Are Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) recommended for patients with diabetes mellitus for the prevention of proteinuria and kidney disease?

From the Guidelines

ACE inhibitors or Angiotensin Receptor Blockers (ARBs) are strongly recommended for patients with diabetes mellitus to prevent or slow the progression of proteinuria and kidney disease, particularly in those with albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g) or hypertension. These medications are typically started when a diabetic patient shows early signs of kidney damage or has hypertension. The usual starting dose depends on the specific medication, with gradual titration based on blood pressure response and kidney function 1.

Key Considerations

• ACE inhibitors and ARBs have proven benefits for prevention of chronic kidney disease (CKD) progression, particularly in patients with diabetes, hypertension, eGFR <60 mL/min/1.73 m2, and UACR ≥300 mg/g creatinine 1.
• In patients with lower levels of albuminuria (30–299 mg/g creatinine), ACE inhibitor or ARB therapy at maximum tolerated doses can reduce progression to more advanced albuminuria, slow CKD progression, and reduce cardiovascular events 1.
• Monitoring of kidney function and potassium levels is crucial when starting these medications, typically 1-2 weeks after initiation and after dose changes.
• Side effects may include dry cough (more common with ACE inhibitors), dizziness, and elevated potassium levels.
• A blood pressure level <130/80 mmHg is recommended to reduce cardiovascular disease (CVD) mortality and slow CKD progression among all people with diabetes, with lower blood pressure goals considered based on individual anticipated benefits and risks 1.

Medication Selection

• ACE inhibitors (such as lisinopril, enalapril, and ramipril) and ARBs (such as losartan, valsartan, and irbesartan) are considered to have similar benefits and risks 1.
• The choice between ACE inhibitors and ARBs should be based on individual patient factors, such as tolerance and comorbidities.
• If one class is not tolerated, the other should be substituted, as both classes have been shown to provide cardiovascular benefit without significantly increasing the risk of end-stage kidney disease 1.

From the FDA Drug Label

1. 3 Nephropathy in Type 2 Diabetic Patients Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension In this population, losartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation)

• Angiotensin Receptor Blockers (ARBs), such as losartan, are recommended for patients with diabetes mellitus for the prevention of proteinuria and kidney disease.
• The use of ACE inhibitors is not directly mentioned in the provided drug label for the prevention of proteinuria and kidney disease in patients with diabetes mellitus, but it can be inferred that they may have a similar effect due to their similar mechanism of action.
• However, according to the label, dual blockade of the Renin-Angiotensin System (RAS) with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, and in most patients, no benefit has been associated with using two RAS inhibitors concomitantly 2.

From the Research

ACE Inhibitors and ARBs in Diabetes Mellitus

• ACE inhibitors and ARBs have been shown to slow the progression of diabetic kidney disease by lowering urine protein levels, lowering blood pressure, and slowing disease progression 3, 4.
• The combination of ACE inhibitors and ARBs may offer greater benefits for patients with diabetic kidney disease, although the ONTARGET study reported no benefit with combination therapy compared to monotherapy 3.
• Higher doses of ACE inhibitors or ARBs may be required to reduce proteinuria and slow the progression of renal disease in diabetic patients 4.
• ACE inhibitors have been shown to reduce proteinuria and delay the decline in renal function in insulin-dependent diabetic patients with established nephropathy 5.

Prevention of Proteinuria and Kidney Disease

• ACE inhibitors and ARBs have been demonstrated to reduce proteinuria and prevent the progression of kidney disease in diabetic patients 4, 5, 6.
• The addition of mineralocorticoid receptor blockers to ACE inhibitors or ARBs may further decrease proteinuria in patients with chronic kidney disease 7.
• ARBs have been shown to reduce diabetic nephropathy and complications related to nephropathy, and may be as effective as ACE inhibitors in cardiovascular protection 6.

Recommendations

• ACE inhibitors and ARBs are recommended for patients with diabetes mellitus to prevent proteinuria and kidney disease 3, 4, 6.
• The choice between ACE inhibitors and ARBs should be based on individual patient characteristics and comorbidities 6.
• Higher doses of ACE inhibitors or ARBs may be required to achieve optimal benefits in reducing proteinuria and slowing disease progression 4.