Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care

Background: poorly controlled hypertension is independently associated with mortality, cardiovascular risk and disease progression in chronic kidney disease (CKD). In the UK, CKD stage 3 is principally managed in primary care, including blood pressure (BP) management. Controlling BP is key to improving outcomes in CKD. This study aimed to investigate associations of BP control in people with CKD stage 3.Methods: 1,741 patients with CKD 3 recruited from 32 general practices for the Renal Risk in Derby Study underwent medical history, clinical assessment and biochemistry testing. BP control was assessed by three standards: National Institute for Health and Clinical Excellence (NICE), National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Descriptive statistics were used to compare characteristics of people achieving and not achieving BP control. Univariate and multivariate logistic regression was used to identify factors associated with BP control.Results: the prevalence of hypertension was 88%. Among people with hypertension, 829/1426 (58.1%) achieved NICE BP targets, 512/1426 (35.9%) KDOQI targets and 859/1426 (60.2%) KDIGO targets. Smaller proportions of people with diabetes and/or albuminuria achieved hypertension targets. 615/1426 (43.1%) were only taking one antihypertensive agent. On multivariable analysis, BP control (NICE and KDIGO) was negatively associated with age (NICE odds ratio (OR) 0.27; 95% confidence interval (95% CI) 0.17-0.43) 70–79 compared to &lt;60), diabetes (OR 0.32; 95% CI 0.25-0.43)), and albuminuria (OR 0.56; 95% CI 0.42-0.74)). For the KDOQI target, there was also association with males (OR 0.76; 95% CI 0.60-0.96)) but not diabetes (target not diabetes specific). Older people were less likely to achieve systolic targets (NICE target OR 0.17 (95% CI 0.09,0.32) p?&lt;?0.001) and more likely to achieve diastolic targets (OR 2.35 (95% CI 1.11,4.96) p?&lt;?0.001) for people &gt;80 compared to?&lt;?60).Conclusions: suboptimal BP control was common in CKD patients with hypertension in this study, particularly those at highest risk of adverse outcomes due to diabetes and or albuminuria. This study suggests there is scope for improving BP control in people with CKD by using more antihypertensive agents in combination while considering issues of adherence and potential side effects.<br/

Living Well on Haemodialysis: feasibility and acceptability trial of an online Acceptance and Commitment Therapy (ACT) programme for people receiving kidney haemodialysis

Background People receiving kidney haemodialysis need psychological support. Objectives To assess feasibility and acceptability of a 4-week online video-based Acceptance and Commitment Therapy (ACT) programme for people receiving kidney haemodialysis. Design Single group before-and-after study. Participants People with end-stage kidney disease currently receiving dialysis, who had received in-centre haemodialysis at least 90 days in the last two years. Measures Recruitment, retention and engagement (feasibility); weekly and post-programme feedback (acceptability); pre-intervention and 4-week follow-up (potential outcome measures): kidney disease quality of life (KDQOL-SF), psychological flexibility (Acceptance and Action Scale) and acceptance of illness (Acceptance of Illness Scale). Results The study recruited 13 participants of whom 85% completed at least half the programme and 69% completed the whole programme. Health and medical treatment issues were the main known reasons for non-participation and drop-out. Of the 16 separate elements of the programme (four ‘story’ videos and 12 videos explaining ACT techniques), 13 were positively evaluated by at least 75% of participants. Of 11 aspects of the programme, 8 were positively evaluated by at least 75% of participants, and 89% found the programme easy to use, understood how it worked, found it easy to access, trusted the information, had no technical difficulties, and understood the activities. However, only 66.7% agreed the programme was interesting and only 62.5% agreed they enjoyed the programme. All responding participants indicated they would recommend the programme to people starting dialysis. The direction of change was positive for 17/21 potential outcome measures, with significant (p < 0.05) improvements in psychological flexibility and energy/fatigue. Conclusions An online video-based ACT intervention was feasible and acceptable for people receiving kidney haemodialysis and the results provide pilot data for a planned larger trial

Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and validation using primary care data from the UK.

OBJECTIVE: To develop and validate a prognostic model to inform risk stratified decisions on frequency of monitoring blood tests during long term methotrexate treatment. DESIGN: Retrospective cohort study. SETTING: Electronic health records within the UK's Clinical Practice Research Datalink (CPRD) Gold and CPRD Aurum. PARTICIPANTS: Adults (≥18 years) with a diagnosis of an immune mediated inflammatory disease who were prescribed methotrexate by their general practitioner for six months or more during 2007-19. MAIN OUTCOME MEASURE: Discontinuation of methotrexate owing to abnormal monitoring blood test result. Patients were followed-up from six months after their first prescription for methotrexate in primary care to the earliest of outcome, drug discontinuation for any other reason, leaving the practice, last data collection from the practice, death, five years, or 31 December 2019. Cox regression was performed to develop the risk equation, with bootstrapping used to shrink predictor effects for optimism. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data from 13 110 (854 events) and 23 999 (1486 events) participants were included in the development and validation cohorts, respectively. 11 candidate predictors (17 parameters) were included. In the development dataset, the optimism adjusted R2 was 0.13 and the optimism adjusted Royston D statistic was 0.79. The calibration slope and Royston D statistic in the validation dataset for the entire follow-up period was 0.94 (95% confidence interval 0.85 to 1.02) and 0.75 (95% confidence interval 0.67 to 0.83), respectively. The prognostic model performed well in predicting outcomes in clinically relevant subgroups defined by age group, type of immune mediated inflammatory disease, and methotrexate dose. CONCLUSION: A prognostic model was developed and validated that uses information collected during routine clinical care and may be used to risk stratify the frequency of monitoring blood test during long term methotrexate treatment

Innovations in coastline management with natural and nature-based features (NNBF): lessons learned from three case studies

Coastal communities around the world are facing increased coastal flooding and shoreline erosion from factors such as sea-level rise and unsustainable development practices. Coastal engineers and managers often rely on gray infrastructure such as seawalls, levees and breakwaters, but are increasingly seeking to incorporate more sustainable natural and nature-based features (NNBF). While coastal restoration projects have been happening for decades, NNBF projects go above and beyond coastal restoration. They seek to provide communities with coastal protection from storms, erosion, and/or flooding while also providing some of the other natural benefits that restored habitats provide. Yet there remain many unknowns about how to design and implement these projects. This study examines three innovative coastal resilience projects that use NNBF approaches to improve coastal community resilience to flooding while providing a host of other benefits: 1) Living Breakwaters in New York Harbor; 2) the Coastal Texas Protection and Restoration Study; and 3) the South Bay Salt Pond Restoration Project in San Francisco Bay. We synthesize findings from these case studies to report areas of progress and illustrate remaining challenges. All three case studies began with innovative project funding and framing that enabled expansion beyond a sole focus on flood risk reduction to include multiple functions and benefits. Each project involved stakeholder engagement and incorporated feedback into the design process. In the Texas case study this dramatically shifted one part of the project design from a more traditional, gray approach to a more natural hybrid solution. We also identified common challenges related to permitting and funding, which often arise as a consequence of uncertainties in performance and long-term sustainability for diverse NNBF approaches. The Living Breakwaters project is helping to address these uncertainties by using detailed computational and physical modeling and a variety of experimental morphologies to help facilitate learning while monitoring future performance. This paper informs and improves future sustainable coastal resilience projects by learning from these past innovations, highlighting the need for integrated and robust monitoring plans for projects after implementation, and emphasizing the critical role of stakeholder engagement.Environmental Biolog

Assessment of proteinuria in patients with chronic kidney disease stage 3: albuminuria and non-albumin proteinuria

Background and ObjectiveProteinuria assessment is key in investigating chronic kidney disease (CKD) but uncertainty exists regarding optimal methods. Albuminuria, reflecting glomerular damage, is usually measured, but non-albumin proteinuria (NAP), reflecting tubular damage, may be important. This study investigated the prevalence and associations of albuminuria and NAP, and the optimum number of urine specimens required.Methods1,741 patients with CKD stage 3, recruited from primary care, underwent medical history, clinical assessment, blood sampling, and submitted three early morning urine samples for albumin to creatinine ratio (uACR) and protein to creatinine ratios (uPCR). Albuminuria was defined as uACR ?3 mg/mmol in at least two of three samples. Isolated NAP was defined as uPCR ?17 mg/mmol in two of three samples and uACR &lt;3 mg/mmol in all three. Prevalence and associations of albuminuria and NAP, degree of agreement between single uACR and average of three uACRs, and urine albumin to protein ratio (uAPR = uACR/uPCR) were identified.ResultsAlbuminuria prevalence was 16% and NAP 6%. Using a &lt;1 mg/mmol threshold for uACR reduced NAP prevalence to 3.6%. Independent associations of albuminuria were: males (OR 3.06 (95% CI, 2.23–4.19)), diabetes (OR 2.14 (1.53–3.00)), lower estimated glomerular filtration rate ((OR 2.06 (1.48–2.85) 30–44 vs 45–59), and high sensitivity CRP ((OR 1.70 (1.25–2.32)). NAP was independently associated with females (OR 6.79 (3.48–13.26)), age (OR 1.62 (1.02–2.56) 80 s vs 70–79) and high sensitivity CRP ((OR 1.74 (1.14–2.66)). Of those with uPCR?17 mg/mmol, 62% had uAPR&lt;0.4. Sensitivity of single uACR was 95%, specificity 98%, PPV 90%. Bland Altman plot one vs average of three uACRs showed: mean difference 0.0064 mg/mmol (SD 4.69, limits of agreement ?9.19 to +9.20, absolute mean difference 0.837).ConclusionsIn CKD stage 3, albuminuria has associations distinct from those of isolated NAP (except for inflammatory markers). Single uACR categorised albuminuria but average of three performed better for quantification

The association between polyclonal combined serum free light chain concentration and mortality in individuals with early chronic kidney disease

A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (&gt;43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P &lt;0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC &gt;43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P &lt;0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation

Genome-wide profiling of blood pressure in adults and children

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms. Subsequently, genetic risk scores for systolic blood pressure and diastolic blood pressure were calculated in an independent adult population (n=2072) and a child population (n=1034). The explained variance of the genetic risk scores was evaluated using linear regression models, including sex, age, and body mass index. Genetic risk scores, including also many nongenome-wide significant single nucleotide polymorphisms, explained more of the variance than scores based only on very significant single nucleotide polymorphisms in adults and children. Genetic risk scores significantly explained ≤1.2% (P=9.6*10(-8)) of the variance in adult systolic blood pressure and 0.8% (P=0.004) in children. For diastolic blood pressure, the variance explained was similar in adults and children (1.7% [P=8.9*10(-10)] and 1.4% [P=3.3*10(-5)], respectively). These findings suggest the presence of many genetic loci with small effects on blood pressure regulation both in adults and children, indicating also a (partly) common polygenic regulation of blood pressure throughout different periods of life