Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: A Randomized Clinical Trial.

Rationale & Objective: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs. Study Design: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial. Setting & Participants: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion. Intervention: Continuation with a CNI-based regimen or switch to belatacept for 12 months. Outcomes: Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness. Results: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss. Limitations: The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year. Conclusions: We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate. Funding: The trial has received a financial grant from Bristol-Myers Squibb. Trial Registration: EudraCT no. 2013-001178-20.

Cost effectiveness of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in patients with CKD in Norway and Sweden.

BACKGROUND: Hyperkalaemia is common in patients with chronic kidney disease (CKD) and is associated with a range of adverse outcomes. Historically, options for management of chronic hyperkalaemia in the outpatient setting have been limited. Novel oral potassium binders provide a safe, effective therapy for maintenance of normokalaemia in patients with CKD, but despite being approved for reimbursement in many countries, prescription data indicate uptake has been slower than anticipated. This analysis aimed to demonstrate the value to patients and the healthcare system of the potassium binder sodium zirconium cyclosilicate (SZC) for treatment of hyperkalaemia in patients with CKD in Norway and Sweden. METHODS: A published simulation model reflecting the natural history of CKD was adapted to the Norwegian and Swedish settings and used to predict long-term health economic outcomes of treating hyperkalaemia with SZC versus usual care. RESULTS: SZC was highly cost effective compared to usual care in Norway and Sweden, with incremental cost-effectiveness ratios of €14,838/QALY in Norway and €14,352/QALY in Sweden, over a lifetime horizon. The acquisition cost of SZC was largely offset by cost savings associated with reductions in hyperkalaemia events and hospitalisations; a modest overall increase in costs was predominantly attributable to costs associated with gains in life years compared with usual care. SZC remained cost effective in all scenarios examined. CONCLUSIONS: SZC was estimated to be cost effective for treating hyperkalaemia. Consequently, improving access to a clinically effective, safe and cost-effective therapy, such as SZC, may result in considerable benefits for CKD patients with hyperkalaemia.

Effect of spironolactone on vascular stiffness in hemodialysis patients: a randomized crossover trial.

Background: The role of spironolactone treatment in hemodialysis patients is debated, but a survival benefit is suggested. Mineralocorticoids and chronic kidney disease have been linked to cardiovascular fibrosis. Therefore, we hypothesized that spironolactone would affect vascular stiffness, cardiac systolic, and diastolic function in hemodialysis patients. Methods: This was a randomized crossover study in hemodialysis patients supplemented with an echocardiographic case series. All outcomes reported here were secondary in the trial and were assessed without blinding. Block randomization and allocation determined treatment order. Participants received 50 mg spironolactone daily for 12 weeks and untreated observation for another 12 weeks. Pulse wave velocity (PWV) was measured before and after treatment and observation. Doppler-echocardiography was conducted before and after treatment. Systemic arterial compliance indexed to body surface area (SACi), left ventricular ejection fraction (LVEF), the peak early diastolic mitral inflow velocity (E), the peak late diastolic mitral inflow velocity (A), and the peak early diastolic myocardial lengthening velocity (E') were measured. E/A and E/E' were then calculated. Statistical analyses were conducted per protocol. A generalized linear mixed model with random participant effects was used for PWV. The Wilcoxon signed-rank test was used for echocardiographic variables. Results: Thirty participants were recruited, 18 completed follow-up, and 17 were included in PWV-analyses. Spironolactone treatment showed a tendency toward an increase in PWV of 1.34 (95% confidence interval: -0.11 to 2.78) m/s, which was not statistically significant (P = 0.07). There were no significant changes in any of the other variables (LVEF, E/A, E/E', or SACi). Conclusions: We found no evidence supporting an effect of 12-week administration of spironolactone 50 mg daily on vascular stiffness, cardiac systolic, or diastolic function in hemodialysis patients.

Effects of spironolactone on extrasystoles and heart rate variability in haemodialysis patients: a randomised crossover trial.

BACKGROUND: Spironolactone treatment reduces mortality in haemodialysis (HD) patients. The objective of this study was to evaluate if spironolactone affects cardiac electric activity in this population. METHODS: Participants were randomised to start with spironolactone 50 mg daily or observation (12 weeks) with subsequent washout (6 weeks) and crossover to the other intervention (12 weeks). Long-term electrocardiograms were recorded and assessed with blinding to treatment. The primary outcome was premature ventricular complexes (PVC), and secondary outcomes were atrial premature contractions (APC) and heart rate variability (HRV). RESULTS: Thirty participants were recruited, and data for 16 participants were included in the analysis. Treatment was associated with an increase in PVCs by 9.7 [95% confidence interval (CI): 1.5 to 18] h-1. HRV time-domain variables increased during treatment, the standard deviation of all beat-to-beat intervals by 18 (95% CI: 3.3 to 32) milliseconds (ms) and the standard deviation of the averages of beat-to-beat intervals in all 5-min segments of the entire recording by 16 (95% CI: 1.5 to 30) ms. There were no significant differences in other variables. CONCLUSION: Spironolactone treatment increases PVCs in HD, indicating a possible proarrhythmic effect. However, improved cardiac autonomic function, as indicated by an increased HRV, may contribute to the survival benefit from spironolactone treatment in HD patients.

Implementation of a decision aid for recognition and correction of volume alterations (Recova®) in haemodialysis patients.

BACKGROUND: Fluid overload is associated with mortality in haemodialysis patients, and 30% of patients remain fluid-overloaded after dialysis. The aim of this study was to evaluate if implementation of Recova®, a decision aid combining clinical assessment with bioimpedance spectroscopy, facilitates individualization of target weight determination and thereby contributes to improved fluid status in maintenance haemodialysis patients. METHODS: The impact of the implementation was measured as the proportion of participants at an adequate target weight at the end of the study, assessed as change in symptoms, hydration status, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Nurses were instructed to use Recova every 2 weeks, and the process of the intervention was measured as frequencies of fluid status assessments, bioimpedance measurements, and target weight adjustments. RESULTS: Forty-nine patients at two haemodialysis units were enrolled. In participants with fluid overload (n = 10), both overhydration and fluid overload symptom score decreased. In fluid-depleted participants (n = 20), target weight adjustment frequency and the estimated target weight increased. The post-dialytic negative overhydration was reduced, but NT-proBNP increased. CONCLUSIONS: Implementation of Recova in haemodialysis care increased the monthly frequencies of bioimpedance measurements and target weight adjustments, and it contributed to symptom reduction. TRIAL REGISTRATION: The Uppsala County Council Registry of Clinical Trials: FoU 2019-0001-15.

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics.

BACKGROUND: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. METHODS: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). RESULTS: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). CONCLUSIONS: Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.

Systematic Fluid Assessment in Haemodialysis: Development and Validation of A Decision Aid.

BACKGROUND: About a third of patients undergoing haemodialysis have poorly controlled fluid status, which may affect survival. Clinical assessment is subjective and imprecise, which has led to the increasing use of devices based on bioimpedance spectroscopy (BIS). However, BIS cannot provide a simple target applicable to all patients. Our aim was to develop and validate a decision aid combining clinical assessment of fluid status with information from BIS in target weight determination. METHODS: The decision aid was based on empirical experience and a literature review identifying physiological parameters already used in the clinical assessment of fluid status. Content validity was established by patient representatives, interdisciplinary stakeholders and external experts, who assessed item relevance and comprehensiveness. Reliability was assessed by inter-rater agreement analysis between nurses assessing typical patient cases. RESULTS: The decision aid for Recognition and Correction of Volume Alterations (RECOVA) consists of three parts (1) a scoring system; (2) thresholds and triggers; (3) a decision aid algorithm. Agreement between raters in the assessment of symptoms was almost perfect, with Intraclass Correlation Coefficient > 0.90. Agreement in clinical response was only fair, but increased to moderate, with training and self-reported confidence. CONCLUSION: RECOVA may enable systematic clinical assessment of fluid status, facilitating early recognition of fluid alterations, and incorporation of bioimpedance into target weight management. However, implementation into clinical practice will require training of staff. Clinical intervention studies are required to evaluate if RECOVA facilitates response to and correction of recognised fluid alterations.

Real-World Associations of Renin-Angiotensin-Aldosterone System Inhibitor Dose, Hyperkalemia, and Adverse Clinical Outcomes in a Cohort of Patients With New-Onset Chronic Kidney Disease or Heart Failure in the United Kingdom.

Background Dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) may be modified to manage associated hyperkalemia risk; however, this approach could adversely affect cardiorenal outcomes. This study investigated real-world associations of RAASi dose, hyperkalemia, and adverse clinical outcomes in a large cohort of UK cardiorenal patients. Methods and Results This observational study included RAASi-prescribed patients with new-onset chronic kidney disease (n=100 572) or heart failure (n=13 113) first recorded between January 2006 and December 2015 in Clinical Practice Research Datalink and linked Hospital Episode Statistics databases. Odds ratios associating hyperkalemia and RAASi dose modification were estimated using logistic generalized estimating equations with normal (<5.0 mmol/L) serum potassium level as the reference category. Patients with serum potassium ≥5.0 mmol/L had higher risk of RAASi down-titration (adjusted odds ratios, chronic kidney disease: 1.79 [95% CI, 1.64-1.96]; heart failure: 1.33 [95% CI, 1.08-1.62]). Poisson models were used to estimate adjusted incident rate ratios of adverse outcomes based on total RAASi exposure (<50% and ≥50% of the guideline-recommended RAASi dose). Incidence of major adverse cardiac events and mortality was consistently higher in the lower dose group (adjusted incident rate ratios: chronic kidney disease: 5.60 [95% CI, 5.29-5.93] for mortality and 1.60 [95% CI, 1.55-1.66] for nonfatal major adverse cardiac events; heart failure: 7.34 [95% CI, 6.35-8.48] for mortality and 1.85 [95% CI, 1.71-1.99] for major adverse cardiac events). Conclusions The results of this real-world analysis highlight the potential negative impact of suboptimal RAASi dosing and the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation.

Brain natriuretic peptide reflects individual variation in hydration status in hemodialysis patients.

INTRODUCTION: Fluid management in hemodialysis patients is a controversial topic. Brain natriuretic peptide (BNP) is secreted from the heart in response to volume overload, and may be a marker of overhydration in hemodialysis patients. Our aim was to investigate the correlation between BNP and overhydration in a cohort of hemodialysis patients, and to find out whether BNP and overhydration correlate in repeated measurements within individuals with elevated BNP. METHODS: The study was prospective, observational, and had a cross-sectional part and a longitudinal follow-up. The distribution of BNP was investigated in a cohort of 64 hemodialysis patients. Blood samples and bioimpedance spectroscopy measurements were performed before midweek dialysis. Subsequently, 11 study participants with elevated BNP concentrations (>500 pg/mL) were assessed in another nine dialysis sessions each. These individuals also had their cardiac function and heart rate variability (HRV) examined. FINDINGS: BNP was above 500 pg/mL in 38% of the participants, and correlated positively with overhydration (rs = 0.381), inflammation and malnutrition, but not with systolic blood pressure. In comparison to participants with BNP below 500 pg/mL, participants with elevated BNP were older, had lower muscle strength, lower bodyweight and lower levels of hemoglobin and albumin. Echocardiography revealed cardiac anomalies in all 11 participants in the longitudinal follow-up, and HRV, as measured by SDNN, was pathologically low. In repeated measurements, the between-individuals variation of BNP in relation to overhydration was greater (SD = 0.581) than the within-person variation (SD = 0.285). DISCUSSION: BNP correlates positively to overhydration, malnutrition, and inflammation. In a subgroup of patients with elevated BNP, who are mainly elderly and frail, BNP reflects individual variation in hydration status, and hence seems to be a modifiable marker of overhydration. These data suggest that BNP is best applied for measuring changes in hydration status within an individual over time.

The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD. METHODS: A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses. RESULTS: Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia. CONCLUSION: This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK.

AIMS: At present, the clinical burden of hypokalaemia and hyperkalaemia among European heart failure patients, and relationships between serum potassium and adverse clinical outcomes in this population, is not well characterized. The aim of this study was to investigate associations between mortality, major adverse cardiac events, and renin-angiotensin-aldosterone system inhibitor (RAASi) discontinuation across serum potassium levels, in a UK cohort of incident heart failure patients. METHODS AND RESULTS: This was a retrospective observational cohort study of newly diagnosed heart failure patients listed in the Clinical Practice Research Datalink, with a first record of heart failure (index date) between 2006 and 2015. Hypokalaemia and hyperkalaemia episodes were defined as the number of serum potassium measurements exceeding each threshold (<3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L), without such a measurement in the preceding 7 days. Risk equations developed using Poisson generalized estimating equations were utilized to estimate adjusted incident rate ratios (IRRs) relating serum potassium and clinical outcomes (death, major adverse cardiac event, and RAASi discontinuation). Among 21,334 eligible heart failure patients, 1969 (9.2%), 7648 (35.9%), 2725 (12.8%), and 763 (3.6%) experienced episodes of serum potassium <3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively. The adjusted IRRs for mortality exhibited a U-shaped association pattern with serum potassium. Relative to the reference category (4.5 to <5.0 mmol/L), adjusted IRRs for mortality were estimated as 1.98 (95% confidence interval: 1.69-2.33), 1.23 (1.12-1.36), 1.35 (1.14-1.60), and 3.02 (2.28-4.02), for patients with serum potassium <3.5, ≥5.0 to <5.5, ≥5.5 to <6.0, and ≥6.0 mmol/L, respectively. The adjusted IRRs for major adverse cardiac events demonstrated a non-statistically significant relationship with serum potassium. Discontinuation of RAASi therapy exhibited a J-shaped trend in association with serum potassium. Compared with the reference category (4.5 to <5.0 mmol/L), adjusted IRRs were estimated as 1.07 (0.89-1.28) in patients with serum potassium <3.5 mmol/L, increasing to 1.32 (1.14-1.53) and 2.19 (1.63-2.95) among those with serum potassium ≥5.5 to <6.0 and ≥6.0 mmol/L, respectively. CONCLUSIONS: In UK patients with new onset heart failure, both hypokalaemia and hyperkalaemia were associated with increased mortality risk, and hyperkalaemia was associated with increased likelihood of RAASi discontinuation. Our results demonstrate the potential importance of serum potassium monitoring for heart failure outcomes and management.

Treatment of iron deficiency in patients with chronic kidney disease: A prospective observational study of iron isomaltoside (NIMO Scandinavia)
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AIMS: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, -effectiveness, and safety of iron isomaltoside (Monofer®, Pharma-cosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice. MATERIALS AND METHODS: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care. RESULTS: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment. In patients with a baseline Hb < 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb ≥ 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was > 1,000 mg. There were no serious adverse drug reactions. One non-serious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery. CONCLUSION: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.

AIMS: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients. MATERIALS AND METHODS: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management. RESULTS: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy. LIMITATIONS: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves. CONCLUSIONS: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

Serum potassium as a predictor of adverse clinical outcomes in patients with chronic kidney disease: new risk equations using the UK clinical practice research datalink.

BACKGROUND: To address a current paucity of European data, this study developed equations to predict risks of mortality, major adverse cardiac events (MACE) and renin angiotensin-aldosterone system inhibitor (RAASi) discontinuation using time-varying serum potassium and other covariates, in a UK cohort of chronic kidney disease (CKD) patients. METHODS: This was a retrospective observational study of adult CKD patients listed on the Clinical Practice Research Datalink, with a first record of CKD (stage 3a-5, pre-dialysis) between 2006 and 2015. Patients with heart failure at index were excluded. Risk equations developed using Poisson Generalized Estimating Equations were utilised to estimate adjusted incident rate ratios (IRRs) between serum potassium and adverse outcomes, and identify other predictive clinical factors. RESULTS: Among 191,964 eligible CKD patients, 86,691 (45.16%), 30,629 (15.96%) and 9440 (4.92%) experienced at least one hyperkalaemia episode, when defined using serum potassium concentrations 5.0-< 5.5 mmol/L, 5.5-< 6.0 mmol/L and ≥ 6.0 mmol/L, respectively. Relative to the reference category (4.5 to < 5.0 mmol/L), adjusted IRRs for mortality and MACE exhibited U-shaped associations with serum potassium, with age being the most important predictor of both outcomes (P < 0.0001). A J-shaped association between serum potassium and RAASi discontinuation was observed; estimated glomerular filtration rate was most predictive of RAASi discontinuation (P < 0.0001). CONCLUSIONS: Hyperkalaemia was associated with increased mortality and RAASi discontinuation risk. These risk equations represent a valuable tool to predict clinical outcomes among CKD patients; and identify those likely to benefit from strategies that treat hyperkalaemia, prevent RAASi discontinuation, and effectively manage serum potassium levels.

Perspectives on clinical use of bioimpedance in hemodialysis: focus group interviews with renal care professionals.

BACKGROUND: Inadequate volume control may be a main contributor to poor survival and high mortality in hemodialysis patients. Bioimpedance measurement has the potential to improve fluid management, but several dialysis centers lack an agreed fluid management policy, and the method has not yet been implemented. Our aim was to identify renal care professionals' perceived barriers and facilitators for use of bioimpedance in clinical practice. METHODS: Qualitative data were collected through four focus group interviews with 24 renal care professionals: dieticians, nephrologists and nurses, recruited voluntarily from a nation-wide selection of hemodialysis centers, having access to a bioimpedance-device. The participants were connected to each other and a moderator via equipment for telemedicine and the sessions were recorded. The interviews were semi-structured, focusing on the participants' perceptions of use of bioimpedance in clinical practice. Thematic content analysis was performed in consecutive steps, and data were extracted by employing an inductive, interactive, comparative process. RESULTS: Several barriers and facilitators to the use of bioimpedance in clinical practice were identified, and a multilevel approach to examining barriers and incentives for change was found to be applicable to the ideas and categories that arose from the data. The determinants were categorized on five levels, and the different themes of the levels illustrated with quotations from the focus groups participants. CONCLUSIONS: Determinants for use of bioimpedance were identified on five levels: 1) the innovation itself, 2) the individual professional, 3) the patient, 4) the social context and 5) the organizational context. Barriers were identified in the areas of credibility, awareness, knowledge, self-efficacy, care processes, organizational structures and regulations. Facilitators were identified in the areas of the innovation's attractiveness, advantages in practice, and collaboration. Motivation, team processes and organizational capacities appeared as both barriers and facilitators.

Clinical praxis for assessment of dry weight in Sweden and Denmark: A mixed-methods study.

Overhydration is an independent predictor of mortality in hemodialysis (HD) patients. More than 30% of HD patients are overhydrated, motivating the development of new methods for assessing hydration status. This study surveyed clinical praxis and local guidelines for dry weight (DW) assessment in Swedish and Danish HD units, and examined if differences in routines and utilization of bioimpedance spectroscopy (BIS) and other assistive technology affected frequency of DW adjustments and blood pressure (BP) levels. Cross-sectional information on praxis, guidelines and routines, plus treatment-related data from 99 stratified patients were collected. Qualitative data were analyzed with content analysis and interpreted in convergence with statistical analysis of quantitative data in a mixed-methods design. Local guidelines concerning DW existed in 54% of the units. A BIS device was present in 52%, but only half of those units used it regularly, and no correlations to frequency of DW adjustments or BP were found. HD nurses were authorized to adjust DW in 60% of the units; in these units, the frequency of DW adjustments was 1.6 times higher and systolic BP pre-HD 8 mmHg lower. There is a wide variation in routines for DW determination, and there are indications that authorization of HD nurses to adjust DW may improve DW assessment. BIS is sparsely used; its implementation may have been delayed by uncertainty over how to manage the device and interpret measurements. Hence, better methods and guidelines for assessing DW and using BIS need to be developed.

Heart rate variability is decreased in chronic kidney disease but may improve with hemoglobin normalization.

BACKGROUND: Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization. METHODS: Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 +/- 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function. RESULTS: Hemoglobin level increased from 100.7 +/- 12.6 g/L to 142.4 +/- 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 +/- 39.2 ms compared with 147.5 +/- 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 +/- 350.2 ms2 and 1,368.9 +/- 957.4 ms2 compared with 717.3 +/- 484.5 ms2 and 2,228.3 +/- 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 +/- 432.7 ms2 (p<0.05) and in total power to 1,731.0 +/- 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 +/- 33.8 ms (p=ns). CONCLUSIONS: CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation.

Hemorheological and hemodynamic changes in predialysis patients after normalization of hemoglobin with epoetin-alpha.

OBJECTIVE: Changes in blood viscosity and total peripheral resistance may contribute to increased blood pressure during partial correction of renal anemia with erythropoietin. An increase in hemoglobin level is followed by decreases in cardiac output and left ventricular mass. We examined how normalization of hemoglobin in predialysis patients affects both hemorheological and hemodynamic variables. MATERIAL AND METHODS: Twelve moderately anemic predialysis patients (hemoglobin 115.9+/-7.8 g/l) received epoetin-alpha with the aim of achieving a normal hemoglobin level (135-160 g/l). Hemorheological variables were measured using rotational viscometry. Cardiac index was determined by means of Doppler echocardiography. RESULTS: After 48 weeks, the hematocrit level had increased from 37.9%+/-3.0% to 47.0%+/-3.1% (p<0.0001). Blood viscosity increased from 3.84+/-0.33 to 4.59+/-0.4 mPa x s (p<0.001). Blood viscosity standardized to a hematocrit level of 45% and a plasma viscosity of 1.31 mPa x s did not change. Plasma viscosity, erythrocyte aggregation tendency and erythrocyte fluidity remained unchanged. The cardiac index decreased from 2.64+/-0.57 to 2.19+/-0.72 l/min/m(2) (p<0.05). The total peripheral resistance index increased from 3270+/-985 to 4013+/-1046 (dyn x s/cm(5))m(2) (p<0.05). Blood pressure remained constant, but the amount of antihypertensive medication used increased by 30%. CONCLUSIONS: Hemoglobin normalization in predialysis patients raised blood viscosity and total peripheral resistance due to an increase in hematocrit level, without other consistent hemorheological changes. Antihypertensive therapy had to be increased in many patients to maintain an acceptable blood pressure. The cardiac index was reduced, which may have prevented further development of left ventricular hypertrophy.

Effect of switching from subcutaneous to intravenous administration of epoetin-alpha in haemodialysis patients: results from a Swedish multicentre survey.

OBJECTIVE: In 2002, many haemodialysis patients were switched from subcutaneous (s.c.) to intravenous (i.v.) administration of epoetin-alpha following reports of antibody formation and development of pure red-cell aplasia in patients treated via the s.c. route. We evaluated the possible effect of this change in the route of administration on haemoglobin (Hb) levels and epoetin-alpha requirements. MATERIAL AND METHODS: This retrospective survey involved 223 haemodialysis patients from 25 Swedish centres. Variables were recorded before and after a mean period of 213 days (range 89-297 days) after the change in the route of administration. RESULTS: The mean epoetin-alpha do had to be increased from 159+/-104 to 185+/-122 U/kg/week (p<0.0001) to maintain a constant Hb level (121+/-12 vs 120+/-11 g/l). Plasma ferritin, albumin, C-reactive protein, iron, iron transferrin saturation and body mass index remained constant. The relative increase in epoetin-alpha dose was negatively correlated with the s.c. dose prior to the switch (R=-0.3; p<0.0001), with the most pronounced dose increases occurring in patients who received a low s.c. dose. CONCLUSIONS: A switch from s.c. to i.v. administration of epoetin-alpha in haemodialysis patients was accompanied by an increase in the mean dose requirement of 15%. This increase may be less pronounced in patients receiving high s.c. doses prior to the switch.

Reduced hemodialysis adequacy after hemoglobin normalization with epoetin.

BACKGROUND: Increased hemoglobin (Hb) levels and higher blood viscosity could reduce hemodialyzer clearance. We examined hemodialysis (HD) adequacy after treatment with epoetin alfa aimed at normalizing Hb levels. METHODS: Thirty-three HD patients were randomly allocated to achieve a normal Hb level (135-160 g/L) or a subnormal (control) Hb level of 90-120 g/L. HD adequacy was assessed by Kt/V measurement. RESULTS: In the 24 evaluable patients, Hb levels reached 144 +/- 11 g/L in the normal Hb group (n=10) and 109 +/- 10 g/L in the subnormal group (n=14). Single-pool Kt/V decreased from 1.25 +/- 0.19 to 1.15 +/- 0.13 (p<0.01) in the normal Hb group, but remained constant in the subnormal group (1.26 +/- 0.26 and 1.26 +/- 0.28). CONCLUSIONS: Normalization of Hb with epoetin alfa in HD patients resulted in a slight but statistically significant reduction in Kt/V. Therefore, when Hb is normalized, an increased dialysis dose could be necessary to maintain dialysis adequacy.