In a patient with worsening urine albumin to creatinine ratio on amlodipine, should I add an ACE inhibitor or switch to an ARB?

From the Guidelines

For a patient with worsening urine albumin to creatinine ratio on amlodipine, adding an ACE inhibitor is generally recommended rather than switching to an ARB or adding an ARB. This approach is based on the well-established renoprotective effects of ACE inhibitors, which can reduce proteinuria and slow the progression of kidney disease, working synergistically with calcium channel blockers like amlodipine 1. The combination of an ACE inhibitor and amlodipine provides both blood pressure control and specific protection against albuminuria through different mechanisms. ACE inhibitors decrease intraglomerular pressure by dilating efferent arterioles and reduce proteinuria beyond their blood pressure-lowering effects. Key considerations include monitoring kidney function and potassium levels 1-2 weeks after starting therapy and being alert for potential side effects such as cough, angioedema, and hyperkalemia. If the patient develops an intolerable cough on the ACE inhibitor, then switching to an ARB like losartan would be appropriate as ARBs provide similar renoprotective benefits with fewer cough-related side effects. It's crucial to titrate the ACE inhibitor to the maximal tolerated dose, as not maximizing these therapies due to concerns about serum creatinine rise would be considered suboptimal care 1. Moreover, the use of ACE inhibitors and ARBs in combination should be avoided due to the lack of benefits on cardiovascular disease (CVD) or chronic kidney disease (CKD) and the increased risk of adverse events such as hyperkalemia and/or acute kidney injury (AKI) 1. Given the most recent evidence from 2024, the focus should be on maximizing the dose of the ACE inhibitor while closely monitoring for potential side effects and adjusting the treatment plan as necessary to optimize outcomes for the patient 1.

From the FDA Drug Label

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) The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3. 0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]) Treatment with losartan resulted in a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death Losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy

Adding an ACE inhibitor or switching to an ARB may be beneficial for a patient with worsening urine albumin to creatinine ratio.

• Losartan, an ARB, has been shown to reduce the rate of progression of nephropathy in patients with type 2 diabetes and proteinuria 2.
• The decision to add an ACE inhibitor or switch to an ARB should be based on individual patient factors, such as blood pressure control and presence of other comorbidities.
• It is not explicitly stated in the label whether to add an ACE inhibitor or switch from amlodipine to an ARB, but losartan may be administered with other antihypertensive agents 2.
• Amlodipine is a calcium-channel blocker, and its effects on proteinuria are not directly addressed in the provided labels.
• Considering the patient is already on amlodipine, adding an ACE inhibitor could be a viable option to reduce proteinuria, but this is not directly supported by the provided labels.
• Switching to an ARB, such as losartan, may be beneficial in reducing proteinuria and slowing the progression of nephropathy, as supported by the RENAAL study 2.

From the Research

Patient Management with Worsening Urine Albumin to Creatinine Ratio

In a patient with a worsening urine albumin to creatinine ratio who is currently on cardiol and amlodipine, the decision to add an ACE inhibitor (Acer) or switch to an Angiotensin Receptor Blocker (ARB) depends on several factors.

• The patient's current medication regimen and the presence of any contraindications to ACE inhibitors or ARBs should be considered.
• According to the study 3, multiple clinical guidelines recommend an ACE inhibitor or ARB in patients with elevated albuminuria, which can be measured through urine albumin-to-creatinine ratio (ACR).
• The study 4 found that among hypertensive US adults with albuminuria, the prevalence of ACE inhibitor/ARB utilization was lower than expected, suggesting that these medications are underutilized in patients who could benefit from them.

Considerations for Adding an ACE Inhibitor or Switching to an ARB

When deciding whether to add an ACE inhibitor or switch to an ARB, consider the following:

• The patient's kidney function and the presence of any kidney disease should be taken into account, as ACE inhibitors and ARBs can have different effects on kidney function 5.
• The study 6 found that a fixed combination of rosuvastatin with an ACE inhibitor (lisinopril) and a calcium antagonist (amlodipine) can effectively control hypercholesterolemia and arterial hypertension.
• The optimal cutoff values for the urine albumin-to-creatinine ratio (UACR) may vary depending on the population being studied, as found in the study 7.

Potential Next Steps

Potential next steps in managing the patient's worsening urine albumin to creatinine ratio could include:

• Adding an ACE inhibitor to the patient's current medication regimen, as recommended by clinical guidelines 3.
• Switching the patient from amlodipine to an ARB, depending on the patient's individual needs and medical history.
• Monitoring the patient's kidney function and urine albumin-to-creatinine ratio closely to assess the effectiveness of any changes to their medication regimen 4, 5.