Serum potassium variability as a predictor of clinical outcomes in patients with cardiorenal disease or diabetes: a retrospective UK database study

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.

Automated summary

This study investigated the impact of time and variability of serum potassium on adverse clinical outcomes in patients with chronic kidney disease, resistant hypertension, heart failure, and diabetes. The results suggest that patterns of hyperkalaemia are associated with adverse clinical outcomes, and regular monitoring can help manage hyperkalaemia and prevent adverse events.