RAAS Inhibitor Prescription and Hyperkalemia Event in Patients

Hyperkalemia is common in patients treated with renin–angiotensin–aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2–4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4–5 CKD was 3-fold higher compared with patients with eGFR 60 ml/min/1.73 m2. RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event (74.2% discontinued therapy, 3.2% received a reduced dose, and 22.6% reduced the number of RAASi drugs). This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia.To get more news about RaaS, you can visit glprobotics.com official website.
Chronic kidney disease (CKD), defined as decrease in kidney function manifested as presence of structural or functional kidney abnormalities or estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2, has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease (which is the leading cause of death in CKD). Blood pressure lowering therapy has shown to prevent the onset of poor cardiovascular outcomes and delay the progression of kidney disease (1, 2).

Several randomized clinical trials have clearly shown that inhibition of the renin-angiotensin aldosterone system (RAAS) can reduce the risk of death and slow disease progression in patients with heart failure (HF), CKD, and diabetes (3–7). Therefore, evidence-based treatment guidelines recommend the use of RAAS inhibitors (RAASis) as first-line blood pressure lowering therapy for patients with CKD and proteinuria, and diabetes and hypertension (8–10). Moreover, the guidelines specifically recommend the use of maximum tolerated dose of RAASis, since results of clinical trials demonstrated that best treatment benefits were obtained with moderate to high doses (8–10).

However, the use of these drugs may be limited, since they can cause hyperkalemia (11) (typically defined as serum potassium levels 5.5 mmol/L), which can be further exacerbated when these drugs are used in combination (12).

Several recommendations for minimizing the risk of hyperkalemia have been provided by current treatment guidelines, including: avoiding RAASi therapy in patients at risk of hyperkalemia, discontinuing drugs that can interfere with renal potassium excretion before initiating RAAS inhibitors, titrating the dose of the RAASis, and performing regular monitoring of potassium serum levels (8–10). Moreover, if hyperkalemia develops after initiating therapy, it is recommended to discontinue or lower the dose of RAAS inhibitors (8–10).

Therefore, there is a substantial gap between recommendations in treatment guidelines and the real-world practice in the use of RAASis. This point is crucial, since discontinuation of RAASis after the onset of hyperkalemia may increases the risk of poor outcomes, with a combined deleterious effect of hyperkalemia and withdrawal of RAASi on prognosis (13).

Studies that have assessed whether hyperkalemia can affect subsequent RAASi treatment regimen are limited. Recent population-based studies are limited by the inclusion of relatively small proportions of patients with CKD (14) or according to renal function, (15) predominance of males in assessed cohorts (96%) (16), and small size [n = 238 (17) and 258 (18) patients].

Therefore, we conducted a CKD-population-based retrospective cohort study on adult patients with CKD to determine the prevalence of patients treated with RAASis and distribution of the use of RAASis in different CKD stages. Moreover, we evaluated the incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia.