From the Guidelines
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be used cautiously in patients with impaired renal function, with careful monitoring of kidney function and electrolytes, as they can be beneficial in protecting kidney function in patients with chronic kidney disease (CKD), diabetes, and proteinuria by reducing intraglomerular pressure and slowing disease progression. When initiating these medications in patients with impaired renal function, start with lower doses (such as lisinopril 2.5-5mg daily or losartan 25mg daily) and titrate gradually while monitoring serum creatinine, estimated glomerular filtration rate (eGFR), and potassium levels within 1-2 weeks of initiation or dose changes, as recommended by the 2020 KDIGO clinical practice guideline 1. A rise in serum creatinine up to 30% from baseline is generally acceptable and often indicates effective reduction in intraglomerular pressure. However, these medications should be temporarily held or discontinued if creatinine rises more than 30% or if hyperkalemia (potassium >5.5 mEq/L) develops, as suggested by the 2021 KDIGO clinical practice guideline 1.
Some key points to consider when using ACE inhibitors and ARBs in patients with impaired renal function include:
- Monitoring kidney function and electrolytes closely, especially when initiating or changing doses of these medications
- Starting with lower doses and titrating gradually to minimize the risk of adverse effects
- Being aware of the potential for hyperkalemia and taking steps to prevent it, such as monitoring potassium levels and adjusting doses as needed
- Considering alternative medications or adjusting treatment plans for patients with bilateral renal artery stenosis or severe heart failure, as they are at higher risk for acute kidney injury with these medications, as noted in a study published in the Journal of the American Society of Nephrology 1.
Overall, the use of ACE inhibitors and ARBs in patients with impaired renal function requires careful consideration and monitoring to minimize the risk of adverse effects and maximize the potential benefits of these medications. The most recent and highest quality study, the 2021 KDIGO clinical practice guideline 1, provides guidance on the use of these medications in patients with CKD and highlights the importance of careful monitoring and dose adjustment to minimize the risk of adverse effects.
From the FDA Drug Label
5.3 Renal Function Deterioration Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan potassium tablets. Monitor renal function periodically in these patients Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan potassium tablets [see Drug Interactions (7.3) and Use in Specific Populations (8.7)] .
Angiotensin-Converting Enzyme (ACE) Inhibitors and Kidney Function: The use of losartan potassium tablets, which act on the renin-angiotensin system, can cause changes in renal function, including acute renal failure, especially in patients with pre-existing renal conditions such as renal artery stenosis, chronic kidney disease, or severe congestive heart failure.
- Key Considerations:
- Patients with impaired renal function are at higher risk of developing acute renal failure.
- Monitor renal function periodically in these patients.
- Consider withholding or discontinuing losartan potassium tablets if a clinically significant decrease in renal function occurs 2. It is crucial to carefully monitor and manage patients with impaired renal function who are taking losartan to minimize the risk of renal function deterioration.
From the Research
Angiotensin-Converting Enzyme and Kidney Function
- The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in regulating blood pressure and kidney function 3, 4, 5, 6.
- Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to slow the progression of nephropathy in patients with or without diabetes 3, 5.
- These drug classes have proven therapeutic benefits, particularly in patients with renal insufficiency, and may provide renoprotective effects that are nonblood pressure-dependent 3, 4.
Safety Issues and Contraindications
- Many physicians fail to use ACE inhibitors and ARBs in patients with renal insufficiency due to concerns about potential increases in serum creatinine or potassium levels 3.
- However, studies have shown that acute increases in serum creatinine of up to 30% to 35% after initiating ACE inhibitor therapy are associated with long-term preservation of renal function 3.
- The appropriate use of diuretics can mitigate against profound increases in serum potassium, and withdrawal of an ACE inhibitor should only occur when the rise in creatinine exceeds this threshold or hyperkalemia develops 3.
Combination Therapy and Alternative Treatments
- Calcium channel blockers (CCBs) have individual pharmacological and therapeutic properties that may vary, but as a group, they are effective antihypertensive agents in patients with renal disease 4.
- CCBs may have an advantage in combination with ACE inhibitors and/or ARBs, and non-dihydropyridine calcium channel blockers (NDHPs) may slow the progression of type 2 diabetic nephropathy with overt proteinuria almost to a similar extent as observed with ACE inhibitors 4.
- Aldosterone antagonists may reduce protein excretion, eGFR, and systolic blood pressure in adults with mild to moderate chronic kidney disease (CKD), but may increase the risk of hyperkalemia, acute kidney injury, and gynaecomastia when added to ACE inhibitors and/or ARBs 7.