Microalbumin

Microalbuminuria is defined as excretion of 30-300 mg of albumin per 24 hours (or 20-200 mcg/min or 30-300 mcg/mg creatinine) on 2 of 3 urine collections. ^{[1, 2]}

The detection of low levels of albumin excretion (microalbuminuria) has been linked to the identification of incipient diabetic kidney disease. This phase calls for aggressive management to prevent or retard overt diabetic nephropathy.

The reference ranges for microalbumin are detailed in the table below. ^{[3, 4]}

Table 1. American Diabetic Association Classification of Microalbuminuria (Open Table in a new window)

A normal finding for albumin in urine is less than 2 mg/dL, with normal albumin/creatinine ratios being as follows ^[5] :

• Males: < 17 mg albumin/g creatinine
• Females: < 25 mg albumin/g creatinine

The etiologies of microalbuminuria are as follows: ^[6]

• Early proteinuria of any cause

• Acute hyperglycemia

• Urinary tract infection

• Marked hypertension

• Congestive heart failure

• Menses (false positive)

Causes of overt proteinuria are as follows:

• Amyloidosis

• Bladder tumor

• Congestive heart failure

• Glomerulonephritis

• Goodpasture syndrome

• Heavy metal poisoning

• Nephrotoxic drugs

• Polycystic kidney disease

• Preeclampsia

• Systemic lupus erythematosus

• Urinary tract infection

Specifics for collection and panels are as follows:

• Specimen type: Urine

• Container: Plastic urine tube

• Collection method: 24-hour collection or random urine specimen

• Specimen volume: 5 mL

Other instructions are as follows:

• No preservatives in 24-hour collection container

• Confirm positive findings with second specimen

Microalbuminuria is defined as excretion of 30-300 mg of albumin per 24 hours (or 20-200 mcg/min or 30-300 mcg/mg creatinine) on 2 of 3 urine collections. ^[1]

The detection of low levels of albumin excretion (microalbuminuria) has been linked to the identification of incipient diabetic kidney disease. This phase calls for aggressive management, to prevent or retard overt diabetic nephropathy.

Microalbuminuria is a predictor of outcome in patients with renal disease. Additionally, it is a predictor of morbidity and mortality in patients who do not have evidence of significant renal disease. In patients with hypertension, microalbuminuria has been correlated to left ventricular hypertrophy. Both in hypertensive and normotensive patients, microalbuminuria predicts an increased risk of cardiovascular morbidity and mortality.

Although 24-hour excretion has traditionally been preferred, the albumin/creatinine ratio has been shown to be a similarly valid screening tool for diabetic nephropathy. ^{[7, 8]}

In a study of patients who had suffered a minor stroke/transient ischemic attack (TIA), Strain et al found evidence that the presence of microalbuminuria can help in predicting future major adverse cardiac events (MACEs). The investigators reported that in study patients with microalbuminuria (in these cases, an albumin/creatinine ratio of >2.5 mg/mol in men or >3.5 mg/mol in women), the risk of a MACE by 90 days was greater than in those with a low albumin/creatinine ratio, the hazard ratio being 1.66. Moreover, the 90-day mortality rate was more than five times greater in patients with microalbuminuria. However, the report stated that microalbuminuria did not have a high enough positive or negative predictive value to be used alone in predicting outcomes in patients with minor stroke/TIA, with the investigators instead finding it to be reliable when employed in combination with patient age and stroke/TIA history. ^[9]

Indications/Applications

See the list below:

• Annual screening for microalbuminuria is indicated for all individuals with diabetes mellitus.

• Screening for microalbuminuria is used in the diagnosis of renal dysfunction. ^[3]

• In diabetic and hypertensive patients, microalbuminuria is a predictor of future development of clinical renal disease. It is also a predictor of cardiovascular morbidity and mortality.

Considerations

Doing a 24-hour urine collection for proteinuria and creatinine clearance is unnecessary because a spot urine sample to measure urine albumin to creatinine ratio is quite sufficient for diagnosis and therapy. ^[4] More importantly, exercise, dietary protein, and sustained upright posture tend to increase albumin excretion rates.

Conventional 24-hour urine collection for albumin shows wide variation in excretion of albumin in urine. Additionally, it is very inconvenient to the patient. The albumin-creatinine ratio in early morning spot urine collected on awakening (before breakfast or exercise) is considered as a valid test for albumin excretion in urine. It is simple and inexpensive; it does not require a timed 24-hour collection of urine; and, most importantly, it gives a quantitative result that correlates well with 24-hour urine values over a wide range of protein excretion. A ratio of albumin (mcg/L) to creatinine (mg/L) of less than 30 is normal; a ratio of 30-300 signifies microalbuminuria and values above 300 are considered as macroalbuminuria. ^[4] On a standard urine dipstick, 10-20 mg/dL is the minimal detection limit of protein. If the dipstick is positive, then the patient likely has microalbuminuria. ^[4] Microalbuminuria is not detectable by the urine dipstick.

Reduction in glomerular filtration rate is usually preceded by microalbuminuria. Microalbuminuria signals the renal and cardiovascular complications from diabetes and, therefore, all diabetic patients should have their urine tested for microalbumin on an annual basis. It is unnecessary to test microalbuminuria in patients with established proteinuria. Antihypertensive therapy decreases albuminuria and diminishes its progression even in normotensive diabetic patients. ^[10]

Therapy with angiotensin-converting enzyme inhibitors (ACEI) reduces the risk of overt nephropathy associated with microalbuminuria in type 1 and 2 diabetes, and similar effect is also seen in patients with type 2 diabetes treated with angiotensin receptor blockers (ARB). ^{[11, 12]} Insufficient data exist to validate the use of combination ACEI and ARB therapy in patients with microalbuminuria. The Heart Outcome Prevention Evaluation (HOPE) study demonstrated that diabetic patients with microalbuminuria treated with ACEI have a significantly lower risk of cardiovascular morbidity and mortality. ^[12]

Albuminuria is a risk factor for progressive renal function loss. Albuminuria can be reduced effectively by inhibitors of renin-angiotensin system (RAS). Maximum reduction of albuminuria to the lowest possible level should be the goal of renoprotective therapy. ^[13] Up-titration of benazepril or losartan against proteinuria showed further benefit on renal outcome in patients without diabetes but with proteinuria and renal insufficiency. ^[14]