What is the management for an elevated Albumin-to-Creatinine Ratio (ACR) in Diabetes Mellitus (DM) patients?

From the Guidelines

An elevated Albumin-to-Creatinine Ratio (ACR) in Diabetes Mellitus (DM) patients requires prompt treatment with an angiotensin-converting enzyme inhibitor (ACE inhibitor) or an angiotensin receptor blocker (ARB), as recommended by the most recent guidelines 1. The management of an elevated ACR in DM patients involves a multifaceted approach, including:

• Medications: ACE inhibitors or ARBs, such as lisinopril or losartan, should be initiated and titrated to the maximum tolerated dose while monitoring kidney function and potassium levels 1.
• Lifestyle modifications:
  • Strict blood glucose control (target HbA1c <7%)
  • Blood pressure management (target <130/80 mmHg)
  • Dietary sodium restriction (<2300mg daily)
  • Moderate protein intake (0.8g/kg/day) are equally important in managing an elevated ACR in DM patients 1. Regular follow-up testing of ACR every 3-6 months is necessary to monitor response to treatment. If ACR continues to worsen despite these interventions, referral to a nephrologist is recommended. The use of ACE inhibitors or ARBs in patients with an elevated ACR is supported by the most recent guidelines, which emphasize their role in reducing the risk of progressive kidney disease 1. In particular, the 2025 guidelines from the American Diabetes Association recommend the use of ACE inhibitors or ARBs in nonpregnant people with diabetes and hypertension, especially those with moderately or severely increased albuminuria 1. Overall, the management of an elevated ACR in DM patients requires a comprehensive approach that incorporates both pharmacological and lifestyle interventions, with a focus on reducing the risk of progressive kidney disease and improving long-term outcomes.

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, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%

The management for an elevated Albumin-to-Creatinine Ratio (ACR) in Diabetes Mellitus (DM) patients includes the use of losartan, which has been shown to reduce the rate of progression of nephropathy and decrease proteinuria by an average of 34% 2. The treatment goals for these patients should include controlling blood pressure and reducing proteinuria to slow the progression of kidney disease. Key points to consider in the management of these patients include:

• 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 2
• Blood pressure control is essential in the management of patients with diabetic nephropathy
• Losartan has been shown to reduce the risk of doubling of serum creatinine, end-stage renal disease (ESRD), and death in patients with type 2 diabetes and nephropathy 2

From the Research

Management of Elevated Albumin-to-Creatinine Ratio (ACR) in Diabetes Mellitus (DM) Patients

The management of elevated ACR in DM patients involves several strategies, including:

• The use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which have been shown to reduce albuminuria in patients with diabetes mellitus 3
• Combination therapy with an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker, which can reduce albuminuria and blood pressure in diabetic patients with nephropathy 4
• The use of ACE inhibitors with either a thiazide diuretic or a calcium channel blocker, which can also reduce albuminuria and blood pressure in hypertensive type 2 diabetics 5

Key Findings

Key findings from the studies include:

• SGLT-2 inhibitors were associated with a statistically significant reduction in albuminuria compared to placebo or active control, with a weighted mean difference of -25.39% 3
• The combination of an ACEI with an angiotensin II receptor blocker reduced ACR by 56%, while the combination of an ACEI with a calcium channel blocker reduced ACR by 54% 4
• The use of an ACE inhibitor with a diuretic resulted in a greater reduction in albuminuria compared to the combination with a calcium channel blocker 5

Monitoring and Diagnosis

Monitoring and diagnosis of diabetic kidney disease is crucial, and the use of urine albumin-to-creatinine ratio (UACR) is recommended as a sensitive and early indicator of kidney damage 6

• However, the ACR may not be a reliable predictor of incident diabetes in pre-diabetic individuals, as an elevated hazard rate for developing diabetes with doubling of ACR disappeared after adjustment for covariates 7