Microalbuminuria

Microalbuminuria is defined as a small or moderate increase of albumin excretion in the urine. A confirmed albumin:creatinine ratio (ACR) of 3 mg/mmol or more should be regarded as clinically significant.

The criteria for clinically significant proteinuria have been changed from an ACR of 30 mg/mmol or more to 3 mg/mmol or more. This is because there is evidence that increasing cardiovascular risk correlates with a continuum of levels of proteinuria and starts at an ACR well below 30 mg/mmol¹.

Measurement²

Urinary albumin or urinary protein loss should be quantified for:

• People with diabetes.

• People without diabetes with a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m².

• People with a GFR of 60 ml/min/1.73 m² or more if there is a strong suspicion of chronic kidney disease (CKD).

The National Institute for Health and Care Excellence (NICE) guidance has recommended that an early-morning urinary ACR should be used in preference to other tests of proteinuria, as ACR offers greater sensitivity for the detection of lower but clinically significant levels of proteinuria. This is also a more convenient test than a 24-hour collection.

Urinary ACR should be used in preference to protein:creatinine ratio (PCR), as it has greater sensitivity than PCR for low levels of proteinuria. However, PCR can be used as an alternative for quantification and monitoring of levels of proteinuria of ACR of 70 mg/mmol or more. ACR is the recommended method for people with diabetes.

These approximate equivalents may be useful:

• ACR 30 mg/mmol = PCR 50 mg/mmol = urinary protein excretion 0.5 g/24 hours.

• ACR 70 mg/mmol = PCR 100 mg/mmol = urinary protein excretion 1 g/24 hours.

NB: false positive results can occur after heavy exercise or with urinary tract infection.

For the initial detection of proteinuria, if the ACR is between 3 mg/mmol and 70 mg/mmol, this should be confirmed by a subsequent early-morning sample. If the initial ACR is 70 mg/mmol or more, a repeat sample need not be tested.

Classification

The Kidney Disease Improving Global Outcomes (KDIGO) categories for albumin:creatinine ratios are as follows²:

• A1: ACR <3 mg/mmol - normal to mildly increased.

• A2: ACR 3-30 mg/mmol - moderately increased.

• A3: ACR >30 mg/mmol - severely increased.

Significance of microalbuminuria

Microalbuminuria is associated with generalised endothelial destruction and has been shown to be an independent risk factor associated with diabetes, CKD, cardiovascular disease, hypertension, venous thromboembolism and all-cause mortality¹.

Diabetes

Children and adults with type 2 diabetes may have microalbuminuria at presentation, as they may have had latent disease for years. Microalbuminuria is not usually present at the time of diagnosis of type 1 diabetes.

Annual screening of a first-pass morning urine specimen for microalbuminuria (estimation of ACR) with measurement of serum creatinine at the same time is recommended³⁴. Children with type 1 diabetes should be screened from the age of 12 years³.

CKD²

Markers of kidney disease include albuminuria (ACR more than 3 mg/mmol), urine sediment abnormalities, electrolyte and other abnormalities due to tubular disorders, abnormalities detected by histology, structural abnormalities detected by imaging, and a history of kidney transplantation. Patients should be tested for proteinuria if they have any of the following risk factors:

• GFR ≤60 ml/min/1.73 m².

• Diabetes.

• Hypertension.

• Cardiovascular disease.

• Structural renal tract disease, multiple renal calculi or prostatic hypertrophy.

• Multisystem diseases with potential kidney involvement - eg, systemic lupus erythematosus.

• Family history of CKD stage 5 or hereditary kidney disease.

• Haematuria.

Increased ACR and decreased GFR are associated with increased risk of adverse outcomes for patients with CKD. Increased ACR and decreased GFR in combination multiply the risk of adverse outcomes.

People with CKD and an ACR of 70 mg/mmol or more should be referred for specialist assessment, unless this is already known to be caused by diabetes and already appropriately treated. Patients with an ACR of 30 mg/mmol or more together with haematuria should also be referred.

Cardiovascular disease

Microalbuminuria has been shown to be an independent predictor for coronary heart disease, cardiovascular disease and all-cause mortality in the general population⁵.

Management

CKD

In patients with significant proteinuria, important objectives of therapy to delay the progression of CKD are to optimise blood pressure control and reduce proteinuria. All patients should be offered angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor receptor antagonists. See the separate Chronic Kidney Disease article.

Diabetes

See the separate Diabetic Nephropathy article. For people with diabetes, suspect renal disease other than diabetic kidney disease if⁶:

• There is absence of progressive retinopathy.

• Blood pressure is particularly high.

• Proteinuria develops suddenly.

• Significant haematuria is present.

• There is presence of systemic ill health.

Hypertension

See the separate Hypertension Treatment article. Follow normal hypertension guidelines⁷.