Optimizing autologous stem cell collections for patients with multiple myeloma receiving G-CSF and Plerixafor: A single center project.

BACKGROUND: Increasing indications for cellular therapy collections have stressed our healthcare system, with autologous collections having a longer than desired wait time until apheresis collection. This quality improvement initiative was undertaken to accommodate more patients within existing resources. STUDY DESIGN AND METHODS: Patients with multiple myeloma who underwent autologous peripheral blood stem cell collection from October 2022 to April 2023 were included. Demographic, mobilization, laboratory, and apheresis data were retrospectively collected from the medical record. RESULTS: This cohort included 120 patients (49.2% male), with a median age of 60 years. All received G-CSF and 95% received pre-emptive Plerixafor approximately 18 hours pre-collection. Most (79%) had collection goals of at least 8 × 106/kg CD34 cells, with 63% over 70 years old having this high collection goal (despite 20 years of institutional data showing <1% over 70 years old have a second transplant). With collection efficiencies of 55.9%, 44% of patients achieved their collection goal in a single day apheresis collection. A platelet count <150 × 103/µL on the day of collection was a predictor for poor mobilization; among 27 patients with a low baseline platelet count, 17 did not achieve the collection goal and 2 failed to collect a transplantable dose. CONCLUSIONS: With minor collection goal adjustments, 15% of all collection appointments could have been avoided over this 6-month period. Other strategies to accommodate more patients include mobilization modifications (Plerixafor timing or substituting a longer acting drug), utilizing platelet counts to predict mobilization, and modifying apheresis collection volumes or schedule templates.

Is there a role of the kidney failure risk equation in optimizing timing of vascular access creation in pre-dialysis patients?

BACKGROUND: The aims of this study were to assess the utility of using the Kidney Failure Risk Equation (KFRE) as an indicator to guide timing of vascular access creation in pre-dialysis patients. MATERIALS AND METHODS: Patients referred for vascular access creation had KFRE calculated at the time of assessment and compared to standard criteria for referral. Receiver operating characteristic curves were produced for each parameter. The outcomes at 3 months, 6 months, and 1 year were used as time points for analysis. RESULTS: Two hundred and three patients were assessed, and full data sets were available on 190 (94.6%). Access was created in 156 patients (82.1%) with a fistula in 153 (98.7%). Only 65.7% initiated dialysis within the follow up period. Those patients with an AV access created (n = 156) 37 (23.7%) did not reach end stage over the entire follow up period. Of the remaining patients (n = 119) that reached end stage 72.2% (n = 86) started on an AVF/AVG and 27.7% (n = 33) on a CVC. Using ROC analysis for referral eGFR, ACR and KFRE predicting dialysis initiation predictors resulted in C statistics for eGFR, ACR, and KFRE2 of 0.68 (0.58-0.79), 0.75 (0.65-0.84), and 0.72 (0.62-0.81) at 3 months; 0.73 (0.65-0.81), 0.70 (0.62-0.78), and 0.75 (0.67-0.81) at 6 months; and 0.65 (0.57-0.72); 0.67 (0.59-0.75), and 0.68 (0.61-0.77) at 12 months. CONCLUSIONS: In a group of patients referred for vascular access creation the predictive models are relatively poor when applied to initiation of dialysis. The application of current guidelines to fistula creation appears to result in a high rate of unnecessary fistula formation and non-use. The study requires further evaluation in a test set of patients to confirm these findings and also identify where such risk based approaches may need modification.

Risk factors associated with COVID-19 severity among patients on maintenance haemodialysis: a retrospective multicentre cross-sectional study in the UK.

OBJECTIVES: To assess the applicability of risk factors for severe COVID-19 defined in the general population for patients on haemodialysis. SETTING: A retrospective cross-sectional study performed across thirty four haemodialysis units in midlands of the UK. PARTICIPANTS: All 274 patients on maintenance haemodialysis who tested positive for SARS-CoV-2 on PCR testing between March and August 2020, in participating haemodialysis centres. EXPOSURE: The utility of obesity, diabetes status, ethnicity, Charlson Comorbidity Index (CCI) and socioeconomic deprivation scores were investigated as risk factors for severe COVID-19. MAIN OUTCOMES AND MEASURES: Severe COVID-19, defined as requiring supplemental oxygen or respiratory support, or a C reactive protein of ≥75 mg/dL (RECOVERY trial definitions), and its association with obesity, diabetes status, ethnicity, CCI, and socioeconomic deprivation. RESULTS: 63.5% (174/274 patients) developed severe disease. Socioeconomic deprivation associated with severity, being most pronounced between the most and least deprived quartiles (OR 2.81, 95% CI 1.22 to 6.47, p=0.015), after adjusting for age, sex and ethnicity. There was no association between obesity, diabetes status, ethnicity or CCI with COVID-19 severity. We found no evidence of temporal evolution of cases (p=0.209) or clustering that would impact our findings. CONCLUSION: The incidence of severe COVID-19 is high among patients on haemodialysis; this cohort should be considered high risk. There was strong evidence of an association between socioeconomic deprivation and COVID-19 severity. Other risk factors that apply to the general population may not apply to this cohort.

Results of a pilot feasibility randomised controlled trial exploring the use of an electronic patient-reported outcome measure in the management of UK patients with advanced chronic kidney disease.

OBJECTIVES: The use of routine remote follow-up of patients with chronic kidney disease (CKD) is increasing exponentially. It has been suggested that online electronic patient-reported outcome measures (ePROMs) could be used in parallel, to facilitate real-time symptom monitoring aimed at improving outcomes. We tested the feasibility of this approach in a pilot trial of ePROM symptom monitoring versus usual care in patients with advanced CKD not on dialysis. DESIGN: A 12-month, parallel, pilot randomised controlled trial (RCT) and qualitative substudy. SETTING AND PARTICIPANTS: Queen Elizabeth Hospital Birmingham, UK. Adult patients with advanced CKD (estimated glomerular filtration rate ≥6 and ≤15 mL/min/1.73 m2, or a projected risk of progression to kidney failure within 2 years ≥20%). INTERVENTION: Monthly online ePROM symptom reporting, including automated feedback of tailored self-management advice and triggered clinical notifications in the advent of severe symptoms. Real-time ePROM data were made available to the clinical team via the electronic medical record. OUTCOMES: Feasibility (recruitment and retention rates, and acceptability/adherence to the ePROM intervention). Health-related quality of life, clinical data (eg, measures of kidney function, kidney failure, hospitalisation, death) and healthcare utilisation. RESULTS: 52 patients were randomised (31% of approached). Case report form returns were high (99.5%), as was retention (96%). Overall, 73% of expected ePROM questionnaires were received. Intervention adherence was high beyond 90 days (74%) and 180 days (65%); but dropped beyond 270 days (46%). Qualitative interviews supported proof of concept and intervention acceptability, but highlighted necessary changes aimed at enhancing overall functionality/scalability of the ePROM system. LIMITATIONS: Small sample size. CONCLUSIONS: This pilot trial demonstrates that patients are willing to be randomised to a trial assessing ePROM symptom monitoring. The intervention was considered acceptable; though measures to improve longer-term engagement are needed. A full-scale RCT is considered feasible. TRIAL REGISTRATION NUMBER: ISRCTN12669006 and the UK NIHR Portfolio (CPMS ID: 36497).

Development of an electronic patient-reported outcome measure (ePROM) system to aid the management of patients with advanced chronic kidney disease.

BACKGROUND: Effective management of patients with chronic kidney disease (CKD) relies on timely detection of clinical deterioration towards end stage kidney failure. We aimed to design an electronic Patient-Reported Outcome Measure (ePROM) system, which would allow patients with advanced CKD (pre-dialysis) to: (i) remotely self-report their symptoms using a simple and secure online platform; (ii) share the data with the clinical team in real-time via the electronic patient record to help optimise care. We adopted a staged development process which included: a systematic review of PROMs used in CKD; formation of a co-design team; prototype system design/development, user acceptance testing and refinement; finalisation of the system for testing in a pilot/feasibility trial. RESULTS: A co-design team was convened, including patients with lived experience of CKD; clinical team members; IT/Informatics experts; academics; and Birmingham Clinical Trials Unit representatives. A prototype system was developed and iterative changes made before finalisation during a series of operational meetings. The system allows patients to remotely self-report their symptoms; provides tailored self-management advice; allows monitoring of real-time patient ePROM data; sends automated notifications to the patient/clinical team in the advent of a severe symptom report; and incorporates longitudinal ePROM symptom data into the electronic patient record. Feasibility of the system will be evaluated as part of the National Institute for Health Research funded RePROM (Renal electronic Patient-Reported Outcome Measure) pilot trial (ISRCTN12669006). CONCLUSIONS: Routine ePROM collection with real-time feedback has the potential to improve outcomes and reduce health service costs. We have successfully developed a trial-ready ePROM system for advanced CKD, the feasibility of which is currently being explored in a pilot trial. Assuming feasibility is demonstrated, formal evaluation of efficacy will take place in a future multi-centre randomised controlled trial.

Use of an electronic patient-reported outcome measure in the management of patients with advanced chronic kidney disease: the RePROM pilot trial protocol.

INTRODUCTION: Chronic kidney disease (CKD) affects up to 16% of adults in the UK. Patient quality of life is particularly reduced in end-stage renal disease and is strongly associated with increased hospitalisation and mortality. Thus, accurate and responsive healthcare is a key priority. Electronic patient-reported outcome measures (ePROMs) are online questionnaires which ask patients to self-rate their health status. Evidence in oncology suggests that the use of ePROM data within routine care, alongside clinical information, may enhance symptom management and improve patient outcomes. However, National Health Service (NHS)-based ePROM research in CKD is lacking. This pilot trial will assess the feasibility of undertaking a full-scale randomised controlled trial (RCT) in patients with CKD within the NHS. METHODS AND ANALYSIS: The renal ePROM pilot trial is an investigator-led single-centre, open-label, two-arm randomised controlled pilot trial of 66 participants ≥18 years with advanced CKD. Participants will be randomised to receive either usual care or usual care supplemented with an ePROM intervention. Participants within the intervention arm will be asked to submit monthly self-reports of their health status using the ePROM system. The system will provide tailored information to patients in response to each report and notify the clinical team of patient deterioration. The renal clinical team will monitor for ePROM notifications and will respond with appropriate action, in line with standard clinical practice. Measures of study feasibility, participant quality of life and CKD severity will be completed at 3 monthly intervals. Health economic outcomes will be assessed. Clinicians will record treatment decision-making. Acceptability and feasibility of the protocol will be assessed alongside outcome measure and intervention compliance rates. Qualitative process evaluation will be conducted. ETHICS AND DISSEMINATION: The findings will inform the design of a full-scale RCT and the results will be submitted for publication in peer-reviewed journals. The study has ethical approval. TRIAL REGISTRATION NUMBERS: ISRCTN12669006; Pre-results.

Association between urinary free light chains and progression to end stage renal disease in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at an increased risk of developing end-stage renal disease (ESRD). We assessed for the first time whether urinary free light chains (FLC) are independently associated with risk of ESRD in patients with CKD, and whether they offer incremental value in risk stratification. MATERIALS AND METHODS: We measured urinary FLCs in 556 patients with CKD from a prospective cohort study. The association between urinary kappa/creatinine (KCR) and lambda/creatinine (LCR) ratios and development of ESRD was assessed by competing-risks regression (to account for the competing risk of death). The change in C-statistic and integrated discrimination improvement were used to assess the incremental value of adding KCR or LCR to the Kidney Failure Risk Equation (KFRE). RESULTS: 136 participants developed ESRD during a median follow-up time of 51 months. Significant associations between KCR and LCR and risk of ESRD became non-significant after adjustment for estimated glomerular filtration rate (eGFR) and albumin/creatinine ratio (ACR), although having a KCR or LCR >75th centile remained independently associated with risk of ESRD. Neither KCR nor LCR as continuous or categorical variables provided incremental value when added to the KFRE for estimating risk of ESRD at two years. CONCLUSIONS: Urinary FLCs have an association with progression to ESRD in patients with CKD which appears to be explained to a degree by their correlation with eGFR and ACR. Levels above the 75th centile do have an independent association with ESRD, but do not improve upon a current model for risk stratification.

Arterial stiffness alone does not explain arteriovenous fistula outcomes.

INTRODUCTION: Marked arterial adaptation is critical in permitting and sustaining the increased blood flow within an arteriovenous fistula (AVF). The aim of this investigation was to evaluate markers of arterial disease and their association with the early post-operative AVF outcomes. METHODS: We included all patients in whom an AVF had been performed after enrolment to the Renal Impairment In Secondary Care (RIISC) study. Primary AVF failure (PFL) was defined as thrombosis at six-week review. All patients underwent BP Tru and Vicorder pulse wave analysis assessments and also had assays of advanced glycation end-products prior to AVF formation. These were correlated with the short-term AVF outcomes. RESULTS: One hundred and eight AVFs were created in 86 patients. The primary patency (PPT) group were found to have significantly higher body mass index (BMI) (p = 0.01). Intraluminal vein diameter was significantly greater in the PPT group than the PFL group (p≤0.01). Mean augmentation index and augmentation index 75 was significantly higher in the PPT group than the PFL group (p = 0.03 and 0.03, respectively). Aortic pulse wave velocity was slower in the PPT group at 10.2 m/s than the PFL group at 10.8 m/s (p = 0.32). Advanced glycation end-product measurements did not vary significantly between the PPT and PFL groups (p = 0.4). Logistic regression analysis provided a predictive model, which demonstrated a predictive value of 78.1% for AVF patency at 6 weeks. CONCLUSIONS: All patients in this end-stage renal disease cohort have significant aortic stiffness. The results for pulse wave velocity were slower in the PPT group suggesting a tendency towards stiffer vessels and PFL.

Health-Related Quality of Life Impacts Mortality but Not Progression to End-Stage Renal Disease in Pre-Dialysis Chronic Kidney Disease: A Prospective Observational Study.

BACKGROUND: Chronic kidney disease (CKD) is associated with reduced health-related quality of life (HRQL). However, the relationship between pre-dialysis CKD, HRQL and clinical outcomes, including mortality and progression to end-stage renal disease (ESRD) is unclear. METHODS: All 745 participants recruited into the Renal Impairment In Secondary Care study to end March 2014 were included. Demographic, clinical and laboratory data were collected at baseline including an assessment of HRQL using the Euroqol EQ-5D-3L. Health states were converted into an EQ-5Dindex score using a set of weighted preferences specific to the UK population. Multivariable Cox proportional hazards regression and competing risk analyses were undertaken to evaluate the association of HRQL with progression to ESRD or all-cause mortality. Regression analyses were then performed to identify variables associated with the significant HRQL components. RESULTS: Median eGFR was 25.8 ml/min/1.73 m2 (IQR 19.6-33.7ml/min) and median ACR was 33 mg/mmol (IQR 6.6-130.3 mg/mmol). Five hundred and fifty five participants (75.7%) reported problems with one or more EQ-5D domains. When adjusted for age, gender, comorbidity, eGFR and ACR, both reported problems with self-care [hazard ratio 2.542, 95% confidence interval 1.222-5.286, p = 0.013] and reduced EQ-5Dindex score [hazard ratio 0.283, 95% confidence interval 0.099-0.810, p = 0.019] were significantly associated with an increase in all-cause mortality. Similar findings were observed for competing risk analyses. Reduced HRQL was not a risk factor for progression to ESRD in multivariable analyses. CONCLUSIONS: Impaired HRQL is common in the pre-dialysis CKD population. Reduced HRQL, as demonstrated by problems with self-care or a lower EQ-5Dindex score, is associated with a higher risk for death but not ESRD. Multiple factors influence these aspects of HRQL but renal function, as measured by eGFR and ACR, are not among them.

Serum tryptase concentration and progression to end-stage renal disease.

BACKGROUND: Mast cell activation can lead to nonclassical activation of the Renin-Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease. We stratified patients by use of angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEi/ARB). MATERIALS AND METHODS: This was a prospective cohort study of 446 participants recruited into the Renal Impairment in Secondary Care study. Serum tryptase was measured at recruitment by sandwich immunoassay. Cox regression analysis was undertaken to determine variables associated with progression to end-stage renal disease or death. RESULTS: Serum tryptase concentration was independently associated with progression to end-stage renal disease but not with death. In patients treated with ACEi or ARB, there was a strong independent association between higher tryptase concentrations and progression to end-stage renal disease; when compared to the lowest tertile, tryptase concentrations in the middle and highest tertiles had hazard ratios [HR] of 5·78 (95% confidence interval [CI] 1·19-28·03, P = 0·029) and 6·19 (95% CI 1·49-25·69, P = 0·012), respectively. The other independent risk factors for progression to end-stage renal disease were lower age, male gender, lower estimated glomerular filtration rate and higher urinary albumin creatinine ratio. CONCLUSION: Elevated serum tryptase concentration is an independent prognostic factor for progression to end-stage renal disease in patients with chronic kidney disease who are receiving treatment with an ACEi or ARB.

Patients with multiple myeloma have excellent long-term outcomes after recovery from dialysis-dependent acute kidney injury.

OBJECTIVES: The aim of this study was to report the long-term outcomes in patients with multiple myeloma (MM) who receive dialysis treatment for acute kidney injury (AKI) due to myeloma cast nephropathy and subsequently recover renal function. METHODS: Patients presenting with dialysis-dependent AKI secondary to myeloma cast nephropathy and subsequently recovering independent renal function between January 2005 and December 2012 were included in this study. Both renal and haematological parameters were collected at multiple time points as part of routine clinic practice. Factors associated with renal function and overall survival (OS) were determined. RESULTS: Twenty-four patients fulfilled the criteria for inclusion. Mean age was 62.1 years; 75% were male and 75% were of White ethnicity. The median OS was 64.1 months (95% confidence interval [CI] 34.8-93.3). Twenty-three (95.8%) patients remained dialysis-independent until death or end of follow-up; one patient required further haemodialysis treatment during the follow-up period. The independent determinant of worse OS was a known history of chronic kidney disease (CKD) at presentation. Shorter length of time on haemodialysis and higher percentage reduction in clonal serum FLC at day 21 from baseline predicted better excretory renal function (estimated glomerular filtration rate) at 6 months. CONCLUSION: In this series, the large majority of patients with MM and dialysis-dependent AKI secondary to myeloma cast nephropathy who recovered independent renal function had no requirement for further dialysis. Survival following recovery of renal function is good, and early variables are independently associated with survival and future renal function.

Caveolin-1 single-nucleotide polymorphism and arterial stiffness in non-dialysis chronic kidney disease.

BACKGROUND: Arteriosclerosis is an independent predictor of increased cardiovascular mortality in chronic kidney disease (CKD). Histologically it is characterized by hypertrophy and fibrosis of the arterial media wall leading to increased arterial stiffness and end-organ damage. Caveolin-1 acts as an intracellular signalling pathway chaperone in human fibrotic and vascular diseases. The purpose of this study was to assess the association between caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD cohort and in a cohort with more severe CKD. METHODS: Two prospectively maintained patient cohorts with non-dialysis CKD were studied: 144 patients in the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion criteria and DNA sampling availability. At entry to each cohort database, each patient's initial arterial PWV was measured, as well as their anthropomorphic and biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman technology. RESULTS: The CAV1 rs4730751 SNP CC genotype was associated with lower arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s; coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022]; these relationships held following adjustment for other important confounders. CONCLUSIONS: This replicated study suggests potential utility of the studied CAV1 SNP as a genetic biomarker in CKD and a role for CAV1 in the development of arteriosclerosis in this setting. Further studies are warranted to further explore the basic science driving these clinical observations.

Serum polyclonal immunoglobulin free light chain levels predict mortality in people with chronic kidney disease.

OBJECTIVE: To determine whether elevated serum polyclonal free light chain (FLC) levels predict mortality in a population of individuals with chronic kidney disease (CKD). PATIENTS AND METHODS: From January 2, 2006, through July 31, 2007, we recruited a cohort of 848 people with CKD who were not receiving renal replacement therapy and did not have monoclonal gammopathy. We measured serum kappa FLC and lambda FLC isotype levels to determine combined FLC (cFLC) levels. The cohort was prospectively followed up for a median of 63 months (interquartile range, 0-93 months). Cox regression analysis was performed to determine variables predictive of mortality. RESULTS: High cFLC levels were an independent risk factor for death (hazard ratio [HR], 2.71; 95% CI, 1.98-3.70; P<.001). Other independent risk factors were age (HR, 1.79; 95% CI, 1.52-2.10; P<.001), South Asian ethnicity (HR, 0.33; 95% CI, 0.14-0.64; P=.02), preexisting cardiovascular disease (HR, 1.59; 95% CI, 1.09-2.31; P=.02), and high-sensitivity C-reactive protein (HR, 1.13; 95% CI, 1.00-1.28; P=.04). Neither estimated glomerular filtration rate nor albuminuria was an independent risk factor for death. CONCLUSION: High cFLC levels independently predict mortality in people with CKD.

The periodontal health component of the Renal Impairment In Secondary Care (RIISC) cohort study: a description of the rationale, methodology and initial baseline results.

INTRODUCTION: Chronic kidney disease (CKD) is associated with significant morbidity and mortality. There is a need to identify novel and modifiable risk factors in such patients. The periodontal component of the Renal Impairment In Secondary Care (RIISC) study aims to evaluate the association between chronic periodontitis and CKD progression. METHODS: The RIISC study is a prospective, observational cohort study of patients with CKD from a renal clinic at a hospital in the West Midlands region of the UK. Patients undergo a periodontal examination and plaque and saliva sampling. To benchmark the oral health status of the RIISC cohort, we compared it to the Adult Dental Health Survey 2009 (ADHS), a representative survey of the oral health of community dwelling adults in the UK. RESULTS: Of the first 500 patients recruited into the RIISC study, 469 patients underwent a dental examination and 80 (17%) were edentulous. Among dentate subjects, patients within RIISC were significantly more likely to have any (OR 4.0 95% CI 2.7-5.9) or severe (OR 3.8 95% CI 2.5-5.6) periodontitis compared to the ADHS sample. CONCLUSION: The prevalence and severity of chronic periodontitis in this cohort of CKD patients is markedly higher than a geographically matched control population.

Allopurinol is an independent determinant of improved arterial stiffness in chronic kidney disease: a cross-sectional study.

BACKGROUND: Arterial stiffness is increased in patients with CKD and is a powerful predictor of cardiovascular morbidity and mortality. Use of the xanthine oxidase inhibitor allopurinol has been shown to improve endothelial function, reduce left ventricular hypertrophy and possibly improve cardiovascular outcome. We explored the relationship between use of allopurinol and arterial stiffness in patients with chronic kidney disease (CKD). METHODS: Cross-sectional observational study of 422 patients with CKD with evidence of, or at high risk of, renal disease progression. Arterial stiffness was determined by carotid-femoral pulse wave velocity (PWV). RESULTS: The mean age was 63 ± 16 years, median estimated glomerular filtration rate was 25 (interquartile range: 19-31) ml/min/1.73 m(2) and mean PWV was 10.2 ± 2.4 m/s. Seventy-seven patients (18%) were receiving regular allopurinol, 61% at a dose of 100 mg/day (range: 50-400 mg/day). Patients receiving allopurinol had significantly lower peripheral pulse pressure, central pulse pressure, central systolic blood pressure, serum uric acid level tissue advanced glycation end product levels but comparable high-sensitivity C-reactive protein levels. Use of allopurinol was associated with lower PWV. After adjusting for age, gender, ethnicity, tissue advanced glycation end product level, peripheral pulse pressure, smoking pack years, presence of diabetes mellitus and use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker, the use of allopurinol remained a significant independent determinant of PWV (mean difference: -0.63 m/s; 95% CI, -0.09 to -1.17 m/s, p = 0.02). CONCLUSION: In patients with CKD, use of allopurinol is independently associated with lower arterial stiffness. This study provides further justification for a large definitive randomised controlled trial examining the therapeutic potential of allopurinol to reduce cardiovascular risk in people with CKD.

Optimising the accuracy of blood pressure monitoring in chronic kidney disease: the utility of BpTRU.

BACKGROUND: Accurate blood pressure monitoring is critical for the management of chronic kidney disease, but changes in management in secondary care clinics may be based on a single blood pressure reading, with a subsequent lack of accuracy. The aim of this study was to evaluate a fully automated sphygmomanometer for optimising the accuracy of blood pressure measurements in the setting of secondary care renal clinics. METHODS: Patients had routine blood pressure measurements with a calibrated DINAMAP PRO400 monitor in a clinical assessment room. Patients then underwent repeat assessment with a DINAMAP PRO400 monitor and BpTRU device and subsequent 24 hour ambulatory blood pressure monitoring (ABPM). RESULTS: The BpTRU systolic (± SD) reading (117.3 ± 14.1 mmHg) was significantly lower than the routine clinic mean systolic blood pressure (143.8 ± 15.5 mmHg; P < 0.001) and the repeat blood pressure taken with a DINAMAP PRO400 monitor in a quiet room (129.9 ± 19.9 mmHg; P < 0.001). The routine clinic mean diastolic (82.4 ± 11.2 mmHg) was significantly higher than the BpTRU reading (78.4 ± 10.0 mmHg; P < 0.001). Clinic BpTRU measurements were not significantly different to the daytime mean or overall mean of 24 hour ABPM. CONCLUSIONS: In patients with CKD, routine clinic blood pressure measurements were significantly higher than measurements using a BpTRU machine in a quiet room, but there was no significant difference in this setting between BpTRU readings and 24 hour ABPM. Adjusting clinic protocols to utilise the most accurate blood pressure technique available is a simple manoeuvre that could deliver major improvements in clinical practice.

The natural history of, and risk factors for, progressive chronic kidney disease (CKD): the Renal Impairment in Secondary care (RIISC) study; rationale and protocol.

BACKGROUND: Chronic kidney disease (CKD) affects up to 16% of the adult population and is associated with significant morbidity and mortality. People at highest risk from progressive CKD are defined by a sustained decline in estimated glomerular filtration rate (eGFR) and/or the presence of significant albuminuria/proteinuria and/or more advanced CKD. Accurate mapping of the bio-clinical determinants of this group will enable improved risk stratification and direct the development of better targeted management for people with CKD. METHODS/DESIGN: The Renal Impairment In Secondary Care study is a prospective, observational cohort study, patients with CKD 4 and 5 or CKD 3 and either accelerated progression and/or proteinuria who are managed in secondary care are eligible to participate. Participants undergo a detailed bio-clinical assessment that includes measures of vascular health, periodontal health, quality of life and socio-economic status, clinical assessment and collection of samples for biomarker analysis. The assessments take place at baseline, and at six, 18, 36, 60 and 120 months; the outcomes of interest include cardiovascular events, progression to end stage kidney disease and death. DISCUSSION: The determinants of progression of chronic kidney disease are not fully understood though there are a number of proposed risk factors for progression (both traditional and novel). This study will provide a detailed bio-clinical phenotype of patients with high-risk chronic kidney disease (high risk of both progression and cardiovascular events) and will repeatedly assess them over a prolonged follow up period. Recruitment commenced in Autumn 2010 and will provide many outputs that will add to the evidence base for progressive chronic kidney disease.

Achieving an early myeloma response in patients with kidney impairment.

There is increasing evidence, particularly in severe acute kidney injury, that treatment of multiple myeloma with regimens that include dexamethasone in combination with novel chemotherapy agents are associated with an early disease response in most patients. However, the evidence to guide the optimal chemotherapy regimen in patients with kidney impairment is limited, and treatment choices are complicated by the effect of kidney function on drug dosing. Here, we summarize the current status of this field, with a particular focus on chemotherapy regimens that are based on dexamethasone and novel agents and an outline of those areas in which further work is needed to improve the evidence base.

Why did I start dialysis? A qualitative study on views and expectations from an elderly cohort of patients with end-stage renal failure starting haemodialysis in the United Kingdom.

BACKGROUND: It is now common for elderly patients with end-stage kidney disease to be offered treatment by dialysis. However, what these patients expect from dialysis is not known. Therefore, the purpose of this study was to elucidate the expectations of elderly patients starting dialysis and to investigate whether their views change after 6 months on this treatment. METHODS: This was a prospective observational qualitative study of patients commencing haemodialysis in our centre from 2006 to 2007. Data were collected by interview and review of case notes at the time of starting dialysis and after 6 months of treatment. Patients were asked about their expectations from dialysis, symptoms, and views on advance care planning. RESULTS: Data were collected from 22 patients (mean age 69.1 years) within a month from starting dialysis. Seventy per cent of these patients had attended a pre-dialysis clinic for at least 4 months previously; despite this, many of the patients complained about having had little choice in starting dialysis and seemed uncertain about what dialysis would involve. Even so, over 90% of those interviewed were optimistic about dialysis, had high expectations from treatment and were not keen to discuss advance care planning at first interview. Sixteen patients were re-interviewed at 6 months (four patients had died meanwhile and two had been transferred to other centres). After 6 months, there was a change in patients' attitude, with only 45% of them still finding dialysis acceptable and more patients now keen to discuss advance care planning. Symptom burden was higher at 6 months than at initiation of dialysis treatment. CONCLUSION: Most elderly patients have unrealistic expectations from dialysis at the start of treatment. There is a need for more specific counselling of these patients to ensure that they make informed decisions about treatment modality and have realistic expectations if they chose to receive RRT.

Recent advances in the pathogenesis and management of cast nephropathy (myeloma kidney).

Multiple myeloma is an incurable plasma cell malignancy that is often accompanied by renal failure; there are a number of potential causes of this, of which cast nephropathy is the most important. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. Consequently, there is an ongoing focus on the pathological basis of cast nephropathy and the optimal treatment regimens in this setting, including effective chemotherapy regimens to reduce light chain production and emerging extracorporeal techniques to remove circulating light chains. This paper bridges recent advances in the pathogenesis and management of cast nephropathy in multiple myeloma.