What to do next in an abnormal Urine Albumin-to-Creatinine Ratio (UACR)?

From the Guidelines

For an abnormal urine albumin-to-creatinine ratio (UACR), first confirm the result with a repeat test within 3 months, as transient elevations can occur, and if consistently elevated (≥30 mg/g), implement ACE inhibitors or ARBs, which reduce proteinuria and slow kidney disease progression, as recommended by the most recent guidelines 1. The management of abnormal UACR involves a multifaceted approach, including:

• Medications: ACE inhibitors or ARBs like lisinopril (starting at 10 mg daily) or losartan (50 mg daily) are recommended for patients with UACR ≥30 mg/g, as they have been shown to reduce proteinuria and slow kidney disease progression 1.
• Blood pressure control: Optimize blood pressure to <130/80 mmHg, as recommended by the American Diabetes Association and other guidelines 1.
• Blood glucose control: Target HbA1c <7% in diabetic patients, as recommended by the American Diabetes Association 1.
• Lifestyle modifications: Reduce sodium intake to <2300 mg/day, moderate protein consumption (0.8 g/kg/day), increase physical activity, and maintain a healthy weight, as these changes can help slow kidney disease progression and reduce cardiovascular risk 1.
• Regular monitoring: Monitor kidney function with eGFR and UACR every 3-6 months to assess response to treatment, as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) and American Diabetes Association guidelines 1.
• Nephrology referral: Consider referral for severely elevated UACR (>300 mg/g), rapidly declining kidney function, or if eGFR falls below 45 ml/min/1.73m², as these patients may require more specialized care and management 1. These interventions are crucial because albuminuria indicates kidney damage and predicts cardiovascular disease risk, making early intervention vital for preventing progression to more severe kidney disease 1.

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])

• Abnormal UACR is defined as a urinary albumin to creatinine ratio ≥300 mg/g
• The study showed that losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy
• The primary endpoint of the study was the time to first occurrence of any one of the following events: doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death
• Treatment with losartan resulted in a 16% risk reduction in this endpoint
• For patients with abnormal UACR, treatment with losartan may be considered to reduce the risk of doubling of serum creatinine, ESRD, and death 2

From the Research

Abnormal UACR Management

In patients with abnormal urinary albumin-to-creatinine ratio (UACR), management strategies often involve the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) to reduce the risk of cardiovascular and renal outcomes.

• The use of ACE inhibitors or ARBs in patients with diabetes and albuminuria has been shown to reduce the risk of end-stage renal disease (ESRD) and doubling of serum creatinine levels 3.
• A meta-analysis of placebo-controlled clinical trials found that ACE inhibitors and ARBs reduced the incidence of new-onset diabetes and had favorable effects on cardiovascular and non-cardiovascular mortality 4.
• The selection of additional antihypertensive therapies should be based on the presence of concomitant cardiovascular and metabolic conditions, as well as patient-specific factors such as race 5.

Treatment Options

Treatment options for patients with abnormal UACR include:

• ACE inhibitors, which have been shown to reduce the risk of ESRD and doubling of serum creatinine levels in patients with diabetes and albuminuria 3.
• ARBs, which have been shown to reduce the risk of ESRD and doubling of serum creatinine levels in patients with diabetes and albuminuria, and may be preferred for diabetic patients with albuminuria 3.
• Combination therapy with diuretics or beta-blockers, which can improve blood pressure control and reduce the risk of cardiovascular outcomes 6.

Guideline Recommendations

Guideline recommendations for the management of abnormal UACR include:

• The use of ACE inhibitors or ARBs as first-line antihypertensive therapy in patients with albuminuria, as recommended by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) 5.
• The use of ACE inhibitors or ARBs in patients with diabetes and albuminuria to reduce the risk of ESRD and doubling of serum creatinine levels, as recommended by the American Diabetes Association 3.
• National trends in guideline-concordant ACE inhibitor/ARB utilization have been examined, and it has been found that there is a significant gap in preventive care delivery for adults with hypertension and albuminuria 7.