From the Guidelines
ACE inhibitors are recommended as first-line therapy for patients with chronic kidney disease (CKD), particularly those with albuminuria, as they slow the progression of kidney disease and provide cardiovascular benefits, as supported by the 2020 KDIGO clinical practice guideline 1. The use of renin-angiotensin system (RAS) inhibitors, such as ACE inhibitors, has been shown to slow the progression of kidney disease in persons with albuminuria and hypertension, independent of their effects on blood pressure 1. Key considerations for the use of ACE inhibitors in CKD include:
- Starting at a low dose and gradually titrating upward while monitoring kidney function and potassium levels
- Close monitoring of serum potassium and serum creatinine levels within 2 to 4 weeks of initiation of or change in dose
- Avoiding combination therapy with ARBs due to increased adverse effects without significant additional benefit 1
- Considering alternative agents, such as mineralocorticoid receptor antagonists, for patients with resistant hypertension or those who develop hyperkalemia during ACE inhibitor therapy The benefits of ACE inhibitors in CKD are thought to be due to their ability to reduce intraglomerular pressure, decrease proteinuria, and slow CKD progression, as well as provide cardiovascular benefits by reducing blood pressure and left ventricular hypertrophy 1. However, caution is needed in patients with bilateral renal artery stenosis, and these medications should be temporarily held during acute illness with volume depletion. Patients should be informed about potential side effects, including dry cough, which may require switching to an ARB if intolerable. Overall, the use of ACE inhibitors in CKD is supported by strong evidence and should be considered a key component of therapy for patients with albuminuria and hypertension.
From the Research
Adverse Effects of ACE Inhibitors in CKD
- The main adverse effects of ACE inhibitors are hypotension, renal function impairment, and hyperkalemia 2.
- The risk of hyperkalemia increases gradually in relation to declining eGFR, with no apparent threshold for contraindicating ACE inhibitors 3.
- Dual RAAS-blockade is no longer advocated in patients with CKD due to safety issues, and combination of ACE inhibitors with moderate reduction in dietary sodium intake is a better alternative 2.
Efficacy and Safety of ACE Inhibitors in CKD
- ACE inhibitors are first-line therapy in patients with CKD, and their safety aspects are discussed in relation to their pharmacological action, drug-drug interactions, and drug-diet interactions 2.
- The intensified treatment regimens based on ACE inhibitors can potentially improve renoprotection, but increase the risk of adverse effects 2.
- ACE inhibitors in combination with ARB are superior in reducing urine albumin excretion and urine protein excretion, but are associated with decreased GFR and increased rates of hyperkalemia and hypotension 4.
Monitoring and Prescription of ACE Inhibitors in CKD
- Prescription of ACE inhibitors/ARBs is common in all stages of CKD, with over 50% of patients in the CKD-at-risk group and in CKD stages 1-5 receiving these medications 5.
- Most patients undergo serum creatinine monitoring, but potassium monitoring is less frequent, and this should be improved in clinical practice 5.
- The risk score for hyperkalemia can separate high-risk patients from low-risk patients, and should be validated in other populations before it is ready for use in clinical practice 3.
Alternative Therapies for CKD
- There is increasing evidence to support the role of sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy in patients with CKD, including data from the designated kidney outcome trials 6.
- SGLT2 inhibitors represent a promising therapeutic option for patients with diabetic and nondiabetic CKD to slow disease progression 6.