium channel in the collecting duct. We then discuss the physiological basis for traditional and novel therapies for the treatment of nephrotic oedema. Despite being the cardinal symptom of nephrosis, few clinical studies guide clinicians to the rational use of therapy. This is reflected in the scarcity of publications in this field; it is time to undertake new clinical trials to direct clinical practice.

Indexing dialysis dose for gender, body size and physical activity: Impact on survival.

Current practice basing dialysis dose on urea distribution volume (V) has been questioned. We explored the impact on survival of scaling dialysis dose (Kt) to parameters reflective of metabolic activity. In a multicentre prospective cohort study of 1500 patients on thrice-weekly haemodialysis, body surface area (BSA) and resting energy expenditure (REE) were estimated using validated equations and physical activity by the Recent Physical Activity Questionnaire. Total energy expenditure (TEE) was estimated from REE and physical activity data. Kt was calculated from delivered (single-pool Kt/V)*Watson V. Kt/BSA, Kt/REE and Kt/TEE were then calculated at baseline and 6 monthly during follow-up for 2 years. In adjusted Cox models Kt/TEE, Kt/BSA, Kt/REE, in that order, had lower hazard ratios for death than single-pool Kt/V. On the basis of adjusted survival differences, putative minimum target doses were estimated for Kt/BSA as 27119 ml/m2 and Kt/TEE as 25.79 ml/kcal. We identified spKt/V values equivalent to these estimated targets, ranging from 1.4 to 1.8 in patient groups based on gender, body size and physical activity. For sedentary patients, the minimum target dose was 1.4 for large males, 1.5 for small males and 1.7 for women. For active patients the target was 1.8 irrespective of gender and body-weight. Patients achieving these individualised minimum targets had greater adjusted two-year survival compared to those achieving conventional minimum targets. Metabolic activity related parameters, such as Kt/TEE and Kt/BSA, may have a clinically important role in scaling haemodialysis dose. Using such parameters or their spKt/V equivalents to adjust minimum target doses based on gender, body size and habitual physical activity may have a positive impact on survival.