Renin–Angiotensin–Aldosterone Blockers and Hyperkalemia
As previously discussed, the development of hyperkalemia with RAASi therapy poses a therapeutic dilemma in patients with CKD, heart failure, and hypertension as guidelines recommend the preferential use of these drugs in these patient populations (Table 1).[15–18] The development of hyperkalemia often leads to reductions in dosing, or worse, drug discontinuation. For example, National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KIDGO) advocates for use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) at efficacious doses because of their cardiorenal protective properties. Unfortunately, despite these recommendations, patients with CKD stage 3–4, heart failure, or diabetes mellitus may not be receiving effective doses of RAASi therapy because of hyperkalemia risk. In data obtained from a retrospective analysis of a database from the United States, it was discovered 62% of patients received a lower than recommended dose of RAASi therapy, whereas only 22% were receiving the recommended dose. These medications were discontinued in 15% of patients in which the above listed conditions were present. The study found 38% of patients had their medication either down titrated or discontinued when their serum K+ was 5.1–5.4 mEq/l, and in 47% of cases the medications were modified when the serum K+ was at least 5.5 mEq/l. Development of hyperkalemia is also cited as a reason to specifically avoid mineralocorticoid blockers despite evidence that these drugs reduce proteinuria, are cardioprotective, and provide a survival benefit in CKD patients.[20,21] In one real world study, 74% of patients who discontinued a mineralocorticoid blocker because of hyperkalemia did not restart during the following year.
Nonoptimal use of RAASi therapy has been associated with adverse outcomes. In a cohort of elderly hospitalized heart failure patients with CKD, 4-year survival data in a subgroup who did not receive optimal therapy with ACE inhibitors was only 3%. By contrast, the cumulative survival increased six-fold from 3 to 19% when these patients were discharged on ACE inhibitors. To summarize, it is difficult to achieve optimized therapeutic dosage of RAASi in patients who can most benefit from this therapy because of the potential risk of hyperkalemia; however, as discussed below, there are new treatment options, which may mitigate the risk of hyperkalemia and facilitate the use of these drugs.
Curr Opin Nephrol Hypertens. 2020;29(1):29-38. © 2020 Lippincott Williams & Wilkins