What is the importance of Angiotensin-Converting Enzyme inhibitors (ACE inhibitors) or Angiotensin Receptor Blockers (ARB) in Chronic Kidney Disease (CKD)?

From the Guidelines

ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are essential for managing chronic kidney disease (CKD) as they slow disease progression and reduce morbidity, mortality, and improve quality of life. These medications work by blocking the renin-angiotensin-aldosterone system (RAAS), reducing pressure within the kidneys' filtering units (glomeruli), and minimizing protein leakage into urine (proteinuria) 1. The 2020 KDIGO clinical practice guideline recommends initiating treatment with an ACEI or ARB in patients with diabetes, hypertension, and albuminuria, and titrating these medications to the highest approved dose that is tolerated 1.

Benefits of ACEIs and ARBs in CKD

• Reduce the progression of kidney disease in persons with albuminuria and hypertension independent of their effects on blood pressure 1
• Protect kidney function and slow disease progression
• Reduce protein leakage into urine (proteinuria) and slow the decline in glomerular filtration rate (GFR)
• Beneficial for CKD patients with diabetes or hypertension

Monitoring and Dosage Adjustment

• Kidney function and potassium levels should be monitored within 1-2 weeks of initiating ACEIs or ARBs, as they can cause potassium retention and a temporary decrease in GFR
• Dosage should be adjusted based on blood pressure response and kidney function, with the goal of maximizing kidney protection while minimizing side effects like cough (more common with ACEIs) or hyperkalemia

Combination Therapy

• Combination therapy with ACEIs and ARBs is harmful and should be avoided in patients with diabetes and CKD 1
• Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, are effective for resistant hypertension, and the FIDELIO trial reported that treatment with finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and type 2 diabetes already on RAS blockade resulted in lower risks for CKD progression and cardiovascular events 1

Recommendations

• The 2021 KDIGO clinical practice guideline recommends starting RASI therapy (ACEI or ARB) for people with high BP, CKD, and severely increased albuminuria (CKD G1 to G4; albuminuria category A3) without diabetes 1
• The guideline suggests starting RASI therapy (ACEI or ARB) for people with high BP, CKD, and moderately increased albuminuria (CKD G1 to G4; albuminuria category A2) without diabetes 1

From the FDA Drug Label

7.3 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure. 7.3 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including lisinopril, may result in deterioration of renal function, including possible acute renal failure.

Importance of ACE inhibitors and ARBs in CKD:

• ACE inhibitors and ARBs are important for patients with Chronic Kidney Disease (CKD) because they help to slow the progression of kidney disease.
• They do this by reducing proteinuria and slowing the decline in glomerular filtration rate (GFR).
• However, the provided drug labels do not directly answer why ACE inhibitors and ARBs are important for CKD, they only provide information on potential interactions and side effects.
• It can be inferred that ACE inhibitors and ARBs are beneficial for CKD patients, but the exact reason is not explicitly stated in the provided drug labels 2 3.

From the Research

Importance of ACEs and ARBs in CKD

• ACEs and ARBs are crucial in managing hypertension and albuminuria, primary goals in treating chronic kidney disease (CKD) 4.
• These medications have significant renoprotective effects, particularly in patients with high albuminuria, and their benefits appear more pronounced in those with advanced CKD 4, 5.
• ACEIs and ARBs reduce the odds of kidney failure by 39% and 30%, respectively, compared to placebo, and also decrease the risk of major cardiovascular events 6.

Benefits of ACEs and ARBs

• ACEIs significantly decrease the odds of kidney events, cardiovascular events, cardiovascular death, and all-cause death when compared to placebo 5.
• ARBs also show benefits, although to a lesser extent than ACEIs, in reducing kidney events and cardiovascular outcomes 5, 6.
• Both ACEIs and ARBs are associated with a higher risk of hyperkalemia, but their benefits in preventing kidney and cardiovascular outcomes outweigh this risk 5, 6.

Usage Trends and Guidelines

• Despite guidelines recommending ACEIs and ARBs as first-line therapy for hypertensive patients with CKD and proteinuria, their prescription rates are lower than expected, especially in younger patients and those with earlier stages of CKD 7, 8.
• Studies have shown an increase in ACE/ARB use over the years, but this trend appears to have plateaued, highlighting the need for further research into barriers to care and factors influencing their use 8.