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).

End-stage kidney disease patients from ethnic minorities and mortality in coronavirus disease 2019.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) adversely affects patients who are older, multimorbid, and from Black, Asian or minority ethnicities (BAME). We assessed whether being from BAME is independently associated with mortality in end-stage kidney disease (ESKD) patients with COVID-19. METHODS: Prospective observational study in a single UK renal center. A study was conducted between March 10, 2020 and April 30, 2020. Demographics, socioeconomic deprivation (index of multiple deprivation), co-morbidities (Charlson comorbidity index [CCI]), and frailty data (clinical frailty score) were collected. The primary outcome was all-cause mortality. Data were censored on the 1st June 2020. FINDINGS: Overall, 191 of our 3379 ESKD patients contracted COVID-19 in the 8-week observation period; 84% hemodialysis, 5% peritoneal dialysis, and 11% kidney transplant recipients (KTR). Of these, 57% were male and 67% were from BAME groups (43% Asian, 17% Black, 2% mixed race, and 5% other). Mean CCI was 7.45 (SD 2.11) and 3.90 (SD 2.10) for dialysis patients and KTR, respectively. In our cohort, 60% of patients lived in areas classified as being in the most deprived 20% in the United Kingdom, and of these, 77% of patients were from BAME groups. The case fatality rate was 29%. Multivariable cox regression demonstrated that BAME (hazard ratio [HR]: 2.37, 95% CI: 1.22-4.61) was associated with all-cause mortality after adjustment for age, deprivation, co-morbidities, and frailty. Associations with all-cause mortality persisted in sensitivity analyses in patients from South Asian (HR: 2.52, 95% CI: 1.24-5.12) and Black (HR: 2.43, 95% CI: 1.04-5.67) ethnic backgrounds. DISCUSSION: BAME ESKD patients with COVID-19 are just over twice as likely to die compared to White patients, despite adjustment for age, deprivation, comorbidity, and frailty. This study highlights the need to develop strategies to improve BAME patient outcomes in future outbreaks of COVID-19.

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.

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.

Variability in parathyroid hormone assays confounds clinical practice in chronic kidney disease patients.

BACKGROUND: Intact parathyroid hormone (iPTH) measurements are used to guide therapy in renal patients, but variability in results can occur depending on the assay used. This study has investigated iPTH assay variation in North West England and paired data with regional audit data to determine clinical relevance of assay variability. METHODS: Thirty-seven haemodialysis patients had blood taken (EDTA plasma, and serum), and samples were processed at 17 laboratories that analyse iPTH for North West dialysis patients. Correction factors were calculated and applied to the iPTH assay results to enable direct comparisons. These correction factors were also applied to Regional Audit data to determine if iPTH assay variability explains the variation in unit performance in achieving PTH targets. RESULTS: The iPTH results from the 37 patients were significantly different when either analysed by different assays and/or different laboratories (P < 0.001). The Abbott Architect method consistently produced the highest iPTH results. Of the 37 patients, between 49% and 65% would achieve the Kidney Disease: Improving Global Outcomes (KDIGO) iPTH target depending on the assay used. When results were adjusted using correction factors, 21% of the patients would require a change of management according to guidelines. Data from all haemodialysis units submitted for the regional audit were adjusted to the Roche assay and this led to a small change in achievement of KDIGO iPTH targets in individual units when compared to each other. CONCLUSIONS: A combination of iPTH assay variability and diversity in clinical management leads to variation in achieving iPTH targets. Both need to be improved and/or standardized to improve patient care.

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.

The association of chronic kidney disease-mineral bone disorder and cardiovascular risk.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

Calcium and magnesium flux in automated peritoneal dialysis.

BACKGROUND: Calcium and magnesium balance in continuous ambulatory peritoneal dialysis (CAPD) has been extensively studied with several of the different formulations of fluid available. Calcium and magnesium balance in automated PD (APD) is less well studied and the effect on Ca and Mg flux is unknown. Data on glucose polymer solutions are also lacking. This prospective observational study was undertaken to examine mass transfer of Ca and Mg in APD patients. METHODS: 12 patients on APD were studied for two 24-hour periods using, alternately, 1.75 mmol/L and 1.25 mmol/L Ca (Dianeal PD1 and Dianeal PD4; Baxter Healthcare, Newbury, UK) 1.36% glucose-based dialysis fluid for the 9-hour overnight dialysis, followed by a 15-hour daytime dwell of glucose polymer-based fluid (icodextrin). Serum ionized Ca, serum Mg, and dialysate Ca and Mg concentrations were measured at the beginning and end of each period. Mass transfer was calculated as millimoles per exchange. RESULTS: During rapid overnight exchanges with Dianeal PD1 and PD4, mass transfer of Mg and Ca did not show significant correlations with serum levels when using PD1 fluid; however, mass transfer of Mg, but not Ca, was significantly correlated to serum levels when using PD4 fluid. During the long dwell with icodextrin, dialysate drain volume was the most significant factor determining the flux of both Ca and Mg. CONCLUSION: Mass transfer of Ca and Mg in APD patients using conventional dialysis fluid was not related to drain volume in this study, which differs to studies in CAPD. Flux of Ca and Mg during icodextrin use was found to be dependent on ultrafiltration rate and not dialysate or serum concentration.

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.

Vascular calcification in chronic kidney disease: a clinical review.

Vascular calcification, which is associated with arterial stiffness, is now known to be an important predictor of cardiovascular and all-cause mortality in patients with renal disease. This calcification starts developing in the early stages of chronic kidney disease (CKD) and is present in over 50% of patients at the time of dialysis commencement. Once calcification is present it continues to progress, though some medications have been shown to slow this progression. Vascular calcification and bone abnormalities are now both encompassed by the term of CKD-mineral bone disorder and are thought to be part of the same disease process in CKD. Vascular calcification and arterial stiffness have been extensively researched in the renal population and many factors are known to be associated with their presence and progression. This calcification is an important factor to be considered in the management of the renal patient but there are different methods available for its measurement. These details will be discussed further in this review along with evidence available for management of this important complication of renal disease.

Vascular calcification: lessons from scientific models.

Patients with chronic kidney disease have increased cardiovascular mortality from a combination of increased atherosclerotic disease, left ventricular hypertrophy and increased prevalence of vascular calcification (VC). Previously VC was thought to be a passive process which involved the deposition of calcium and phosphate into the vessel wall. However, recent studies have shown that VC is a highly regulated, cell-mediated process similar to bone formation, in that it is associated with expression of bone-related proteins, such as type I collagen and alkaline phosphatase. Animal and in vitro models of VC have shown that a multitude of factors including phosphate, matrix gla protein (MGP) and fetuin are involved in regulating VC. Certain factors induce calcification whereas others inhibit the process. Despite these insights, it is still not fully known how VC is regulated and a treatment for VC remains elusive. Ongoing research will hopefully elucidate these mechanisms and thereby produce targets for future therapeutic intervention. This review will highlight some of the scientific models of VC and how they have increased the understanding of this complex process.

Clinical management of disturbances of calcium and phosphate metabolism in dialysis patients.

Management of chronic kidney disease-mineral bone disorder can be difficult in renal patients. This review aims to explain why the control of disturbed calcium, phosphate, parathyroid hormone and vitamin D metabolism is important in dialysis patients. The methods available to regulate these parameters include diet, phosphate binders, dialysate calcium, native vitamin D, active vitamin D derivatives and calcimimetics. An overview of current treatment guidelines will be discussed.

Small bowel angiodysplasia in a patient on haemodialysis: difficulties in diagnosis and management.

Angiodysplasia is a common cause of gastrointestinal blood loss in patients with end stage renal disease. Diagnosis is especially difficult when the angiodysplastic lesions are concentrated in the small bowel. This report describes a case of a patient on haemodialysis who had transfusion-dependent anaemia from small bowel angiodysplasia. Endoscopic treatment was unsuccessful, tranexamic acid caused complications with thrombosis, and thalidomide showed no benefit. This case report highlights the problems in the diagnosis and management of this condition in patients on haemodialysis. Early diagnosis and optimisation of the patient for treatment is key to the successful outcomes of such patients.

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.