Microalbuminuria

What is microalbuminuria?

Microalbuminuria is defined as a small or moderate increase of albumin excretion in the urine:

• A small amount of albumin is normally present in urine (less than 30 mg per day, or an albumin:creatinine ratio (ACR) of less than 3 mg/mmol).

• Urinary albumin excretion of between 30 mg to 300 mg per day, or uACR between 3 mg/mmol and 30 mg/mmol, is termed microalbuminuria.

• Urinary albumin excretion of over 300 mg per day, or uACR over 30 mg/mmol, is termed macroalbuminuria or sometimes simply albuminuria.¹

The KDIGO nomenclature favours the terms 'moderately increased albuminuria' and 'severely increased albuminuria' in place of microalbuminuria and macroalbuminuria respectively.²

Microalbuminuria is an important early marker of renal target organ damage, and is also thought to indicate generalised endothelial dysfunction. It is a powerful predictor of cardiovascular and renal disease risk in both diabetic and non-diabetic individuals.³

Microalbuminuria is not detected by standard urine dipsticks, although it can be measured by some albumin-specific dipsticks.

Measurement⁴

Recognising microalbuminuria helps to identify individuals at higher risk of cardiovascular and renal disease.

The National Institute for Health and Care Excellence (NICE) recommends that a urinary ACR measurement should be used for the initial detection of proteinuria in:

• Adults, children, and young people with diabetes.

• Adults with a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m².

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

• Children and young people without diabetes if their creatinine levels are above the upper limit of the age-appropriate reference range.

ACR offers greater sensitivity for the detection of lower but clinically significant levels of proteinuria than other tests. 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: transient microalbuminuria can be caused by the following:⁵

• Strenuous exercise.

• Emotional stress.

• Concurrent infection or fever.

• Obesity.

• Heart failure.

• Sleep apnoea.

Transient microalbuminuria as a result of these conditions does not indicate any underlying renal damage, and should resolve within several days.

Orthostatic (or postural) proteinuria is relatively common in younger people, and causes low-level albuminuria on standing. It is benign.⁶ It typically causes albuminuria that is present on urine samples taken during the day (whilst awake and upright), but absent on early morning samples (taken after lying down for a prolonged time asleep).

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 follows:²

• 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 dysfunction and has been shown to be an independent risk factor associated with diabetes, CKD, cardiovascular disease, hypertension, venous thromboembolism and all-cause mortality.³

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 recommended.⁷⁸ Children with type 1 diabetes should be screened from the age of 12 years.⁷

CKD⁴

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.

NICE recommends testing for CKD using an eGFR based on serum creatinine levels and urine ACR if they have any of the following risk factors:

• Diabetes.

• Hypertension.

• Previous episode of acute kidney injury.

• Cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease, or cerebral vascular disease).

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

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

• Gout.

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

• Incidental detection of haematuria or proteinuria.

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 population.⁹

Management of microalbuminuria

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 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 if:¹⁰

• 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