What is the role of Angiotensin-Converting Enzyme Inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) in patients with advanced Chronic Kidney Disease (CKD) stage 4?

From the Guidelines

In advanced chronic kidney disease (CKD) stage 4, both ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are recommended for people with severely increased albuminuria, as stated in the KDIGO 2024 clinical practice guideline 1. These medications remain beneficial for blood pressure control, reducing proteinuria, and slowing CKD progression even at this advanced stage. Common ACEIs include lisinopril (10-40 mg daily), enalapril (5-40 mg daily in divided doses), or ramipril (2.5-10 mg daily). ARB options include losartan (25-100 mg daily), valsartan (80-320 mg daily), or irbesartan (150-300 mg daily). Start at the lower dose range and titrate cautiously. Close monitoring is essential, with serum creatinine and potassium checks within 1-2 weeks of initiation or dose changes. Expect a temporary 20-30% increase in creatinine, which is acceptable if it stabilizes, as noted in 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. However, discontinue if creatinine rises more than 30% or if hyperkalemia (potassium >5.5 mEq/L) develops. Avoid concurrent use of NSAIDs and supplement with diuretics if volume overload occurs. These medications work by blocking the renin-angiotensin-aldosterone system, reducing intraglomerular pressure and proteinuria while providing cardioprotective benefits. Despite the risk of worsening kidney function, the long-term benefits often outweigh risks when properly monitored. Key considerations include:

• Starting with a lower dose and titrating cautiously
• Close monitoring of serum creatinine and potassium
• Avoiding concurrent use of NSAIDs
• Supplementing with diuretics if volume overload occurs
• Discontinuing if creatinine rises more than 30% or if hyperkalemia develops. The most recent guideline from KDIGO 2024 1 supports the use of RASi (ACEi or ARB) for people with CKD and severely increased albuminuria, without diabetes. In contrast, the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1 provides additional context on the importance of blood pressure control in patients with CKD, but the KDIGO 2024 guideline 1 takes precedence due to its recency and focus on CKD management.

From the Research

ACE Inhibitors or ARBs in Advanced CKD

• The use of ACE inhibitors or ARBs in patients with advanced chronic kidney disease (CKD) is a topic of interest, with studies suggesting that these medications may slow the progression of renal disease 2, 3.
• A study published in 2002 found that ACE inhibitors were associated with a 55-75% lower risk of worsening renal function in patients with chronic renal insufficiency, although the benefit was inversely related to the severity of renal impairment at baseline 2.
• Another study published in 2021 found that the combination of ACE inhibitors and ARBs was superior to low-dose ACE inhibitors or ARBs in reducing urine albumin excretion and urine protein excretion, but was associated with decreased glomerular filtration rate (GFR) and increased rates of hyperkalemia and hypotension 4.
• A cross-sectional study published in 2025 found that ARBs and ACE inhibitors were only used in 28% of hypertensive patients with CKD stage G1-G5, despite guideline recommendations 5.
• A study published in 2018 noted that the benefit of ACE inhibitors and ARBs in the advanced stage of renal insufficiency cannot yet be conclusively assessed, but that these medications may still have a cardio-protective effect 3.
• A study published in 2020 found no difference in risk for progression to end-stage renal disease (ESRD) or mortality across patterns of RAS inhibitor use in patients with eGFRs < 30 mL/min/1.73 m2 6.

Key Findings

• ACE inhibitors and ARBs may slow the progression of renal disease in patients with advanced CKD 2, 3.
• The combination of ACE inhibitors and ARBs may be superior to low-dose ACE inhibitors or ARBs in reducing urine albumin excretion and urine protein excretion, but may be associated with decreased GFR and increased rates of hyperkalemia and hypotension 4.
• ARBs and ACE inhibitors are underused in patients with CKD, despite guideline recommendations 5.
• The benefit of ACE inhibitors and ARBs in the advanced stage of renal insufficiency is unclear, but these medications may still have a cardio-protective effect 3.
• Further research is needed to identify optimal prescribing strategies of RAS inhibitors during advanced stages of CKD 6.