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Background: Risk-based thresholds for arteriovenous (AV) access creation has been proposed to aid vascular access planning. We aimed to assess the clinical impact of implementing the Kidney Failure Risk Equation (KFRE) for vascular access referral., Methods: A total of 16 102 nephrology-referred chronic kidney disease (CKD) patients from the Swedish Renal Registry 2008-18 were included. The KFRE was calculated repeatedly, and the timing was identified for when the KFRE risk exceeded several pre-defined thresholds and/or the estimated glomerular filtration rate was <15 mL/min/1.73 m2 (eGFR15). To assess the utility of the KFRE/eGFR thresholds, cumulative incidence curves of kidney replacement therapy (KRT) or death, and decision-curve analyses were computed at 6 and 12 months, and 2 years. The potential impact of using the different thresholds was illustrated by an example from the Swedish access registry., Results: The 12-month specificity for KRT initiation was highest for KFRE >50% {94.5 [95% confidence interval (CI) 94.3-94.7]} followed by KFRE >40% [90.0 (95% CI 89.7-90.3)], while sensitivity was highest for KFRE >30% [79.3 (95% CI 78.2-80.3)] and eGFR <15 mL/min/1.73 m2 [81.2 (95% CI 80.2-82.2)]. The 2-year positive predictive value was 71.5 (95% CI 70.2-72.8), 61.7 (95% CI 60.4-63.0) and 47.2 (95% CI 46.1-48.3) for KFRE >50%, KFRE >40% and eGFR <15, respectively. Decision curve analyses suggested the largest net benefit for KFRE >40% over 2 years and KFRE >50% over 12 months when it is important to avoid the harm of possibly unnecessary surgery. In Sweden, 54% of nephrology-referred patients started hemodialysis in a central venous catheter (CVC), of whom only 5% had AV access surgery >6 months before initiation. Sixty percent of the CVC patients exceeded KFRE >40% a median of 0.8 years (interquartile range 0.4-1.5) before KRT initiation., Conclusions: The utility of using KFRE >40% and KFRE >50% is higher compared with the more traditionally used eGFR threshold <15 mL/min/1.73 m2 for vascular access planning., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Non-traumatic lower extremity amputation (LEA) is a severe complication during dialysis. To inform decision-making for physicians, we developed a multivariable prediction model for LEA after starting dialysis., Methods: Data from the Swedish Renal Registry (SNR) between 2010 and 2020 were geographically split into a development and validation cohort. Data from Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) between 1997 and 2009 were used for validation targeted at Dutch patients. Inclusion criteria were no previous LEA and kidney transplant and age ≥40 years at baseline. A Fine-Gray model was developed with LEA within 3 years after starting dialysis as the outcome of interest. Death and kidney transplant were treated as competing events. One coefficient, ordered by expected relevance, per 20 events was estimated. Performance was assessed with calibration and discrimination., Results: SNR was split into an urban development cohort with 4771 individuals experiencing 201 (4.8%) events and a rural validation cohort with 4.876 individuals experiencing 155 (3.2%) events. NECOSAD contained 1658 individuals experiencing 61 (3.7%) events. Ten predictors were included: female sex, age, diabetes mellitus, peripheral artery disease, cardiovascular disease, congestive heart failure, obesity, albumin, haemoglobin and diabetic retinopathy. In SNR, calibration intercept and slope were -0.003 and 0.912, respectively. The C-index was estimated as 0.813 (0.783-0.843). In NECOSAD, calibration intercept and slope were 0.001 and 1.142 respectively. The C-index was estimated as 0.760 (0.697-0.824). Calibration plots showed good calibration., Conclusion: A newly developed model to predict LEA after starting dialysis showed good discriminatory performance and calibration. By identifying high-risk individuals this model could help select patients for preventive measures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes., Methods: We studied patients referred to nephrologist care, listed on the Swedish Renal Registry during 2007-2017, who developed advanced CKD (eGFR<30 ml/min per 1.73 m 2 ) while on RAS inhibitor therapy. Using target trial emulation techniques on the basis of cloning, censoring, and weighting, we compared the risks of stopping within 6 months and remaining off treatment versus continuing RAS inhibitor therapy. These included risks of subsequent 5-year all-cause mortality, major adverse cardiovascular events, and initiation of kidney replacement therapy (KRT)., Results: Of 10,254 prevalent RAS inhibitor users (median age 72 years, 36% female) with new-onset eGFR <30 ml/min per 1.73 m 2 , 1553 (15%) stopped RAS inhibitor therapy within 6 months. Median eGFR was 23 ml/min per 1.73 m 2 . Compared with continuing RAS inhibition, stopping this therapy was associated with a higher absolute 5-year risk of death (40.9% versus 54.5%) and major adverse cardiovascular events (47.6% versus 59.5%), but with a lower risk of KRT (36.1% versus 27.9%); these corresponded to absolute risk differences of 13.6 events per 100 patients, 11.9 events per 100 patients, and -8.3 events per 100 patients, respectively. Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model., Conclusions: In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT., (Copyright © 2021 by the American Society of Nephrology.)

Objective: To identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease., Design: Nationwide observational cohort study., Setting: National Swedish Renal Registry of patients referred to nephrologists., Participants: Patients had a baseline eGFR between 10 and 20 mL/min/1.73 m 2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017., Main Outcome Measures: The strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m 2 in increments of 1 mL/min/1.73 m 2 . An eGFR between 6 and 7 mL/min/1.73 m 2 (eGFR 6-7 ) was taken as the reference., Results: Among 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m 2 ), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR 15-16 . Compared with dialysis initiation at eGFR 6-7 , initiation at eGFR 15-16 was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR 10-14 v eGFR 5-7 ) and the achieved eGFRs in IDEAL (eGFR 7-10 v eGFR 5-7 ), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial., Conclusions: Very early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Swedish Research Council, Center of Innovative Medicine Karolinska, and Stockholm City Council. JJC has consulted for Baxter and AstraZeneca and received grant support from AstraZeneca, Viforpharma, and Astellas, all outside the submitted work; CMC has received consultation, advisory board membership, or research funding from the Ontario Ministry of Health, Sanofi, Johnson and Johnson, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim, and Baxter, all outside the submitted work; CW has received consultation and advisory board membership honorariums from AstraZeneca, Akebia, Bayer, Boehringer-Ingelheim, Gilead, GSK, MSD, Sanofi-Genzyme, and Tricida, outside the present work. KJJ has received grant support from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and speaker honorariums from Fresenius Medical Care, outside the submitted work. FJC has received grant support from the National Institute for Health Research and Kidney Research UK and honorariums from Baxter. ME has received payment for advisory boards and lectures and research funding from Astellas Pharma, Astra Zeneca, Vifor Pharma, and Fresenius, all outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The safety of restarting angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) after acute kidney injury (AKI) is unclear. There is concern that previous users do not restart ACEI/ARB despite ongoing indications. We sought to determine the risk of adverse events after an episode of AKI, comparing prior ACEI/ARB users who stop treatment to those who continue., Methods: We conducted two parallel cohort studies in English and Swedish primary and secondary care, 2006-2016. We used multivariable Cox regression to estimate hazard ratios (HR) for hospital admission with heart failure (primary analysis), AKI, stroke, or death within 2 years after hospital discharge following a first AKI episode. We compared risks of admission between people who stopped ACEI/ARB treatment to those who were prescribed ACEI/ARB within 30 days of AKI discharge. We undertook sensitivity analyses, including propensity score-matched samples, to explore the robustness of our results., Results: In England, we included 7303 people with AKI hospitalisation following recent ACEI/ARB therapy for the primary analysis. Four thousand three (55%) were classified as stopping ACEI/ARB based on no prescription within 30 days of discharge. In Sweden, we included 1790 people, of whom 1235 (69%) stopped treatment. In England, no differences were seen in subsequent risk of heart failure (HR 1.10; 95% confidence intervals (CI) 0.93-1.30), AKI (HR 0.90; 95% CI 0.77-1.05), or stroke (HR 0.99; 95% CI 0.71-1.38), but there was an increased risk of death (HR 1.27; 95% CI 1.15-1.41) in those who stopped ACEI/ARB compared to those who continued. Results were similar in Sweden: no differences were seen in risk of heart failure (HR 0.91; 95% CI 0.73-1.13) or AKI (HR 0.81; 95% CI 0.54-1.21). However, no increased risk of death was seen (HR 0.94; 95% CI 0.78-1.13) and stroke was less common in people who stopped ACEI/ARB (HR 0.56; 95% CI 0.34-0.93). Results were similar across all sensitivity analyses., Conclusions: Previous ACEI/ARB users who continued treatment after an episode of AKI did not have an increased risk of heart failure or subsequent AKI compared to those who stopped the drugs.

Disturbances in calcium metabolism are common in individuals with chronic kidney disease (CKD), but whether they are associated with subsequent kidney function decline is less clear. In a CKD 3-5 cohort of 15,755 adult citizens of Stockholm with creatinine tests taken during 2006-2011 and concurrent calcium testing at cohort entry, we investigated the association between baseline serum calcium and the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI) decline using linear mixed models. Mean (SD) baseline corrected serum calcium was 9.6 (0.5) mg/dL. Mean (95%-confidence interval [CI]) eGFR decline was -0.82 (-0.90; -0.74) mL/min/1.73 m 2 /year. In advanced CKD stages, higher baseline serum calcium was associated with less rapid kidney function decline. The adjusted change (95%-CI) in eGFR decline associated with each mg/dL increase in baseline serum calcium was -0.10 (-0.28; 0.26), 0.39 (0.07; 0.71), 0.34 (-0.02; 0.70) and 0.68 (0.36; 1.00) mL/min/1.73 m 2 /year for individuals in CKD stage 3a, 3b, 4, and 5, respectively. In a subgroup of patients using vitamin D supplements, the association between baseline serum calcium and CKD progression was eliminated, especially in CKD stage 3b and 4. To conclude, in individuals with CKD stage 3b to 5, lower baseline corrected serum calcium, rather than higher baseline serum calcium, associated with a more rapid CKD progression. Lower serum corrected calcium seems to be indicative for vitamin D deficiency.

Aims: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD., Methods and Results: We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or ≥60 ml/min/1.73 m 2 , respectively. An eGFR ≥60 ml/min/1.73 m 2 and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD., Conclusions: The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

SCREAM (Stockholm CREAtinine Measurements project) was initiated in 2010 in collaboration with the healthcare provider of Stockholm County healthcare to quantify potential medication errors, estimate the burden of chronic kidney disease (CKD) and to illustrate the value of incorporating measures of kidney function into the medical decision process. Because most patients are unaware of their CKD and diagnoses are seldom issued, SCREAM took advantage of the commonness of serum/plasma creatinine testing, which can be used to estimate the glomerular filtration rate (eGFR) and classify the stage of CKD severity. SCREAM is periodically updated, and at present contains healthcare information of all residents in Stockholm region during 2006–2019 (about 3 million people), enriched with a broad range of laboratory measurements for those in whom creatinine or albuminuria has been measured (about 1.8 million people). This health information was linked with national administrative and quality registries via the unique personal identification number of each Swedish citizen, conforming the richest characterization in Sweden of the population's journey through health and disease. This review discusses the context of its creation, strengths and weakness, key findings and plans for the future. We summarize our findings related to the burden of CKD in Sweden, its adverse health risks (such as risk of infections, cancer or dementia) and how underlying kidney function alters the risk–benefit ratio of common medications. Results have had clinical impact and demonstrate the importance of population‐based research in the spectrum of clinical research to improve health. [ABSTRACT FROM AUTHOR]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF)., Methods and Results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m 2 and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus ≥60 ml/min/1.73 m 2 , from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus ≥6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively., Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient subgroups and discontinuations., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Use and dosing of guideline‐directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real‐life patterns of dose titration and discontinuation of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor–neprilysin inhibitors (ARNI). Methods and results: New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (n = 8426), ARB (n = 2303), beta‐blockers (n = 10 476), MRA (n = 17 421), and ARNI (n = 29 546) were identified. Over 12 months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta‐blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0–86.9 per 100 patient‐years across the treatment groups. Conclusion: Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up‐titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just‐in‐time decision support for patients and health care providers. [ABSTRACT FROM AUTHOR]

Background: The sudden occurrence of stroke often leads to impaired physical, emotional, and cognitive abilities. Many stroke survivors therefore require support from their family members. However, little is known about the effects of a stroke event on the spouses' employment transition probabilities. The aim of this study was twofold 1) to investigate whether a first ever stroke has an effect on employment transition probabilities for employed and unemployed spouses and 2) to analyze whether heterogeneity with respect to age, gender, education and comorbidities influence the size of the effect.Method: Data for this population-based cohort study were extracted from Swedish national registries from 2005 to 2016. The national sample consisted of 1818 spouses of first ever stroke survivors during 2010 and 2011, and 7399 matched controls that were employed or unemployed during 5 years prior stroke onset. Effects of stroke on spousal employment transitions were analyzed using linear regression, stratified by employment status prior to stroke onset.Results: Employed spouses prior stroke onset reduced their employment by - 1.3 percentage points (95% CI, - 2.4, - 0.2). The data also indicated that employed spouses with lower age, comorbid conditions, and low educational attainment may be at even greater risk of transitioning to unemployment. On the other hand, stroke events appear to have limited impact on spouses that were unemployed prior to stroke onset.Conclusion: The risk of transitioning to unemployment appears to increase after stroke onset for spouses of stroke survivors, and disadvantaged groups may be at even greater risk. Thus, it is important for policy-makers to implement interventions to ensure that these groups of spouses have the possibilities to combine their caregiving role and remaining in the labor market. [ABSTRACT FROM AUTHOR]

Background Although patient-reported outcome measures (PROMs) are gaining increased interest in developing health care quality and are a useful tool in person-centered care, their use in routine care is still limited. The aim of this study is to describe the implementation and initial results of PROMs via the Swedish Renal Registry (SRR) on a national level. Methods After testing and piloting the electronic PROM application, nationwide measures were carried out in 2017 for completing the RAND-36 questionnaire online or by paper in a wide range of chronic kidney disease (CKD) patients (Stages 3–5, dialysis and transplantation) through the SRR. Cross-sectional results during the first year were analyzed by descriptive statistics and stratified by treatment modality. Results A total of 1378 patients from 26 of 68 renal units (39%) completed the questionnaire. The response rate for all participating hemodialysis units was 38.9%. The CKD patients had an impaired health profile compared with a Swedish general population, especially regarding physical functions and assessed general health (GH). Transplanted patients had the highest scores, whereas patients on dialysis treatment had the lowest scores. The youngest age group assessed their physical function higher and experienced fewer physical limitations and less bodily pain than the other age groups but assessed their GH and vitality (VT) relatively low. The oldest age group demonstrated the lowest health profile but rated their mental health higher than the other age groups. The older the patient, the smaller the difference compared with persons of the same age in the general population. Conclusions Nationwide, routine collection of PROMs is feasible in Sweden. However, greater emphasis is needed on motivating clinical staff to embrace the tool and its possibilities in executing person-centered care. CKD patients demonstrate impaired health-related quality of life, especially regarding limitations related to physical problems, GH and VT/energy/fatigue. [ABSTRACT FROM AUTHOR]