What is the degree of decline in renal function when initiating an Angiotensin-Converting Enzyme (ACE) inhibitor?

From the Guidelines

When initiating an ACE inhibitor, kidney function typically drops by about 15-30% in the first few weeks of treatment, but an increase in creatinine of up to 50% above baseline is considered acceptable. This decrease in glomerular filtration rate (GFR) is generally considered acceptable and expected as part of the medication's therapeutic effect, as noted in the 2012 European Society of Cardiology guidelines 1. The decline occurs because ACE inhibitors reduce pressure in the efferent arteriole of the kidney, which decreases intraglomerular pressure. This hemodynamic change is actually part of the kidney-protective effect of these medications in the long term, despite causing a short-term reduction in filtration.

Some key points to consider when monitoring kidney function in patients taking ACE inhibitors include:

• An increase in creatinine of up to 50% above baseline, or 266 μmol/L (3 mg/dL)/eGFR <25 mL/min/1.73 m2, whichever is the smaller, is acceptable, as stated in the 2012 guidelines 1.
• If urea, creatinine, or potassium does rise excessively, consider stopping concomitant nephrotoxic drugs (e.g. NSAIDs) and other potassium supplements or retaining agents (triamterene, amiloride) and, if no signs of congestion, reducing the dose of diuretic, as recommended in the 2012 guidelines 1.
• It's essential to monitor kidney function within 1-2 weeks after starting an ACE inhibitor, particularly in patients with pre-existing kidney disease, heart failure, or those taking diuretics or NSAIDs concurrently, as advised in the 2008 European Society of Cardiology guidelines 1.
• Patients should be advised to maintain adequate hydration and temporarily stop the medication during periods of acute illness that may cause dehydration, as suggested in the 2009 American College of Cardiology Foundation/American Heart Association guidelines 1.

Overall, while a decrease in kidney function is expected when initiating an ACE inhibitor, careful monitoring and management can help minimize the risks and ensure the benefits of these medications are realized.

From the FDA Drug Label

Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with lisinopril alone. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Patients with acute myocardial infarction in the GISSI-3 trial treated with lisinopril had a higher (2.4% versus 1. 1% in placebo) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration).

The exact amount of kidney function drop is not specified in the provided text, but it is mentioned that minor increases in blood urea nitrogen and serum creatinine were observed in patients treated with lisinopril.

• In patients with hypertension, the increase was observed in about 2% of patients.
• In patients with heart failure on concomitant diuretic therapy, the increase was observed in 11.6% of patients.
• In patients with acute myocardial infarction, the incidence of renal dysfunction was 2.4% versus 1.1% in placebo, with a doubling or more of the baseline serum creatinine concentration. 2

From the Research

Kidney Function Drop when Initiating an ACE Inhibitor

• The drop in kidney function when initiating an ACE inhibitor can be significant, with studies showing an early rise in serum creatinine levels, approximately 25% above the baseline, after initiation of ACE inhibitor or ARB therapy 3.
• This rise in serum creatinine is more acute during the first 2 weeks of therapy and is more gradual during the third and fourth weeks of therapy 3.
• The serum creatinine level is likely to stabilize after about 4 weeks, provided patients have a normal salt and fluid intake 3.
• 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.
• 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 4.

Factors Influencing Kidney Function Drop

• The severity of renal impairment at baseline is inversely related to the rate of risk reduction of worsening renal function 3.
• Patients with normal renal function are likely to show a much smaller rise in serum creatinine level, approximately 10% above the baseline, mostly occurring during the first week after initiation of therapy, with subsequent stabilization 3.
• Patients with heart failure, volume depletion, or bilateral renal artery stenosis experienced a significant rise in serum creatinine level, much higher in magnitude and rate than that experienced by those with renal insufficiency 3.

Safety Issues and Recommendations

• The use of ACE inhibitors and ARBs in patients with chronic renal disease is safe, with a strong association between acute increases in serum creatinine and long-term preservation of renal function 4.
• Withdrawal of an ACE inhibitor should occur only when the rise in creatinine exceeds 30% over baseline during the first 2 months after initiation of therapy or hyperkalemia develops 3, 4.
• The appropriate use of diuretics mitigates against profound increases in serum potassium 3, 4.