From the Guidelines
Treatment for high ACR should prioritize renin-angiotensin-aldosterone system (RAS) inhibition with ACE inhibitors or ARBs as the first-line agent, due to their proven benefits in preventing CKD progression and reducing cardiovascular events. According to the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1, ACE inhibitors or ARBs are recommended for patients with diabetes, hypertension, and ACR ≥30 mg/g.
Key aspects of treatment include:
- Using ACE inhibitors (like lisinopril 10-40 mg daily) or ARBs (such as losartan 50-100 mg daily) to reduce protein leakage in urine and protect kidney function
- Controlling blood pressure to levels below 130/80 mmHg
- Achieving tight glucose control with a target HbA1c below 7% for diabetic patients
- Implementing lifestyle modifications, such as:
- Reducing sodium intake to less than 2,300 mg daily
- Adopting a heart-healthy diet
- Maintaining a healthy weight
- Exercising regularly (at least 150 minutes weekly)
- Quitting smoking
- Limiting alcohol consumption
- Regularly monitoring kidney function and ACR levels to assess treatment effectiveness, as recommended by the ADA and KDIGO 1.
It is essential to note that the combination of ACE inhibitors and ARBs is not recommended due to the increased risk of hyperkalemia and acute kidney injury (AKI), as highlighted in the 2022 report 1. Instead, RAS inhibition with ACEi or ARBs should be the primary approach for treating high ACR, with consideration of additional therapies, such as SGLT2 inhibitors or GLP-1 receptor agonists, in specific cases.
From the FDA Drug Label
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 (doubling of serum creatinine, end-stage renal disease (ESRD), or death). Treatment with losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints.
The treatment for high ACR (Albumin to Creatinine Ratio), in the context of type 2 diabetes with nephropathy, is losartan, which has been shown to reduce the risk of doubling of serum creatinine, end-stage renal disease, and death by 16% 2.
- Key benefits of losartan in this context include:
- Reduction in proteinuria by an average of 34%
- Reduction in the rate of decline in glomerular filtration rate by 13%
- Important considerations: The effects of losartan may vary across different patient subgroups, and the results should be interpreted with caution.
From the Research
Treatment for High ACR
The treatment for high Albumin-to-Creatinine Ratio (ACR) typically involves the use of certain medications to reduce proteinuria and slow the progression of kidney disease.
- Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) are commonly recommended as first-line therapy for patients with hypertension and chronic kidney disease (CKD) with proteinuria 3, 4, 5.
- A systematic review and meta-analysis found that ARBs reduced the risk of end-stage renal disease (ESRD) by 23% in patients with diabetes and albuminuria, while ACEIs were not associated with a decreased risk of ESRD 4.
- Another study found that ACE inhibitor/ARB usage in patients with albuminuria ≥300 mg/g was 55.3% among adults with diabetes and 33.4% among those without diabetes in 2013-2018 5.
- The addition of spironolactone to ACEIs or ARBs has been shown to have an anti-proteinuric effect in patients with persistent proteinuria, particularly in those with higher levels of albuminuria and impaired estimated glomerular filtration rate (eGFR) 6.
Medication Usage
The usage of these medications can vary depending on the patient's age, kidney function, and other factors.
- A study found that the prescription rate of ARBs/ACEIs was lower in patients aged <75 years with CKD stage G1-G5 (23%) compared to patients aged ≥75 years with CKD stage G1-G3 (41%) 3.
- Another study found that ACE inhibitor/ARB underutilization represents a significant gap in preventive care delivery for adults with hypertension and albuminuria, with an estimated 1.6 million adults not receiving these medications 5.