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-< 55 mmol/L, 55-< 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.