Kidney Function and Potassium Monitoring After Initiation of Renin-Angiotensin-Aldosterone System Blockade Therapy and Outcomes in 2 North American Populations

Abstract

Background: Clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker therapy. However, evidence is lacking about whether follow-up testing reduces therapy-related adverse outcomes.

Methods and results: We conducted 2 population-based retrospective cohort studies in Kaiser Permanente Northern California and Ontario, Canada. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACE inhibitor or angiotensin II receptor blocker therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. We also developed and externally validated a risk score to identify patients at risk of having abnormally high serum creatinine and potassium values in follow-up. We identified 75 251 matched pairs initiating ACE inhibitor or angiotensin II receptor blocker therapy between January 1, 2007, and December 31, 2017, in Kaiser Permanente Northern California. Follow-up testing was not significantly associated with 30-day all-cause mortality in Kaiser Permanente Northern California (hazard ratio, 0.75 [95% CI, 0.54-1.06]) and was associated with higher mortality in 84 905 matched pairs in Ontario (hazard ratio, 1.32 [95% CI, 1.07-1.62]). In Kaiser Permanente Northern California, follow-up testing was significantly associated with higher rates of hospitalization with acute kidney injury (hazard ratio, 1.66 [95% CI, 1.10-2.22]) and hyperkalemia (hazard ratio, 3.36 [95% CI, 1.08-10.41]), as was observed in Ontario. The risk score for abnormal potassium provided good discrimination (area under the curve [AUC], 0.75) and excellent calibration of predicted risks, while the risk score for abnormal serum creatinine provided moderate discrimination (AUC, 0.62) but excellent calibration.

Conclusions: Routine laboratory monitoring after ACE inhibitor or angiotensin II receptor blocker initiation was not associated with a lower risk of 30-day mortality. We identified patient subgroups in which targeted testing may be effective in identifying therapy-related changes in serum potassium or kidney function.

Keywords: acute kidney injury; follow-up studies; humans; kidney; potassium.

Figures

Figure 1.. Cohort assembly diagram for patients at KPNC, January 1, 2007- December 31, 2017.

Abbreviations: ACEi, Angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.

Figure 2.. Associations between follow-up testing after ACEi/ARB initiation and outcomes.

All KPNC models adjusted for a priori confounders: time from prescription to follow-up test date, class of index prescription (ACEi, ACEi/thiazide, ARB, ARB/thiazide), percentage of maximum daily dosage of index prescription, prior peripheral artery disease, receipt of NSAIDs, and receipt of diuretics. KPNC models additionally adjusted for covariates differing at baseline: prior valvular disease, prior atrial flutter/fibrillation, receipt of potassium-sparing diuretics, antiarrhythmic drugs, and anticoagulants, number of primary care visits in the prior year, time from baseline SCr measurement to index date and time from baseline potassium measurement to index date. Abbreviations: ACEi, Angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; AKI, acute kidney injury; NSAID, non-steroidal anti-inflammatory drug; SCr, serum creatinine

Figure 3.. Calibration plots of risk scores for abnormal laboratory results after ACEi/ARB initiation, by 5-unit risk score increments, in the Ontario validation cohort.

Abbreviations: ACEi, Angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.