What is the expected increase in creatinine (Cr) levels when starting Angiotensin Receptor Blockers (ARBs) or Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)?

From the Guidelines

When starting Angiotensin Receptor Blockers (ARBs) or Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), an increase in serum creatinine of up to 30% from baseline is generally considered acceptable and does not warrant discontinuation of therapy. This elevation typically occurs within the first 2-4 weeks of treatment and should stabilize thereafter. Medications in these classes include losartan, valsartan, candesartan (ARBs) and sacubitril/valsartan (ARNI) 1. If creatinine increases more than 30% or continues to rise after the initial period, further evaluation is necessary, including assessment for renal artery stenosis, volume depletion, or concomitant use of nephrotoxic medications like NSAIDs. The creatinine elevation occurs because these medications reduce efferent arteriolar tone in the kidney, decreasing glomerular filtration pressure. This hemodynamic effect actually provides long-term renoprotection despite the initial creatinine rise. Regular monitoring of renal function and electrolytes (particularly potassium) is recommended at baseline, 1-2 weeks after initiation, after dose increases, and periodically thereafter, especially in patients with pre-existing renal impairment or those taking other medications affecting kidney function.

Some key points to consider:

• The 30% increase in creatinine is a general guideline and may vary depending on individual patient factors 1.
• Monitoring of renal function and electrolytes is crucial to ensure safe use of ARBs and ARNIs 1.
• The benefits of ARBs and ARNIs in reducing morbidity and mortality outweigh the risks of initial creatinine elevation in most patients 1.
• Patients with pre-existing renal impairment or those taking other medications affecting kidney function require closer monitoring 1.

Overall, the decision to continue or discontinue ARBs or ARNIs should be based on individual patient factors and the potential benefits and risks of treatment.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Expected Increase in Creatinine Levels

When starting Angiotensin Receptor Blockers (ARBs) or Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), the expected increase in creatinine (Cr) levels can be summarized as follows:

• A strong association exists between acute increases in serum creatinine of up to 30% to 35% after initiating ACE inhibitor therapy and long-term preservation of renal function 2.
• Patients with preexisting chronic renal insufficiency who achieved their blood pressure control goals were likely to demonstrate an early rise in serum creatinine levels, approximately 25% above the baseline 3.
• The rise in serum creatinine was more acute (by approximately 15% from the baseline) during the first 2 weeks of therapy and was more gradual (additional approximately 10%) during the third and fourth weeks of therapy 3.
• In patients with chronic renal insufficiency, there is a strong association between early (within the first 2 months) and moderate (not exceeding 30% over baseline) rise in serum creatinine and slowing of the renal disease progression in the long run 3.

Factors Influencing Creatinine Increase

Several factors can influence the increase in creatinine levels when starting ARBs or ARNIs, including:

• Baseline renal function: Patients with more advanced renal insufficiency are more likely to experience a greater increase in serum creatinine levels 2, 3.
• Blood pressure control: Achieving blood pressure control goals can lead to a greater increase in serum creatinine levels 3.
• Use of diuretics: Concomitant use of diuretics can mitigate against profound increases in serum potassium and may influence the increase in creatinine levels 2, 3.
• Age: Older patients may have more advanced renal insufficiency at lower serum creatinine levels 3.

Clinical Implications

The increase in creatinine levels when starting ARBs or ARNIs has important clinical implications:

• Monitoring of serum creatinine and potassium levels is essential to ensure safe use of these medications 4.
• Treatment discontinuation should only occur if serum creatinine levels rise above 30% over baseline during the first 2 months after initiation of therapy or if hyperkalemia develops 2, 3.
• High-dose ARB treatment can be safe and effective in patients with chronic kidney disease, with minimal increases in serum creatinine and potassium levels 5.