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BACKGROUND: Potassium binders mitigate hyperkalemia, allowing patients to maintain their renin-angiotensin-aldosterone-system inhibitor (RAASi) treatment. This study characterized patients treated with first- or second-generation potassium binders, usage patterns and their effectiveness in reducing potassium levels, and changes in RAASi treatment in a Swedish population-based study.

METHODS: A National Cohort included patients who had record of a treatment episode with a first-generation or second-generation potassium binder between 2018 and 2022. A Mid-Sweden Cohort included patients from the National Cohort who also had a record of a potassium measurement within the 60 days prior to beginning potassium binder treatment. Comorbidities, prior medication use, persistence with potassium binder treatment, subsequent changes in potassium levels and RAASi treatment were evaluated. Persistence was analyzed using the Kaplan-Meier estimator and changes in potassium levels were assessed using linear mixed-effects models.

RESULTS: 23,892 treatment episodes involving 14,235 patients (mean age 70 years, 33% women) were followed in the National Cohort, and 4860 episodes involving 3179 patients (mean age 72 years, 34% women) in the Mid-Sweden Cohort. Patients treated with second-generation potassium binders had more comorbidities and higher median persistence with treatment compared to those on first-generation potassium binders, 112.5 (95% CI:112.5-117.5) vs. 87.5 (95% CI: 87.5-87.5) days in the National Cohort; 165.5 (95% CI: 121.0-198.0) vs. 97.6 (95% CI: 87.5-110.0) days in the Mid-Sweden Cohort. Both first- and second-generation potassium binders reduced potassium levels from baseline by day 15, 5.7 [95% CI: 4.5-6.8] mmol/L to 4.7 [95% CI: 3.6-5.9] mmol/L and 5.5 (95% CI: 4.3-6.7) mmol/L to 4.9 (95% CI: 3.8-6.1) mmol/L, respectively. Dose reduction or discontinuation of renin-angiotensin system inhibitors (RASi) or mineralocorticoid receptor antagonists (MRAs) was found in 31.4% and 47.7%, respectively, within 120 days of initiating therapy.

CONCLUSION: Both potassium binders effectively reduced potassium levels, but frequent discontinuation or dose reduction of RAASi therapy were still observed during this period. The adjustments of RAASi therapy, despite the achievement of normokalemia within 15 days, may be premature and warrants careful reconsideration to ensure optimal patient outcomes.

Background: The heterogeneous features of enamel renal syndrome (ERS) make diagnosis and treatment challenging. The main symptoms are disturbed amelogenesis and nephrocalcinosis. Bi-allelic likely pathogenic (LP) or pathogenic (P) variants in FAM20A have been associated with the syndrome since 2012. Affected patients often receive extensive dental treatment because of deviant orofacial morphology. However, knowledge about long-term prognosis and treatment guidelines are still lacking. The complex nature of ERS might endanger both dental and general health. The purpose of this article is to highlight the risks of overlooking the symptoms of the syndrome, and to discuss management strategies, surveillance and prognosis.

Case presentation: We report the management of a case with suspected ERS after initial dental treatment elsewhere with no adjustment for the syndrome. Dental treatment was revised and followed for 8 years. Complementary medical examinations were conducted, and ERS was genetically confirmed, revealing homozygosity for a LP c.755_757del, p.(Phe252del) variant in FAM20A. The nephrological investigation revealed medullary calcium deposits, normal renal function and hypophosphatemia. Urine analysis revealed hypocitraturia and hypocalciuria. Accordingly, the patient now medicates with potassium citrate to decrease the risk of progressive renal stone formation.

Conclusion: We herein describe a patient with confirmed ERS with an 8-year follow-up. Diagnostic delay until adulthood led to complicated dental treatment. The results of nephrological investigations are presented. The importance of dental and medical multidisciplinary management in syndromic disorders affecting the formation of the enamel is also exemplified. The dental prognosis after rehabilitation is likely affected by anatomical variations and patient cooperation. The prognosis for renal function seems to be good. However, lifelong surveillance of renal function is recommended. Registration: The ethics committee in Uppsala, Sweden, determined that ethical approval was not necessary in this case (2019-04835). Informed consent was obtained from the participant in writing and is documented in the medical records.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD.

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.

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 euro14,838/QALY in Norway and euro14,352/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.

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/Eʹ, 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.

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.

Background

Chronic fluid overload is an independent predictor of mortality in haemodialysis. Clinical assessment of fluid status is subjective and unprecise, and 30% of the patients remain fluid overloaded at target/dry weight. This study evaluates the effects of implementing a decision aid, Recova®, which combines a systematised fluid status procedure with bioimpedance spectroscopy, for individualised dry weight determination in haemodialysis.

Methods

Nurses at two haemodialysis units were instructed to use Recova® every two weeks, assessing the study participants’ fluid status and adjusting their dry weights, as appropriate. The impact of the intervention was measured as proportion of participants at an adequate dry weight at the end of the study, assessed as change in symptoms, hydration status and N-terminal pro-brain natriuretic peptide (NT-proBNP). The process of the intervention was measured as frequencies of fluid status assessments, bioimpedance measurements and dry weight adjustments.

Results

Forty-nine patients were enrolled. In seven out of ten participants with fluid overload symptoms and bioimpedance-measured overhydration, symptoms and overhydration pre dialysis had decreased (2 to 0, p = 0.033 and 3.8 to 2.9 L, p = 0.047), by the end of the study. In 13 out of 20 participants with symptoms of fluid depletion and underhydration, there was a significant increase in dry weight (72.8 to 73.4 kg, p = 0.024), but also in NT-proBNP (6,230 to 9,625, p = 0.018). In groups of participants in which clinical assessments and BIS measurements were in conflict, fluid status was not affected.

Conclusions

Implementation of Recova® increased the monthly frequencies of bioimpedance measurements and dry weight adjustments. At the end of the study, participants with fluid overload had decreased symptoms and decreased OH. Participants with negative OH and fluid depletion symptoms had increased dry weight and reduced negative OH. Recova® may contribute to improved fluid management in haemodialysis.

Background: Chronic fluid overload is an independent predictor of mortality inhemodialysis. Clinical assessment of fluid status is subjective and unprecise, and 30% of the patients remain fluid overloaded at dry weight. This study evaluates the effects of implementing a recently developed decision aid, Recova®, which combines a systematized fluid status procedure with bioimpedance spectroscopy, for individualized dry weight determination in hemodialysis.

Methods: The study was a prospective implementation intervention carried out at two hemodialysis units. The impact of the intervention was measured as the proportion of participants at an adequate dry weight at the end of the study, assessed as change in symptoms, hydration status, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Hemodialysis nurses were instructed to use Recova® every two weeks, assessing the study participants’ fluid status and adjusting their dry weights as appropriate. The process of the intervention was measured as frequencies of fluid status assessments, bioimpedance measurements, and dry weight adjustments.

Results: Forty-nine patients were enrolled. In participants with fluid overload (n = 10), both bioimpedance-measured overhydration and fluid overload symptom score decreased. In fluid-depleted participants (n = 20), dry weight adjustment frequency and dry weight increased. The post-dialytic negative overhydration was reduced, but NTproBNP increased. In the remaining 19 participants, with low volume status scores, no significant changes were observed.

Conclusions: Recova® defines how and when dry weight should be evaluated in hemodialysis patients. Its purpose is to provide the multidisciplinary team with a common language, and thereby facilitate early recognition and appropriate response to fluid alterations. Implementation of Recova® in hemodialysis care increased the monthly frequencies of bioimpedance measurements and dry weight adjustments, and contributedto symptom reduction.

Background

About a third of patients undergoing haemodialysis have poorly controlled fluid status, which may affectsurvival. Clinical assessment is subjective and imprecise, which has led to the increasing use of devices based on bioimpedancespectroscopy (BIS). However, BIS cannot provide a simple target applicable to all patients. Our aim was to developand validate a decision aid combining clinical assessment of fluid status with information from BIS in target weightdetermination.

Methods

The decision aid was based on empirical experience and a literature review identifying physiological parametersalready used in the clinical assessment of fluid status. Content validity was established by patient representatives, interdisciplinarystakeholders and external experts, who assessed item relevance and comprehensiveness. Reliability was assessedby 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 scoringsystem; (2) thresholds and triggers; (3) a decision aid algorithm. Agreement between raters in the assessment of symptomswas almost perfect, with Intraclass Correlation Coefficient > 0.90. Agreement in clinical response was only fair, but increasedto 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 clinicalpractice will require training of staff. Clinical intervention studies are required to evaluate if RECOVA facilitates response toand correction of recognised fluid alterations.