Do Angiotensin-Converting Enzyme (ACE) inhibitors protect renal function?

From the Guidelines

ACE inhibitors do not have a proven renoprotective effect in all patients, particularly those with type 1 and type 2 diabetes who are normotensive with or without high albuminuria, as demonstrated by two long-term, double-blind studies 1. However, in certain contexts, such as in patients with diabetes and existing kidney disease, ACE inhibitors may be beneficial in slowing kidney disease progression when used at maximum tolerated doses. Key points to consider include:

• The use of ACE inhibitors or ARBs is recommended for patients with diabetes and kidney disease, but the evidence for their renoprotective effects is not universal 1.
• Maximum tolerated doses of ACE inhibitors or ARBs should be used to slow kidney disease progression, rather than low doses that may not provide benefit 1.
• The combination of ACE inhibitors and ARBs should be avoided due to higher adverse event rates, including hyperkalemia and acute kidney injury 1.
• Patients with diabetes and kidney disease may benefit from ACE inhibitors in terms of reducing mortality and slowing CKD progression, even with an eGFR <30 mL/min/1.73 m2 1.
• Regular monitoring of kidney function and potassium levels is necessary for patients taking ACE inhibitors, and treatment should be long-term or indefinite for chronic conditions. In clinical practice, the decision to use ACE inhibitors should be based on individual patient factors, including the presence of diabetes, hypertension, and existing kidney disease, as well as careful consideration of the potential benefits and risks. The most recent and highest quality study 1 suggests that ACE inhibitors may not be universally beneficial for all patients, and their use should be tailored to specific clinical contexts.

From the FDA Drug Label

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 ACE inhibitors, including lisinopril, may result in deterioration of renal function, including possible acute renal failure.

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

The FDA drug label does not directly answer the question of whether ACE inhibitors protect renal function. While it discusses potential risks of renal function deterioration with certain concomitant medications, it does not provide information on the protective effects of ACE inhibitors on renal function. 2 3

From the Research

Renal Protection by ACE Inhibitors

• ACE inhibitors have been shown to effectively reduce systemic vascular resistance in patients with hypertension, heart failure, or chronic renal disease, which contributes to their long-term renoprotective effects in patients with diabetic and non-diabetic renal disease 4.
• The renal mechanisms underlying the renal adverse effects of ACE inhibitors, such as intrarenal efferent vasodilation with a consequent fall in filtration pressure, are also involved in their renoprotective effects 4.
• ACE inhibitors can decrease proteinuria, which is an important clinical advantage, particularly in nephrotic patients 5, 6.
• The reduction in proteinuria is suggested to be related to the fall in filtration fraction and the reduction in glomerular filtration rate at the onset of therapy, which can be considered a trade-off for long-term renal protection in patients with diabetic and non-diabetic chronic renal disease 4.

Patient-Specific Considerations

• Patients with heart failure, diabetes mellitus, and/or chronic renal failure are at the greatest risk for renal adverse effects, but they can also expect the greatest benefit from ACE inhibitors 4.
• Elderly patients with diabetes mellitus, coronary heart disease, or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients 5.
• Patients with renal insufficiency may require dose reduction of ACE inhibitors, and those at risk for renal artery stenosis or pretreated with diuretics should receive a low ACE inhibitor dosage initially 5.

Safety and Efficacy

• The main adverse effects of ACE inhibitors are hypotension, renal function impairment, and hyperkalemia, which can be mitigated by careful dosing and monitoring of renal function and serum potassium levels 4, 7.
• Dual RAAS-blockade is no longer advocated in patients with CKD due to safety issues, and combination of ACE inhibitors with moderate reduction in dietary sodium intake is a better alternative 7.
• ACE inhibitors can slow the progression of diabetic nephropathy, and combination therapy with angiotensin receptor blockers may be beneficial, but the potential for hyperkalemia may limit its utility 8.