Why should patients with substantial chronic proteinuria be on an Angiotensin-Converting Enzyme inhibitor (ACEi)?

From the Guidelines

Patients with substantial chronic proteinuria should be on an angiotensin-converting enzyme inhibitor (ACEi) to reduce protein excretion and slow the progression of kidney disease. According to the most recent guideline evidence from the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1, ACEi therapy is recommended as first-line treatment for patients with glomerulonephritis (GN) and proteinuria. The guideline suggests uptitrating an ACEi or ARB to maximally tolerated or allowed daily dose.

Key Points to Consider

• ACEi medications like lisinopril (starting at 5-10mg daily, titrating up to 20-40mg as tolerated), enalapril (5-40mg daily in divided doses), or ramipril (2.5-20mg daily) are effective options 1.
• When starting an ACEi, kidney function and potassium levels should be monitored within 1-2 weeks of initiation and after dose increases, with regular follow-up every 3-6 months thereafter.
• ACEi therapy works by decreasing intraglomerular pressure through dilation of the efferent arteriole, which reduces hyperfiltration and protein leakage across the glomerular membrane.
• These medications also have anti-inflammatory and anti-fibrotic effects that help preserve kidney function, as supported by studies demonstrating their antiproteinuric effects in patients with diabetic kidney disease (DKD) and non-DKD 1.
• Patients should be aware that a small rise in creatinine (up to 30%) after starting therapy is expected and not necessarily concerning, but persistent elevations require dose adjustment or discontinuation.

Benefits of ACEi Therapy

• Reduces protein excretion and slows the progression of kidney disease
• Has anti-inflammatory and anti-fibrotic effects that help preserve kidney function
• Is particularly beneficial for patients with diabetic nephropathy, hypertensive nephrosclerosis, and many forms of glomerulonephritis where proteinuria is a prominent feature 1

From the Research

Rationale for ACEi Use in Patients with Substantial Chronic Proteinuria

• Patients with substantial chronic proteinuria should be on an ACEi due to their ability to reduce proteinuria and slow the progression of kidney disease 2, 3, 4.
• ACEis have been shown to be effective in reducing proteinuria in both diabetic and nondiabetic patients with chronic kidney disease 2, 3.
• The combination of an ACEi and an ARB has been found to be more effective in reducing proteinuria than either agent alone 3.
• ACEis, such as enalapril, have been found to be effective in reducing albuminuria in patients with diabetic nephropathy 2, 3.
• The use of ACEis in patients with chronic kidney disease and proteinuria has been recommended by Japanese guidelines as first-line therapy 5.

Mechanism of Action

• ACEis work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates the release of aldosterone, leading to increased blood pressure and proteinuria 4.
• The reduction in proteinuria seen with ACEi use is thought to be due to a decrease in intraglomerular pressure and a reduction in the permeability of the glomerular capillaries 4.

Clinical Implications

• The use of ACEis in patients with substantial chronic proteinuria has been associated with a reduction in the progression of kidney disease and a decrease in the risk of cardiovascular events 2, 3, 4.
• ACEis should be considered as part of the treatment regimen for patients with chronic kidney disease and proteinuria, particularly those with diabetic nephropathy 2, 3, 5.