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Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events. [ABSTRACT FROM AUTHOR]

Objectives To assess mortality and cardiovascular and renal outcomes among patients with chronic kidney disease (CKD) (primary objective), with a particular focus on heart failure (HF) risk following diagnosis of CKD (secondary objective) in Spain. Methods We conducted an observational study comprising cross-sectional and longitudinal retrospective analyses using secondary data from electronic health records. For the primary objective, adults with prevalent CKD [estimated glomerular filtration rate (eGFR) <60 or ≥60 mL/min/1.73 m2 with a urine albumin:creatinine ratio (UACR) ≥30 mg/g at the index date (1 January 2017)] were included. For the secondary objective, adults with incident CKD in 2017 were enrolled. Results In the prevalent population, 46 786 patients with CKD without HF [75.8 ± 14.4 years, eGFR 51.4 ± 10.1 mL/min/1.73 m2; 75.1% on renin–angiotensin system inhibitors (RASis)] and 8391 with CKD and HF (79.4 ± 10.9 years, eGFR 46.4 ± 9.8 mL/min/1.73 m2) were included. In the prevalent population, the risk of all-cause death {hazard ratio [HR] 1.107 [95% confidence interval (CI) 1.064–1.153]}, HF hospitalization [HR 1.439 (95% CI 1.387–1.493)] and UACR progression [HR 1.323 (95% CI 1.182–1.481)] was greater in those patients with CKD and HF versus CKD only. For the incident population, 1594 patients with CKD without HF and 727 with CKD and HF were included. Within 24 months from the CKD diagnosis (with/without HF at baseline), 6.5% of patients developed their first HF hospitalization. Although 60.7% were taking RASis, only 3.4% were at maximal doses and among diabetics, 1.3% were taking sodium-glucose cotransporter-2 inhibitors. Conclusions The presence of HF among CKD patients markedly increases the risk of outcomes. CKD patients have a high risk of HF, which could be partially related to insufficient treatment. [ABSTRACT FROM AUTHOR]

Background Hyperkalaemia is an electrolyte abnormality associated with adverse clinical outcomes; however, few studies have investigated the relationship with patterns of hyperkalaemia over time. This study explored the impact of time spent in a hyperkalaemic state and variability of serum potassium (sK+) on major adverse cardiovascular events (MACE) and all-cause mortality in patients with chronic kidney disease (CKD), resistant hypertension, heart failure and diabetes. Methods Cohorts comprised adult patients diagnosed with CKD stage 3+, resistant hypertension, heart failure or diabetes, and/or renin–angiotensin–aldosterone system inhibitor prescription, between 1 January 2003 and 30 June 2018, from the UK Clinical Practice Research Datalink. Associations between percentage of follow-up spent in a hyperkalaemic state (sK+ ≥5.0 mmol/L, ≥5.5 mmol/L, ≥6.0 mmol/L) or sK+ variability (standard deviation above or below median standard deviation) and all-cause mortality or MACE were investigated. Results For sK+ ≥5.0 mmol/L, time spent in a hyperkalaemic state was associated with reduced risk of all-cause mortality across all cohorts. For higher sK+ thresholds, this trend was attenuated or reversed; for time spent in a hyperkalaemic state at sK+ ≥6.0 mmol/L, an increased risk of mortality was seen in the overall cohort and for patients with diabetes, resistant hypertension or prescribed renin–angiotensin–aldosterone system inhibitors, with no consistent association seen for patients with CKD or heart failure. Risk of MACE in the overall cohort and in patients with CKD, diabetes or resistant hypertension increased with time spent in a hyperkalaemic state at all sK+ thresholds; however, no correlation was seen in patients with heart failure or those receiving dialysis. High sK+ variability was associated with a higher risk of MACE compared with low sK+ variability across most sK+ categories in the overall population and in all disease cohorts, except patients on dialysis; however, no association between sK+ variability and all-cause mortality was observed. Conclusions Patterns of hyperkalaemia, including time spent in hyperkalaemia and sK+ variability, are associated with adverse clinical outcomes. Regular monitoring of sK+ in high-risk populations in broader community, primary care and outpatient settings may enable guideline-recommended management of hyperkalaemia and help avoid adverse events. [ABSTRACT FROM AUTHOR]

Background Users of guideline-recommended renin–angiotensin–aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database. Methods This exploratory, retrospective analysis utilized data from the UK's Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed. Results Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8–75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure. Conclusions These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated. [ABSTRACT FROM AUTHOR]

Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin-angiotensin-aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction. While the renin-angiotensin-aldosterone system and growth factors, such as transforming growth factor-beta (TGF-β), are almost always part of the process, there are rare experimental observations of PAI- 1 expression without their interaction. Here we review the literature on PAI-1 and its role in vascular, fibrotic and oxidative injury as well as work suggesting potential areas of intervention in the pathogenesis of multiple disorders. [ABSTRACT FROM AUTHOR]

Background: Management trends in early chronic kidney disease (CKD) and their associations with clinical outcomes have not previously been reported. Methods: We evaluated incident (Stage G3A) CKD patients from an integrated health care system in 2004-06, 2007-09 and 2010-12 to determine adjusted trends in screening (urinary protein quantification), treatment [prescription for angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and statin] and nephrology referral. For the same time periods, adjusted rates for mortality, progression to Stage G4 CKD and hospitalization for myocardial infarction or heart failure were calculated and compared across time periods. Results: There were 728, 788 and 956 patients with incident CKD in 2004-06, 2007-09 and 2010-12, respectively. Adjusted rates of proteinuria quantification (31, 39 and 51 screens/100 person-years), statin prescription (53, 63 and 64 prescriptions/ 100 person-years) and nephrology referral (2, 3 and 5 referrals/100 person-years) all increased over time (P for trend <0.001 in all cases). ACEI/ARB prescription rates did not change (88, 83 and 80 prescriptions/100 person-years, P = 0.68). Adjusted death rates (7, 5 and 6 deaths/100 person-years), CKD progression (9, 10 and 7 progressors/100 person-years) and cardiovascular hospitalization (10, 8 and 9 hospitalizations per 100/person-years) did not change (P for trend >0.4 in all cases). Conclusion: In this integrated health care system, management of incident CKD over the past decade has intensified. [ABSTRACT FROM AUTHOR]