From the Guidelines
ACE inhibitors are a cornerstone therapy for managing chronic kidney disease, particularly in patients with proteinuria or diabetes, and should be initiated in patients with hypertension and CKD stage 3 or higher, or stage 1 or 2 with albuminuria, to slow kidney disease progression. These medications, including lisinopril (10-40 mg daily), enalapril (5-40 mg daily), and ramipril (2.5-20 mg daily), help slow CKD progression by reducing intraglomerular pressure and proteinuria, as supported by the 2019 KDOQI US commentary on the 2017 ACC/AHA hypertension guideline 1. They work by blocking the conversion of angiotensin I to angiotensin II, which decreases efferent arteriolar constriction in the kidney, thereby reducing glomerular hypertension and subsequent kidney damage.
When starting ACE inhibitors, kidney function and potassium levels should be monitored within 1-2 weeks of initiation, as these medications can cause an initial decrease in GFR and may lead to hyperkalemia, as noted in the 2022 diabetes management in chronic kidney disease consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1. A rise in serum creatinine up to 30% is acceptable and often indicates effective hemodynamic changes. ACE inhibitors are particularly beneficial in diabetic nephropathy and should be considered even in patients with advanced CKD, though dose adjustments may be necessary, as recommended in the 2021 diabetes management in chronic kidney disease synopsis of the 2020 KDIGO clinical practice guideline 1.
Some key points to consider when using ACE inhibitors in CKD management include:
- Monitoring kidney function and potassium levels closely after initiation
- Adjusting doses as necessary to minimize adverse effects
- Using ACE inhibitors in combination with other treatments, such as dietary sodium restriction and optimal blood pressure control, to maximize kidney protection
- Avoiding the combination of ACE inhibitors and ARBs due to increased risk of hyperkalemia and AKI, as cautioned in the 2019 commentary on the 2017 ACC/AHA hypertension guideline 1 and the 2015 Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management 1.
Overall, the use of ACE inhibitors in CKD management is supported by strong evidence, including the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, and should be considered a key component of treatment plans for patients with CKD, particularly those with proteinuria or diabetes.
From the Research
Role of ACE Inhibitors in CKD
- ACE inhibitors play a crucial role in managing Chronic Kidney Disease (CKD) by reducing proteinuria and slowing the progression of renal disease 2, 3, 4.
- These inhibitors lower glomerular capillary pressure, decrease proteinuria, and may halt progressive glomerular injury and loss of renal function in experimental CKD 3.
- ACE inhibitor therapy generally lowers systemic blood pressure, does not alter renal function, and decreases proteinuria in patients with CKD 3, 4.
Combination Therapy with ACE Inhibitors
- Combination therapy with ACE inhibitors and angiotensin receptor blockers (ARBs) reduces proteinuria and prevents structural lesions more effectively than either drug alone in experimental diabetic and non-diabetic CKD 2.
- The addition of aldosterone antagonists to ACE inhibitors and/or ARBs may be beneficial in reducing proteinuria and preventing progression of CKD, but increases the risk of hyperkalaemia 5, 6.
- The Remission Clinic protocol, which involves combination therapy with maximum tolerated doses of ACE inhibitors and ARBs, is the most powerful tool to prevent progression to end-stage renal disease (ESRD) in non-diabetic proteinuric CKD 2.
Benefits and Risks of ACE Inhibitors in CKD
- ACE inhibitors may reduce protein excretion, estimated glomerular filtration rate (eGFR), and systolic blood pressure in adults with CKD, but may increase the risk of hyperkalaemia, acute kidney injury, and gynaecomastia 6.
- The effects of ACE inhibitors on kidney failure, major cardiovascular events, and death in people with proteinuric CKD are uncertain, and further studies are needed to determine their long-term benefits and risks 6.
- ACE inhibitors are generally well-tolerated in patients with CKD, but may cause transient reductions in renal function, particularly in those with bilateral renal artery stenosis or congestive heart failure 4.