Initial and Recurrent Hyperkalemia Events in Patients With CKD in Older Adults: A Population-Based Cohort Study

Abstract

Background: The risk of hyperkalemia is elevated in chronic kidney disease (CKD); however, the initial and recurrent risk among older individuals is less clear. Objectives: We set out to examine the initial and 1-year recurrent risk of hyperkalemia by level of kidney function (estimated glomerular filtration rate, eGFR) in older adults (≥66 years old). Design: Population-based, retrospective cohort study Settings: Ontario, Canada Participants: 905 167 individuals (≥66 years old) from 2008 to 2015. Measurements: Serum potassium values Methods: Individuals were stratified by eGFR (≥90, 60-89, 30-59, 15-29 mL/min/1.73 m2) and examined for the risk of incident hyperkalemia (K ≥ 5.5 mEq/L) using adjusted Cox proportional hazards models. The 1-year risk of recurrent hyperkalemia was examined using multivariable Andersen-Gill models. Results: Among a population of 905 167 individuals (15% eGFR ≥ 90, 58% eGFR 60-89, 25% eGFR 30-59, 3% eGFR 15-29) with a potassium measurement, there were a total of 18 979 (2.1%) individuals with hyperkalemia identified. The event rate (per 1000 person-years) and adjusted hazard ratio (HR) of hyperkalemia was inversely associated with eGFR (mL/min; eGFR >90 mL/min: 8.8, referent, 60-89 mL/min: 11.8 HR 1.41; eGFR 30-59: 39.8, HR 4.37; eGFR 15-29: 133.6, 13.65) and with an increasing urine albumin-to-creatinine ratio (ACR, mg/mmol; ACR< 3: 14, referent, ACR 3-30: 35.1, HR 1.98; ACR >30: 93.7, 4.71). The 1-year event rate and adjusted risk of recurrent hyperkalemia was similarly inversely associated with eGFR (eGFR ≥ 90: 10.1, referent, eGFR 60-89: 14.4, HR 1.47; eGFR 30-59: 54.8, HR 4.90; eGFR 15-29: 208.0, HR 12.98). Among individuals with a baseline eGFR of 30 to 59 and 15 to 29, 0.9 and 3.8% had greater than 2 hyperkalemia events. The relative risk of initial and recurrent hyperkalemia was marginally higher with RAAS blockade. Roughly 1 in 4 individuals with hyperkalemia required hospitalization the day of or within 30 days after their hyperkalemia event. Limitations: Limited to individuals aged 66 years and above. Conclusions: Patients with low eGFR are at a high risk of initial and recurrent hyperkalemia. Trial registration: N/A

Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care

“…The associations observed were stronger, as expected, in our analysis modelling with a per‐protocol approach. Although, in relative terms, recurrent hyperkalaemias appeared earlier among patients who continued MRA therapy, in absolute terms it occurred in a large proportion of patients whether or not they stopped MRA: 63% of those who continued and 50% of those who did not at 2 years, in keeping with other data on recurrent hyperkalaemia 36 . Similarly, elevated rate of recurrent events was observed in high‐risk populations, such as those with history of heart failure and chronic kidney disease.…”

“…63% of those who continued and 50% of those who did not at 2 years, in keeping with other data on recurrent hyperkalaemia. 36 Similarly, elevated rate of recurrent events was observed in high-risk populations, such as those with history of heart failure and chronic kidney disease. This is likely because other factors such as chronic kidney disease, type 4 renal tubular acidosis and use of ACEi/ARB also contribute to the risk of hyperkalaemia.…”

Urinary Potassium Excretion and Progression From Advanced CKD to Kidney Failure

“…The presence and severity of baseline CKD associate with more common use of medications such as ACE inhibitors, ARBs, and diuretics that may impact potassium homeostasis. 13 , 14 Also, as the severity of CKD increases, so too does the proportion of potassium that is rectally excreted. 15 Therefore, urinary potassium excretion may not fully reflect dietary potassium intake in these cases.…”

“…Third, as our study population had advanced CKD at baseline, we must interpret the results within the advanced CKD context. For instance, medications such as ACE inhibitors, ARBs, and diuretics may affect potassium homeostasis 13 , 14 and are commonly used in patients with CKD although this limitation is shared with most prior studies 6 , 8 , 9 on this topic and were adjusted for within our analyses. Fourth, urinary potassium excretion was based on a single index measurement rather than on repeated measures, which limited our ability to capture the dynamic nature of this variable.…”

Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

“…In the cohorts of patients with no overt CKD at baseline, the risk of hyperkalaemia exponentially increased for lower GFR [ 4 ]. The prevalence of chronic hyperkalaemia estimated in cohorts of CKD patients ranged from 5.6% in patients with a mean eGFR of 62 mL/min/1.73 m 2 to over 50% in the more advanced CKD stages [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”