The online version of this article (https://doi.org/10.1186/s12882-018-1007-1) contains supplementary material, which is available to authorized users.
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.
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.
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).
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.
Additional file 1: Table S1. Read and International Classification of Diseases (ICD-10) codes used to define heart failure and chronic kidney disease. Example of the time-updating methodology used during data structuring. Table S2. Incidence of death, major adverse cardiac event and renin-angiotensin-aldosterone system inhibitor discontinuation observed in chronic kidney disease patients, stratified by serum potassium category. Table S3. Model output for final risk equations, re-estimated using patient-intervals restricted to a maximum duration of 30 days. (DOCX 58 kb)12882_2018_1007_MOESM1_ESM.docx
Additional file 2: Figure S1. Illustrative example of time-updated patient-intervals based on timing of serum potassium measurements. eGFR: estimated glomerular filtration rate; K+: serum potassium; MACE: major adverse cardiac event. (TIF 260 kb)12882_2018_1007_MOESM2_ESM.tif
Additional file 3: Figure S2. Validation of adjusted incident rate ratios for death (A) and MACE (B) as a function of serum potassium against those published by Luo et al. Black: estimated in the present study (UK CKD stage 3+ patients); grey: estimated by Luo et al. (US CKD stage 3+ patients). Error bars represent 95% confidence intervals. (TIFF 41 kb)12882_2018_1007_MOESM3_ESM.tiff
Additional file 4: Figure S3. Adjusted incident rate ratios for death (A), MACE (B) and RAASi discontinuation (C) as a function of serum potassium in patients stratified by CKD stage. Black: CKD 3a patients; dark grey: CKD 3b patients; mid-grey: CKD 4 patients; light grey: CKD 5 patients. Incident rate ratios were adjusted to account for confounding patient demographics, clinical histories and comorbidities, clinical measurements, and medication usage, as reported in Table 4. CKD: chronic kidney disease; MACE: major adverse cardiac event; RAASi: renin-angiotensin-aldosterone system inhibitor. Error bars represent 95% confidence intervals. (TIFF 63 kb)
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- 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
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