From the Guidelines
No, ACE inhibitors and ARBs are not contraindicated in stage 3 chronic kidney disease (CKD3); in fact, they are often recommended treatments. These medications, including lisinopril, enalapril, losartan, and valsartan, can be beneficial for patients with CKD3, particularly those with proteinuria or concurrent hypertension or diabetes, as they reduce the risk of kidney end points, such as rate of eGFR decline, 50% decline in eGFR, and incident kidney failure 1.
Key Considerations
- Typical starting doses should be at the lower end of the dosing range (e.g., lisinopril 5-10mg daily or losartan 25-50mg daily) with gradual titration as tolerated.
- Close monitoring is essential, including checking serum creatinine and potassium within 1-2 weeks of starting therapy.
- A rise in creatinine up to 30% from baseline is acceptable and often expected due to these drugs' effect on glomerular hemodynamics.
- Therapy should be reassessed if creatinine increases more than 30% or if hyperkalemia (potassium >5.5 mEq/L) develops.
Benefits of ACE/ARBs in CKD3
- Provide renoprotection by reducing intraglomerular pressure
- Decrease proteinuria
- Slow CKD progression through their effects on the renin-angiotensin-aldosterone system, as supported by the 2019 commentary on the 2017 ACC/AHA hypertension guideline 1.
Monitoring and Adjustments
- Regular monitoring of renal function and electrolytes is crucial to ensure safe use of ACE inhibitors and ARBs in patients with CKD3.
- Adjustments to the treatment plan may be necessary based on the patient's response to therapy and the presence of any adverse effects.
From the FDA Drug Label
- 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. Avoid use of aliskiren with losartan in patients with renal impairment (GFR <60 mL/min).
The FDA drug label does not explicitly state that ACE/ARBs are contraindicated in CKD3, but it does advise to avoid combined use of RAS inhibitors and to avoid use of aliskiren with losartan in patients with renal impairment (GFR <60 mL/min), which includes CKD3.
- Key points:
- Monitor renal function periodically in patients receiving losartan and NSAID therapy.
- Closely monitor blood pressure, renal function, and electrolytes in patients on losartan and other agents that affect the RAS.
- No benefit has been associated with using two RAS inhibitors concomitantly in most patients. 2
From the Research
ACE/ARBs in CKD3
- ACE/ARBs are not contraindicated in CKD3, but their use requires careful consideration of the potential benefits and risks 3, 4.
- Studies have shown that ACEIs and ARBs can provide renal protection and reduce the risk of cardiovascular events in patients with CKD, including those with stage 3 disease 3, 4.
- However, the use of ACEIs and ARBs in advanced CKD (stages 4-5) is more controversial, and some studies suggest that they may not be beneficial in these patients 5, 6.
- A network meta-analysis of randomized clinical trials found that ACEIs significantly decreased the odds of kidney events, cardiovascular events, cardiovascular death, and all-cause death in non-dialysis CKD3-5 patients, while ARBs had a more modest effect 4.
- Another study found that ACEIs and ARBs can cause worsening renal failure in some patients, particularly older hypertensive patients with ischemic hypertensive nephropathy 6.
Considerations for Use
- The decision to use ACE/ARBs in CKD3 patients should be based on individual patient characteristics, including the presence of proteinuria, hypertension, and cardiovascular disease 3, 4.
- Patients with CKD stage 3 should be monitored closely for changes in renal function and electrolyte levels when taking ACE/ARBs 4, 6.
- The potential benefits of ACE/ARBs in reducing cardiovascular risk and slowing CKD progression should be weighed against the potential risks of hyperkalemia, hypotension, and worsening renal function 4, 6.