Is it recommended to start Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin Blobking Agent (ARB) with Chronic Kidney Disease (CKD) stage 4 and Impaired Renal Function?

From the Guidelines

Starting an Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) is recommended for patients with Chronic Kidney Disease (CKD) stage 4 and impaired renal function, particularly those with proteinuria or hypertension, as it helps slow CKD progression and reduce cardiovascular risk. According to the most recent guideline from the Kidney Disease: Improving Global Outcomes (KDIGO) [ 1 ], the use of Renin-Angiotensin System inhibitors (RASI), including ACE inhibitors and ARBs, is recommended for patients with CKD and severely increased albuminuria.

Key Considerations for Initiating ACE Inhibitors or ARBs in CKD Stage 4

• The choice of initial therapy should be based on evidence that RASI reduces both cardiovascular event rates and kidney end points among patients with CKD [ 1 ].
• Common ACE inhibitors include lisinopril, enalapril, or ramipril, and ARB options include losartan or valsartan.
• These medications should be administered using the highest approved dose that is tolerated to achieve the benefits described [ 1 ].
• Changes in blood pressure, serum creatinine, and serum potassium should be checked within 2-4 weeks of initiation or increase in the dose of a RASI [ 1 ].
• Hyperkalemia associated with the use of RASI can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping RASI [ 1 ].

Monitoring and Adjustments

• Serum creatinine and potassium should be monitored closely, and a rise in creatinine up to 30% from baseline may be acceptable, but larger increases may require dose reduction or discontinuation [ 1 ].
• Starting with a lower dose and titrating slowly while monitoring kidney function and electrolytes is the safest approach.
• Consider reducing the dose or discontinuing ACEi or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment [ 1 ].

Conclusion is not needed as per the guidelines, the above information is based on the latest evidence [ 1 ] and [ 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. 7.4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy Avoid use of aliskiren with losartan in patients with renal impairment (GFR <60 mL/min).

Key Considerations:

• Patients with Chronic Kidney Disease (CKD) stage 4 have compromised renal function.
• The use of ACE inhibitors or Angiotensin Receptor Blockers (ARBs) in patients with renal impairment requires careful consideration.
• Dual blockade of the RAS is generally avoided due to increased risks of hypotension, hyperkalemia, and changes in renal function.
• Monitoring of blood pressure, renal function, and electrolytes is crucial in patients with renal impairment.

Recommendation: It is not recommended to start ACE inhibitors or ARBs in patients with CKD stage 4 and impaired renal function without careful consideration and close monitoring of renal function, electrolytes, and blood pressure 2, 3.

From the Research

Recommendations for ACE Inhibitor or ARB Use in CKD Stage 4

• The use of Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) is recommended for patients with Chronic Kidney Disease (CKD) stage 4 and impaired renal function, as they have been shown to slow the progression of kidney disease 4, 5.
• ACE inhibitors are considered the first-line treatment for patients with CKD and hypertension, with ARBs being used as an alternative if ACE inhibitors are not tolerated 4, 6.
• The combination of ACE inhibitors and ARBs has been shown to be effective in reducing urine albumin excretion and urine protein excretion, but may increase the risk of hyperkalemia and hypotension 7.

Safety Considerations

• The main adverse effects of ACE inhibitors are hypotension, renal function impairment, and hyperkalemia, which can be mitigated by reducing dietary sodium intake or adding diuretics 6.
• The safety of ACE inhibitors and ARBs in patients with CKD stage 4 and impaired renal function should be carefully monitored, with regular checks of blood pressure, kidney function, and electrolyte levels 6, 8.
• Up-titration of ACE inhibitors and ARBs may be appropriate in patients with CKD stage 4 and impaired renal function, provided that the patient is adequately monitored 8.

Treatment Goals

• The treatment goal for patients with CKD stage 4 and impaired renal function is to achieve a blood pressure of less than 130/80 mmHg, which can help to slow the progression of kidney disease 4.
• The use of ACE inhibitors or ARBs can help to achieve this goal, in addition to lifestyle modifications and other antihypertensive medications 4.