Creatinine and Potassium Levels After Initiation of RAASIs for Chronic Kidney Disease

A new study showed increases in creatinine levels and hyperkalemia after initiation of renin angiotensin aldosterone system inhibitors (RAASIs) therapy were not associated with emergency department visits or hospitalizations, despite being a common reason for discontinuation of this therapy.

RAASIs are often used in patients with chronic kidney disease (CKD), but elevations in serum creatinine and potassium levels can occur, leading some patients to discontinue treatment. The incidence and risks of RAASI use and discontinuation are not well characterized in community practice.

Researchers at Brigham & Women’s Hospital in Boston, MA, sought to determine whether acute increases in creatinine levels and hyperkalemia after initiation of RAASI therapy were associated with a risk of emergency department visits, hospitalization, or mortality at 1 year in patients with chronic kidney disease.

Katherine G. Garlo and coauthors conducted a prospective cohort study including 4661 individuals with nondialysis CKD newly prescribed a RAASI or a diuretic who were treated at 36 outpatient primary care offices affiliated with Brigham & Women’s Hospital and Massachusetts General Hospital, Boston, from January 1, 2009, through December 31, 2011. Individuals receiving a new prescription for a diuretic were used to provide context. All participants had a baseline measure of renal function and at least 1 follow-up measurement of creatinine and potassium levels within 90 days of the prescription. Data were analyzed from January 1, 2009, through December 31, 2012. The main outcomes included emergency department visits, hospitalizations, and mortality within 1 year.

In this cohort study, increases in creatinine level and hyperkalemia after initiation of RAASI therapy were not associated with emergency department visits or hospitalizations and often resolved at a second measurement. Mortality was increased among individuals with an increase in creatinine level of at least 30% but the association was not significant after adjustment.

A total of 4661 individuals were included in the analysis (2506 [53.8%] women; mean [SD] age, 71 [14]; 3931 [84.3%] white; and 4198 [90.1%] with CKD stage 3). Of these, 2354 individuals (50.5%) received RAASIs and 2307 (49.5%) received diuretics.

Creatinine level increase of at least 30% after RAASI therapy initiation was found in 158 of 2354 individuals (6.7%); hyperkalemia of greater than 5.0 mEq/L, in 251 of 2354 (10.7%). Increases in creatinine level of at least 30% (unadjusted odds ratio [OR], 1.40; 95% CI, 0.89-2.21), hyperkalemia (unadjusted OR, 1.15; 95% CI, 0.64-2.06), and therapy discontinuation (unadjusted OR, 1.01; 95% CI, 0.71-1.46) were not associated with ED visits or hospitalizations, which was consistent with results from competing risk analyses.

Initial increases in creatinine level of at least 30% were associated with mortality in the total cohort (adjusted OR [aOR], 2.17; 95% CI, 1.45-3.25). However, the effect was only independent for diuretics (aOR, 2.27; 95% CI, 1.41-3.66) and not for RAASIs (aOR, 1.82; 95% CI, 0.83-3.99).

Findings from this study suggest that increases in creatinine level were independently associated with mortality among individuals prescribed diuretics but not RAASIs. Acute creatinine and potassium level disturbances after initiation of RAASI therapy in individuals with CKD were not associated with ED visits or hospitalizations, despite therapy continuation.

The study authors suggested that structured laboratory monitoring during RAASI therapy initiation may guide appropriate continuation of therapy in the outpatient setting, but closer monitoring may be needed for individuals with acute increases in creatinine levels.

Reference:

Garlo KG, Bates DW, Seger DL, Fiskio JM, Charytan DM. Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease. JAMA Netw Open. 2018;1(7):e183874. doi: 10.1001/jamanetworkopen.2018.3874.