Rishi V Parikh1, Danielle M Nash2,3,4, Amit X Garg2,3,4,5, Alan S Go1,6,7,8,9,10, K Scott Brimble11, Maureen Markle-Reid3,12, Thida C Tan1, Eric McArthur2, Farzien Khoshniat-Rad1, Manish M Sood2,13, Sijie Zheng14,15, Leonid Pravoverov14,15, Gihad E Nesrallah4,16,17. 1. Division of Research, Kaiser Permanente Northern California, Oakland (R.V.P., T.C.T., F.K.-R., A.S.G.). 2. ICES, Ontario, Canada (D.M.N., E.M., M.M.S., A.X.G.). 3. Department of Health Research Methods, Evidence, and Impact (D.M.N., M.M.-R., A.X.G.), McMaster University, Hamilton, Ontario, Canada. 4. Ontario Renal Network, Toronto, Canada (D.M.N., G.E.N., A.X.G.). 5. Department of Medicine, Western University, London, Ontario, Canada (A.X.G.). 6. Departments of Epidemiology (A.S.G.). 7. Biostatistics (A.S.G.). 8. Medicine (A.S.G.). 9. University of California, San Francisco (A.S.G.). 10. Department of Medicine (Nephrology) and Health Research and Policy, Stanford University School of Medicine, CA (A.S.G.). 11. Department of Medicine (K.S.B.), McMaster University, Hamilton, Ontario, Canada. 12. School of Nursing (M.M.-R.), McMaster University, Hamilton, Ontario, Canada. 13. Division of Nephrology, University of Ottawa, Ontario, Canada (M.M.S.). 14. Nephrology Service Line, The Permanente Medical Group (S.Z., L.P.). 15. Department of Nephrology, Kaiser Permanente Oakland Medical Center, CA (S.Z., L.P.). 16. Humber River Hospital, Toronto, Ontario, Canada (G.E.N.). 17. Department of Medicine, University of Toronto, Ontario, Canada (G.E.N.).
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.
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.
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