From the Guidelines
ACE inhibitors can be used in patients with chronic kidney disease (CKD) and are often recommended for these patients, as they help protect kidney function by reducing intraglomerular pressure and decreasing proteinuria, as stated in the 2014 AHA/ACC guideline 1. The use of ACE inhibitors in CKD patients has been shown to reduce microalbuminuria and progression towards end-stage renal dysfunction, as noted in the European Heart Journal guidelines 1. When starting an ACE inhibitor in a CKD patient, it is essential to begin with a lower dose and titrate slowly while monitoring kidney function and potassium levels. For example, lisinopril might be started at 2.5-5 mg daily instead of 10 mg. Blood tests should be performed within 1-2 weeks of initiation to check for acute kidney injury (a rise in creatinine >30%) or hyperkalemia. If significant hyperkalemia (potassium >5.5 mEq/L) or acute kidney injury occurs, the medication may need to be reduced or discontinued. Key considerations for using ACE inhibitors in CKD patients include:
- Monitoring serum creatinine levels, as they may initially increase when ACE inhibitors are introduced, and thereafter return to baseline in most patients 1
- Avoiding use in patients with renal artery stenosis, as stated in the European Heart Journal guidelines 1
- Using alternative treatments, such as angiotensin receptor blockers (ARBs), in patients who are intolerant to ACE inhibitors, as recommended in the 2014 AHA/ACC guideline 1
From the FDA Drug Label
Patients with acute myocardial infarction in the GISSI-3 trial treated with lisinopril had a higher (2.4% versus 1. 1% in placebo) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration). Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis [see Warnings and Precautions (5. 4)]. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy.
Use of ACE inhibitors in patients with CKD:
- Caution is advised when using ACE inhibitors, such as lisinopril, in patients with chronic kidney disease (CKD) due to the potential for worsening renal function.
- Monitoring of renal function is recommended, especially in patients with pre-existing renal impairment or those receiving concomitant diuretics.
- Dose adjustment may be necessary to minimize the risk of adverse effects on renal function.
- The decision to use an ACE inhibitor in a patient with CKD should be made on a case-by-case basis, taking into account the potential benefits and risks of therapy 2.
From the Research
Use of ACE Inhibitors in Patients with CKD
- ACE inhibitors are considered first-line therapy in patients with chronic kidney disease (CKD) 3.
- The main adverse effects of ACE inhibitors in CKD patients are hypotension, renal function impairment, and hyperkalemia 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 3.
Monitoring and Prescription of ACE Inhibitors in CKD Patients
- ACE inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are commonly prescribed in patients with CKD, with over 50% of patients in the CKD-at-risk group and in CKD stages 1-5 receiving these medications 4.
- Serum creatinine (Scr) is monitored in most ACEI/ARB-treated patients, but potassium monitoring is less frequent, highlighting the need for improved clinical practice 4.
Effects of ACE Inhibitors on Clinical Outcomes in CKD Patients
- ACE inhibitor use is associated with reductions in mortality and hospitalization in ambulatory chronic systolic heart failure patients with mild to moderate CKD 5.
- Exposure to ACEi/ARB after acute kidney injury (AKI) is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident CKD 6.
- Combination of ACEI with ARB is superior to low-dose ACEI or ARB in reducing urine albumin excretion, urine protein excretion, and blood pressure in CKD patients, but is associated with decreased glomerular filtration rate (GFR) and increased rates of hyperkalemia and hypotension 7.